Clinical Research Regulation For India and Kenya

Last content review/update: November 26, 2024

Overview

In accordance with the 2019-CTRules and the Hdbk-ClinTrial, the Drugs Controller General of India (DCGI), who heads the Central Drugs Standard Control Organization (CDSCO), is responsible for reviewing and approving clinical trial applications for all new drugs, investigational new drugs (INDs), and imported drugs to be registered in India. Additionally, per the 2019-CTRules, the G-ICMR, and IND-31, the DCGI and a DCGI-registered ethics committee (EC) must approve a clinical trial application prior to the sponsor (also known as applicant) initiating the trial, except in the case of non-regulatory academic/research clinical trials that only require EC approval. Refer to the Scope of Review section for detailed information on non-regulatory academic/research clinical requirements. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.)

As per the 2019-CTRules and the Hdbk-ClinTrial, the scope of the DCGI assessment includes a review of applications for IND and new drug clinical trials, global clinical trials (GCTs), and post marketing studies (Phases I-IV). Per Notice18Feb20, which clarifies information provided in IND-31, the 2019-CTRules are only applicable to new drugs and investigational new drugs. (Note: the Hdbk-ClinTrial has not yet been updated to fully align with the 2019-CTRules.)

The 2019-CTRules defines a “new drug” as:

A drug, including active pharmaceutical ingredients or phytopharmaceutical drugs, that has not been used in the country to any significant extent
A drug that has already been approved by the DCGI and is now proposed to be marketed with modified or new claims
A fixed dose combination of two (2) or more drugs, individually approved for earlier specific claims, and which are now proposed to be combined for the first time in a fixed ratio, or, if the ratio of ingredients in an already marketed combination is proposed to be changed
A modified or sustained release form of a drug, or novel drug delivery system of any drug approved by the DCGI
A vaccine, recombinant Deoxyribonucleic Acid (r-DNA)-derived product, living modified organism, monoclonal antibody, cell, or stem cell derived product, gene therapeutic product, or xenografts intended to be used as a drug

Per the 2019-CTRules and IND-31, the above listed drugs, excluding the modified/sustained drug forms and biological drug products, will be deemed new for four (4) years from the date of first approval. The modified/sustained drug forms and biological products including vaccines should always be viewed as new drugs. See also IND-6 for additional information on the revised definition of “new drug” under the 2019-CTRules.

The 2019-CTRules defines an IND as a new chemical or biological entity or a product having therapeutic indication but that has never been tested on human beings, and as also noted in IND-31, has not been approved as a drug for marketing in any country.

In addition, according to IND-31, the DCGI review and approval process may be conducted in parallel with the institutional or independent EC review for each clinical trial site. However, per the 2019-CTRules and the Hdbk-ClinTrial, CDSCO must confirm that the EC approvals for each participating site have been obtained per the protocol prior to approving the initiation of the study. (See the Scope of Review section for more information.)

Clinical Trial Review Process

As set forth in the 2019-CTRules and the Hdbk-ClinTrial, the DCGI is responsible for reviewing and approving clinical drug applications. The evaluation timeline is dependent upon whether the investigational drugs under review are developed outside India, or discovered, researched, and manufactured in India. (Refer to the Timeline of Review section for detailed CDSCO timeline information.)

Per the Hdbk-ClinTrial, upon receipt of an application (via Form CT-04 which is found in the 2019-CTRules), a CDSCO official is responsible for conducting the initial administrative review. If the application is deemed complete, the official forwards the application along with a summary of the evaluation and a statement referring the proposal to a Subject Expert Committee (SEC) for further technical review. If the proposal is not accepted by the SEC, the sponsor may request additional consideration of the proposal by the Technical Committee. Otherwise, only the SEC’s recommendations are required for the DCGI (CDSCO) to issue a final decision to the Technical or Apex Committee. Additionally, per Notice31Jan24, CDSCO’s SEC Division is responsible for conducting meetings to evaluate IND proposal submissions. See the Submission Process section for CDSCO submission requirements.

Per the Hdbk-ClinTrial, SECs are usually comprised of six (6) experts representing various therapeutic areas, including pharmacologists/clinical pharmacologists, and medical specialists. However, Order13Jan20, issued in accordance with the 2019-CTRules, indicates that SECs will be comprised of eight (8) medical experts, specifically one (1) pharmacologist and seven (7) medical specialists. Per the Hdbk-ClinTrial, SECs are responsible for advising CDSCO with in-depth evaluations of non-clinical data (including pharmacological and toxicological data) and clinical trial data (Phases I-IV) provided by the sponsors for approval. The 2019-CTRules further notes that the DCGI may, when required, constitute one (1) or more of these expert committees or group of experts with specialization in relevant fields to evaluate scientific and technical drug-related issues.

Additionally, per Order13Jan20, SECs will evaluate and advise the DCGI on proposals in various categories for the approval of new drug and clinical trial applications. These include the following: new drug substances of chemical and biological origin including vaccines and r-DNA derived products; subsequent approval of new drug and biological products including vaccines and r-DNA derived products already approved in the country; global clinical trials; fixed dose combinations of two (2) or more drugs to be introduced for the first time in the country; causality analysis, drug safety, or any other technical matter requiring expert advice in the opinion of the Ministry of Health and Family Welfare (MOHFW) or the DCGI. See Order13Jan20 for the complete terms of reference required to constitute SECs.

Once an SEC has completed its review, the Hdbk-ClinTrial indicates that the committee sends its comments via email to CDSCO. CDSCO will then compile any written SEC comments requiring sponsor clarification or modification and sends this feedback to the sponsor. The sponsor must submit a written reply to CDSCO, which is also sent to the SEC for review.

Following receipt of the sponsor’s response, the DCGI (CDSCO) will issue a final decision by official communication (permission, rejection, or resubmission) to the Technical or Apex Committee. In the case of a sponsor’s request for reconsideration, CDSCO will review the resubmitted application and send it to the SEC again, or, to the Technical Committee per the sponsor’s request. Following the SEC’s review, the DCGI (CDSCO) will send a final decision to the Technical or Apex Committee. If CDSCO rejects the reconsideration request, the agency will send a letter to the sponsor to communicate this decision. Refer to the Hdbk-ClinTrial for additional timeline information.

Per the 2022-CTRules-3rdAmdt, which amends the 2019-CTRules, upon obtaining approval from the DCGI, the sponsor must notify CDSCO via Form CT-06A (see 2022-CTRules-3rdAmdt) prior to initiating the clinical trial. The DCGI will then record the information provided on this form and it will become part of the official record known as the approval of the DCGI. The DCGI grants permission to initiate a clinical trial via either Form CT-06 (see 2019-CTRules) or as an automatic approval via Form CT-4A (see 2019-CTRules). 2022-CTRules-3rdAmdt further states that when the DCGI approves a clinical trial of a new drug already approved outside India per the 2019-CTRules, the sponsor must also notify CDSCO via Form CT-06A, and this record will become part of the official record known as the guaranteed approval of the DCGI.

Per the 2019-CTRules, the DCGI’s permission to initiate a clinical trial granted via either Form CT-06 or as an automatic approval via Form CT-4A will remain valid for two (2) years from the date of its issue, unless extended by the DCGI as noted in the 2019-CTRules and IND-31.

In addition, per the 2019-CTRules, an investigator should not implement any deviations from or changes to the protocol without the sponsor’s agreement and after obtaining the EC’s prior review and documented approval or favorable opinion of the amendment. All protocol amendments should be submitted to the DCGI in writing along with the EC approval letter. Similarly, the G-ICMR indicates that the EC must review and approve any protocol amendments, major deviations, or violations prior to those changes being implemented.

The 2019-CTRules explains that the exception to this requirement is when it is necessary to eliminate an immediate hazard to the trial participant or when the changes involved are only logistical or administrative in nature. In this case, the EC as well as the DCGI must be notified immediately of all such exceptions. The DCGI should be notified of administrative or logistical changes or minor amendments in the protocol within 30 days.

The Hdbk-ClinTrial and the 2019-CTRules also note that application reviews should be based on the following evaluation parameters:

Assessment of risk versus benefit to the patients
Innovation vis-à-vis existing therapeutic option
Unmet medical need in the country
Safety/dosage/investigational tests (e.g., pharmacogenetic tests)
Any additional information or study(ies) needed before marketing approval for inclusion in package insert/ summary product characteristic (SmPC) post marketing

See IND-46 for additional information on conducting clinical trials in India. For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see the G-GeneThrpy and the G-StemCellRes.

(See the Submission Process and Submission Content sections for detailed submission requirements.)

Waiving Local Clinical Trials

As delineated in the 2019-CTRules and IND-31, the DCGI, with the approval of the Central Government, may waive the requirement to conduct a local trial for a new drug already approved outside India. Order7Aug24, in accordance with Rule 101 in the 2019-CTRules, further specifies that the United States, the United Kingdom, Japan, Australia, Canada, and the European Union are the countries for which the DCGI may waive a local clinical trial for applications requesting permission to conduct a clinical trial and for applications requesting permission to import or manufacture new drugs in the following new drug categories:

Orphan drugs for rare diseases
Gene and cellular therapy products
New drugs used in pandemic situations
New drugs used for special defense purpose
New drugs having significant therapeutic advance over the current standard care

The 2019-CTRules explains that for applications to request permission to import or manufacture a new drug, a local clinical trial may be waived if the following conditions are met:

The new drug is approved and marketed in the countries specified by the DCGI in Order7Aug24, and no major unexpected serious adverse events have been reported, or
The DCGI has already granted permission to conduct a Global Clinical Trial with the new drug that is currently ongoing in India and this new drug has also been approved for marketing in one (1) of the countries to be specified by the DCGI in Order7Aug24, and
There is no probability or evidence, on the basis of existing knowledge, of any difference in the metabolism of the new drug by the Indian population, or any factor that may affect the pharmacokinetics, pharmacodynamics, and safety and efficacy of the new drug, and
The applicant has committed in writing to conducting a Phase IV clinical trial to establish the new drug’s safety and efficacy per the DCGI-approved formulation

For countries that do not meet the waiver eligibility requirements, the 2019-CTRules states that these applications must be approved by the DCGI within 90 working days from the date of application receipt. Refer to the Manufacturing & Import section for detailed information on import requirements for new drugs already approved outside of India. See also IND-6 for additional information on local clinical trial waivers to import or manufacture new drugs under the 2019-CTRules.

Revising New Drug Definition and Waivers of Local Clinical Trial Data

2-3, 7, 10-11, 18, 22, 25, 31-33, 38, and 79

Preface, 4.0, 5.0-5.2, 5.22, 8.2, and Appendix 8.3

4.8 (Table 4.2) and 7.0-7.1

7.11 and Annexures I, II, and III

4, 11.2, and Annexures I and II

1

4-6 and 12

Chapter I (2), Chapter II (3), Chapter III (11), Chapter V (19-26, and 28), Chapter X (75 (7) and 80 (7)), Chapter XIII (100-101), First Schedule (3), Second Schedule (1 and Table 1), Third Schedule (1 and Table 4), Fourth Schedule (7), and Eighth Schedule (Forms CT-04, CT-4A, and CT-06)

Last content review/update: July 2, 2024

Overview

In accordance with the PPA, the CTRules, the G-KenyaCT, and KEN-21, Kenya’s Pharmacy and Poisons Board (PPB), together with its Expert Committee on Clinical Trials (ECCT), is responsible for reviewing, evaluating, and approving applications for clinical trials using registered or unregistered investigational products (IPs). The G-KenyaCT specifies that the scope of the PPB’s assessment includes all clinical trials (Phases I-IV). As delineated in the CTRules, the G-KenyaCT, and KEN-21, the PPB review and approval process may not be conducted in parallel with the ethics committee (EC) review. Rather, EC approval must be obtained prior to applying for PPB approval. As delineated in the STI-Act and G-ECBiomedRes, the principal investigator or the head of a research institution must obtain a favorable opinion from an EC accredited by the National Commission for Science, Technology and Innovation (NACOSTI) and a NACOSTI research license prior to initiating a study.

Clinical Trial Review Process

Pharmacy and Poisons Board

Per the CTRules and the G-KenyaCT, the PPB, through the ECCT, communicates the decision to approve, request additional information, or reject the application to the sponsor or the representative in writing within 30 working days of receiving a valid application. The G-KenyaCT indicates that in the case of rejection, the applicant may appeal and provide additional information to satisfy PPB requirements. In specific cases, the PPB may decide to refer the matter to external experts for recommendation.

As specified in the G-KenyaCT, each ECCT member, prior to reviewing the application, will declare any conflict of interest in the study and should have no financial or personal interests, which could affect their impartiality. During the protocol review, the reviewers must use the standard criteria (including available clinical and non-clinical data etc.) defined by the PPB. Confidentiality must be maintained during the review. Per the CTRules and the G-KenyaCT, the PPB/ECCT’s review must consider:

The reliability and robustness of the data generated in the clinical trial, taking into account statistical approaches, design of the clinical trial, and methodology, including sample size and randomization, comparator, and endpoints
Compliance with the requirements concerning the manufacturing and import of IPs and auxiliary medicinal products
Compliance with the labelling requirements
The completeness and adequateness of the investigator's brochure

Regarding protocol amendments, the CTRules and the G-KenyaCT stipulate that any new information affecting the conduct/management of the trial, safety of the participants, and manufacture of the IP necessitating changes to the protocol, consent form, and trial sites require immediate submission of the amended documents to PPB for review and approval. Arrangements must be in place to take appropriate urgent safety measures to protect participants against any immediate hazard where new events relating to the conduct of the trial, or the development of the IP are likely to affect the safety of the participants. A copy of a favorable opinion letter from the EC on record must be submitted with the request for approval of a proposed amendment to the PPB. PPB approval must be obtained for all substantial amendments. Minor amendments or administrative changes may be implemented after getting the EC’s approval, but a record of these amendments must be kept for possible inspection by the PPB. See Submission Process and Submission Content sections for additional details on amendment submissions. Also, see the G-KenyaCT for examples of substantial amendments.

In addition, per the G-KenyaCT, the sponsor or the representative is required to request approval annually from the PPB at least six (6) weeks prior to the expiration of the previous approval.

Per the CTRules and the G-KenyaCT, the PPB may withdraw the authorization to conduct a clinical trial if it finds that the safety of the participants in the trial is compromised or that the scientific reasons for conducting the trial have changed. Additionally, per the CTRules, the PPB may revoke the approval if it determines that the IP has expired or is not usable.

As delineated in the G-KenyaCT, the PPB may inspect clinical trial sites to ensure that the generally accepted principles of good clinical practice (GCP) are met. The objectives of the inspection are to:

Ensure that participants are not subjected to undue risks and that their rights, safety, and wellbeing are protected
Validate the quality of the data generated
Investigate complaints
Verify the accuracy and reliability of clinical trial data submitted to the PPB in support of research or marketing applications
Assess compliance with PPB guidelines and regulations governing the conduct of clinical trials
Provide real-time assessment of ongoing trials

Per CRO-Inspect, the PPB is responsible for inspecting clinical trial and bioequivalence study sites that generate data for registration of medicines. The PPB requires that these sponsor and contract research organization sites comply with applicable good practices, including GCP, good laboratory practice (GLP), and good documentation practices. Based on risk assessments, the PPB will determine compliance with generally accepted good practice through inspections and, where appropriate, document reviews. In addition, see Cert-Emrgcy for information about GCP and good manufacturing practice certifications during emergencies.

Special Circumstances and Public Health Emergencies

The CTRules delineates that the PPB may, in special circumstances, authorize the conduct of a clinical trial under fast-track procedures or non-routine procedures. PPB may recognize and use clinical trial decisions, reports, or information from other competent authorities authorizing fast-track clinical trials. The special circumstances may include:

A public health emergency
The rapid spread of an epidemic disease
Any other circumstance as may be determined by the PPB

The G-KenyaCT outlines PPB’s scope of assessment of a clinical trial application during a public health emergency. The PPB will conduct an expedited review and liaise with relevant stakeholders (including relevant ECs and other oversight bodies) to facilitate a holistic review of an application in a fast-track manner. The following prioritization criteria must be applied in the selection of applications for expedited review:

Epidemiology of the emergency
Morbidity and mortality associated with the emergency and/or condition under study
Supporting scientific data/information available for the IP at the time of submission
Feasibility of the implementation of the trial design within the context of the emergency
Benefit impact of the intervention and/or trial design

In addition, PPB’s assessment will consider the following:

The research does not compromise the response to an outbreak or appropriate care
Studies are designed to yield scientifically valid results under the challenging and often rapidly evolving conditions of disasters and disease outbreak
The research is responsive to the health needs or priorities of the disaster victims and affected communities and cannot be conducted outside a disaster situation
The participants are selected fairly and adequate justification is given when particular populations are targeted or excluded, for example, health workers
The potential burdens and benefits of research participation and the possible benefits of the research are equitably distributed
The risks and potential individual benefits of experimental interventions are assessed realistically, especially when they are in the early phases of development
Communities are actively engaged in study planning to ensure cultural sensitivity, while recognizing and addressing the associated practical challenges
The individual informed consent of participants is obtained from individuals capable of giving informed consent
Research results are disseminated, data are shared, and any effective interventions developed or knowledge generated are made available to the affected communities

National Commission for Science, Technology and Innovation

STI-Act stipulates that NACOSTI issues research licenses if it finds that the conduct of the research is beneficial to the country and will not adversely affect any aspect of the nature, environment, or security of the country. The license issued will have NACOSTI’s seal and will indicate the commencement and expiration of the research. In addition, NACOSTI maintains a register of all persons granted a license, which is available for public inspection during normal working hours free of charge.

KEN-31 states that if a research license application does not meet the conditions required under the STI-Act, NACOSTI must reject the application and communicate the reasons to the applicant. Any person may appeal NACOSTI’s decision to the Cabinet Secretary within 30 days of being notified of the decision. For approved research, NACOSTI may conduct an evaluation to assess compliance with the conditions of the license. If the research project has not been completed within the stipulated period, the researcher may apply for renewal of the license and pay the requisite fee. The researcher is expected to apply for renewal by attaching a progress report instead of a proposal. KEN-31 indicates that the duration of the research license is one (1) year.

Forward and 1

Glossary of Terms, Introduction, 1.1, 1.7-1.25, 1.189, 1.492-1.506, 1.519-1.534, 1.557-1.574, and Annex 7

3A, 3B, and 25A

Part IV

Part II (Sections 4 and 5), Part IV (Sections 11 and 18), and Part V (Sections 19 and 23)

Regulatory Fees

Last content review/update: June 21, 2024

Central Drugs Standard Control Organization

As per the 2019-CTRules, IND-43, and IND-42, a sponsor (also known as applicant) is responsible for a paying a fee to the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), to submit a clinical trial application. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.)

The 2019-CTRules and IND-43 specify that Form CT-04 should be accompanied by one (1) of the following officially mandated fees:

3,00,000 Rupees for Phase I (human) clinical trials
2,00,000 Rupees for Phase II (exploratory) clinical trials
2,00,000 Rupees for Phase III (confirmatory) clinical trials
2,00,000 Rupees for Phase IV clinical trials
50,000 Rupees for reconsideration of application for permission to conduct clinical trial

According to the 2019-CTRules, the sponsor must also submit a fee of 5,000 Rupees per product with an application for permission to manufacture or import the investigational product (IP) to be used in a clinical trial.

In addition, the 2019-CTRules states that no fee is required to be paid along with the clinical trial application if a trial is being conducted by an institution or an organization wholly or partially funded or owned by the Central Government of India or one of India’s state government institute(s).

See also IND-31 for additional information on CDSCO fee requirements.

In addition, IND-24 indicates that for applications submitted to the National Single Window System (NSWS) portal (IND-3), users should pay any required fees directly to CDSCO or any other ministry/department/state responsible for processing the application via the NSWS portal (IND-3). At this time, however, per IND-14, only a few CDSCO steps and processes (e.g., medical device related registration, manufacturing/import applications and drug manufacturing/import applications) have been moved to the NSWS portal (IND-3).

Payment Instructions

As described in the 2019-CTRules and IND-43, payment must be made electronically via the Bank of Baroda, Kasturba Gandhi Marg, New Delhi-110001, any other Bank of Baroda branch, or any other bank approved by the Ministry of Health and Family Welfare (MOHFW) via the State Bank of India’s SBIePay payment gateway, which is accessed from the SUGAM portal (IND-59). The payment should be credited to: Head of Account, 0210-Medical and Public Health, 04-Public Health, 104-Fees and Fines per the 2019-CTRules, also known as the head of Fees & Fines, according to IND-42.

According to IND-43 and IND-42, once the user validates the payment information in the SUGAM portal (IND-59), the payment request is redirected to the SBIePay payment gateway. When the payment is submitted, the bank payment gateway will confirm that the payment was successful, and the user will be redirected to the online payment status page in the SUGAM portal (IND-59) to view the e-Challan (payment receipt).

IND-43 and IND-42 also specify that the online payment will take two (2) to three (3) days to be credited to the National Portal of India’s Payment & Account Office. Therefore, users are requested to initiate online payments at least three (3) days prior to submitting an application to CDSCO. Refer to IND-43 and IND-42 for detailed fee requirements and online payment instructions via the SUGAM portal (IND-59).

(Note: Although the fees listed in IND-43 are correct, the SUGAM portal (IND-59) and associated documentation as well as CDSCO’s Pre-Screening Checklist (IND-32) have not yet been aligned with the 2019-CTRules in terms of referencing the new application form (CT-04). However, the ClinRegs team is regularly monitoring the CDSCO website for new developments and will post the most current sources as they become available.)

Chapter V (21), Chapter XIII (102), Sixth Schedule, and Eighth Schedule (Form CT-04)

1 (INDs) and 3 (Global Clinical Trials)

1 and 6

Last content review/update: July 2, 2024

Pharmacy and Poisons Board

Per the PPA and the G-KenyaCT, the sponsor or the representative is responsible for paying a fee to the Pharmacy and Poisons Board (PPB) to submit a clinical trial application for authorization. The PPB currently requires a non-refundable application fee of $1,000 USD, or the equivalent in Kenya Shillings at the prevailing bank rates.

Payment Instructions

As stated in Annex 2 of the G-KenyaCT, payment is to be made by a bank check payable to the “Pharmacy and Poisons Board” and presented to the PPB’s accounts office upon submitting the application.

Payment can also be made by electronic fund transfer (EFT) to the PPB Bank account, if required. The sponsor or the representative is responsible for all bank charges associated with the EFT. Details of the EFT payment should be obtained from the PPB prior to initiating such a transaction.

National Commission for Science, Technology and Innovation

As delineated in KEN-31, the National Commission for Science, Technology and Innovation (NACOSTI) charges a fee that varies depending on the applicant’s status as Kenyan or non-Kenyan, and standing as a researcher (i.e., student, public/private institution, private company). The fees are non-refundable and also apply to research license renewals. Details on additional requirements are provided in the Submission Content section.

Student, Undergraduate/Diploma: East African Community (EAC) Countries – 100 Kenya Shillings; Kenyan Citizens – 100 Kenya Shillings; Rest of Africa – 200 Kenya Shillings; Non-Africans - $150 USD
Research (Masters): EAC Countries – 1,000 Kenya Shillings; Kenyan Citizens – 1,000 Kenya Shillings; Rest of Africa – 2,000 Kenya Shillings; Non-Africans - $350 USD
Research (PhD): EAC Countries – 2,000 Kenya Shillings; Kenyan Citizens – 2,000 Kenya Shillings; Rest of Africa – 4,000 Kenya Shillings; Non-Africans - $400 USD
Post-Doctoral: EAC Countries – 5,000 Kenya Shillings; Kenyan Citizens – 5,000 Kenya Shillings; Rest of Africa – 10,000 Kenya Shillings; Non-Africans - $500 USD
Public Institutions: Kenyan Citizens – 10,000 Kenya Shillings
Private Institutions, Commercial/Market Research, Companies: Kenyan Citizens – 20,000 Kenya Shillings

See KEN-31 for information on service charges.

Payment Instructions

Per KEN-31, NACOSTI has migrated payment services for research licensing to the eCitizen platform (KEN-12). East African citizens have the following payment options on KEN-12 with a Kenya Shillings account: mobile money via Mpesa Express or Paybill Number 222222; or these other available payments via KEN-12:

Airtel Money
Kenya Commercial Bank
Co-operative Bank
Pesaflow Direct
National Bank
RTGS

KEN-31 indicates that non-Kenyans should use the US Dollar account on KEN-12 with these payment options:

Kenya Commercial Bank (USD)
Co-operative Bank (USD)
NBK (USD)
Equity Cash
Debit/credit/prepaid card

1.7-1.12 and Annex 2

3A and 25A

Ethics Committee

Last content review/update: June 21, 2024

Overview

As delineated in the 2019-CTRules and IND-31, India has a decentralized process for the ethical review of clinical trial applications, and requires ethics committee (EC) approval for each trial site. Because there is no national EC in the country, ECs are based at either institutions/organizations, or function independently, and must meet the requirements set forth in the 2019-CTRules and the G-ICMR. Prior to initiating and throughout the duration of a trial, every trial site must be overseen by an EC registered with the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO). (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.)

Ethics Committees for Biomedical and Health Research

Per the 2019-CTRules, CDSCO requires institutions that intend to conduct biomedical and health research to have an EC that reviews and oversees this type of research study. In addition, CDSCO has also established a separate registration and monitoring system for ECs that review biomedical and health research. See the Scope of Review section for additional information on biomedical and research study requirements.

Ethics Committee Composition

Pursuant to the 2019-CTRules and the G-ICMR, an institutional/independent EC should be multidisciplinary and multi-sectorial, representing a mixed gender and age composition. ECs that review clinical trial applications and those that review biomedical and health research share the same composition criteria including affiliations, qualifications, member specific roles and responsibilities, as well as terms of reference and review procedures.

The 2019-CTRules and the G-ICMR state that an EC should appoint from among its members a chairperson (from outside the institution) and a member secretary (generally from inside the institution). The other members should represent a balance of affiliated and non-affiliated medical/non-medical and scientific/non-scientific persons, including the lay public. Per the 2019-CTRules and the G-ICMR, preferably 50% of the members should not be affiliated with the institution.

As per the 2019-CTRules and the G-ICMR, the composition should include the following:

Chairperson from outside the institute (Vice Chairperson (optional))
One (1) to two (2) basic medical scientists (preferably one (1) pharmacologist)
One (1) to two (2) clinicians from various institutions
Legal expert(s) or retired judge
One (1) social scientist/representative of non-governmental voluntary agency
One (1) philosopher/ethicist/theologian
One (1) lay person from the community
Member secretary (Alternative Member secretary optional)
One (1) member whose primary area of interest/specialization is non-scientific
At least one (1) member independent of the institution/trial site

Additionally, per the 2019-CTRules, EC members are required to:

Be familiar with key clinical regulatory requirements as delineated in the 2019-CTRules and the G-ICMR that reference both the Declaration of Helsinki (IND-63) and the most recently updated International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (IND-41)
Have post-graduate qualifications and experience in their fields if representing basic medical scientists/clinicians
Represent the specific patient group as much as possible based on the research area requirement

Terms of Reference, Review Procedures, and Meeting Schedule

As delineated in the 2019-CTRules and the G-ICMR, EC members should be made aware of their roles and responsibilities. The terms of reference should also include a statement on terms of appointment including duration and conditions; policy for removal/replacement; resignation procedure; meeting frequency; payment of processing fee to EC for review; honorariums to members and invited experts; maintenance of EC documentation and communication records, etc. Each committee should specify these terms in its own standard operating procedures (SOPs) that should be made available to each member.

In addition, per the 2019-CTRules and the G-ICMR, members should have no conflict of interest, and should voluntarily withdraw from the EC while making a decision on an application if a proposal evokes a conflict of interest. The G-ICMR indicates the term of membership is generally two (2) to three (3) years, and may be extended.

In terms of training, the G-ICMR also specifies each member must:

Provide a recent signed Curriculum Vitae (CV) and training certificates on human research protection and good clinical practice (GCP) guidelines, if applicable
Either be trained in human research protection and/or GCP at the time of induction into the EC, or undergo training and submit training certificates within six (6) months of appointment (or as per institutional policy)
Be willing to undergo training or update their skills/knowledge during their tenure as an EC member

Further, if required, the 2019-CTRules and the G-ICMR, state subject experts could also be invited to offer their views, which must be recorded; however, the experts would not have any voting rights. Only members independent of the trial and the trial sponsor (also known as applicant) should vote/provide opinions in study related matters. In addition, all records must be safely maintained after the completion or termination of the study for at least five (5) years from the date of the trial’s completion or termination (both hard and soft copies).

The G-ICMR specifies that all EC members should review all proposals. Members should be given at least one (1) week to review the proposal and related documents, except in the case of expedited reviews. The Member Secretary should screen the proposals for their completeness and categorize them into three (3) types according to risk level: exemption from review, expedited review, or full committee review. An investigator cannot decide that a protocol falls in the exempted category without an EC review. Per the 2019-CTRules and the G-ICMR, a minimum of five (5) members is required for the quorum.

For detailed EC procedures and information on other administrative processes, see the 2019-CTRules, the G-ICMR, and IND-5. See also IND-27 and IND-28 for the Indian Council of Medical Research (ICMR)’s research conduct policies.

2.1, 2.8, 4.0-4.4, 4.10, Tables 4.1-4.3, Glossary, and Annex 1

Chapters I, III-IV, and V (19-20 and 25); Third Schedule (1 and Table 1); and Eighth Schedule (Forms CT-01 and CT-02)

Sections 1-4

32-33

Last content review/update: July 2, 2024

Overview

As per the G-KenyaCT, the G-ECBiomedRes, and KEN-30, Kenya requires an independent review of research through a National Commission for Science, Technology and Innovation (NACOSTI)-accredited ethics committee (EC) in one (1) of the local institutions charged with the responsibility of conducting research in human participants. KEN-25 provides a list of the accredited institutional ECs.

Ethics Committee Composition

As delineated in the G-ECAccred, institutional ECs should consist of at least seven (7) members, or an odd number above seven (7). The G-ECBiomedRes states that these members should be multidisciplinary and multisectoral in composition, collectively encompass relevant scientific expertise, balanced age and gender distribution, and include laypersons representing community interests and concerns. Per the G-ECAccred, the composition should meet the following requirements:

At least one (1) member with knowledge and understanding of Kenyan law
At least one-third of the members must be female, and one-third must be male
At least one (1) member who is unaffiliated with the institution
At least two (2) members must have research expertise and experience, one (1) of whom must be in the health field
At least one (1) member must be a lay member
For ECs reviewing clinical research, at least two (2) members must be clinicians, one (1) of whom is currently in active practice or clinical research
Reflect the regional and ethnic diversity of the people of Kenya

The chairperson must also have some basic training and/or experience in bioethics and leadership. All EC appointments are the responsibility of the institution’s administrative head. See the G-ECAccred and the G-ECBiomedRes for detailed institutional EC requirements.

Terms of Reference, Review Procedures, and Meeting Schedule

Per G-ECBiomedRes, ECs need to have independence from political, institutional, professional, and market influences. As delineated in the G-ECAccred, the G-ECBiomedRes, and the STI-Regs, institutional ECs must operate within written standard operating procedures (SOPs) which delineate the EC’s process for conducting reviews. Per the G-ECAccred, SOPs should include but are not limited to information on EC scope, responsibility, and objectives, institutions served, committee functions, terms and conditions of member appointment, business procedures including meeting schedules and types of reviews, documentation, recordkeeping, and archiving procedures, quorum requirements, communication procedures, and complaint process and dispute resolution procedures. Per the G-ECAccred and the STI-Regs, these documents must be provided to NACOSTI.

Per the G-ECAccred, the quorum for NACOSTI-accredited EC meetings must be:

At least 50 percent of the membership must form the quorum
A lay person must be present in all meetings
For ECs reviewing clinical research, at least two (2) members must be clinicians, one (1) of whom is currently in active practice or clinical research.

The G-ECBiomedRes also defines quorum requirements:

The minimum number of members required to compose a quorum (e.g., more than half the members)
The professional qualifications requirements (e.g., physician, lawyer, statistician, paramedical, or layperson) and the distribution of those requirements over the quorum; no quorum should consist entirely of members of one (1) profession or one (1) gender; a quorum should include at least one (1) member whose primary area of expertise is in a non-scientific area, and at least one (1) member who is independent of the institution/research site

Per G-ECBiomedRes, EC member terms of appointment should be established that include the duration of an appointment, the policy for the renewal of an appointment, the disqualification procedure, the resignation procedure, and the replacement procedure. A statement of the conditions of appointment should be drawn up that includes the following:

A member should be willing to publicize their full name, profession, and affiliation
All reimbursement for work and expenses, if any, within or related to an EC should be recorded and made available to the public upon request
A member should sign a confidentiality agreement regarding meeting deliberations, applications, information on research participants, and related matters

Regarding training, EC members should have initial and continued education regarding the ethics and science of biomedical research. The conditions of appointment should indicate the availability and requirements of introductory training, as well as on-going continuing education. This education may be linked to cooperative arrangements with other ECs in the area, country, and region.

For detailed institutional EC requirements and information on other administrative processes, see the G-ECAccred and the G-ECBiomedRes. See KEN-17 and KEN-26 for examples of accredited EC submission and review guidelines.

Review Process, Submission Forms, Electronic Submission, SERU Applicant SOPs, and Contact Us

Definition of Terms, 1.0, 2.0, 3.0, 4.0, and Annexes I-III

1 and 7.1

1.188-1.212 and 1.492-1.496

The Science, Technology and Innovation (Registration and Accreditation of Research Institutions) Regulations, 2014 (Third Schedule); and The Science, Technology and Innovation (Relevance and Quality Assurance in Research) Regulations, 2014 (Part II)

Scope of Review

Last content review/update: June 21, 2024

Overview

The primary scope of information assessed by ethics committees (ECs) relates to maintaining and protecting the rights, safety, and well-being of all research participants, especially those in vulnerable populations, in accordance with the requirements set forth in the 2019-CTRules, the G-ICMR, the G-Children, the Declaration of Helsinki (IND-63), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (IND-41). (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these populations).

The 2019-CTRules and the G-ICMR also state that ECs must ensure an independent, timely, and competent review of all ethical aspects of the research protocols. They must act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants, and they must verify the adequacy of confidentiality and privacy safeguards. Per the G-Children, ECs providing opinions on studies involving children should also include members with pediatric expertise. The expert(s) may be permanent EC members or invited as subject experts to provide advice and be consulted on an ad-hoc basis.

See also the G-AI-BiomedRes for EC review guidelines for biomedical and health research proposals involving artificial intelligence-based tools and technologies.

Role in Clinical Trial Approval Process

As per the 2019-CTRules, the G-ICMR, and IND-31, the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), and a DCGI-registered EC must approve a clinical trial application prior to the sponsor (also known as applicant) initiating the trial, except in the case of non-regulatory academic clinical trials that only require EC approval. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.) According to IND-31, the DCGI review and approval process may be conducted in parallel with the EC review for each clinical trial site. However, per the 2019-CTRules and the Hdbk-ClinTrial, CDSCO must confirm the EC approvals for each participating site have been obtained per the protocol prior to approving the initiation of the study. (Note: the Hdbk-ClinTrial has not yet been updated to fully align with the 2019-CTRules.)

The 2019-CTRules, the Hdbk-ClinTrial, and IND-31 specify that an EC must grant a separate approval for each trial site to be used, and the DCGI must be informed of each approval. A trial may only be initiated at each respective site after obtaining an EC approval for that site. The 2019-CTRules and IND-31 further state that if a site does not have an EC, it may obtain approval from another site’s EC provided that it is located within the same city or within a radius of 50 kilometers of the trial site. The DCGI should be notified of the EC’s approval within 15 working days of the approval being granted per the 2019-CTRules. Per the 2019-CTRules and IND-31, the EC of each site should notify the DCGI of its approval and provide a copy within 15 working days of making this decision. Refer to IND-36 for the Indian Council of Medical Research (ICMR)’s EC clinical trials application form.

During a clinical trial, per the 2019-CTRules, an investigator should not implement any deviations from or changes to the trial protocol without agreement by the sponsor and after obtaining the EC’s prior review and documented approval or favorable opinion of the amendment. All protocol amendments should be submitted to the DCGI in writing along with the EC’s approval letter.

The 2019-CTRules further states that the exception to this requirement is when it is necessary to eliminate an immediate hazard to the trial participant or when the changes involved are only logistical or administrative in nature. In this case, the EC as well as the DCGI must be notified immediately of all such exceptions. The DCGI should also be notified of administrative or logistical changes or minor amendments in the protocol within 30 days.

As delineated in the 2019-CTRules, ECs also have a continuing responsibility to monitor approved clinical trials and biomedical and health research studies to ensure ethical compliance throughout the study duration.

For all studies, the G-ICMR indicates that ECs must review and approve any protocol amendments, major deviations, or violations at regular intervals.

There is no stated expiration date for an EC approval in the 2019-CTRules or the G-ICMR. However, per the 2019-CTRules, in the event that an EC revokes its approval of a clinical protocol, it must record its reasons for doing so and immediately communicate this decision to the investigator as well as to the DCGI.

Per the 2019-CTRules, the EC must also maintain data, record, registers and other documents related to the functioning and review the clinical trial for a period of five (5) years after completion of the study. For detailed EC review procedures and information on other administrative processes, see the 2019-CTRules, the G-ICMR, IND-5, and IND-27. See also IND-36 for the EC clinical trial application form, and IND-52 for other commonly used EC review forms.

The G-ICMR further states that research during humanitarian emergencies and disasters can be reviewed by an EC through an expedited review and scheduled/unscheduled full committee meetings, and this may be decided by the member secretary on a case-by-case basis depending on the urgency and need. If an expedited review is done, full ethical review should follow as soon as possible. The EC should also closely monitor the conduct and outcome of research. See Section 12.5 of the G-ICMR for additional information on EC review requirements during humanitarian emergencies.

For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see G-GeneThrpy and G-StemCellRes.

Academic Clinical Trials

As defined by the 2019-CTRules, an academic clinical trial is a clinical trial of a drug already approved for a certain claim and initiated by any investigator, academic or research institution for a new indication or new route of administration, or, new dose or new dosage form, where the results of such a trial are intended to be used only for academic or research purposes and not for seeking DCGI approval or regulatory authority approval in any country for marketing or commercial purpose.

The 2019-CTRules and IND-31 specify that an academic clinical trial does not require DCGI approval as long as the following conditions are met:

The trial is approved by the EC, and
The data generated is not intended for submission to the DCGI

In addition, per the 2019-CTRules and IND-31, the EC should inform the DCGI about the academic trials it has approved and cases where there could be an overlap between the clinical trial for academic and regulatory purposes. If the DCGI does not comment to the EC within 30 days from receiving EC notification, it should be presumed that DCGI permission is not required. See also IND-6 for additional information on academic trial approval requirements.

IND-25 further explains that a drug import license is not required for EC-approved academic trials that will be using a permitted drug formulation with a new indication, a new route of administration, a new dose, or a new dosage form. See the Manufacturing & Import section for detailed information.

Biomedical and Health Research

According to the 2019-CTRules and the G-ICMR, biomedical and health research is defined as studies that include basic research, applied and operational research, or clinical research designed primarily to increase scientific knowledge about diseases and conditions (physical or socio-behavioral); their detection and cause; and evolving strategies for health promotion, prevention, or the amelioration of disease and rehabilitation.

As discussed in Notice15Sept19 and Chapter IV of the 2019-CTRules, any institution or organization that intends to conduct biomedical and health research involving human participants is required to have an EC to review and oversee the conduct of such research before the study is initiated and throughout its duration. See also IND-28 for ICMR’s biomedical and health research conduct policies, and IND-6 for additional information on the regulation of biomedical and health research under the 2019-CTRules.

The EC must also be registered with the designated authority within the Ministry of Health and Family Welfare (MOHFW)’s Department of Health Research (DHR). Refer to the Oversight of Ethics Committees section for detailed registration requirements.

Multicenter Research

As delineated in the G-ICMR, in a multicenter research study, all of the participating study sites are required to obtain approval from their respective ECs. Each EC may conduct a separate review, or the ECs may decide to designate a main EC, with the others choosing to accept its decision. The study sites also typically follow a common protocol to avoid duplication of effort, wastage of time, and issues arising with communication between committees.

Per the G-ICMR, in the event that sites choose to have separate EC reviews, the following requirements must be met:

The participating site ECs/Secretariats should establish communication with one another
If any EC does not grant approval for a study at a site, the reasons must be shared with other ECs and should be considered
The EC can suggest site-specific protocols and informed consent modifications as per local needs

A separate review may be requested for studies with a higher degree of risk, clinical trials, or intervention studies where conduct may vary depending on the site, or, for any other reason that requires closer review and attention. See the G-ICMR for additional participating site requirements when a primary EC is selected for common EC review.

Per the G-ICMR, when the multicenter research study designates one (1) main EC, the nominated EC members that represent the participating sites may attend the meeting of the elected EC. The designated EC should also be in India and be registered with the relevant authority (either the DCGI or the DHR depending on the type of study). In addition, the decision to conduct a common review is only applicable for ECs in India. In the case of international collaboration for research and approval by a foreign institution, the local participating study sites would be required to obtain approval from a local EC. Refer to the G-ICMR for detailed information on multicenter studies that use the common review practice and involve international collaborations.

The G-ICMR further notes that the local site requirements (e.g., informed consent, research implementation and its monitoring) may be performed by the local EC, which would require good communication and coordination between the researchers and the EC secretariats representing the participating sites.

See the G-MultictrResRev for additional guidelines on streamlining the ethics review process for multicenter biomedical and health research studies conducted by the ICMR or its network of institutions.

3.1

7.11 and Annexures I, II, and III

1.0-1.1, 2.1, 2.3, 2.8-2.9, 4.0, 4.2, 4.7-4.8, 4.11, Tables 4.1-4.3, 12.5, Glossary, and Annex 1

4, 11.2, and Annexures I and II

Preface, 4.0, 5.0-5.2, 8.2, and 8.3

Chapter I, Chapter III (7, 11, and 13), Chapter IV (15-17), Chapter V (19-20, 25, and 28), and Third Schedule (1, 3, and Table 4)

1-4

Regulations on Biomedical and Health Research (BHR) and Academic Trials

Introduction and Sections 1-4, and 6

2, 11, and 31-35

1.27 and 3.1

Last content review/update: July 2, 2024

Overview

According to G-ECBiomedRes, the primary scope of information assessed by the institutional ethics committees (ECs) relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial. The G-ECAccred further states that the National Commission for Science, Technology and Innovation (NACOSTI) accredits ECs in order to uphold the standard of ethics review in the country; develop public confidence and trust in the national research system; facilitate equitable access to research and human health records in health facilities; and facilitate coordination and collaboration among ECs. See the G-ECAccred and the G-ECBiomedRes for detailed ethical review guidelines.

Role in Clinical Trial Approval Process

As per the G-KenyaCT and KEN-21, the Pharmacy and Poisons Board (PPB)’s review and approval of a clinical trial application is dependent upon obtaining approval by an accredited institutional EC. Consequently, the PPB and EC reviews may not be conducted in parallel.

As set forth in the G-ECBiomedRes, ECs must be constituted to ensure an independent and competent review and evaluation of all ethical aspects of clinical trials. ECs must review research involving human participants to ensure they meet these ethical principles:

Respect for persons, including respect of autonomy, protection of vulnerable groups, and protection of privacy and confidentiality
Beneficence
Justice, which in research means equitable distribution of the benefits and the burdens

For additional details on the principles and benchmarks for ethical review, see G-ECBiomedRes.

Per the G-ECBiomedRes, expedited review may be permitted for protocols involving no more than minimal risk to research participants.

The G-ECBiomedRes indicates that all ECs should carry out regular monitoring of approved protocols involving human participants. In case of any adverse events, the EC should report this immediately to Kenya’s National Bioethics Committee (NBC).

Per the G-ECBiomedRes, with collaborative research projects, the collaborating investigators, institutions, and countries must function as equal partners with safeguards to avoid exploitation of local researchers and participants. An external sponsoring agency should submit the research protocol to their country’s EC, as well as the Kenyan EC where the research is to be conducted. Further, this research must be responsive to the health needs of Kenya and reasonably accessible to the community in which the research was conducted. Consideration should be given to the sponsoring agency agreeing to maintain health services and faculties established for the purposes of the study in Kenya after the research has been completed. Such collaborative research must have a local/Kenyan co-principal investigator.

1.0-1.2

3.0, 3.1, 4.1, 4.2, 6.0, and 7.1

Glossary of Terms and 1.188- 1.212 and 1.492-1.496

Ethics Committee Fees

Last content review/update: June 21, 2024

As indicated in the G-ICMR, ethics committees (ECs) may charge a reasonable fee to cover the expenses related to optimal functioning to conduct reviews. EC members may also be given reasonable compensation for their time attending EC meetings, and every institution should allocate adequate funds to ensure the smooth functioning of the EC.

4.14

Last content review/update: July 2, 2024

As per the G-KenyaCT, G-ECBiomedRes, and KEN-30, Kenya requires an independent review of research through a National Commission for Science, Technology and Innovation (NACOSTI)-accredited ethics committee (EC) in one (1) of the local institutions charged with the responsibility of conducting research in human participants. The EC fee to review a clinical trial application will vary depending on the institution. See KEN-25 and KEN-38 for lists of NACOSTI-accredited institutional ECs. For an example of institutional fee requirements charged by the Scientific and Ethics Review Unit (SERU) at the Kenya Medical Research Institute (KEMRI), see KEN-27.

Where do I get a letter of ethical approval before applying for a research license?

1, 4.1, and 7.1

Glossary of Terms

Oversight of Ethics Committees

Last content review/update: June 21, 2024

Overview

In accordance with the 2019-CTRules and IND-31, all ethics committees (ECs) that review drug clinical trials are required to register with the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), prior to reviewing and approving a clinical trial protocol. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.) As delineated in Notice15Sept19 and Chapter IV of the 2019-CTRules, all ECs that review biomedical and health research studies are required to register with the designated authority within the Ministry of Health and Family Welfare (MOHFW)’s Department of Health Research (DHR). According to IND-50, the DHR’s Office for Ethics Committee Registration has been designated as the entity responsible for coordinating and monitoring registrations for ECs overseeing biomedical and health research in India. This office will receive applications for registration of ECs and will review and make decisions on EC registrations/re-registrations.

See also IND-69 for an application submission checklist to re-register ECs. Refer to IND-49 for a list of registered ECs, and IND-48 for a list of re-registered ECs.

Registration, Auditing, and Accreditation

Registration Provisions for Clinical Trial Ethics Committees

As specified in the 2019-CTRules and Notice1Aug18, ECs that intend to review clinical trial research protocols must submit Form CT-01 via the SUGAM portal (IND-59) to register with the DCGI. The DCGI, in turn, will review the application within 45 working days from the date of receipt and, if satisfied with the information provided, grant the EC's registration request via Form CT-02. Per 2022-CTRules-3rdAmdt, provided that no communication has been received from the DCGI within the stated period of 45 working days, the EC registration will be deemed granted by the DCGI, and such registration will be regarded as legally valid for all purposes and the applicant will be authorized to initiate a clinical trial in accordance with these rules. 2022-CTRules-3rdAmdt further states that once the EC has obtained provisional approval from the DCGI per the 2019-CTRules, the committee must also notify CDSCO via Form CT-02A, which will become part of the official record known as the guaranteed registration of the DCGI.

Per the 2019-CTRules and IND-53, the EC registration will remain valid for a period of five (5) years from the date of issue, unless suspended or cancelled sooner. The EC may apply for registration renewal via the IND-59 using Form CT-01 and should include all additional required documentation 90 days prior to the registration’s expiration date. The registration will remain in force until the DCGI passes a new registration order as long as the application is received within the specified 90-day deadline. Following the DCGI’s review of the application and inspection report, if any, and provided that there are no changes to the documentation included in the original application, the EC’s request for registration renewal will be granted within 45 working days from the date of application receipt. See also IND-42 and IND-43 for detailed fee requirements and online payment instructions via IND-59.

The 2019-CTRules also states that if the EC fails to comply with any of the registration conditions, the DCGI may, after giving the EC an opportunity to show cause as to why such an order should not be passed, prepare an order in writing to suspend or cancel the EC registration for such period as deemed necessary. The suspended or cancelled EC can appeal to the DCGI within the period specified in the show cause notice, and, after consideration, the DCGI may respond by taking one (1) or more of the following actions:

Withdraw the notice
Issue a warning to the EC describing the deficiency or defect observed during an inspection
Reject the results of the clinical trial
Suspend for a specified period or cancel the registration, or
Debar its members to oversee any future trial for a specified period

The aggrieved EC may file an appeal to the Government of India (Central Government) within 60 working days. The Central Government may subsequently pass an order in response to the appeal within 60 working days from the date of the appeal filing.

The EC must also allow CDSCO officials to enter the committee premises to inspect any records, data, documents, or other materials related to a clinical trial. The EC must provide adequate replies to any queries raised by the inspecting authority in relation to the conduct of the trial as noted in the 2019-CTRules.

Registration Provisions for Biomedical and Health Research Ethics Committees

As explained in Notice15Sept19 and IND-51, ECs planning to review biomedical and health research studies are initially required to register on the DHR’s National Ethics Committee Registry for Biomedical and Health Research (NECRBHR) website (IND-51). The NECRBHR facilitates the receipt and processing of application submissions and assists the DHR’s Office of Ethics Committee Registration. An authorized signatory/responsible person must complete the EC Applicant Registration Form (IND-38) and submit it online on the NECRBHR website (IND-51). Once the NECRBHR verifies the application and approves the account registration, the applicant will receive an email with login instructions to apply electronically via the DHR’s NAITIK portal (IND-54). See IND-66 for a checklist of NECRBHR registration requirements.

Per the 2019-CTRules, the EC must submit an application to the NECRBHR using Form CT-01 along with the required information and documentation specified in Table 1 of the Third Schedule of the 2019-CTRules. Upon receipt of the application, the DHR’s Office of Ethics Committee Registration (designated authority) must grant provisional registration to the EC for a period of two (2) years. Final registration will be granted to the EC on Form CT-03 when the DHR has completed its review of the application and the associated documentation. The final registration will remain valid for a period of five (5) years from the date of its issue, unless suspended or cancelled sooner.

The EC may also apply to request registration renewal using Form CT-01 along with the specified documentation at least 90 days prior to the final registration’s expiration date. The final registration will remain in force until the DHR completes its review of the renewal application provided that the following conditions are met:

The DHR does not require the EC to provide a new set of documents
There have been no changes in the submitted documents since the final registration was granted, and
The EC submits a certificate to the DHR validating that the documents have not changed

Following a review of the registration renewal application and further inquiry to confirm there have been no documentation changes, the DHR will renew the EC’s registration on Form CT-03 within 45 working days from the date of application receipt. The renewed registration will remain valid for five (5) years from the date of its issue, unless suspended or cancelled sooner.

The 2019-CTRules further states that if the EC fails to comply with any of the registration conditions, the DHR may, after giving the EC an opportunity to show cause as to why such an order should not be passed, prepare an order in writing to suspend or cancel the EC registration for such period as deemed appropriate. The suspended or cancelled EC can appeal to the DHR, and after consideration, the DHR may respond by taking one (1) or more of the following actions:

Issue a warning to the EC describing the deficiency or defect observed, which may adversely affect the rights or well-being of the study participants
Suspend the EC for a specified period or cancel the registration, or
Debar its members from overseeing any future biomedical health research for a specified period

The aggrieved EC may file an appeal to the Government of India (Central Government) within 45 working days. In response to the appeal, as deemed necessary, and after giving the EC an opportunity to be heard, the Central Government may subsequently pass an order considered appropriate to the case.

(Note: The registration provisions for biomedical and health research ECs in Notice15Sept19 and IND-51 have not yet been aligned with the 2019-CTRules in terms of explaining the application submission process. The 2019-CTRules does not specify that the application submission process is electronic as is stated in Notice15Sept19 and IND-51. Further, only Notice15Sept19 and IND-51 specify that the DHR’s Office of Ethics Committee Registration is the designated authority. However, the ClinRegs team is regularly monitoring the CDSCO website for new developments and will post the most current sources as they become available.)

Additional Provisions for Clinical Trial and Biomedical and Health Research Ethics Committees

In addition to requiring all ECs to register with the relevant regulatory authority (the DCGI or the DHR), the G-ICMR specifies that ECs should be encouraged to seek recognition, certification, and accreditation from established national and international bodies (e.g., the SIDCER-FERCAP Foundation, the Association for the Accreditation of Human Research Protection Programs (AAHRPP), CDSCO, and the Quality Council of India through National Accreditation Board for Hospitals and Healthcare Providers (NABH), etc.). Although voluntary, the G-ICMR states that these certifications and accreditations should be continually updated to help with quality assurance and quality improvement and ensure that ECs comply with best practices to protect research participants.

4.1 and 4.15

Chapter III (6, 8-11, and 14), Chapter IV, and Chapter V (19-20 and 25), Third Schedule (Table 1), and Eighth Schedule (Forms CT-01, CT-02, and CT-03)

2-3, 12, and Form CT-02A

32-33

1 and 6

Registration of Ethics Committees reviewing Biomedical & Health Research

Last content review/update: July 2, 2024

Overview

As set forth in the STI-Act and KEN-32, the National Commission for Science, Technology and Innovation (NACOSTI) is the central body responsible for the oversight, promotion, and coordination of research. NACOSTI’s role is to regulate and ensure quality in the science, technology, and innovation sector, and to advise the Kenyan government on related matters. As per the G-ECAccred, NACOSTI has delegated the task of reviewing research proposals for ethical clearance to accredited institutional ethics committees (ECs) to ensure that research conducted in the country observes high research ethics standards.

Per the G-ECBiomedRes, Kenya's National Bioethics Committee (NBC) advises NACOSTI on research ethics. In addition, NBC offers dispute resolution if an applicant is dissatisfied with the decision of an EC. Finally, the NBC must terminate research at any stage if it is found to be harmful to the participants.

Registration, Auditing, and Accreditation

As per the STI-Regs and the G-ECAccred, NACOSTI is responsible for accrediting institutional ECs. Per the G-ECAccred, the application requirements for accreditation are:

A completed application form (KEN-10 or Annex III of the G-ECAccred)
Copy of the standard operating procedures (SOPs)
Copies of abridged curriculum vitaes (CVs) (no more than four (4) pages) for each member of the proposed EC (including the training attended)
Profile of the organization/institution detailing the areas of competence (no more than four (4) pages)

Upon creating an account in NACOSTI’s Kenya National Research Information System (KENRIS) (KEN-23), users can perform the following functions:

Researchers: Apply for researcher registration, register and track applications, and maintain research profile
Research Institutions: Apply for new research institution registration, maintain/update data, and submit annual reports
Institutional ECs: Apply for accreditation, preview and track accreditation proposals, submit annual reports, and maintain/update data

Per the G-ECAccred, NACOSTI issues a certificate of accreditation to accredited institutional ECs, which is valid for three (3) years from the date of NACOSTI’s notification. All accredited ECs must submit annual reports to NACOSTI by July 31st for review and monitoring. Applications for renewal of accreditation should be made six (6) months before expiry of the accreditation period. Failure to renew accreditation or failure to maintain the appropriate standards for continuity of accreditation will mean that the accredited status of the EC will lapse at the end of the current accreditation period. Accreditation must be terminated if the accredited committee fails to maintain the required standards. For re-accreditation review purposes, ECs must provide the SOPs under which they will operate. The SOPs are not required as part of the annual reporting process, unless they have been amended, but are required to be stated/included for the re-accreditation review process (every three (3) years). See the G-ECAccred for additional details on the accreditation process.

See the Site/Investigator Selection section for more information on the sponsor and site’s registration and application requirements.

1.0, 2.0, 4.0, and Annex III

4.1 and 7.1

Part II

The Science, Technology and Innovation (Relevance and Quality Assurance in Research) Regulations, 2014 (Part II)

Submission Process

Last content review/update: June 21, 2024

New Info (Not Yet in Profile)

DCGI notices related to regulatory submissions through the SUGAM Portal:

Notice from December 26, 2024 - Submission of Clinical Trial Site Addition and change of Principal Investigator applications for global clinical trials, clinical trials of new drugs, subsequent new drugs, investigational new drugs, fixed dose combinations, and bioavailability & bioequivalence studies
Notice from February 24, 2025 - Submission of Clinical Trial Site Addition and change of Principal Investigator applications for clinical trials of biological products (vaccine and rDNA)

Overview

In accordance with the 2019-CTRules, the Hdbk-ClinTrial, the G-ICMR, and IND-31, the sponsor (also known as the applicant) is required to submit a clinical trial application to the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), to obtain authorization to conduct a clinical trial in India. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.) The investigator must also obtain ethics committee (EC) approval from a DCGI-registered EC prior to initiating a study. According to IND-31, the DCGI review and approval process may be conducted in parallel with the EC review for each clinical trial site. However, per the 2019-CTRules and the Hdbk-ClinTrial, CDSCO must confirm the EC approvals for each participating site have been obtained per the protocol prior to approving the initiation of the study. (Note: the Hdbk-ClinTrial has not yet been updated to fully align with the 2019-CTRules.)

For specific guidelines regarding gene therapy and stem cell therapy clinical trial submissions, see G-GeneThrpy and G-StemCellRes.

Regulatory Submission

SUGAM Pre-Submission Registration

As explained in IND-42, CDSCO created the SUGAM portal (IND-59) to be used by applicants to apply for no objection certificates (NOCs), licenses, registration certificates, permissions, and approvals. Once submitted, applicants can track their applications, respond to queries, and download CDSCO issued permissions. According to IND-20, importers, Indian agents, foreign enterprises that hold an Indian subsidiary, and corporate users can register on the SUGAM portal (IND-59).

Per IND-42, users are required to complete a registration form requesting access to the SUGAM portal (IND-59) along with uploading the required identification (ID) documentation. IND-42 specifies that the authorized signatory/responsible person in an organization should complete the registration form. After registration is approved, the user is required to submit hard copies of identification (ID), proof of undertaking, and address to the CDSCO office. Registration will be approved by CDSCO only after evaluation of the submitted documents. IND-20 further notes that the email ID provided in the registration form should be an official email ID as all correspondence with CDSCO via the SUGAM portal (IND-59) will be completed using this registered email ID. Additionally, IND-20, the user will receive login credentials on the registered email ID after completion of the verification process from the CDSCO office. For detailed registration instructions, see IND-42 and IND-20.

NSWS Portal Pre-Submission Registration

Per Notice1Jan24, CDSCO launched the National Single Window System (NSWS) portal (IND-3) that will eventually serve as a one-stop shop for all approvals, licenses, registrations, and clearances. IND-24 further explains NSWS portal (IND-3) is a digital platform that is designed to integrate the services provided by various ministries, departments, and states thereby enabling users to identify and apply for regulatory approvals and registrations per their business requirements in a single location. According to IND-14, once the implementation process is completed, various regulatory documents including approvals, applications, and records will be accessible via the NSWS portal (IND-3). At this time, however, per Notice1Jan24 and Notice16Jan24, only a few CDSCO steps and processes (e.g., medical device related registration, manufacturing/import applications, and drug manufacturing/import applications) have been moved to the NSWS portal (IND-3). Per IND-24, while the NSWS portal (IND-3) does not charge a fee for registration, users are required to pay any fees required by CDSCO or any other ministry/department/state to process applications submitted for approval via the NSWS portal (IND-3).

IND-24 indicates that to access the NSWS portal (IND-3) services, users are required to sign up by registering with an email address and mobile phone, and then creating a business profile. As explained in IND-61, to complete the business profile, users are required to have a tax identification number known as a Permanent Account Number (PAN)). According to IND-33, a PAN is issued by the Income Tax Department within the Indian Ministry of Finance. Both domestic and foreign users can apply for a PAN using the appropriate application form.

Per IND-62 and IND-64, the user’s PAN will need to be verified using Digital Signature Certificate (DSC) for the created business profile. The steps involved in this process include adding authorized signatory information, registering the DSC, and verifying the PAN details against the registered DSC. IND-62 and IND-64 also note that users will need to have emBridge software installed on their computers to serve as a connecting link between the NSWS portal (IND-3) and DSC. Please refer to IND-62 and IND-64 for detailed instructions on completing this registration process which is required to apply for approval and registrations. See also IND-4 for a complete list of NSWS portal (IND-3) user guides.

Submissions

As indicated in the Notice15Jan18, all clinical trial application submissions must be submitted electronically via CDSCO’s SUGAM portal (IND-59). Refer to IND-42 for instructions on uploading forms and related documentation via the SUGAM portal (IND-59).

Per IND-7, CDSCO has introduced a new protocol for the submission of regulatory affairs related documents to facilitate the transition from hard copy to soft copy document submission. As explained in Notice12Oct23 and IND-7, effective immediately, CDSCO’s Clinical Research Unit (CRU) Division is requesting that stakeholders submit bulky dossiers, documents, query replies, and similar materials in soft copy format. The soft copies should be submitted in PDF format and ideally less 20 MB on a CD or pen drive to the CRU Division or submitted via email to cru.division@cdsco.nic.in. The files will then be forwarded to the appropriate Division along with the stakeholder’s cover letter.

The DCA-DCR delineates that English should be used for specific documents included in the clinical trial application submission. For the informed consent form and patient information sheet, English and/or the vernacular language of the participant(s) should be used. English should also be used for the package inserts.

In addition, per Notice31Jan24, CDSCO’s Subject Expert Committee (SEC) Division is responsible for conducting meetings to evaluate investigational new drug (IND) proposals. Applicants are requested to submit a copy of their proposal presentation only to the appropriate SEC division via the SUGAM portal (IND-59) after receiving an invitation letter from CDSCO, and well in advance of the scheduled meeting.

Ethics Review Submission

As indicated in the 2019-CTRules, the Hdbk-ClinTrial, the G-ICMR, and IND-31, India requires all clinical trials of drugs involving human participants to be reviewed by a DCGI-registered EC. Because the submission process at individual institutional ECs will vary, applicants should review and follow their institution’s specific requirements. The G-ICMR also specifies that investigators should submit research proposals as soft or hard copies to the EC Secretariat for review in the prescribed format and required documents as per EC standard operating procedures (SOPs).

31-33

Summary, 1, and 4

About Us and Registration & Login

General – What is PAN? and Introduction – Types of PAN Applications

Who can register on CDSCO online portal? and How do I get my login credentials on CDSCO online portal?

5.0-5.2 and Appendix 8.3

4.0-4.2, 4.8, and 4.10

7.11 and Annexures I, II, and III

4, 11.2, and Annexures I and II

Appendix VIII and Schedule D(II)

Chapter I (2), Chapter II (3), Chapter V (19-22, and 25), Second Schedule (1), Third Schedule (1 and Tables 3, 6, and 7), and Eighth Schedule (Forms CT-04, CT-4A, and CT-06)

Last content review/update: July 2, 2024

Overview

In accordance with the PPA, the STI-Act, the CTRules, the G-KenyaCT, the G-ECBiomedRes, KEN-21, and KEN-16, Kenya requires the sponsor or the representative to obtain clinical trial authorization from the Pharmacy and Poisons Board (PPB)’s Expert Committee on Clinical Trials (ECCT) and an independent ethics review through a National Commission for Science, Technology and Innovation (NACOSTI)-accredited ethics committee (EC) in a local institution. In addition, the STI-Act and KEN-31 specify that applicants must obtain a research license from NACOSTI prior to initiating a study. The G-KenyaCT also states that the PPB review and approval process may not be conducted in parallel with the EC review. EC approval must be obtained prior to applying for PPB approval.

Regulatory Submission

Pharmacy and Poisons Board

As described in the G-KenyaCT and KEN-16, the sponsor or the representative is expected to submit the clinical trial application electronically via the PPB online system (KEN-16). The clinical trial application form is available in KEN-16. Per the G-KenyaCT, in the event of a multicenter clinical trial, the sponsor should only file one (1) application to the PPB. According to KEN-34, all application documents should be signed, dated, and version referenced, if applicable, and should be in English. See Annex 7 of the G-KenyaCT to view a flowchart of the submission and approval process.

Per the G-KenyaCT, upon receipt of a clinical trial application, the PPB’s Clinical Trial Division of the Product Safety Department screens the application package for completeness. When an application for a clinical trial is accepted, an acknowledgement of receipt will be issued with a reference number for each application. This PPB/ECCT reference number must be quoted in all correspondence concerning the application in the future. This will be communicated through email to the applicant or through KEN-16.

Per the G-KenyaCT, sponsors (applicants) can request pre-submission meetings with the PPB to discuss pertinent issues prior to making a formal submissions. The request must be made via KEN-16 or in an official letter and include the following information:

Background information on the disease to be treated
Background information on the product
Quality development
Non-clinical development
Clinical development
Regulatory status
Rationale for seeking advice
Proposed questions and applicant’s positions

In addition, per the G-KenyaCT, the letter must be addressed to the Chief Executive Officer of the PPB and sent to admin@pharmacyboardkenya.org and copied to cta@pharmacyboardkenya.org. The request for a meeting should propose two (2) different dates for the meeting at least three (3) weeks away.

Per G-KenyaCT, any new information that affects the conduct/management of the trial; safety of the participants; and manufacture of the product necessitating changes to the protocol, consent form, and trial sites, etc. will require immediate submission of the amended documents to the PPB for review and approval. Minor amendments or administrative changes may be implemented after getting the EC’s approval, but a record of these amendments must be kept for possible inspection by the PPB.

National Commission for Science, Technology and Innovation

Per KEN-31, an application for a NACOSTI research license should be submitted online via the Research Information Management System (RIMS) (KEN-24).

Ethics Review Submission

Each institutional EC has its own required submission procedures, which can differ significantly regarding the application format and number of copies. See KEN-17 for an example of a NACOSTI-accredited EC’s guidelines.

1.0 and 4.1

Glossary of Terms, Introduction, 1.1-1.29, 1.182-1.185, 1.492-1.496, and Annexes 1-7

25A

Parts II, IV, V, and X and Fourth Schedule

Part II (Section 4)

Submission Content

Last content review/update: June 21, 2024

Regulatory Authority Requirements

As per the 2019-CTRules, the Hdbk-ClinTrial, IND-32, and IND-35, documentation must be submitted to the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), as part of the approval process for investigational new drugs (INDs) will depend upon the type of application, phase of the study, stage in drug development process, and/or objective of the study. Information that may be required is included in the lists below (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Form CT-04 (the clinical trial application form including sponsor (also known as applicant) name; sponsor nature/constitution and contact information; clinical trials site contact information and details; contact information for person responsible for compensation payment, if any; correspondence address; new drug/investigational new drug name(s) and details (i.e., therapeutic class, dosage form, composition, and indications); clinical trial phase; protocol number with date; and ethics committee (EC) and investigator names)
Treasury Challan receipt demonstrating payment of corresponding fee or transaction ID
Chemical and pharmaceutical information
Animal pharmacology data
Animal toxicology data
Human clinical pharmacology data
Active ingredient information (for INDs and global clinical trials (GCTs))
Formulation data (for INDs and GCTs)
Therapeutic class (for INDs and GCTs)
Regulatory status in India and in other countries
Proposed study status in other participating countries and any approvals, withdrawals, discontinuation of approval, etc. (for GCTs)
Affidavit stating study has not been discontinued in any country (for GCTs)
Prescribing information
Testing protocol(s) for quality control testing
Clinical study protocol
Dosage form
Justification and schematic diagram/flow chart proposed study and design (for INDs and GCTs)
Number of patients globally (for GCTs) and number of patients to be enrolled from India (for INDs and GCTs)
Details of all sites selected and assessment for suitability of sites and investigators (with contact details)
EC registration status of the selected sites
Relevance of study, investigational drug, or any specific study aspects to the health care needs of India
Innovation vis-à-vis existing therapeutic options
Unmet medical need in the country (as applicable)
Any India-specific safety/dosage concerns/investigational tests to be done
Clinical study reports should be submitted per the International Council for Harmonisation (ICH) Common Technical Document (CTD) (IND-68)
Protocol safety measures per toxicological studies; early clinical studies, approved product insert for marketed product, and published literature
Investigator’s Brochure (IB)
Investigational Medicinal Products Dossier (IMPD) (for (GCTs))
Affidavit stating the IB information is correct and based on facts (for GCTs)
Source of bulk drugs (for INDs)
Treasury Challan with Application for Grant of License to Import New Drug or Investigational New Drug for Clinical Trial or Bioavailability or Bioequivalence Study or for Examination, Test and Analysis (CT-16) (IND-11) (for GCTs)
Sponsor authorization letter (for GCTs)
Details of biological specimens to be exported and the online application for export no objection certificate (NOC) for biological samples on the SUGAM portal (IND-59) (for GCTs) (See IND-1 for the application form to request a NOC to export biological samples) (Refer to the Specimens topic for more information on specimen import/export)
Case Report Form (CRF)
Informed consent form (ICF) and patient information sheet (See Required Elements section for additional information)
Investigator(s) undertaking
EC approvals (if available)
Clinical study report(s)
Investigator list in India and site address

See the 2019-CTRules, the Hdbk-ClinTrial, IND-32, and IND-35 for detailed DCGI application submission requirements. See also IND-22 for details on the IND-59 approval process for GCTs and IND-31 for clinical trial FAQs. (Note: The Hdbk-ClinTrial has not yet been updated to fully align with the 2019-CTRules.)

Refer to the 2019-CTRules and IND-31 to obtain detailed submission requirements for applications to conduct a clinical trial using an already approved new drug with a new indication, a new dosage form/new route of administration, a modified release dosage form, or a new drug with an additional strength.

Ethics Committee Requirements

Each institutional EC has its own application form and clearance requirements, which can differ significantly regarding the number of copies to be supplied and application format requirements. However, per the G-ICMR, the requirements listed below are basically consistent and shared by all of the Indian ECs:

Cover letter to the Member Secretary
Type of review requested
Application form for initial review (IND-39)
Informed consent document (in English and the local language(s)) including translation and back translation certificates, if applicable
Case record form/questionnaire
Recruitment procedures (e.g., advertisement, notices) if applicable
Patient instruction card, diary, etc., if applicable
IB (as applicable for drugs, biological, or device trials)
Details of funding agency/sponsor and fund allocation, if applicable
Investigators’ Curriculum Vitaes (CVs)
Conflict of interest statement, if applicable
Good Clinical Practice (GCP) training certificate for investigators (preferably within last five (5) years)
Any other research ethics/other training evidence, if applicable as per EC standard operating procedures (SOPs)
List of ongoing research studies undertaken by the principal investigator, if applicable
Investigator’s undertaking statement with all participating investigator signatures
Regulatory permissions (as applicable)
Relevant administrative approvals (such as Health Ministry’s Screening Committee (HMSC) approval for international trials)
Institutional Committee for Stem Cell Research (IC-SCR) Registration (IND-72), if applicable
Memorandum of Understanding (MoU) in case of studies involving collaboration with other institutions, if applicable
Clinical trial agreement between the sponsors, investigator, and the head of the institution(s), if applicable
Clinical trial registration documentation (preferable)
Insurance policy (it is preferable to have the policy as well as the insurance certificate) for study participants indicating conditions of coverage, date of commencement and date of expiry of coverage of risk (if applicable)
Indemnity policy, clearly indicating the conditions of coverage, commencement date, and expiry date of risk coverage (if applicable)
Any additional document(s), as required by EC (such as other EC clearances for multicentric studies)
Protocol

Furthermore, the ICMR has prepared a generic application for initial review (IND-39) that may be used by the EC. The form is also included in the bulleted list above.

Clinical Protocol

As delineated in the 2019-CTRules, the Hdbk-ClinTrial, and the G-ICMR, the clinical study protocol should include the following elements:

Title page
Table of contents
Brief summary (See G-ICMR)
Study rationale
Study objective
Study design and methodology
Study population
Justification of inclusion/exclusion of vulnerable populations (See G-ICMR)
Participant eligibility and recruitment procedures
Study assessments
Study conduct stating the types of activities that would be included (e.g., medical history, type of physical examination, etc.)
Study treatment
Ethical consideration
Study monitoring and supervision
Investigational product management (See Investigational Products topic for detailed coverage of this subject)
Data analysis
Undertaking by the Investigator statement
Appendices

The G-ICMR also mentions the following requirements:

Study duration
Justification for placebo, benefit-risk assessment, plans to withdraw; if standard therapies are to be withheld, justification for the same
Informed consent procedure and sample of the patient/participant information sheet and informed consent forms including audiovisual recording, if applicable, and informed consent for stored samples
Plan to maintain the privacy and confidentiality of the study participants
Adverse events/adverse drug reactions
For research involving more than minimal risk, an account of management of risk or injury
Proposed compensation, reimbursement of incidental expenses and management of research related injury/illness during and after research period
Provision of ancillary care for unrelated illness during the duration of research
Account of storage and maintenance of all data collected during the trial
Plans for publication of results while maintaining confidentiality of participants’ personal information/identity

For detailed information on these elements, see the 2019-CTRules, the Hdbk-ClinTrial, and the G-ICMR.

10-11 and 31-33

1 (INDs) and 3 (Global Clinical Trials)

Preface, 3, 5.0, 5.1, 5.2, and Appendix 8.3 and 8.4

4.0-4.1, 4.8, and 4.10

Chapter V (19-22), Second Schedule (1, 3, and Tables 1-4), Third Schedule (1 and Tables 1-4, and 6-7), Fourth Schedule (Table 3), Sixth Schedule, and Eighth Schedule (Forms CT-04, CT-4A, CT-06, and CT-16)

Last content review/update: July 2, 2024

Regulatory Authority Requirements

Pharmacy and Poisons Board

As per the CTRules, the G-KenyaCT, and KEN-34, the following documentation must be submitted (signed, dated, and version referenced) to the Pharmacy and Poisons Board (PPB) (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Cover letter
Study protocol
Proof of study registration in the Pan African Clinical Trials Registry (KEN-19)
Patient information leaflet and informed consent form (ICF)
Investigators brochure (IB) and package inserts
Investigational Medicinal Product Dossier (IMPD), including stability data for the investigational product (IP)
Adequate data and information on previous studies and phases to support the current study
Good manufacturing practice (GMP) certificate of the IP from the site of manufacture issued by a competent health authority in the manufacturer’s jurisdiction of origin
Certificate of analysis of the IP
Pictorial sample of the IPs, including the labeling text
Signed investigator(s) curriculum vitae(s) (CV(s)), including that of the study pharmacist (the CV should include the current workload of the principal investigator (PI))
Evidence of contractual agreement between the relevant parties
Evidence of recent good clinical practice (GCP) training of the core study staff
Data and Safety Monitoring Board (DSMB) information, including the charter, composition, and meeting schedule
Detailed study budget
Financial declaration by the sponsor and PI (KEN-2 and Annex 5 of the G-KenyaCT)
No conflict of interest declaration by the sponsor and PI
Signed declarations by the sponsor, PI, and the monitor that the study will be carried out according to the protocol and applicable laws, regulations, and GCP requirements (KEN-1 and Annex 4 of the G-KenyaCT)
Indemnity cover for PI, investigators, and study pharmacist
Clinical trials insurance cover for the study participants
Copy of favorable opinion letter from local ethics committee (EC)
Copy of current practice licenses for the investigators and study pharmacist
Copy of approval letter(s) from collaborating institutions or other regulatory authorities, if applicable
For multicenter/multi-site studies, an addendum for each of the proposed sites including, among other things, the sites’ capacity to carry out the study (e.g., personnel, equipment, laboratory)
A signed statement by the applicant indicating that all information contained in, or referenced by, the application is complete and accurate, and is not false or misleading (Annex 4 of the G-KenyaCT)
Payment of fees
Statistical analysis plan
A signed checklist (KEN-34 and Annex 2 of the G-KenyaCT)

Per the G-KenyaCT, a request for approval of an amendment must include a summary of the proposed amendments; the reason for the amendment; the impact of the amendment on the original study objectives; the impact of the amendments on the study endpoints and data generated; and the impact of the proposed amendments on the safety and wellbeing of study participants.

KEN-35 describes the submission content for requesting annual approval from the PPB.

National Commission for Science, Technology and Innovation

Per the STI-Regs and KEN-31, non-Kenyan applicants must be affiliated with a Kenyan institution. Per KEN-31, applicants must apply online through National Commission for Science, Technology and Innovation (NACOSTI)’s Research Information Management System (RIMS) website (KEN-24) and upload the following:

Passport size color photo in JPG or PNG format
Scanned ID/passport in PDF format
Introductory letter from relevant institution signed by an authorized officer
Affiliation letter from relevant local institution for foreigners signed by an authorized officer and valid for one (1) year
Grant letter from the funding agency to support the amount indicated to fund the research
PPB clinical trial approval
Prior Informed Consent (PIC), Mutually Agreed Terms (MAT), or Material Transfer Agreement (MTA) where applicable, for applications to conduct research on genetic resources and derivatives
Approved research proposal in PDF format
Certificate of ethical clearance of the research (see list of accredited ECs in KEN-25)
Evidence of payment as the last page of the uploaded proposal

Per KEN-31, the following conditions apply to the research license:

The research license is valid for the proposed research, site, and specified period
Both the research license and any rights thereunder are non-transferable
NACOSTI may monitor and evaluate the research
The licensee must inform the relevant County Director of Education, County Commissioner, and County Governor before research commencement
Excavation, filming, and collection of specimens are subject to further permissions from relevant government agencies
The research license does not give authority to transfer research materials
The licensee shall submit one (1) hard copy and upload a soft copy of their final report within one (1) year of completion of the research
NACOSTI reserves the right to modify the conditions of the research license including its cancellation without prior notice

KEN-31 states that if the research is not completed within the stipulated period, the applicant may apply for renewal of the research license and pay the requisite fee. A progress report should be submitted with the request for renewal instead of a proposal. The progress report must indicate the objectives and activities that have been accomplished, as well as the research work that has yet to be undertaken. KEN-31 further indicates that submissions requesting renewal should be made at least 30 days prior to the expiration of the approval period.

Ethics Committee Requirements

EC requirements vary depending on the specific EC. See KEN-17 and KEN-26 for examples of accredited EC submission and review guidelines.

As set forth in the G-ECBiomedRes, a foreign sponsoring agency must also submit its research protocol for ethics review according to its own country’s standards. This research must be responsive to the health needs of Kenya and reasonably accessible to the community in which the research was conducted.

Clinical Protocol

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). The CTRules the G-KenyaCT, the G-ECBiomedRes, and KEN-14 outline the key elements of a research protocol in Kenya (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

A project title that adequately captures the essence of the study
The names, addresses, signatures, and updated abridged curriculum vitae of the investigators
Evidence that the PI has prior training in GCP
Contact information for the EC and collaborating institutions
A summary of the project
Introduction, background, and literature review, including nonclinical data
Study objectives, rationale, questions, and hypothesis/es
Study site, design, and methodology
Ethical considerations
Role of investigators
Schedule
References
Budget
Publication policy
Consent explanation - elements of consent explanations
ICF with signature provisions for participants and the PIs
Risks and benefits
Mode of assessment of the safety and efficacy of the IP
Mode of collecting, analyzing, and reporting the statistics of the clinical trial
Source data documents of the clinical trial
Quality control and quality assurance
Confidentiality
Recruitment, selection, treatment, and withdrawal of participants
Compensation and post-trial access program
Undue inducement and coercion
Voluntariness
Alternative treatment(s) if available
Storage of specimens
MTA, where applicable
Data management and statistical analysis

In addition, per the G-KenyaCT, the protocol should have a clear description of study stoppage rules indicating reasons, who makes the decision, and how the decision will be communicated to the PPB and the EC.

6

Guidelines for Proposal Development

Submission Forms

1.0, 4.2, and 6.0

1.48, 1.63, 1.89-1.130, 1.495, 1.533, and Annexes 1-2 and 4-5

The Science, Technology and Innovation (Research Licensing) Regulations, 2014 (Part II)

Part II (Section 4) and Part IV (Section 9)

Timeline of Review

Last content review/update: June 21, 2024

Overview

Based on the 2019-CTRules, the Hdbk-ClinTrial, the G-ICMR, and IND-31, the review and approval of a clinical trial application by the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), is dependent upon obtaining ethics committee (EC) approval from a DCGI-registered EC prior to initiating a study. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.) According to IND-31, the DCGI review and approval process may be conducted at the same time as the EC review for each clinical trial site, except in the case of non-regulatory academic clinical trials that only require EC approval. However, per the 2019-CTRules and the Hdbk-ClinTrial, CDSCO must confirm the EC approvals for each participating site have been obtained per the protocol prior to approving the initiation of the study. (Note: the Hdbk-ClinTrial has not yet been updated to fully align with the 2019-CTRules.)

Regulatory Authority Approval

As specified in the 2019-CTRules and IND-31, upon receipt of a clinical trial application , the DCGI has 90 calendar days to evaluate the application for a new drug or an investigational new drug; 90 calendar days to evaluate a new drug already approved outside India; and 30 days to evaluate a drug discovered, researched, and manufactured in India. Per the Hdbk-ClinTrial, upon receipt of an application, a CDSCO official conducts the initial administrative review. If the application is deemed complete, within four (4) weeks following receipt, the official forwards the application along with a summary of their evaluation and a statement referring the proposal to a Subject Expert Committee (SEC) for further technical review.

The 2019-CTRules further notes that the DCGI may, when required, constitute one (1) or more of these expert committees or group of experts with the specialization in relevant fields to evaluate scientific and technical drug-related issues. The committee/group may submit its recommendations within 60 days from the date of the request. See the Scope of Assessment section for more information on SEC composition and review processes.

Once the SEC has completed its review, the Hdbk-ClinTrial indicates that the committee sends its comments via email to CDSCO. CDSCO will then compile any written SEC comments requiring sponsor (also known as applicant) clarification or modification and send this feedback to the sponsor within one (1) week of receipt. The applicant must submit a written reply to CDSCO within four (4) weeks of receiving the comments, which will, in turn, be sent to the SEC for review.

Following receipt of the sponsor’s response, the DCGI (CDSCO) will issue a final decision by official communication (permission, rejection, or resubmission) to the Technical or Apex Committee within 15 days. In the case of a sponsor’s request for reconsideration, CDSCO will review the resubmitted application and send it to the SEC again or to the Technical Committee per the sponsor’s request. Following the SEC’s review, the DCGI (CDSCO) will send a final decision to the Technical or Apex Committee within 15 days. If CDSCO rejects the reconsideration request, the agency will send a letter to the sponsor to communicate this decision. Refer to the Hdbk-ClinTrial for additional timeline information.

See also IND-22 for details on the SUGAM portal (IND-59) approval process for global clinical trials, and IND-46 for additional information on conducting clinical trials in India.

Per the 2022-CTRules-3rdAmdt, which amends the 2019-CTRules, provided that no communication has been received from the DCGI within the stated period of 90 working days, permission to conduct all new drug or investigational new drug clinical trials as well as clinical trials for new drugs already approved outside India will be deemed granted by the DCGI. This permission will be regarded as legally valid for all purposes and the applicant will be authorized to initiate a clinical trial in accordance with these rules. Similarly, per the 2019-CTRules and IND-31, if the DCGI does not respond within 30 days to applications for drugs developed in India, the sponsor may conclude that permission to conduct the trial has been granted. Refer to the Scope of Assessment section for information on obtaining a waiver for an already approved drug. See also the Manufacturing & Import section for detailed information on import requirements for new drugs already approved outside of India.

For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see the G-GeneThrpy and the G-StemCellRes.

(See also the Submission Process and Submission Content sections for detailed submission requirements.)

Ethics Committee Approval

As per IND-9, the EC review and approval process, which occurs at the same time as the DCGI review and approval, generally takes from four (4) to six (6) weeks. Many study sites also have scientific review committees (SRCs) review the scientific justification of the study. Once the SRC approves the study, it is submitted to the EC for its review and approval.

The G-ICMR indicates that EC members should be given enough time (at least one (1) week) to review the proposal and related documents, except in the case of expedited review. While all EC members should review all submitted proposals, each EC may adopt different procedures for protocol review per their standard operating procedures.

7.11 and Annexures I, II, and III

4.1-4.2, 4.8, and 4.10

4, 11.2, and Annexures I and II

5.0-5.2 and Appendix 8.3

Chapter I (2), Chapter II (3), Chapter V (19-25 and 28), Chapter XIII (100-101), First Schedule (3), Second Schedule (1 and Table 1), Third Schedule (1 and Table 6), and Eighth Schedule (Forms CT-04, CT-4A, and CT-06)

4-6 and 12

India

10-11, 18-19, 22, 25, 31-33, 38, and 79

Last content review/update: July 2, 2024

Overview

Based on the CTRules and the G-KenyaCT, the Pharmacy and Poisons Board (PPB)'s review and approval of an application to conduct a clinical trial is dependent upon obtaining ethics approval from a National Commission for Science, Technology and Innovation (NACOSTI)-accredited ethics committee (EC). Therefore, the PPB and EC reviews may not be conducted in parallel. In addition, the STI-Act and KEN-31 specify that all applicants must obtain a research license from NACOSTI prior to initiating a study.

Regulatory Authority Approval

Pharmacy and Poisons Board

Per the G-KenyaCT, sponsors (or applicants) can request pre-submission meetings to discuss pertinent issues prior to making a formal submission. The request must be made via the PPB online system (KEN-16) or in an official letter addressed to the Chief Executive Officer of the PPB and sent to admin@pharmacyboardkenya.org and copied to cta@pharmacyboardkenya.org. The request for a meeting should propose two (2) different dates for the meeting with the proposed dates being at least three (3) weeks away. (See Submission Process section for details on the content of request.)

Per the G-KenyaCT, upon receipt of a clinical trial application, the PPB’s Clinical Trial Division of the Product Safety Department screens the application package for completeness, which takes five (5) days. If accepted, an automatic system-generated reference number will be issued for each application. If additional information is needed, the sponsor will have 10 days to respond. The PPB aims to respond to applications within 30 working days. The sponsor or the representative must reference the PPB/Expert Committee on Clinical Trials (ECCT) number in all future application-related correspondence. The application is then evaluated by the ECCT and PPB staff according to their respective standard operating procedures. The PPB/ECCT’s decision to approve, request additional information, or reject the application is communicated to the sponsor or the representative in writing within 30 days of receiving a valid application. If additional information is requested, the sponsor has 90 days to respond after which the PPB has 15 days to issue a final decision. In certain cases, the PPB may refer the application to external experts for their recommendation.

Per the G-KenyaCT, the sponsor or the representative is also required to request approval annually from the PPB at least six (6) weeks prior to the expiration of the previous approval. Refer to the Checklist for Submitting a Request for Annual Approval (KEN-35) for relevant documentation requirements.

National Commission for Science, Technology and Innovation

Per KEN-5 and KEN-31, the timeline for NACOSTI’s license application process is 30 days.

KEN-31 states that if a research license application does not meet the conditions required under the STI-Act, NACOSTI must reject the application and communicate the reasons to the applicant. Any person may appeal NACOSTI’s decision to the Cabinet Secretary within 30 days of being notified of the decision.

Ethics Committee Approval

The EC review and approval process timeline will vary by institution.

1.13-1.29, 1.182-1.185, and Annex 7

Part II (Section 4)

Initiation, Agreements & Registration

Last content review/update: June 21, 2024

Overview

As set forth in the 2019-CTRules, the Hdbk-ClinTrial, the G-ICMR, and IND-31, a clinical trial can only commence in India after the sponsor (also known as applicant) receives permission from the Drugs Controller General of India (DCGI) and approval from the respective ethics committees (ECs). The DCGI is head of the Central Drugs Standard Control Organization (CDSCO) and is commonly referred to as the Central Licensing Authority in the Indian regulations. According to the 2019-CTRules and IND-31, non-regulatory clinical trials intended for academic/research purposes only require institutional EC approval. (See the Scope of Review section for additional details). There is no waiting period required following the sponsor’s receipt of these approvals. (Note: the Hdbk-ClinTrial has not yet been updated to fully align with the 2019-CTRules.)

The 2022-CTRules-3rdAmdt, which amends the 2019-CTRules, further indicates that once the sponsor obtains approval from the DCGI for a new drug, an investigational new drug, or a new drug already approved outside India, the sponsor must notify CDSCO via Form CT-06A prior to initiating the clinical trial. The DCGI will then record the information provided on the form and it will become part of the official record known as the automatic approval of the DCGI.

In addition, per the 2019-CTRules and IND-31, the sponsor is required to obtain approval from the DCGI to manufacture or import investigational products (IPs) and to obtain an import license for the shipment of IPs to be used in the trial. (See the Manufacturing & Import section for additional information.)

As explained in the 2019-CTRules and IND-31, the EC should notify the DCGI about the academic trials it has approved and about cases where there could be an overlap between a clinical trial for academic and regulatory purposes. If the DCGI does not provide comments to the EC within 30 days from receiving EC notification, then it should be presumed that DCGI permission is not required.

For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see G-GeneThrpy and G-StemCellRes.

Clinical Trial Agreement

According to the 2019-CTRules, the sponsor must have an agreement with the investigator, which is to be provided to the EC. Furthermore, the investigator must sign an undertaking to conduct the trial in accordance with the protocol, good clinical practice guidelines, and all applicable requirements, among other things. For more details, see Table 4 (Third Schedule) in the 2019-CTRules.

Clinical Trial Registration

Per the 2019-CTRules, the G-ICMR, and IND-31, it is mandatory for all sponsors to register their clinical trials, including academic trials, with the Indian Council of Medical Research (ICMR)’s Clinical Trials Registry - India (CTRI) (IND-57) before initiating a study. Refer to the Scope of Review and Submission Process sections for further information on academic trials.

According to IND-56, registrants are advised to factor in a minimum of 10 to 15 working days for trial review, verification, and validation and the submission must indicate “Not Yet Recruiting” for the trial’s status. A REF number is issued to those registrants who have successfully submitted a trial to IND-57.

In addition, per IND-10, the ICMR has agreed to adopt the United Nation’s recommendations to register and publicly disclose results from all funded or supported clinical trials. The ICMR, along with other participating healthcare bodies, plans to develop and implement policies that require all trials they fund, co-fund, sponsor, or support to be registered in a publicly available registry. All study results will also be released within specified timeframes on the registry or through scientific journal publications.

See the 2019-CTRules, the Hdbk-ClinTrial, IND-32, and IND-35 for detailed DCGI application submission requirements.

7.11 and Annexures I, II, and III

4.1, 4.2, 4.8, and 4.10

4, 11.2, and Annexures I and II

5.0, 5.1, 5.2, and Appendix 8.3

Chapter I (2), Chapter II (3), Chapter V (19-22, 25, and 28), Chapter VIII (52), Chapter IX (67), First Schedule (3), Second Schedule (1 and Table 4), Third Schedule (1, Table 1 and Table 4), Sixth Schedule, and Eighth Schedule (Forms CT-04, CT-4A, CT-06, CT-10, and CT-16)

5-6, 12, and Form CT-06A

10-11, 23-24, 32-33, 37, 64-67, and 71-75

1 (INDs), 2 (New Drugs), 5 (Test License), and 7 (New Drug Formulation)

Last content review/update: July 2, 2024

Overview

In accordance with the PPA, the STI-Act, the G-KenyaCT, the G-ECBiomedRes, KEN-21, and KEN-16, a clinical trial can only commence after the sponsor or the representative receives authorization from Kenya’s Pharmacy and Poisons Board (PPB), and ethics committee (EC) approval from an institutional EC that has been accredited by the National Commission for Science, Technology and Innovation (NACOSTI) prior to initiating a study. ECs are accredited pursuant to the requirements delineated in the G-ECAccred. The G-KenyaCT specifies that the PPB review and approval process may not be conducted in parallel with the EC review. In addition, the STI-Act and KEN-31 state that all applicants must obtain a research license from NACOSTI prior to initiating a study. No waiting period is required following the applicant’s receipt of these approvals. Regarding notifications, KEN-31 requires the licensee to inform the relevant County Director of Education, County Commissioner, and County Governor before commencement of the research. Further, the licensee must disclose to NACOSTI, the institutional ECs, and the relevant national agencies any findings that are of national strategic importance.

As per the PPA and the G-KenyaCT, the sponsor or the representative is required to obtain an import license for the shipment of an investigational product to be used in the trial. (See the Manufacturing & Import section for additional information).

As stated in the G-KenyaCT, Kenyan clinical trials should be conducted in compliance with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (KEN-14).

Clinical Trial Agreement

Prior to initiating the trial, the G-KenyaCT requires that the sponsor agree with investigator(s) on the definition, establishment, and assignment of responsibilities specified in the protocol. These responsibilities include conduct of the trial in compliance with KEN-14 and the approved protocol; data management; unblinding of treatment codes; statistical considerations; and preparation of the final clinical report. The sponsor, in a written document, may agree to transfer all related activities of the clinical trial to designated research institutions. However, all responsibility for the trial lies with the sponsor. Prior to the initiation of the clinical trial, the agreement between the sponsor and investigators should be in writing as part of the protocol submitted for PPB approval or in a separate agreement. The sponsor and investigators must sign and date the protocol of the trial to confirm the agreement.

Clinical Trial Registration

As per the G-KenyaCT, all clinical trials taking place in Kenya must be registered in the PPB’s Online Clinical Trials Registry System (KEN-16). The principal investigator is required to log in and set up an account to register a study.

In addition, as required by KEN-34, all clinical trials taking place in Kenya must be registered in the Pan African Clinical Trials Registry (KEN-19).

1.25, 4, and 5.5

Introduction

1.0, 4.1, and 5.1

Introduction, 1.1, 1.48, 1.63-1.88, 1.346-1.354, and 1.542-1.555

Part III (25A) and Part IV (44)

Parts II, IV, V, and X, and Fourth Schedule

Safety Reporting

Last content review/update: June 21, 2024

Safety Reporting Definitions

In accordance with the 2019-CTRules, the G-ICMR, and IND-42, the following definitions provide a basis for a common understanding of India’s safety reporting requirements:

Adverse Event (AE) – Any untoward medical occurrence (including a symptom/disease or an abnormal laboratory finding) during treatment with a pharmaceutical product in a patient or a human participant not necessarily related to the treatment
Adverse Drug Reaction (ADR) – a noxious and unintended response at doses normally used or tested in humans (in cases of approved pharmaceutical products); a noxious and unintended response at any dose(s) (in cases of new unregistered pharmaceutical products); an untoward medical occurrence seemingly caused by overdosing, abuse/dependence and interactions with other medicinal products (in clinical trials)
Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – an AE or ADR that is associated with death, in-patient hospitalization (in case the study was being conducted on outpatients), prolongation of hospitalization (in case the study was being conducted on in-patients), persistent or significant disability or incapacity, a congenital anomaly or birth defect, or is otherwise life threatening. Per IND-42, Important Medical Events may be considered SAEs when they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one (1) of the outcomes listed in this definition
Unexpected Adverse Drug Reaction – an ADR, the nature or severity of which is not described in the informed consent/information sheet or the applicable product information, such as an investigator’s brochure (IB) for the unapproved investigational product (IP) or package insert/summary of product characteristics for an approved product (G-ICMR)

Safety Reporting Requirements

Per the 2019-CTRules, the sponsor (also known as applicant) and the investigator must forward any SAE/SADR report, after due analysis, within 14 days of the occurrence to the Drugs Controller General of India (DCGI), the ethics committee (EC) Chairman, and the head of the institution where the trial is being conducted. (Note: The DCGI is head of the Central Drugs Standard Control Organization (CDSCO) and is commonly referred to as the Central Licensing Authority in the Indian regulations.)

In the event of an SAE/SADR resulting in death, per the 2019-CTRules, the sponsor or the representative and the investigator must forward the SAE/SADR reports to the DCGI within 14 days of knowledge of this occurrence. The 2019-CTRules and IND-42 also indicate that the EC is also required to forward its report along with its opinion on financial compensation, if any, to be paid by the sponsor or the representative, to the DCGI within 30 days of the incident.

See Table 5 of the 2019-CTRules for details on the data elements required for reporting SAEs/SADRs that occur during a clinical trial.

See the Insurance & Compensation section for additional information on sponsor compensation requirements.

Investigator Responsibilities

As indicated in the 2019-CTRules, the G-ICMR, and IND-42, the investigator must report all SAEs/SADRs to the DCGI, the sponsor or the representative, and the EC, within 24 hours of occurrence. Per the 2019-CTRules, in the event that the investigator fails to report any SAE/SADR within the stipulated period, the investigator is then required to provide reasons for the delay to the DCGI along with the SAE/SADR report for the DCGI’s approval.

In addition, per the G-ICMR, the investigator must submit a report to the DCGI explaining how the SAE/SADR was related to the research within 14 days. According to the 2019-CTRules, the investigator must also promptly report to the EC all changes in the clinical trial activities and all unanticipated problems involving risks to human research participants or others.

Form Completion & Delivery Requirements

As per Notice25Feb21, the investigator, the sponsor or the representative, and the EC must report all SAEs electronically via the SUGAM portal (IND-59). However, follow-up reports pertaining to SAE reports submitted prior to March 14, 2021, will continue to be accepted in paper form. Refer to IND-59 for the SUGAM user manual and video tutorials. See also IND-42 for instructions on how to submit SAE reports (referred to as Due Analysis Reports) via IND-59.

The G-ICMR further states that the investigator may report SAEs/SADRs to the EC through email or fax communication (including on non-working days). Refer to IND-37 for the Indian Council of Medical Research (ICMR)'s EC Serious Adverse Event Reporting Format (Clinical Trials).

2.6, 5.3, 7.1, and Glossary

Chapter I (2), Chapter V (25), Chapter VI (42), and Third Schedule (2-3 and Tables 4-5)

Chapter 8

Last content review/update: July 2, 2024

Safety Reporting Definitions

According to the CTRules and the G-KenyaCT, the following definitions provide a basis for a common understanding of Kenya’s safety reporting requirements:

Adverse Event (or Adverse Experience) (AE) – Any untoward medical occurrence in a participant in a clinical investigation study or intervention product, and which does not necessarily have a causal relationship with the treatment
Adverse Drug Reaction (ADR) – All noxious and unintended responses to a clinical trial study or interventional product related to any dose or all unintended noxious responses to a registered medicinal product which occurs at doses normally used in humans for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function
Serious Adverse Event (SAE) – Any untoward medical occurrence that at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect
Suspected Unexpected Serious Adverse Reaction (SUSAR) – A serious adverse reaction that is not identified in practice, severity, or frequency by the referenced safety information

Safety Reporting Requirements

Investigator Responsibilities

Per G-KenyaCT, the investigator must ensure that all SAEs are reported promptly to Kenya’s Pharmacy and Poisons Board (PPB) within the mandated timelines, as described below. Proper protection procedures or treatments should be administered to trial participants with SAEs.

Sponsor Responsibilities

As indicated in the CTRules and the G-KenyaCT, the sponsor should report to the PPB and all relevant institutions, all SAEs and SUSARs occurring during the course of the trial. The G-KenyaCT specifies that the sponsor should expedite reporting all SAEs to the PPB and the ethics committee (EC), and the sponsor and investigators should immediately undertake appropriate and necessary measures and treatment to protect the trial participants. The CTRules delineates that where a sponsor conducts a clinical trial on the same health product or active pharmaceutical substance in another country, the sponsor must submit a report of any SUSAR or SAE that occurs in the other clinical trial to the PPB. Per the CTRules and the G-KenyaCT, a sponsor must submit an initial report of an fatal or life-threatening SUSAR or SAE as soon as it occurs but, in any case, not later than seven (7) days after the occurrence of the event. The G-KenyaCT indicates that if the initial report is incomplete, the sponsor must submit a completed report based on the initial information within an additional eight (8) days. As required in the CTRules and the G-KenyaCT, a report of the occurrence of a SUSAR or SAE must specify whether the SUSAR or SAE is related to the clinical trial.

As indicated in the CTRules and the G-KenyaCT, other important considerations and timelines include the following (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

The sponsor must notify all the investigators involved in ongoing clinical trials of the investigational product (IP) of all SAEs and SUSARs within 15 calendar days
Any IP-related SAE must receive immediate medical attention and be reported to the PPB
The SAE report form must be completed (including lab results) and submitted to enable causality assessment
All fatal cases must be accompanied by a formal autopsy report, and a verbal autopsy report should be submitted in those exceptional cases where a formal autopsy is not possible
Any frequent IP related AE/ADR must receive immediate medical attention and be reported to the PPB within seven (7) days
The sponsor must submit a report on a SUSAR that is not fatal or life-threatening within 15 days after the occurrence of the event
The principal investigator (PI) is required to submit follow-up information as soon as it becomes available
All additional information should be clearly marked as updated and must include the Protocol Number and Participant Number
Foreign regulatory decisions that affect the safety or use of the product under study must be reported to the PPB within seven (7) days through a detailed report
Literature reports that have implications for the safety of the IP must be submitted within 15 days with a detailed report and a copy of the publication
New information or notification of change in nature, severity, or frequency of risk factors for the product under study or conduct of trial must be submitted within 15 days

Other Safety Reports

The G-ECBiomedRes indicate that ECs should monitor research, and will report to the National Bioethics Committee upon notification of an AE.

The CTRules and the G-KenyaCT state that the sponsor must also submit a safety report to the PPB once a year throughout the clinical trial, or upon request. The purpose of the annual safety report is to briefly describe all new safety information relevant to one (1) or more clinical trial(s), and to assess the safety conditions of the participants enrolled in these trial(s). The safety report must include a log of SAE and SUSAR events. The SAE and SUSAR log should include the following:

Patient Identification
Age
Date of recruitment into the study
Type of SAE or SUSAR
SAE or SUSAR start and end dates
Reason for reporting the event as an SAE or SUSAR
Relation to IP
SAE or SUSAR outcome

Note that the PPB may require more frequent reporting of the safety reports depending on the nature of the clinical trial being implemented. When this is the case, the PPB must communicate the required frequency to the PI and sponsor in writing.

Form Completion & Delivery Requirements

As per the G-KenyaCT and KEN-16, all SAEs and SUSARs must be reported to the PPB via the Pharmacovigilance Electronic Reporting System (PvERS) (KEN-6).

4.1 and 5.1

Glossary of Terms, 1.59, 1.63-1.88, and 1.318-1.339

Part I (2) and Part IV (12)

Progress Reporting

Last content review/update: June 21, 2024

Interim and Annual Progress Reports

As described in the 2019-CTRules and IND-31, the Drugs Controller General of India (DCGI), who heads the Central Drugs Standard Control Organization (CDSCO), requires the sponsor (also known as applicant) to submit a six (6)-month status report for each clinical trial electronically via the CDSCO’s SUGAM portal (IND-59). The report should clarify whether the trial is ongoing, completed, or terminated. In the case of termination, detailed reasons for such termination must be communicated to the DCGI within 30 working days of the termination. In addition, per the 2019-CTRules, an ethics committee (EC) may periodically request study progress reports from the investigators.

As delineated in the 2019-CTRules, sponsors are also required to submit an annual status report for the clinical trial to the DCGI.

The 2019-CTRules further specifies that in cases where trials have been prematurely discontinued for any reason, including a lack of commercial interest in pursuing the new drug application (NDA), the sponsor should submit a summary report within three (3) months. The summary report should provide a brief description of the study, the number of participants exposed to the drug, dose/duration of exposure, details of adverse drug reactions, if any, and the reason for the study’s discontinuation or non-pursuit of the NDA.

See IND-35 for a Checklist of Notification for Annual Status Report documentation requirements to be included in a global clinical trial application.

Final Report

The final report should comply with the format and content guidelines listed in the 2019-CTRules as follows:

Title page
Study synopsis (1 to 2 pages)
List of abbreviations and definitions
Table of contents
EC approval letter(s)
Study team introduction
Study objective
Investigational plan
Trial participants
Efficacy evaluation
Safety evaluation
Discussion and overall conclusion
List of references
Appendices

See the 2019-CTRules for more detailed information on preparing the final report.

See IND-35 for a checklist of documentation requirements to be included in a global clinical trial application pertaining to end of clinical trial notification.

Chapter III (11), Chapter V (25), First Schedule (6), and Third Schedule (3 and Table 6)

36

Checklist of Notification for Annual Status Report; Checklist for Notification for End of GCT

Last content review/update: July 2, 2024

Interim and Annual Progress Reports

As stated in the G-KenyaCT, the sponsor and/or the principal investigator (PI) is required to send progress reports to the Pharmacy and Poisons Board (PPB) on an annual basis, or as may be required, from the date of the trial’s initiation. The progress report should contain the following:

Current status of the study
Summary of the participants screened (e.g., failed screenings, participants enrolled, withdrawn, or lost to follow-up, and other challenges)
Summary of protocol deviations and violations
Updated investigational product Investigator’s Brochure
Drug Safety Update Report
Copy of the latest Data Safety Management Board report
Copy of favorable opinion from the ethics committee (EC) on record
Copy of annual practice license for the investigators and pharmacists
Suspected, Unexpected, Serious Adverse Event (SUSAR) and Serious Adverse Event (SAE) Log

For multisite trials, per the G-KenyaCT, the sponsor or the representative must submit a summarized report for all of the sites and include the information listed above.

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). As per KEN-14, the investigator should promptly provide written reports to the sponsor and the institutional EC on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.

According to the G-KenyaCT, for annual renewal of the study, the sponsor or the representative must submit a copy of the progress report including the documents listed above. The request must also be accompanied by copies of annual practice licenses for the investigators and pharmacists, and a copy of valid insurance coverage for the participants. All documents must be submitted using the PPB’s Online Clinical Trials Registry System (KEN-16). The sponsor or the representative must receive an acknowledgement of this submission before proceeding with the study. These documents must be submitted to the PPB at least six (6) weeks prior to the expiration of the previous approval.

Pursuant to KEN-14, the investigator should submit written summaries of the trial status to the institutional EC annually, or more frequently, if requested.

Final Report

Per the G-KenyaCT, the sponsor must notify the PPB of the end of a clinical trial taking place at a Kenyan site within 15 days. After the trial has been conducted and closed, the applicant must submit an executive summary report of the study within 30 days. This should be followed by a clinical study report within 180 days of the study closure unless otherwise justified. The report must comply with the International Council for Harmonisation's ICH E3 format (KEN-13). The report must include a short but comprehensive summary of the trial’s essential findings and methodology and should also contain a layman’s summary. Additionally, the sponsor must inform the PPB of any results that will be publicly released at least 14 days before release. In addition, upon completion of the trial, as delineated in KEN-14, the investigator is required to submit a final report to the institutional EC summarizing the trial’s outcome.

For multi-site research, the G-ECBiomedRes requires all parties to decide on procedures for drafting a common final report and publication at the onset of the research. Individual sites or institutions must not publish any data until the appropriate authorities accept the combined report.

KEN-31 further indicates that the research license applicant must submit one (1) hard copy and upload a soft copy of the final research report to the National Commission for Science, Technology and Innovation (NACOSTI) within one (1) year of the research’s completion.

4.10 and 4.13

5.1

1.48, 1.63, 1.497-1.506, 1.515-1.518, and 1.533-1.536

Definition of Sponsor

Last content review/update: June 21, 2024

New Info (Not Yet in Profile)

Effective April 1, 2025, the New Drugs and Clinical Trials (Amendment) Rules, 2024 requires registration of Clinical Research Organizations (CROs) with the Central Licensing Authority, which is the Drugs Controller General of India (DCGI), prior to conducting clinical trials or bioavailability or bioequivalence studies of new drugs or investigational new drugs in humans. The rules also outline the registration requirements and procedures for CROs and applicable forms. Per a notice from March 4, 2025, applications for registration must be submitted through the SUGAM Portal.

As per the 2019-CTRules and the G-ICMR, a sponsor (also known as applicant) is defined as an individual, a company, or an institution that takes responsibility for the initiation, management, or financing of a clinical study. The G-ICMR further states that an investigator who independently initiates and takes full responsibility for a trial automatically assumes the role of a sponsor. The 2019-CTRules also indicates that the sponsor may appoint a contract research organization (CRO).

4.0-4.2, 4.8, and 4.10

Chapter I (2)

Last content review/update: July 2, 2024

As per the G-KenyaCT, a sponsor is defined as an individual, a company, an institution, or an organization who takes legal responsibility for the initiation, management, and financing of a trial. According to the G-KenyaCT, a sponsor, in a written document, may agree to transfer all related activities of the clinical trial to designated research institutions. However, all responsibility for the trial lies with the sponsor. The G-ECBiomedRes indicates that sponsors may be foreign, but must comply with certain conditions including affiliating themselves to institutions recognized in Kenya.

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). In accordance with KEN-14, Kenya permits a sponsor to transfer any or all of its trial-related duties and functions to a contract research organization (CRO) and/or institutional site(s). However, the ultimate responsibility for the trial data’s quality and integrity always resides with the sponsor. Any trial-related responsibilities transferred to a CRO should be specified in a written agreement. The CRO should implement quality assurance and quality control.

5.1 and 5.2

4.1 and 6.0

Glossary of Terms, 1.48, 1.63, and 1.68

Site/Investigator Selection

Last content review/update: June 21, 2024

New Info (Not Yet in Profile)

DCGI notices related to regulatory submissions through the SUGAM Portal:

Notice from December 26, 2024 - Submission of Clinical Trial Site Addition and change of Principal Investigator applications for global clinical trials, clinical trials of new drugs, subsequent new drugs, investigational new drugs, fixed dose combinations, and bioavailability & bioequivalence studies
Notice from February 24, 2025 - Submission of Clinical Trial Site Addition and change of Principal Investigator applications for clinical trials of biological products (vaccine and rDNA)

Overview

As stated in the 2019-CTRules, all investigators must possess appropriate qualifications, training, and experience, and should conduct the trials in compliance with Good Clinical Practices (GCPs) and Good Laboratory Practices (GLPs). (See GCLP for the G-ICMR for Good Clinical Laboratory Practices (GCLP), IND-31 for additional laboratory requirement information, and IND-76 for international GCLP guidelines. Investigators should also have access to investigational and treatment facilities as relevant to the protocol.

Per the 2019-CTRules, prior to entering into an agreement with the investigator(s)/institution(s) to conduct a study, the sponsor (also known as applicant) should provide the involved parties with the protocol and an up-to-date investigator’s brochure and allow them sufficient time to review this documentation. The sponsor must also define and allocate all study-related duties and responsibilities to the respective identified person(s) and organization(s) prior to initiating the study.

In addition, per Notice2Dec19, the Central Drugs Standard Control Organization (CDSCO) is preparing a comprehensive database of clinical trial sites and investigators involved in the conduct of global clinical trials in different therapeutic categories by collecting information from various sources. The first phase includes an Excel spreadsheet of sites and investigators involved in global clinical trials (IND-26).

See also IND-28 for the Indian Council of Medical Research (ICMR)’s research conduct policies.

Foreign Sponsor Responsibilities

No information is currently available on foreign sponsor responsibilities.

Data and Safety Monitoring Board

While there are no general requirements for establishing a Data Safety Monitoring Board (DSMB), the G-Children recommends that a DSMB be strongly considered for research involving children in emergency situations.

Multicenter Studies

As delineated in the G-ICMR, in the case of multicenter research studies, all of the participating study sites are required to obtain approval from their respective ethics committees (ECs), which includes the option of each site choosing to accept the review/approval of a primary EC. The study sites also typically follow a common protocol to avoid duplication of effort, wastage of time, and communication issues. See the G-ICMR for additional participating site requirements when a primary EC is selected for common EC review. Also, see the Scope of Review section for additional details.

Further, per the G-ICMR, if a multicenter trial is going to be conducted, the sponsor may organize a coordinating committee or select coordinating investigators. The sponsor must also conduct training for investigators in ethics, GCPs, standard operating procedures (SOPs), and study protocols.

6.5

4.2.3, 4.8 (Table 4.2.3), and 4.10

Chapter III (11), Third Schedule (1, 3, and Table 4), and Fourth Schedule (2)

Last content review/update: July 2, 2024

Overview

The G-KenyaCT, which requires sponsors to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), states that the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical trial and for ensuring that the investigator(s) are qualified by education, training, and experience.

Per the CTRules and the G-KenyaCT, investigators must also meet the following requirements (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Provide evidence of their qualifications and experience through an up-to-date curriculum vitae (CV)
Have a current practice license from the relevant regulatory authority
Be familiar with the characteristics and appropriate use of the investigational product (IP) as described in the protocol, current investigator’s brochure (IB), in the product information, and in other information sources
Have a clear understanding and willingness to obey the ethical, good clinical practice (GCP) and legal requirements in the conduct of the trial
Permit monitoring and auditing of the trial and inspection by the Pharmacy and Poisons Board (PPB) or appointed representatives
Keep a list of appropriately qualified persons to whom the investigator has delegated significant trial-related duties
The principal investigator (PI) must be an appropriately qualified and competent person having practical experience within the relevant professional area and who is responsible for the conduct of the clinical trial at a clinical site
The PI must have a degree in medicine, pharmacy, pharmacology, toxicology, biochemistry, dentistry, or a related discipline from a university recognized in Kenya
The PI must have a valid practice license from the relevant regulatory authority
The PI must have a valid professional indemnity cover
The PI must be a citizen of Kenya or a permanent resident in Kenya
A PI must have had previous experience as a co-investigator in at least two (2) trials in the relevant professional area
Have adequate time and resources to carry out the study (See Annex 6 of the G-KenyaCT for the PPB’s recommended format to document the investigator’s workload)

Further, the G-KenyaCT states that sponsors must ensure that investigators have had formal training in GCPs with proof that a GCP course was attended within the last two (2) years. If training has not been completed, it is the responsibility of the sponsor to organize this training prior to initiating the study. The investigators will need to provide evidence of having obtained this training. As delineated in KEN-14, prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an IB. Furthermore, the sponsor must sign an agreement or contract with the participating institution(s). Additionally, the sponsor must define and allocate all study related duties and responsibilities to the relevant parties participating in the study. (See the Submission Content section for additional information on clinical trial application requirements.)

Institutional Registration

The STI-Act and the STI-Regs require research institutions to register with the National Commission for Science, Technology and Innovation (NACOSTI) and obtain a Certificate of Registration. For detailed guidance on the vetting and approval process, see the STI-Regs and the G-InstitutionRegistration.

Upon creating an account in NACOSTI’s Kenya National Research Information System (KENRIS) (KEN-23), research institutions can apply for new research institution registration, maintain/update data, and submit annual reports. The application for registration of research institutions is also provided in KEN-11, and the reporting tool for registered research institutions is provided in KEN-36.

Foreign Sponsor Responsibilities

The G-ECBiomedRes requires that with collaborative research projects, the collaborating investigators, institutions, and countries must function as equal partners with safeguards to avoid exploitation of local researchers and participants. An external sponsoring agency should submit the research protocol to their country’s EC, as well as the Kenyan EC where the research is to be conducted. Further, this research must be responsive to the health needs of Kenya and reasonably accessible to the community in which the research was conducted. Consideration should be given to the sponsoring agency agreeing to maintain health services and faculties established for the purposes of the study in Kenya after the research has been completed. Such collaborative research must have a local/Kenyan co-principal investigator.

Data and Safety Monitoring Board

The G-KenyaCT indicates that the PPB recommends establishing a Data and Safety Monitoring Board (DSMB) to monitor trials in the following types of studies:

Where the endpoint is such that a highly favorable or unfavorable result, or even a finding of futility at an interim analysis, might ethically require the trial to be terminated early
When there are safety concerns due to the use of a particularly invasive treatment
Where there is prior information suggesting the possibility of serious toxicity with the study treatment
Where the participants involved represent a vulnerable population (e.g., children, pregnant women, elderly, terminally ill, or mentally incapacitated)
When the participants represent a population at higher risk of death or other serious outcomes
When the study is large, of long duration, and multi-center

KEN-14 states that a DSMB may be established to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial.

Per the G-KenyaCT, the DSMB must provide the following documentation to the PPB:

DSMB composition
Copy of DSMB charter
DSMB reports to be submitted to the PPB within two (2) weeks of its deliberations and in the request for annual approval

For multicenter trials, the G-ECBiomedRes requires that centralized data management and analysis should be planned as per G-WHO-DSMB.

Multicenter Studies

Per the G-KenyaCT, for multicenter studies in Kenya, the coordinating investigator should be a Kenyan resident and should assume full responsibility for the trial.

The G-ECBiomedRes requires that multicenter trials conducted simultaneously by several investigators at different sites follow the same protocol. Ideally, these trials should be initiated at the same time at all sites. The sponsor must provide the protocol to the investigators, who will accept the protocol in writing. If approved by the EC of the local host institution, the protocol may be modified to suit the local conditions. Meetings should be organized at the initial and intermediate stages of the trial to ensure uniform procedures at all sites. All sites and parties should also agree on procedures for publication of a final report. Research staff should receive training at every trial site on the uniform procedures. In addition, research staff at all sites should implement standard methods for recruitment and evaluation/monitoring of laboratory procedures and conduct of trial. There must be monitoring to ensure the sites are following the protocol, which must include measures to terminate the participation of some sites, if necessary. Finally, centralized data management and analysis should be planned as per G-WHO-DSMB.

Additional multicenter guidance is delineated in KEN-14:

All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor, and, if required, by the PPB, and given EC approval
The case report forms (CRFs) are designed to capture the required data at all multicenter trial sites
Investigator responsibilities are documented prior to the start of the trial
All investigators are given instructions on following the protocol, complying with a uniform set of standards to assess clinical and laboratory findings, and completing the CRFs
Communication among investigators is facilitated

1.25, 5.5, 5.6, and 5.23

4.1, 5.1, and 6

Glossary of Terms, 1.30-1.88, 1.340-1.345, and Annex 6

Part V

Science, Technology and Innovation (Registration and Accreditation of Research Institutions) Regulations, 2014 (Part II, First Schedule, and Second Schedule)

Part III (7)

Insurance & Compensation

Last content review/update: June 21, 2024

Insurance

The G-ICMR specifies that the sponsor (also known as applicant) should provide insurance coverage or a provision in the budget for possible compensation for trial-related injuries. The G-ICMR also states that it is preferable to have the insurance certificate and the policy for study participants. Further, the policy should explain the conditions of coverage, date of commencement, and expiration date for risk coverage (if applicable). In addition, institutional mechanisms must be established to allow for insurance coverage of trial-related or unrelated illnesses (ancillary care).

The 2019-CTRules states that the ethics committee (EC) also requires a copy of the insurance policy or details regarding compensation for participation and for serious adverse events (SAEs) occurring during the study as part of its submission review process.

With regard to indemnity coverage, the G-ICMR states that an indemnity policy must be included in the documentation for EC review. The policy should clearly indicate the conditions of coverage, date of commencement, and coverage expiration date, if applicable.

Compensation

Injury or Death

In accordance with the 2019-CTRules and the G-ICMR, the sponsor is responsible for providing compensation to research participants and/or their legal heir(s) in the event of trial-related injuries, permanent disability, or death. Per the G-ICMR, in the event the investigator/institution becomes the sponsor in a clinical trial, it is the host institution’s responsibility to provide compensation for research-related injury or harm as determined by the ethics committee (EC).

The 2019-CTRules further notes that the sponsor is responsible for compensating the research participant and/or the legal heir(s) if the trial-related injury, death, or permanent disability to a participant is specifically related to any of the following reasons:

Adverse effects of an investigational product (IP)
Any trial procedures involved in the study
A violation of the approved protocol, scientific misconduct, or negligence by the sponsor, the representative, or the investigator
Failure of the IP to provide the intended therapeutic effect where, the standard care, though available, was not provided to the participant per the protocol
Not providing the required standard care, though available to the participant per the protocol in the placebo-controlled trial
Adverse effects due to concomitant medication excluding standard care, necessitated as part of the approved protocol
Adverse effect on the child in-utero due to a parent’s participation in a trial
Any clinical trial procedures involved in the study leading to a serious adverse event (SAE/serious adverse drug reaction (SADR)

Per the 2019-CTRules and the G-ICMR, the sponsor must also ensure that participants who suffer any trial-related injuries be provided with free medical treatment for such injuries as long as required per the opinion of the investigator (and the EC per the G-ICMR), or until such time it is established that the injury is not related to the clinical trial, whichever is earlier. Per the 2019-CTRules, if the sponsor or the representative fails to provide medical management, the Drugs Controller General of India (DCGI), after a hearing, must issue a written order to suspend or cancel the study or restrict the sponsor, including the representative, from conducting any further clinical trials or taking any other action for such period deemed appropriate for this case. (Note: The DCGI is head of the Central Drugs Standard Control Organization (CDSCO) and is commonly referred to as the Central Licensing Authority in the Indian regulations.)

In the case of a trial-related injury, the 2019-CTRules and IND-31 state that the sponsor is required to provide complete medical management and compensation to the participant within 30 days of receiving an order from the DCGI. In the event of permanent injury or death, the sponsor is required to provide compensation to the participant or to the legal representative/guardian within 30 days of receiving the DCGI’s order. According to IND-31, compensation and medical management requirements are also applicable in the case of injury or death occurring during an academic trial.

The 2019-CTRules explains that in the case of an SAE resulting in death, the DCGI must constitute an independent expert committee to review the incident and make its recommendations to the DCGI for the cause of death and to provide a quantum of compensation. The sponsor or the representative and the investigator must forward their reports, after due analysis, to the DCGI and the head of the institution where the trial was conducted within 14 days of the occurrence. The EC must forward its report along with its opinion on financial compensation, if any, to be paid by the sponsor or the representative within 30 days of receiving the investigator’s report. The DCGI, in turn, must forward the sponsor, investigator, and EC reports to the expert committee chairperson. Following its review, the expert committee must make its recommendations to the DCGI as to the cause of the SAE resulting in death and the quantum of compensation within 60 days from receiving the DCGI’s submission. The DCGI must then consider the expert committee’s recommendations and issue an order within 90 days to the sponsor or the representative specifying the quantum of compensation required to be paid within 30 days of receiving the order.

In the case of an SAE/SADR resulting in permanent disability or any injury other than death, the 2019-CTRules indicates that the sponsor or the representative and the investigator must forward their reports, after due analysis, to the DCGI, the EC chairperson, and the head of the institution where the trial has been conducted within 14 days of the occurrence. The EC, after due analysis, must forward its report along with its opinion on financial compensation, if any, to the DCGI within 30 days of the event occurrence. The DCGI, in turn, must determine the cause of the injury and issue an order, with the option to constitute an independent expert committee, within 60 days of receipt of the report. The DCGI must issue an order within 90 days of receiving the report indicating the quantum of compensation to be paid by the sponsor or the representative within 30 days of receipt of this order.

In the case of an injury not being permanent in nature, per the 2019-CTRules, compensation should be commensurate with the participant’s loss of wages.

Per the 2019-CTRules, in the event that a sponsor or the representative fails to provide compensation to a research participant for trial-related injuries, or to the legal heir(s) in case of death, the DCGI must, after giving an opportunity to show cause why such an order should not be passed by a written order, suspend or cancel the clinical trial, or restrict the sponsor or the representative from conducting any further clinical trials in India or taking any other action deemed fit given the circumstances.

See the 2019-CTRules and the G-ICMR for detailed information on terms of compensation payment.

Trial Participation

The G-ICMR explains that participants may also be compensated for their time and other expenses (e.g., loss of wages, food supplies, and travel). The EC should approve all payments, reimbursement, and medical services provided. Per the G-ICMR, participants should not be required to pay for any expenses incurred beyond routine clinical care and which are research related including patient work-ups, or interventions associated with treatment. If there are provisions, participants may receive additional medical services at no further cost.

Post-Trial Access

The 2019-CTRules and IND-31 explain that the investigator may recommend the sponsor provide post-trial access to the investigational product (IP) free of cost to the participant for such period as deemed necessary by the investigator and the EC. The sponsor must obtain DCGI approval to initiate this plan. The investigator’s recommendation will be based on the following conditions:

If the trial is being conducted for an indication for which no alternative therapy is available, and the IP has been determined to be beneficial
The participant or the legal representative/guardian has consented in writing to use the post-trial IP, and has certified and declared in writing, along with the investigator, that the sponsor must have no liability for post-trial use of the IP

See also IND-6 for additional information on post-trial access to IPs under the 2019-CTRules.

Additionally, per the G-ICMR, the benefits accruing from research should be made accessible to individuals, communities and populations whenever relevant. The EC should consider the need for an a priori agreement between the researchers and sponsors regarding the following:

Efforts should be made to communicate the findings of the research study to the individuals/communities wherever relevant
The research team should make plans wherever applicable for post-research access and sharing of academic or intervention benefits with the participants, including those in the control group
Post-research access arrangements or other care must be described in the study protocol so that the EC may consider such arrangements during its review

G-ICMR further states that if an investigational drug is to be given to a participant post-trial, appropriate regulatory approvals should be in place. In studies with restricted scope, such as student projects, post study benefit to the participants may not be feasible, but conscious efforts should be made by the institution to take steps to continue to support and give better care to the participants.

Post-Trial Access

12, 39-41, and 61

2.5-2.7, 2.11, 4.7, 4.8, Box 4.4(A), 7.1, and 7.16

Chapter I (2), Chapter V (25 and 27), Chapter VI (39-40 and 42), Third Schedule (3, Table 1 and Table 3), and Seventh Schedule

Last content review/update: July 2, 2024

Insurance

As set forth in the G-KenyaCT and the G-ECBiomedRes, the sponsor must provide insurance cover for the study participants and ensure that the clinical trial institution, contract research organization (CRO), and researchers have sufficient insurance cover for the clinical trial. Per the G-KenyaCT, the sponsor’s policies and procedures should address the treatment costs for trial participants in the event of trial-related injuries, and the sponsor should submit this information as part of the clinical trial application (see KEN-34). In addition, a no-fault insurance cover must be obtained for all controlled human infection studies. The International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14) guides sponsors on providing insurance. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

For all sponsor-initiated studies, insurance coverage must be provided by an insurer registered by Kenya’s Insurance Regulatory Authority (IRA), and a valid insurance certificate must be issued by the IRA prior to the trial’s initiation and cover the duration of the study. The insurance certificate must be submitted as evidence to the Pharmacy and Poisons Board (PPB). The certificate must be properly executed by an insurance company under a valid insurance policy which makes explicit reference to the proposed study. In addition, the policy must grant coverage for any participant injury that is causally linked to trial activities. The policy must also cover the investigator(s)’ and the sponsor(s)’ liability in the trial, without excluding any damage which may be attributed to negligence. Moreover, self-insurance of the participants by other entities, such as the National Health Insurance Fund, will not be sufficient.

Further, per the G-KenyaCT, the sponsor must ensure that the investigators and CROs have professional indemnity insurance coverage for the period of the trial. The host institution must also have in place sufficient insurance to meet the potential liability of its investigators, those acting on behalf of the investigators, and its research members.

Compensation

Injury or Death

As specified in the G-KenyaCT and the G-ECBiomedRes, the sponsor is responsible for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries or death. Per the G-ECBiomedRes, participants are entitled to such financial or other assistance as would compensate them equitably for any temporary or permanent impairment or disability. In the case of adverse events, there should be proper assessment, evaluation, and compensation. The G-ECBiomedRes also indicates that when investigational vaccines contain active or live-attenuated micro-organisms, should participants in the control group contract the disease for which a vaccine is being tested, free treatment must be provided.

In addition, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14) provides guidance for sponsors on providing compensation to research participants in the event of trial-related injuries or death. The sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries.

Trial Participation

The G-ECBiomedRes defines compensation to include offers to participants, monetary or otherwise, to offset the time and inconvenience for participating in research.

Post-Trial Access

Per the G-KenyaCT, the sponsor must put in place measures to ensure that the study participants have access to successful investigational products for their disease condition before the products have received a marketing authorization in Kenya, especially for the Phase III clinical trials. The G-ECBiomedRes indicates that when investigational vaccines contain active or live-attenuated micro-organisms, post-trial access to the vaccine should be available to the control group.

4.8 and 5.8

Definitions, 3.2, 4.2, and 5.3

1.48, 1.63-1.130, 1.173-1.181, and 1.437-1.490

Risk & Quality Management

Last content review/update: June 21, 2024

Quality Assurance/Quality Control

In accordance with the 2019-CTRules and the G-ICMR, the sponsor (also known as applicant) is responsible for implementing and maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data generated, recorded, and reported in compliance with the protocol, Good Clinical Practices (GCPs), and all applicable laws and regulations.

Monitoring Requirements

As per the 2019-CTRules, the sponsor must permit clinical trial site inspections by the Drugs Controller General of India (DCGI)-authorized officers. The officers may enter the premises and clinical trial site with or without prior notice to inspect, search, or seize any record, statistical result, document, investigational drug, and other related material. The sponsor must also reply to inquiries raised by the inspecting authority in relation to the conduct of the trial. (Note: The DCGI is head of the Central Drugs Standard Control Organization (CDSCO) and is commonly referred to as the Central Licensing Authority in the Indian regulations.)

In addition, as part of its QA system, the 2019-CTRules notes that investigator(s) may provide periodic study progress reports (PSUR), or regulatory officials or sponsor-designated authorized representatives may provide monitoring and internal audit reports to the ethics committee (EC) to support its recurring clinical trial reviews. An audit certificate may be issued, if available.

Furthermore, the 2019-CTRules requires the investigator to sign an undertaking indicating agreement to maintain adequate and accurate records and to make those records available for audit or inspection by the sponsor, the EC, the Central Licensing Authority, or their authorized representatives, in accordance with regulatory provisions and GCP guidelines. The investigator must agree to fully cooperate with any study-related audit conducted by regulatory officials or authorized representatives of the sponsor.

See IND-35 for a checklist of PSUR documentation requirements to be included in a global clinical trial application, and IND-34 for the DCGI’s GCP Inspection Checklist.

Premature Study Termination/Suspension

As delineated in the 2019-CTRules, when the sponsor fails to comply with any provisions of the DCA-DCR and the 2019-CTRules, the DCGI may, after giving an opportunity to show cause and after affording an opportunity of being heard, by an order in writing, implement one (1) or more of the following actions:

Issue a warning in writing describing the deficiency or defect observed during inspection or otherwise which may affect adversely the right or well-being of a trial participant or the validity of clinical trial conducted
Reject the results of the clinical trial
Suspend for such period as considered appropriate or cancel the permission granted in Form CT-06 or in Form CT-4A
Debar the investigator or the sponsor, including the representatives, from conducting any clinical trial in the future for such period as considered appropriate by the DCGI

The sponsor or the representative may appeal the DCGI’s decision within 60 working days of receipt of the order.

Further, per the 2019-CTRules, in case of studies prematurely discontinued for any reason, including lack of commercial interest in pursuing the new drug application, the sponsor should submit a summary report within three (3) months. The summary report should provide a brief description of the study, the number of patients exposed to the drug, dose and duration of exposure, details of adverse drug reactions, if any, and the reason for discontinuation of the study or non-pursuit of the new drug application.

The 2019-CTRules also indicates that in case of termination of any clinical trial the detailed reasons for such termination must be communicated to the DCGI within 30 working days of such termination.

See IND-35 for a checklist of premature study termination documentation requirements to be included in a global clinical trial application.

4.2.3, 4.10, and 6.1 (Table 6.1)

Chapter V (25, and 29-30), Third Schedule, and Eighth Schedule (Forms CT-4A and CT-06)

Last content review/update: July 2, 2024

Quality Assurance/Quality Control

As stated in the CTRules and the G-KenyaCT, the sponsor is responsible for maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, recorded, and reported in compliance with the protocol, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), the STI-Regs, and other applicable regulatory requirements. QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed. In addition, per the STI-Regs, all persons and research institutions (i.e., sponsors) undertaking research in Kenya must ensure the highest standards and quality of research for the realization of institutional mandates and national priorities.

In addition to complying with KEN-14, the G-KenyaCT indicates QA processes should be developed to ensure:

Regular and continuous monitoring of the study and the implementation of monitoring reports’ recommendations
Submission of the study monitoring plan to the Pharmacy and Poisons Board (PPB) during the initial submission of the application
The clinical trials research site must have valid registrations and approvals
Patient safety and confidentiality are not compromised
Analysis or evaluation of samples is performed in accordance with the protocol and good clinical practice (GCP) principles and, where applicable, the contract/agreement, the work instruction, and associated methods
Adherence to the laboratories’ policies and SOPs
Trial data is recorded and reported accurately, legibly, completely, and in a timely manner
Trial data is archived
Preparation of a work instruction detailing the procedures that will be used to conduct the analysis or evaluation prior to the initiation of sample analysis or evaluation, as necessary
Be built or adapted for the purpose
Have automated equipment for routine hematology, biochemistry, and serology tests
Have procedures for analyzer calibration and quality control
Regular maintenance of all the equipment, including point-of-care equipment
Have a procedure for transporting samples safely and quickly from clinical areas to the laboratory
Have written procedures for all assays, and to validate the assays
Reagents and consumables are used within their expiry dates based on a stock control procedure
Records are kept, including source documents and final reports
Have a procedure for authorizing and releasing results
Have a procedure for ‘flagging’ and notifying medical staff of abnormal results
Have a laboratory information management system, and validate and back up the system
Protective clothing and safety equipment are provided for staff
Have a central alarm system for all fridges and freezers
Have an internal audit program

Per KEN-14, the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:

During protocol development, identify processes and data that are critical to ensure participant protection and the reliability of trial results
Identify risks to critical trial processes and data
Evaluate the identified risks against existing risk controls
Decide which risks to reduce and/or which risks to accept
Document quality management activities and communicate to those involved in or affected by these activities
Periodically review risk control measures to ascertain whether the implemented quality management activities are effective and relevant
In the clinical study report, describe the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken

Per the G-KenyaCT protocol violations and protocol deviations must be reported to the PPB within seven (7) days of the principal investigator (PI) becoming aware of them. The details to be reported must include:

Date of the deviation/violation
Study participant(s) affected
Name of the treating physician
Detailed description of the deviation/violation
Indication whether the study participants were adversely affected by the deviation/violation
Explanation of why the deviation/violation occurred
Measures taken to address the deviation/violation
Measures taken to preclude future recurrence of the deviation/violation

In addition, see G-KenyaCT for information about medical care of trial participants during and following the clinical trial. Also see the Bft-Risk for a standardized approach for evaluating and reporting the balance between the benefits and risks of health products, which includes investigational products (IPs) undergoing clinical trial application.

The CT-Emrgcy provides guidance to sponsors, PIs, and institutions on the conduct of clinical trials during public health emergencies to maximize the safety of research participants, minimize risks to participants and the community, and ensure the integrity of the clinical trials. See CT-Emrgcy for details on a range of issues, including contingency planning, communications with participants, changes to studies, protocol deviations, reporting, and supply of IPs during a public health emergency.

Controlled Human Infection Studies

The G-KenyaCT also provides detailed information on controlled human infection studies (CHIS) requirements to ensure investigator/study personnel compliance with GCP and other QA/QC requirements, including the following:

The well characterized strain of an infectious agent should be administered at a controlled dose and by a specific route to carefully selected adult volunteers
The studies require safe and accurate microbiology, good clinical facilities, careful recruitment, and monitoring
Participants must be monitored for evidence of carriage or infection under medical supervision to anticipate or manage symptoms of disease and adverse events
The value of the information to be gained should clearly justify the risks and the study must have a risk mitigation plan
The investigators should be adequately qualified, trained, and experienced in the conduct of CHIS as well as treating patients with the infectious disease being investigated

For the complete list of requirements, see the G-KenyaCT.

The G-ECBiomedRes provides additional considerations when investigational vaccines contain active or live-attenuated micro-organisms:

The participant to be vaccinated should be given adequate information about the adverse effects.
Should participants in the control group contract the disease for which a vaccine is being tested, free treatment must be provided.
Because the risks associated with vaccines produced by recombinant DNA techniques are not completely known, PPB guidelines must be strictly followed.
Post-trial access to the vaccine should be available to the control group

Monitoring Requirements

As part of its QA system, the G-KenyaCT requires the sponsor to develop an internal audit program. The G-KenyaCT defines an audit as a systematic examination, carried out independently of those directly involved in the trial, to determine whether the conduct of a trial complies with the agreed study protocol and whether data reported are consistent with those on record at the site. Further, the sponsor is required to obtain agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities An investigator must, upon request from any properly authorized officer or employee of PPB, at reasonable times, permit such officer or employee to have access to, and copy and verify any records or reports made by the investigator.

Per KEN-14, the sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency. The sponsor may choose onsite monitoring, a combination of onsite and centralized monitoring, or, where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan).

KEN-31 indicate that the National Commission for Science, Technology and Innovation (NACOSTI) may conduct an evaluation, or cause an evaluation to be conducted, of a research study to assess and evaluate compliance with the conditions of the applicable research license.

Premature Study Termination/Suspension

The G-KenyaCT states that if a trial is terminated by the PI or the sponsor, the PI or the sponsor must inform the PPB not later than 15 days following the termination date. The co-investigators must also be informed as soon as possible and should be advised in writing of potential risks to the research participants, and they must ensure that patients continue to receive medical care. The PPB must be provided with reason(s) for the termination and its impact on the proposed or ongoing trials with respect to the IP, including issues relating to IP accountability and disposal as well as record(s) maintenance. In addition, the PPB may withdraw the authorization to conduct a clinical trial if it finds that the safety of the participants is compromised or that the scientific reasons for conducting the trial have changed.

According to KEN-14, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the EC should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor.

5.0-5.2, 5.5, 5.18-5.19, 5.21, and 6.10

4.2 and 5.3

1.42A, 1.63-1.88, 1.125, 1.437-1.491, 1.497-1.506, 1.525, and 1.533-1.536

The Science, Technology and Innovation (Registration and Accreditation of Research Institutions) Regulations, 2014 (Part III); and The Science, Technology and Innovation (Relevance and Quality Assurance in Research) Regulations, 2014 (Parts I-III)

Part III (8)

Data & Records Management

Last content review/update: June 21, 2024

Electronic Data Processing System

No information is currently available on electronic data processing systems.

Records Management

Per the 2019-CTRules, the sponsor (known as applicant) must keep a record of new drugs manufactured and persons to whom the drugs have been supplied for clinical trial or bioavailability and bioequivalence study or for examination, testing, and analysis. In addition, the 2019-CTRules indicates that the licensed sponsor must maintain records of any imported new drug or substance that indicates the quantity of drug imported, used, and disposed of in any manner including related documentation.

See the Scope of Review section for information on ethics committee management of clinical trial related records.

Chapter VIII (55) and Chapter IX (70)

Last content review/update: July 2, 2024

Electronic Data Processing System

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). As per KEN-14, when using electronic trial data processing systems, the sponsor must ensure that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. Per KEN-14, the sponsor should base their approach to validate such systems on a risk assessment that takes into consideration the intended use and the potential of the system to affect participant protection and reliability of trial results. In addition, the sponsor should maintain standard operating procedures (SOPs) for the systems that cover setup, installation, and use. The responsibilities of the sponsor, investigator, and other parties should be clear, and the system users should be provided with training. Refer to KEN-14 for additional information.

Records Management

According to the G-KenyaCT, it is the responsibility of the investigator and the sponsor to archive safely all trial-related documentation. All Kenyan trial site-related documentation must be archived within the country and not exported. Additionally, the sponsor/applicant must inform the Pharmacy and Poisons Board (PPB)’s Expert Committee on Clinical Trials (ECCT) in writing prior to destroying any trial documents. The notification must include the protocol number, start and end date, and the license number.

The G-KenyaCT states that study documents must be archived for a minimum of 10 years from the end of the study. Also, records must be made available to the PPB within three (3) days if there is a concern regarding the use of a clinical trial drug and/or a risk to the health of the clinical trial participant. In any other case, records must be provided within seven (7) days of request.

Per the STI-Regs, sponsors should store research findings and information regarding research systems in a designated location with clear labels of the subject area. Research findings must be documented in bound books or documents with the research title, author, year, and other relevant information clearly printed on the cover page. A report of research work by staff and the research institution must be submitted to the National Commission for Science, Technology and Innovation (NACOSTI) within two (2) months after publication or compilation of the research report.

In addition, KEN-14 states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.

1.65, 5.5, and 8

Glossary of Terms, 1.48, 1.63, and 1.537-1.541

The Science, Technology and Innovation (Registration and Accreditation of Research Institutions) Regulations, 2014 (Part IV)

Personal Data Protection

Last content review/update: June 21, 2024

Responsible Parties

For the purposes of data protection regulation in India, the ITAct, the ITActAmend, and the IT-SPDIRules delineate responsibilities of the “body corporate.” The body corporate as defined by the ITAct, the ITActAmend, and the IT-SPDIRules refers to any company including a firm, sole proprietorship, or other association of individuals engaged in commercial or professional activities. The IT-SPDIRules further explains that the body corporate or any person on its behalf is the entity responsible for collecting, receiving, possessing, storing, dealing with, or handling personal information, including sensitive personal data and information. (Note: In ClinRegs, the “body corporate” is referred to as “sponsor,” but the requirements may apply to other parties as well).

Data Protection

Data protection in India is currently regulated by the ITAct, the ITActAmend, and the IT-SPDIRules. Per the IT-SPDIRules, the sponsor (or the “body corporate”) must provide a privacy policy for the handling of or dealing with this personal information including sensitive personal data or information. The IT-SPDIRules defines sensitive personal data or information as information relating to password(s); financial information; physical, physiological, and mental health condition(s); sexual orientation; medical records and history; and biometric information. The sponsor must ensure that this policy is available for view by the information providers under a lawful contract. The policy must be published on the sponsor’s or its representative’s website and provide the following:

Clear and easily accessible statements of its practices and policies
The type of personal information including sensitive personal data or information collected
The purpose of collection and usage of such information
Disclosure of information including sensitive personal data or information
Reasonable security practices and procedures

Please refer to the IT-SPDIRules for detailed requirements on implementing security practices and procedures and collecting, disclosing, and transferring sensitive personal data or information.

See also IND-65 for more detailed information on India’s data protection requirements.

Pursuant to the G-LabValidTest, laboratory validation testing is used to ensure that laboratory test data and results are accurate, consistent, and precise, and may include tests that are conducted using residual, archived, unlinked, and anonymous biological samples such as blood, urine, tissue, cells, saliva, DNA, etc. The G-LabValidTest indicates that if the biological samples are linked to different types of personal identifiers (name, address, etc.) or with health-related data (chronic illnesses, prior hospital stays), and other types of potentially sensitive data (travel history, family history), there is a risk for breach of confidentiality and such samples are not recommended for laboratory validation testing without ethics committee (EC) approval. The investigator undertaking laboratory validation testing must also keep the EC informed regarding use of leftover, archived, or anonymous samples. The laboratories involved in the validation of tests/methods, may be exempted from ethical approval when using leftover archived and anonymized samples.

See also the G-AI-BiomedRes for data privacy and confidentiality guidelines in biomedical and health research involving artificial intelligence-based tools and technologies.

Additionally, the Digital Personal Data Protection Act, 2023 was enacted on August 11, 2023, with an effective date to be determined by the Indian Government. The ClinRegs team will update the Personal Data Protection section when more information becomes available.

Consent for Processing Personal Data

As set forth in the IT-SPDIRules, the body corporate or its representative must obtain consent in writing through letter, fax, or email from the provider of the sensitive personal data or information regarding the purpose of usage before collection of such information. The IT-SPDIRules further states that while collecting information directly from the information provider, reasonable steps must be taken to ensure that the information provider receives details regarding the following:

The fact that the information is being collected
The purpose for which the information is being collected
The intended recipients of the information; and
The name and address of the agency that is collecting the information, and the agency that will retain the information

Per the IT-SPDIRules, the body corporate or its representative, must provide an option to the information provider to withhold the requested data or information prior to the collection of information including sensitive personal data or information. The information provider must, at any time, also have the option to withdraw consent given earlier to the sponsor or the sponsor’s representative. This withdrawal of consent must be sent in writing.

1.1, 2.1, and 4.2

Chapter IX (43A)

Part II (22)

2-5

Last content review/update: July 2, 2024

Responsible Parties

For the purposes of data protection requirements, DPA delineates that the sponsor acts as the “data controller” in relation to research data. This is because the sponsor determines the purpose and means of processing personal data. The "data processor" processes personal data on behalf of the data controller. Data controllers and processors must be registered with the Kenya Data Commissioner. Per the DataProtect, an application for registration of a data controller or data processor must be on Form DPR1 (found in the First Schedule of DataProtect) with supporting materials and the required registration fees as specified in the Second Schedule. See the DataProtect for additional details on registration requirements.

Data Protection

Per the DPA, the data controller (sponsor) must ensure that personal data is:

Processed in accordance with the right to privacy of the data subject
Processed lawfully, fairly, and in a transparent manner in relation to any data subject
Collected for explicit, specified, and legitimate purposes and not further processed in a manner incompatible with those purposes
Adequate, relevant, and limited to what is necessary in relation to the purposes for which it is processed
Collected only where a valid explanation is provided whenever information relating to family or private affairs is required
Accurate and, where necessary, kept up to date, with every reasonable step being taken to ensure that any inaccurate personal data is erased or rectified without delay
Kept in a form that identifies the data subjects for no longer than is necessary for the purposes for which it was collected
Not transferred outside Kenya, unless there is proof of adequate data protection safeguards or consent from the data subject

The DataProtect, which implements the DPA, requires data controllers and data processors to develop, publish, and regularly update a policy on their personal data handling practices. The policy should include the nature of personal data collected and held, how a data subject may access their personal data, complaints handling mechanisms, the lawful purpose for processing personal data, and requirements for when personal data is to be transferred outside Kenya. Regarding cross-border transfers of data, a data controller or data processor who is a transferring entity must (before transferring personal data out of Kenya) ascertain that the transfer is necessary. This necessity decision should be based on considerations such as data protection safeguards, an adequacy decision made by the Data Commissioner, and if there is consent of the data subject.

Per the DataProtect, data controllers and/or data processors must retain personal data processed for a lawful purpose and only as long as may be reasonably necessary for the purpose for which the personal data is processed. A data controller or data processor must establish a personal data retention schedule with appropriate time limits and periodic reviews. When the retention period has ended, the personal data must be erased, anonymized, or pseudonymized.

See DataProtect for additional details on data protection, including data subject rights, data protection design and principles, notification of breaches, impact assessments, and exemptions.

See Parts IV-VII of the DPA for detailed requirements on data processing, sensitive personal data, exemptions, and transfer of personal data outside of Kenya. The G-ECBiomedRes requires compliance with the DPA.

Consent for Processing Personal Data

Per the DPA, the data controller (sponsor) or data processor must bear the burden of proof for establishing a data subject’s consent to the processing of their personal data for a specified purpose. For the purposes of processing personal data, consent means any manifestation of express, unequivocal, free, specific, and informed indication of the data subject’s wishes by a statement or by a clear affirmative action, signifying agreement to the processing of personal data relating to the data subject. Unless otherwise provided under the DPA, a data subject has the right to withdraw consent at any time. The withdrawal of consent must not affect the lawfulness of processing based on prior consent before its withdrawal.

The DataProtect requires data controllers and data processors to ensure that a data subject has the capacity to consent and voluntarily gives consent. In seeking consent (prior to the processing), the data subject should be informed of:

The identity of the data controller or data processor
The purpose of each of the processing operations for which consent is sought
The type of personal data that is collected and used
Information about the use of the personal data for automated decision-making, where relevant
The possible risks of data transfers due to absence of an adequacy decision or appropriate safeguards
Whether the personal data processed will be shared with third parties
The right to withdraw consent
The implications of providing, withholding, or withdrawing consent

Per the DataProtect, this information may be presented to the data subject through a written notice, oral statement, audio or video message. The data controller or a data processor must ensure that the data subject has the capacity to voluntarily give consent that is specific to the purpose of processing.

Children

The DPA indicates that in cases where the data subject is a minor, a person who has parental authority or a guardian may exercise personal data protection rights conferred on the subject. With regard to data processing, the DPA requires that every data controller (sponsor) or data processor must not process personal data relating to a child unless consent is given by the child's parent or guardian and the processing is in a manner that protects and advances the rights and best interests of the child. A data controller or data processor must incorporate appropriate mechanisms for age verification and consent to process personal data of a child, including available technology, volume of personal data processed, proportion of such personal data likely to be that of a child, possibility of harm to a child arising out of processing of personal data, and other factors as may be specified by the Kenya Data Commissioner.

Mentally Impaired

The DPA indicates that in cases where the data subject has a mental or other disability, a person duly authorized to act as the participant’s guardian or administrator may exercise personal data protection rights conferred on the subject.

4.2.5

Part I (2), Part III (18) and (25), and Parts IV-VII

No. 263 (Parts I-X) and No. 265 (5, First Schedule, and Second Schedule)

Documentation Requirements

Last content review/update: June 21, 2024

Obtaining Consent

In all Indian clinical trials, a freely given, written informed consent is required to be obtained from each participant to comply with the requirements set forth in the 2019-CTRules, the G-ICMR, and the G-Children.

As per the 2019-CTRules and the G-ICMR, prior to beginning a clinical trial, the investigator is required to obtain ethics committee (EC) approval for the informed consent form (ICF) and the patient information sheet. This documentation must also be supplied to the Drugs Controller General of India (DCGI), prior to the trial’s initiation. The ICF and patient information sheet are ultimately integrated into one (1) document referred to as the ICF. (See the Required Elements section for details on what should be included in the form.) (Note: The DCGI is head of the Central Drugs Standard Control Organization (CDSCO) and is commonly referred to as the Central Licensing Authority in the Indian regulations.)

The 2019-CTRules, the G-ICMR, and the G-Children specify that investigator(s) should provide detailed study information to the research participant or the legal representative/guardian. The ICF content should be briefly and clearly presented orally, and in writing, and in a manner that is easy to understand, commensurate with the comprehension level of the participants, and without coercion or unduly influencing a potential participant to enroll in the trial. Per the G-ICMR, the ICF language should not only be scientifically accurate and simple, but should also be sensitive to the participant’s social and cultural background. In addition, the participant or the legal representative/guardian, should be given adequate time to consider whether to participate. The consent should also be given voluntarily and not be obtained under duress or coercion of any sort or by offering any inducements.

The G-ICMR also states that, in the case of differently abled participants, such as those with physical, neurological, or mental disabilities, appropriate methods should be used to enhance the participants’ understanding (e.g., Braille for the visually impaired).

As delineated in the 2019-CTRules, investigator(s) must obtain an audio-video (AV) recording of the informed consent process for vulnerable participants in clinical trials for a new chemical or molecular entity, including the procedure of providing information to the participant and their understanding of the consent. This AV recording should be retained in the investigator’s files. In cases where clinical trials are conducted on anti-human immunodeficiency virus (HIV) and anti-leprosy drugs, the investigator(s) must only obtain an audio recording of the informed consent process. The investigator(s) is also required to retain the audio recording for their records.

For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see G-GeneThrpy and G-StemCellRes.

Re-Consent

According to the G-ICMR and the G-Children, investigator(s) are required to renew the informed consent of each participant if there are any changes in the ICF related to the study conditions or research procedures, or if new information becomes available during the trial.

Per the G-ICMR and the G-Children, re-consent is applicable in cases in which a participant regains consciousness from an unconscious state and/or recovers mental capacity to understand the research study. If such an event is expected, then procedures to address this circumstance should be explained clearly in the ICF.

The G-ICMR and the G-Children explain that re-consent is required in the following situations:

New information pertaining to the study becomes available that has implications for the participant(s) or that changes the benefit and risk ratio
A research participant who is unconscious regains consciousness or suffered loss of mental competence and regains the ability to understand the research implications
A child becomes an adult during the study, or the parent/legal guardian have changed
Research requires a long-term follow up or an extension
There is a change in treatment modality, procedures, site visits, data collection methods, or tenure of participation which may impact a participant’s decision to continue in the research
There is possibility of identity disclosure through data presentation or photographs (this should be camouflaged adequately) in an upcoming publication
Future research may be carried out on stored biological samples if not anonymized

The partner/spouse may also be required to give additional re-consent in some of the above cases.

Language Requirements

As stated in the 2019-CTRules and the G-ICMR, the ICF should be written in English and/or in a vernacular language that the participant is able to understand.

Documenting Consent

The G-ICMR and the G-Children specify that the participant or the participant’s legal representative/guardian must sign and date the ICF. If the participant is incapable of giving an informed consent, the legal representative/guardian should sign and date the ICF. Where the participant or the legal representative/guardian is illiterate, verbal consent should be obtained in the presence of and countersigned by an impartial witness.

Per the G-ICMR, if the participant or the legal representative/guardian cannot sign, a thumb impression must be obtained. In addition, the investigator(s) who administers the consent should also sign and date the ICF. As stated in the G-ICMR and the G-Children, when written consent as a signature or thumb impression is not possible, verbal consent may be taken with the EC’s approval, in the presence of an impartial witness who should sign and date the consent document, or through an AV recording. Per the G-ICMR, the ICF may also be administered and documented electronically, as long as the EC approves the process first.

As described in the G-ICMR, the following special situations may also arise in administering consent:

The gatekeeper’s (a group’s head/leader or the culturally appropriate authorities), may provide permission on the group’s behalf in writing or audio/video recording and be witnessed
Community consent is required for certain populations in order for participants to be permitted to participate in the research

According to the G-ICMR and the G-Children, a copy of the signed ICF and the patient information sheet should be given to the participant or the legal representative/guardian. Per the G-Children, the investigator should also keep a signed copy of the ICF.

Waiver of Consent

As specified in the G-ICMR and the G-Children, the investigator(s) can apply to the EC for a waiver of consent if the research involves less than minimal risk to participants and the waiver will not adversely affect the rights and welfare of the participants. In addition, per the G-ICMR, the EC may grant a waiver of consent in the following situations:

Research cannot practically be carried out without the waiver and the waiver is scientifically justified
Retrospective studies, where the participants are de-identified or cannot be contacted
Research on anonymized biological samples/data
Certain types of public health studies/surveillance programs/program evaluation studies
Research on data available in the public domain, or
Research during humanitarian emergencies and disasters, when the participant may not be in a position to give consent. An attempt should be made to obtain the participant’s consent as soon as possible

Refer to the Children/Minors section for information on waivers involving children.

See the G-ICMR, IND-5, and IND-27 for additional information on informed consent requirements.

3.1

7.11 and Annexures I, II, and III

2.2, 4.4, 4.8, 5.0, 5.2-5.4, and 5.8

4, 11.2, and Annexures I and II

Chapter III (11) and Third Schedule (2-3 and Tables 1 and 3)

3-6

5

Last content review/update: July 2, 2024

Obtaining Consent

In all Kenyan clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in the CTRules, the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (KEN-14). (Per the G-KenyaCT, research must be conducted in accordance with the requirements set forth in KEN-14.) The informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by a National Commission for Science, Technology and Innovation (NACOSTI)-accredited institutional ethics committee (EC). The ICF must be provided to the Pharmacy and Poisons Board (PPB) with the clinical trial application. (See the Required Elements section for details on what should be included in the form.)

The CTRules, the G-KenyaCT, and the G-ECBiomedRes state that the investigator, or the designated representative, must provide detailed research study information to the participant or legal representative/guardian. Per G-ECBiomedRes, all individual consent must be written and, in no case, should collective community agreement or the consent of a community leader or other authority substitute for an individual informed consent. The G-KenyaCT and the G-ECBiomedRes also specify that the oral and written information concerning the trial, including the ICF, should be easy to understand and presented without coercion or unduly influencing a potential participant to enroll in the clinical trial. None of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or to appear to waive the legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or the representatives from their liabilities for any negligence. The participant or legal representative/guardian should also be given adequate time to consider whether to participate.

Re-Consent

According to the CTRules, the G-KenyaCT, and KEN-14, any change in the ICF due to a protocol modification should be approved by the EC before such changes are implemented. The participant or legal representative/guardian will also be required to re-sign the revised ICF and receive a copy of any amended documentation.

Language Requirements

As stated in the CTRules and the G-KenyaCT, the ICF content should be presented in either English or Kiswahili, and the local spoken language of the area, where applicable. Copies of the English ICF should be submitted to the PPB and to the EC.

Documenting Consent

The CTRules and the G-KenyaCT state that the participant or legal representative/guardian, and the person who conducted the informed consent discussion should sign and personally date the ICF. Where the participant is illiterate, and/or the legal representative/guardian is illiterate, verbal consent should be obtained in the presence of and countersigned by an impartial witness. Before participating in the study, the participant should receive a copy of the signed and dated ICF, and any other written information provided during the informed consent process. The participant or legal representative/guardian should also receive a copy of any updates to the signed and dated ICF.

According to KEN-14, where the participant is illiterate and/or the legal representative/guardian is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:

The written ICF and any other written information to be provided to the participant is read and explained to the participant or legal representative/guardian
The participant or legal representative/guardian have orally consented to the participant’s involvement in the trial, and has signed and dated the ICF, if capable of doing so

Before participating in the study, the participant or legal representative/guardian should receive a copy of the signed and dated ICF.

Waiver of Consent

No information is available.

2, 4.4, 4.8, 8.2, and 8.3

Definitions, 4.1, 4.2, and 4.13

1.48, 1.63, and 1.188-1.212

Part IV (11)

Required Elements

Last content review/update: June 21, 2024

Per the 2019-CTRules, the G-ICMR, and the G-Children, the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

The study involves research and an explanation of its nature and purpose
The expected duration of the participant’s participation
Any benefits reasonably expected from the research to the participant or others; if no benefit is expected, the participant should be made aware of this
The disclosure of specific appropriate alternative procedures or therapies available to the participant
The mechanism by which confidentiality of records identifying the participant will be maintained and who will have access to the participant’s medical records
An explanation about whom to contact for trial-related queries, participant rights, and in the event of any injury
The policy on compensation and/or medical treatment(s) available to the participant in the event of a trial-related injury, disability, or death
Participation is voluntary, the participant can withdraw from the study at any time, and refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled
Any reasonably foreseeable risks or discomforts to the participant resulting from participation
Approximate number of participants enrolled in the study

Additional requirements listed in the G-ICMR and the G-Children include:

Foreseeable extent of information on possible current and future uses of the biological material and of the data to be generated from the research (e.g., storage period of sample/data; probability of material being used for secondary purposes; whether material is to be shared with others; participant’s right to prevent use of their biological sample(s) at any time during or after the study; risk of discovery of biologically sensitive information and provisions to safeguard confidentiality)
Publication, if any, including photographs and pedigree charts
Payment/reimbursement for participation and incidental expenses depending on the type of study
Insurance coverage, if any, for research-related or other adverse events
If there is a possibility that the research could lead to any stigmatizing condition (e.g., HIV and genetic disorders, provision for pre-test and post-test counseling)
Post-research plan/benefit sharing for biological material research and/or if data leads to commercialization

Additional requirements listed in the 2019-CTRules include:

The procedures to be followed, including all invasive procedures
The investigational product (IP) may fail to achieve the intended therapeutic effect
In the case of a placebo-controlled trial, the placebo administered to the participant(s) must not have any therapeutic effect
The anticipated prorated payment, if any, to the participant for participating in the trial
The participant’s responsibilities in participating in the trial
Foreseeable circumstances under which the investigator(s) may remove the participant without consent
The consequences of a participant’s decision to withdraw from the research, and procedures for orderly withdrawal by the participant
The participant or the legal representative/guardian will be notified in a timely manner if significant new findings develop during the study which may affect the participant’s willingness to continue
The particular treatment or procedure may involve risks to the participant (or to the embryo or fetus, if the participant is or may become pregnant), which are currently unforeseeable
Additional costs to the participant that may result from participating in the study
Any other pertinent information
Clinical trial treatment schedule(s) and the probability for random assignment to each treatment

See the Vulnerable Populations and Consent for Specimen sections for further information.

For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see G-GeneThrpy and G-StemCellRes.

3.1

7.11 and Annexures I, II, and III

2.2, 5.0-5.3, and 6.11

4, 11.2, and Annexures I and II

Second Schedule (1) and Third Schedule (2-3 and Tables 1 and 3-4)

Last content review/update: July 2, 2024

Based on the CTRules, the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (KEN-14), the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Title of the project and that the study involves research and an explanation of its nature and purpose
The expected duration of the participant’s participation
The participant’s responsibilities in participating in the trial
Experimental aspects of the study
Approximate number of participants involved in the trial
Trial treatment schedule and the probability for random assignment to each treatment
Principal investigator(s), institution, and ethics committee (EC) contact information, the person(s) to contact for further information regarding the trial and the rights of trial participants, and whom to contact in the event of trial-related injury
Any foreseeable risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
Any expected benefits or prorated payment to the participant; if no benefit is expected, the participant should also be made aware of this
Alternative procedures or treatment that may be available to the participant, including a statement on disclosure of appropriate alternative procedures or courses of treatment that might be advantageous to participants when the research involves non-validated procedures, devices, or therapies
Compensation and/or medical treatment available to the participant or the family or dependents in the event of a trial-related injury
Any additional costs to the participant that may result from participation in the research
The extent to which confidentiality records identifying the participant will be maintained, and if the results of the trial are published, the participant’s identity will remain confidential
That the Pharmacy and Poisons Board (PPB) will be granted direct access to the participant’s original medical records to verify clinical trial procedures and/or data without violating the participant’s confidentiality
The details on storage and exportation of biological samples, if applicable
The details on storage and ownership of personal data
Information about unblinding, if applicable
The extent of the investigator’s responsibility, if any, to provide medical services to the participant
That therapy will be provided free of charge for specified types of research-related injury, including the investigators’ responsibilities in this regard
That participation is voluntary, the participant may withdraw at any time, and refusal to participate will not involve any penalty or loss of benefits, or reduction in the level of care to which the participant is otherwise entitled
That the participant will be informed about the dissemination of findings and about any publication of the participant’s medical information, including photographs and pedigree charts
Foreseeable circumstances under which the investigator(s) may remove the participant without consent
That the participant or legal representative/guardian will be notified in a timely manner if significant new findings develop during the study which may affect the participant’s willingness to continue
Consent to incomplete disclosure, for example, if it is necessary to inform participants that some information is being withheld deliberately and the reasons for that decision; an offer to disclose the purpose at the conclusion of the study can be made

Note that per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

In addition, the CTRules delineates that if the potential participant is a child, the ICF must also contain these elements:

The pathophysiology of the disease or subject of the clinical trial
The methods of diagnosis
The currently available treatment or prevention strategy in the pediatric population
The incidence and prevalence of the disease or subject of the clinical trial in the overall population and in the pediatric population
The evidence and assumptions on key differences between the disease or subject of the clinical trial in the overall population and the pediatric population

4.4 and 4.8

Definitions, 4.1, and 4.2

1.48, 1.63, and 1.188-1.212

Part IV (10 and 11)

Participant Rights

Last content review/update: June 21, 2024

Overview

In accordance with the 2019-CTRules and the G-ICMR, India’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The G-ICMR upholds the Declaration of Helsinki (IND-63). The 2019-CTRules, the G-ICMR, and the G-Children state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process.

The Right to Participate, Abstain, or Withdraw

As stated in the 2019-CTRules, the G-ICMR, and the G-Children, the participant or the legal representative/guardian should be informed that participation is voluntary, the participant may withdraw from the research study at any time, and refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As per the 2019-CTRules, the G-ICMR, and the G-Children, a potential research participant or the legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation or treatment in the case of injury, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

As described in the 2019-CTRules, the G-ICMR, and the G-Children, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. The 2019-CTRules also states that it is the responsibility of the investigator(s) to safeguard the confidentiality of research data to protect the identity and records of research participants.

The Right of Inquiry/Appeal

The 2019-CTRules, the G-ICMR, and the G-Children state that the research participant or the legal representative/guardian should be provided with contact information for the investigator(s) and the ethics committee (EC) to address trial-related inquiries and/or to appeal against a violation of the participant’s rights.

The Right to Safety and Welfare

The G-ICMR clearly states that a research participant’s right to safety and protection of health and welfare must take precedence over the interests of science and society.

See the G-ICMR and IND-27 for additional information on informed consent requirements. Refer to the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.

See also the G-AI-BiomedRes for guidelines on safeguarding participants rights in biomedical and health research involving artificial intelligence-based tools and technologies.

3.1

1.0, 1.1, 2.2, 2.3, 4.0, 5.0-5.2, and 7.1

Chapter III (7 and 11), Chapter V (28) and Third Schedule (3)

1 and 5

Last content review/update: July 2, 2024

Overview

In accordance with the Declaration of Helsinki (KEN-33) principles upheld in the CTRules, the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), Kenya’s ethical standards promote respect for all human beings and safeguard the rights of research participants. A participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

The Right to Participate, Abstain, or Withdraw

As set forth in the CTRules, the G-KenyaCT, the G-ECBiomedRes, and KEN-14, a participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As delineated in the CTRules, the G-KenyaCT, the G-ECBiomedRes, and KEN-14, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study.

The DPA further indicates that data subjects have a right to:

Be informed of how their personal data is to be used
Access their personal data in custody of the data controller (sponsor) or data processor
Object to the processing of all or part of their personal data
Correct false or misleading data
Delete false or misleading data about them

The Right to Privacy and Confidentiality

As per the G-KenyaCT, the G-ECBiomedRes, and KEN-14, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right.

The Right of Inquiry/Appeal

The G-KenyaCT, KEN-14, and the G-ECBiomedRes state that the participant or legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries. Further, the G-ECBiomedRes requires that the ethics committee contact information also be provided.

The Right to Safety and Welfare

The G-ECBiomedRes and KEN-14 state that a research participant’s right to safety and the protection of the participant’s health and welfare must take precedence over the interests of science and society. KEN-14 upholds the Declaration of Helsinki (KEN-33). (See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.)

3.1 and 4.8

3.1, 4.1, and 4.2

1.48, 1.63, and 1.188-1.212

Part IV (26) and Part V (46-47)

Part IV (11 and 17)

Emergencies

Last content review/update: June 21, 2024

Children in Emergency Situations

Per the G-Children, research involving children in emergency situations should only be carried out when it is scientifically justified and cannot be conducted outside this setting. The ethics committee(s) (EC) should review and approve these studies as well as the proposed timeframe in which formal consent will be obtained. If consent cannot be obtained in an emergency, deferred consent is suggested. Deferred consent involves giving minimum information verbally, followed by full details and formal consent later. If the parent/legal guardian is unavailable or unable to give consent, another individual, such as the participant’s doctor or a person nominated by the healthcare provider, can give consent. However, the doctor or a person nominated by the healthcare provider may not be involved in the research. It is recommended that a Data Safety Monitoring Board (DSMB) be strongly considered for these types of studies. See the Children/Minors section for additional pediatric informed consent requirements.

Moreover, per the G-Children, if a child’s parent/legal guardian refuses to give consent once their child is stabilized, the child should not be included in the research, and no further research related procedures/data collection should be done. Additionally, the previously collected data obtained prior to the consent process should not be used without the parent's/legal guardian's permission.

Humanitarian Emergencies

As explained in the G-ICMR, during a humanitarian emergency or disaster, close attention should be paid to the effect of the emergency on perceptions of ethical questions, altered or increased vulnerabilities, provider-patient and researcher-participant relationships, and issues related to integrity of studies and ethical review processes. Obtaining valid informed consent in humanitarian emergencies is a challenge as the decisional capacity of the participants would be so low that they may not be able to differentiate between reliefs offered and research components. This should be very clearly distinguished during the informed consent process. Additional safeguards are required for participants due to their vulnerability, for example, counseling, psychological help, medical advice, and process of stakeholder consultation.

In addition, the G-ICMR indicates that the potential research participants might be under duress and traumatized. Researchers should be sensitive to this situation and are obligated to ensure that the informed consent process is conducted in a respectful manner. Researchers should strive to identify and address barriers to voluntary informed consent and not resort to inducements for research participation. The different roles of researchers, caregivers and volunteer workers must always be clarified, and potential conflict of interest declared. If research involves vulnerable individuals (such as minors), then the legal representative/guardian should give consent. Additional protections might be required in special cases, for example, children with untraceable or deceased relatives. In these situations, consent should be obtained from an individual who is not part of the research team who should be designated by the institution/agency conducting research.

For seeking a waiver of consent, the researchers should give the rationale justifying the waiver. The EC should approve such a waiver after careful discussion on the issue. Refer to the Documentation Requirements section for additional information on waivers of consent. When consent of the participant or the legal representative/guardian is not possible due to the situation, informed consent must be administered to the participant or the legal representative/guardian at a later stage, when the situation allows. However, this should be done only with the prior approval of the EC. See IND-5 for additional information on consent requirements during medical emergencies.

3.1 and 6.5

12.0, 12.2, and 12.5

12

Last content review/update: July 2, 2024

The G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by emergencies. Per the G-KenyaCT, research must be conducted in accordance with KEN-14. As delineated in the G-KenyaCT and the G-ECBiomedRes, in an emergency, if the signed informed consent form (ICF) cannot be obtained from the research participant, the consent of the legal representative/guardian should be obtained. If the prior consent of the participant or legal representative/guardian cannot be obtained, the participant’s enrollment should follow measures specified in the protocol, and/or elsewhere, to ensure compliance with ethics committee (EC) and the Pharmacy and Poisons Board (PPB) requirements. The G-ECBiomedRes requires that the principle of clinical equipoise be applied, which essentially means the participant is not any worse off by enrolling.

During a public health emergency, the G-KenyaCT stipulates that the informed consent of participants must be obtained in individuals capable of giving informed consent. The CT-Emrgcy includes safeguards to protect clinical trial participants during a public health emergency, including the recommendation to reconsent if there are amendments as a result of the emergency.

Per KEN-14, in an emergency, if the signed ICF has not been obtained from the participant or legal representative/guardian, or if an effective treatment is lacking but the investigational product could address the participant’s emergency needs, the clinical trial may be conducted. However, the method used on the participant must be explained clearly in the trial protocol, and the EC must approve the protocol in advance. The participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

4.8

4.1 and 4.2

Participants

1.48, 1.63, 1.188-1.212, and 1.557-1.574

Vulnerable Populations

Last content review/update: June 21, 2024

Overview

As set forth in the 2019-CTRules and the G-ICMR, in all clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. The G-ICMR further describes vulnerable groups and individuals as those who may have an increased likelihood of incurring additional harm, as they may be relatively (or absolutely) incapable of protecting their own interests. According to the G-ICMR, vulnerable populations are characterized as individuals/communities with hierarchical relationships (e.g., prisoners, armed forces personnel, or staff and students at medical, nursing, or pharmacy academic institutions); economically and socially disadvantaged individuals (e.g., persons who are unemployed, abandoned, orphans, have language barriers, or cultural differences); persons below the poverty line; ethnic, religious, or sexual minority groups; tribal and marginalized communities; terminally ill patients or those suffering from stigmatizing or rare diseases; patients in emergency situations; institutionalized persons; homeless persons, nomads, or refugees; minors; women in special situations (e.g., pregnant or lactating women, those with poor decision-making powers, or poor access to healthcare); those with mental illness and cognitively impaired, differently abled, or mentally or physically disabled; or others incapable of personally giving consent.

See the G-ICMR for detailed safeguards that must be complied with when trials involving vulnerable populations are conducted. The G-ICMR also describes research principles that must be upheld during these trials and upholds the Declaration of Helsinki (IND-63). See also the G-AI-BiomedRes for guidelines on safeguarding participants rights in biomedical and health research involving artificial intelligence-based tools and technologies, especially those participants from underrepresented and vulnerable populations.

See the Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these vulnerable populations. See also IND-5 for additional information on consent requirements for vulnerable populations.

For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see the G-GeneThrpy and the G-StemCellRes.

Terminally Ill Patients

Per the G-ICMR, terminally ill patients or patients seeking new treatments are vulnerable as they are ready to give consent for any intervention that could help them. The EC should carefully review protocols and recruitment procedures for these studies and comply with the following requirements:

Additional monitoring should be done to detect any adverse event as soon as possible
A benefit-risk assessment should be performed that considers the potential participant’s perception of benefits and risks
Post-trial access to the medication

Indigenous Peoples

The G-ICMR states that research on tribal populations should only be conducted if it is of a specific therapeutic, diagnostic, and preventative nature with appropriate benefits to the tribal population. A competent administrative authority’s approval, such as the tribal welfare commissioner or the district collector, should be obtained prior to an investigator entering the area. Whenever possible, it is desirable to seek the help of government functionaries/local bodies or registered, non-governmental organizations who work closely with the tribal groups and have their confidence. The tribal leader, or other culturally appropriate authority may serve as the gatekeeper from whom permission to enter and interact should be obtained. A participant’s consent should be taken along as well as consulting with community elders and individuals who know the local language/dialect of the tribal population, and in the presence of appropriate witnesses. Additional precautions should be taken to avoid including children, pregnant women, and elderly people belonging to particularly vulnerable tribal groups. Benefit sharing with the tribal group should also be ensured for any research done using tribal knowledge that may have the potential for commercialization.

Elderly Persons

Permission to conduct clinical trials in geriatric patients must comply with the requirements listed in the Required Elements section. According to 2019-CTRules, geriatric patients should be included in Phase II and Phase III clinical trials at the sponsor’s (also known as the applicant’s) recommendation, in the following circumstances:

The disease intended to be treated is typically a disease of aging
The population to be treated is known to include substantial numbers of geriatric patients
There is specific reason to expect that conditions common in the elderly are likely to be encountered
The new drug is likely to alter the geriatric patient’s response (with regard to safety or efficacy) compared with that of the non-geriatric patient

Persons in Dependent Groups

As indicated in the G-ICMR, while reviewing protocols involving participants who are engaged in subordinate or dependent relationships, the ethics committee (EC) must ensure the following:

Participant enrollment is specifically relevant to the research questions and is not merely a matter of convenience
Extra efforts are required to ensure the autonomy of these individuals is respected, and that they are able to freely decide to participate or deny consent and/or later withdraw from the study without fear of any negative repercussions on their care
Mechanisms to avoid coercion due to being part of an institution or hierarchy should be described in the protocol

Sexual Minorities and Sex Workers

Per the G-ICMR, sexual minorities and sex workers require additional protections as they are more vulnerable to privacy, confidentiality, stigma, discrimination, and exploitation issues during a research study. Research proposals should ensure the dignity of these participants is protected and that they have access to quality healthcare. Investigators should consult the community, if possible, prior to the proposal being finalized. It is also advised that a representative of the sexual minority group/lesbian/gay/bisexual and transgender (LGBT) community attend the EC meeting as a special invitee/member.

7.11 and Annexures I, II, and III

1.1, 2.9, 6.0-6.2, 6.6-6.7, and 6.9-6.10

4, 11.2, and Annexures I and II

First Schedule (3) and Third Schedule (3)

1, 2, and 6

Last content review/update: July 2, 2024

Overview

As per the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), in all Kenyan clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. Vulnerable populations include those participants with diminished autonomy whose decision to participate in a clinical trial may be unduly influenced by the expectation of benefits associated with participation or by coercion. This may include, but is not limited to, children/minors, pregnant women, neonates, fetuses, medical students, members of the uniformed forces, prisoners, orphans, homeless populations, unemployed, internally displaced persons, economically or educationally disadvantaged persons, marginalized social groups, individuals with terminal illnesses, and the mentally challenged. KEN-14 also includes members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include persons in nursing homes, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

Elderly Persons

The G-ECBiomedRes defines an elderly/senior citizen as a person who has attained the age of 65 years. Their physical or mental state may affect their ability to make voluntary decisions regarding their participation in research projects. Such research involving elderly/senior citizens must comply with the following requirements:

Strict adherence to ethical principles
The risk-benefit ratio must be favorable to the research participant
The participants must be protected from gross violation of human rights

Persons in Dependent Groups

Per the G-ECBiomedRes, research involving data collection by superiors on their subordinates involves relationships such as employer-employee, teacher-students, supervisor-staff, sponsor-dependent, and parent-children. This relationship impairs independent consent by the participants leading to complacency. Therefore, research involving the superior/subordinate relationships must fulfill the following requirements:

The superior must strictly follow ethical principles to avoid undue pressure
Subordinates must be protected from gross violation of human rights
The trial design must be based on a need-to-know principle and improve the conditions of the participants

Persons in Low-Resource Communities

The G-ECBiomedRes provides the following requirements related to conducting research on participants in low-resource settings:

Persons in such settings should not be involved in research that could be carried out reasonably well in developed communities
The research should be responsive to the health needs and priorities of the community in which it is to be implemented
Undue inducement to participate in the research must be avoided at all costs

Armed Forces

The G-ECBiomedRes stipulates that research involving the members of the armed forces may be vulnerable because of the conditions of their service, which may affect their ability to make voluntary decisions regarding their participation in research. Such research must be conducted to ensure that:

Participants are protected from gross violations of human rights
There is strict adherence to ethical principles
There is at least one (1) member of the ethics committee approving such research who is an enlisted and authoritative member of the armed forces

Terminally Ill

Per the G-ECBiomedRes, research involving participants who are terminally ill with an incurable medical condition are vulnerable. Their state may affect their ability to make voluntary decisions regarding their participation in research. Such research can only be conducted when:

The objectives of the project(s) cannot be achieved using another non-vulnerable group
There is strict adherence to ethical principles
The risk-benefit ratio should be favorable to the research participant

See the Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these vulnerable populations.

1.61, 3.1, and 4.8

4.2

Glossary of Terms, 1.48, and 1.63

Children/Minors

Last content review/update: June 21, 2024

As per the G-ICMR, children are individuals who have not obtained the legal age of consent, which is 18.

As stated in the G-ICMR, the 2019-CTRules, and the G-Children, in the case of pediatric clinical trials, participants are legally unable to provide written informed consent, and are dependent on their parents/legal guardians to assume responsibility for their participation in a research study.

However, as specified in the 2019-CTRules, all pediatric participants should be informed to the extent compatible with the child’s understanding, and if capable, the pediatric participant should sign and personally date the informed consent form (ICF). In these studies, the following requirements should be complied with:

Written informed consent should be obtained from the parent/legal guardian; however, all pediatric participants should be informed to the fullest extent possible about the study in a language and in terms that they are able to understand
Where appropriate, pediatric participants should additionally provide their assent to enroll in the study, and mature minors and adolescents should personally sign and date a separately designed written assent form
Although a participant’s wish to withdraw from a study must be respected, there may be circumstances in therapeutic studies for serious or life-threatening diseases in which, in the investigator’s and parent’s/legal guardian’s opinion, a pediatric patient’s welfare would be jeopardized by failing to participate in the study. In this situation, continued parental/legal guardian consent should be sufficient to allow participation in the study

The 2019-CTRules further specifies requirements for pediatric studies involving new drugs. These studies must take into account the following issues:

The timing of new drug pediatric studies will depend on the medicinal product, the type of disease being treated, safety considerations, and the efficacy and safety of available treatments
If the new drug is for diseases predominantly or exclusively affecting pediatric patients, clinical trial data should be generated in the pediatric population except for initial safety and tolerability data, which will usually be obtained in adults, unless such initial safety studies in adults would yield little useful information or expose them to inappropriate risk
If the new drug is intended to treat serious or life-threatening diseases, occurring in both adults and pediatric patients, for which there are currently no or limited therapeutic options, the pediatric population should be included in the clinical trials early, following assessment of initial safety data and reasonable evidence of potential benefit; in circumstances where this is not possible, lack of data should be justified in detail
If the new drug has a potential for use in pediatric patients, pediatric studies should be conducted
Pediatric studies should include clinical trials, relative bioequivalence comparisons between pediatric and adult formulations, and pharmacokinetic studies for dose selection across the age ranges of pediatric patients in whom the drug is likely to be used
If the new drug is a major therapeutic advance for the pediatric population, studies should begin early in the drug development, and this data should be submitted with the new drug application

The reviewing ethics committee (EC) should also include members who are knowledgeable about pediatric, ethical, clinical, and psychosocial issues.

Refer to the 2019-CTRules for detailed pediatric study requirements.

Per the G-ICMR, the EC should also perform a benefit-risk assessment to determine whether there is a need to implement additional safeguards/protections to conduct a study involving children. The EC should consider the circumstances of the children to be enrolled in the study including their age, health status, and other factors and potential benefits to other children with the same disease or condition, or to society as a whole. In addition, the G-Children should be consulted for detailed EC assessment criteria to be used to evaluate research studies involving children.

As per the G-Children, following EC approval of the protocol, the informed consent requirement for children may be waived in the following circumstances:

When it is impractical to conduct research since confidentiality of personally identifiable information has to be maintained throughout the study (e.g., a study on the disease/burden of HIV/AIDS)
Research is carried out on publicly available information, documents, records, works, performances, reviews, quality assurance studies, archival materials or third-party interviews, etc.
Research on anonymized biological samples, leftover samples after clinical investigation/research, cell lines, or cell free derivatives (e.g., viral isolates, DNA or RNA from recognized institutions or qualified investigators, samples or data from repositories or registries, etc.) provided permission for future research on these samples has been taken in the previous ICF
In emergency situations when no surrogate consent can be taken
Retrospective studies, where the participants are de-identified or cannot be contacted

Assent Requirements

As delineated in the G-ICMR, the 2019-CTRules, and the G-Children, if the pediatric participant has the capacity for assent, the participant’s affirmative assent is required to participate in a study according to their developmental level and decision-making capacity. Per the 2019-CTRules, mature minors and adolescents should personally sign and date a separately designed written assent form. According to the G-ICMR, mature minors are those from age seven (7) up to age 18.

The G-Children also explains that in addition to the children’s developmental level and capability of understanding, the assent process and form should also take into account their age, maturity, reading level, independence, autonomy as well as cultural and social factors. For children between ages seven (7) and 11, oral assent must be obtained in the presence of their parent/legal guardian. For children between ages 12 and 18, written assent must be obtained.

A child’s dissent or refusal to participate must always be respected, and the child must be informed in an understandable manner that assent may be withdrawn at any time during the study. The EC may also issue a waiver of assent in the following circumstances:

If the research has the potential to directly benefit the child, and this benefit is only available through this study
If the research involves children with intellectual and other developmental disabilities, they may not have the developmental level and intellectual capability to give assent

For details and guidance on preparing and using an assent form, see the G-Children.

1.5, 2, 3.1-3.3, 4.1, and 6.1

6.5

First Schedule (3) and Third Schedule (2)

Last content review/update: July 2, 2024

According to the G-KenyaCT, a minor is someone under 18 years of age. As set forth in the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), when the research participant is a minor, informed consent should be obtained from the parent/guardian. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14. The informed consent forms, assent forms, and the patient information sheets should be in a language that the parent/guardian clearly understand. All pediatric participants should be fully informed about the trial and its risks and benefits in a language and terms that they are easily able to understand.

Per the G-KenyaCT, a minor should take part in the informed consent procedure in a way tailored to their age and mental maturity. If capable, the participant should sign and personally date the written informed consent. In addition, consent given by pediatric participants should not be considered valid without prior approval by the ethics committee (EC).

The CTRules, the G-ECBiomedRes, and the G-KenyaCT state that a study may only be conducted on minors if several conditions are fulfilled including (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Pediatric participants will not be involved in research that might be equally carried out in adults
The purpose of the research is to generate knowledge relevant to the health needs of children
The parent/guardian must provide proxy consent and ensure assent has been obtained to the extent of the child’s capabilities. However, if the minor refuses to participate after proxy consent is given, the minor’s refusal must be respected unless there is no other medical alternative from which the minor could benefit
The risk presented by interventions not intended to benefit the minor is low and commensurate with the importance of the knowledge to be gained
Interventions that are intended to provide therapeutic benefit are likely to be at least as advantageous to the individual child as any available alternative
No incentives or financial inducements are given to the participant or parent/guardian except to provide compensation for expenses and loss of earnings directly related to the participation in the trial

Additionally, per the G-KenyaCT, the trial should also address the following considerations:

Provide useful answers to the study population
The medicine satisfies a need for the population being studied
Children are adequately monitored and protected
If there is no direct benefit to the child, or there is no more than minimal risk to the participant(s)
Trial results will be published
End-of-trial treatment provisions will be made

Assent Requirements

As delineated in the G-KenyaCT, before undertaking research involving children, the investigator must ensure that the agreement (assent) of each child has been obtained to the extent of the child’s capabilities, and a child’s refusal to participate or continue in the research must be respected. Assent is defined as a child’s affirmative agreement to participate in research, where the child is below the age of the majority but old enough to understand the proposed research in general, its expected risks and possible benefits, and the activities expected of them as participants. The G-ECBiomedRes provides that in children above seven (7) years and below 18 years where the parent(s)/guardian(s) gives proxy consent, assent must be obtained from the child.

For an example of an accredited EC’s assent requirements, see the Kenyatta National Hospital-University of Nairobi (KNH-UoN) Ethics and Research Committee’s sample minor assent form (KEN-17).

4.8

Parental Consent for Children and Sample Minor Assent Form

4.2

Glossary of Terms, 1.48, 1.63, and 1.131-1.172

Part IV (10)

Pregnant Women, Fetuses & Neonates

Last content review/update: June 21, 2024

As per the 2019-CTRules and the G-ICMR, clinical studies involving pregnant or nursing women and fetuses require additional safeguards to ensure that the research assesses the risks to the women and the fetuses. The following conditions are required for research to be conducted involving pregnant or nursing women or fetuses.

Per the 2019-CTRules:

Pregnant or nursing women should be included in clinical trials only when the drug is intended for use by pregnant or nursing women, fetuses, or nursing infants, and where the data generated from women who are not pregnant or nursing is unsuitable

Per the G-ICMR:

For studies related to pregnancy termination, only pregnant women who undergo Medical Termination of Pregnancy as per the Medical Termination of Pregnancy Act, 1971 can be included
The research should carry no more than minimal risk to the fetus or nursing infant and the research objective is to obtain new knowledge about the fetus, pregnancy, and lactation
Clinical trials involving pregnant or nursing women would be justified to ensure that these women are not deprived arbitrarily of the opportunity to benefit from investigations, drugs, vaccines, or other agents that promise therapeutic or preventive benefits
Research related to prenatal diagnostic techniques in pregnant women should be limited to detecting fetal abnormalities or genetic disorders as per the Pre-Conception and Pre-Natal Diagnostic Techniques (Regulation and Prevention of Misuse) Act, 1994, amended in 2003, and not used to determine the sex of the fetus
Researchers must provide the ethics committee (EC) with proper justification for including pregnant and nursing women in trials designed to address the health needs of such women or their fetuses or nursing infants
If women of reproductive age are to be recruited, they should be informed of the potential risk to the fetus if they become pregnant, be asked to use an effective contraceptive method, and be told about the options available in case of failure of contraception
A woman who becomes pregnant must not automatically be removed from the study when there is no evidence showing potential harm to the fetus. The matter should be carefully reviewed, and she must be offered the option to withdraw or continue
If the female sexual partner of a male participant gets pregnant during the research study, the EC should review the protocol and informed consent form (ICF) to determine if a plan exists to document this event, and both the pregnant partner and fetus must also be followed for the outcome and reported in the study results
Pregnant women have the right to participate in clinical research relevant to their healthcare needs (e.g., gestational diabetes, pregnancy-induced hypertension, and HIV)
Benefit-risk assessment must be done at all stages for both the mother and the fetus
Research involving pregnant women and fetuses must only take place when the objective is to obtain new knowledge directly relevant to the fetus, the pregnancy, or lactation
Women should not be encouraged to discontinue nursing for the sake of participation in research except in those studies where breastfeeding is harmful to the infant
Appropriate studies on animals and non-pregnant individuals should have been completed, if applicable
Researchers should not participate in decision-making regarding any termination of a pregnancy
No procedural changes, which will cause greater than minimal risk to the woman or fetus, will be introduced into the procedure for terminating the pregnancy solely in the interest of the trial
When research is planned on sensitive topics (e.g., domestic violence, genetic disorders, and/or rape) confidentiality should be strictly maintained and privacy protected

Fetuses and Neonates

As described in the G-Children, study protocols involving neonates should take into consideration that this group is the most vulnerable within the pediatric population in terms of the risk of long-term effects of interventions, including developmental effects. ECs reviewing such proposed protocols should have an advisory member with expertise in neonatal research/care. ECs should scrutinize all proposed research for potential risks and weigh them against the possible benefits and ensure a competent person(s) conducts a proper scientific review of the protocol. In addition, when possible, older children should be studied before conducting studies in younger children and infants.

The consent of one (1) parent is also required for neonate studies where research exposes them to no or minimal risk, or in studies that offer the prospect of direct benefit to the participant. However, for studies that do not offer the prospect of direct benefit or are high-risk, consent from both parents is required. Exceptions to this requirement include the following:

Only one (1) parent has legal responsibility for the care and custody of the child
One (1) parent is deceased, unknown, incompetent, or not available. In such cases, it is the duty of the investigators to provide adequate justification.

A parent who is a minor should not provide consent. If both parents are minors, then enrollment of such a baby should be avoided as much as possible. Investigator(s) should provide adequate justification to the EC to enroll such neonates for research. A legally acceptable representative should provide an informed consent in such situations.

6.1

6.4 and 7.18

First Schedule (3)

Last content review/update: July 2, 2024

Per the G-KenyaCT, research must be conducted in accordance with the requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). In accordance with KEN-14, informed consent requirements for conducting clinical trials with pregnant or nursing women or fetuses follow the general requirements listed in the Required Elements section. Specifically, the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant.

As per the G-ECBiomedRes, research involving pregnant, lactating, and breastfeeding women may pose compromised long-term outcomes for the child. In addition, potential parent(s) can make decisions on behalf of the fetus(es), embryo(s), and zygote(s).

For fetal, embryo, and zygote(s) cases, research should be limited as follows:

Cases that present no harm or offer assistance to the life system of the participants
No procedures should be permitted that are likely to harm them
A fetus ex-utero and alive, embryo, and zygote must not be involved in research unless it is intended to enhance the life of that fetus, embryo, and zygote or unless the research involves no risk to them

Additionally, the following guidelines must be followed for research involving pregnant, lactating, and breastfeeding women:

The research carries no more than minimal risk to the fetuses or nursing infants
Pregnant or nursing women should generally not be clinical trial participants except where such trials are designed to protect or advance the health of the pregnant/nursing women or fetuses/nursing infants, and for which women who are not pregnant or nursing would not be suitable participants
The justification for such research should be that participants must not be arbitrarily deprived of the opportunity to benefit from investigational drugs, vaccines, or other agents that promise therapeutic or preventive benefits

4.8

4.2

1.48 and 1.63

Prisoners

Last content review/update: June 21, 2024

As noted in the G-ICMR, prisoners are included in the description of vulnerable populations due to their diminished autonomy caused by dependency or being under a hierarchical system.

The G-ICMR specifies that during the review process, the ethics committee (EC) must ensure compliance with the following:

Enrolling participants is specifically pertinent to the research questions and is not merely a matter of convenience
Extra efforts are made to respect the autonomy of these individuals because they are in a hierarchical position and may not be in a position to disagree to participate for fear of authority
It is possible for the participant to deny consent and/or later withdraw from the study without any negative repercussions on their care
Mechanisms to avoid coercion due to being part of an institution or hierarchy should be described in the protocol

6.9

Last content review/update: July 2, 2024

Per the G-ECBiomedRes and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14. A research study involving prisoners should ensure that these prospective participants are informed and given the opportunity to make their own decisions without any interference or reprisals from a higher authority. The ethics committee must also ensure that the study will be independently monitored to assure the dignity and rights of the prisoners involved in the research.

1.61

4.2

1.48 and 1.63

Mentally Impaired

Last content review/update: June 21, 2024

The G-ICMR states that, in the case of differently abled participants, such as those with physical, neurological, or mental disabilities, appropriate methods should be used to enhance the participants’ understanding. The G-ICMR also states that the presence of a mental disorder is not synonymous with incapacity of understanding or inability to provide informed consent. However, ethics committees (ECs) have special responsibilities when research is conducted on participants who are suffering from mental illness and/or cognitive impairment. ECs should exercise caution and require researchers to justify exceptions and their need to depart from the guidelines governing research. ECs should ensure that these exceptions are as minimal as possible and are clearly spelled out in the informed consent form. The G-ICMR also upholds the Declaration of Helsinki (IND-63).

As set forth in the MHA2017, every person, including a person with mental illness, must be deemed to have the capacity to make decisions regarding mental healthcare or treatment providing the person has the ability to engage in the following:

Understand the information that is relevant to make a decision on treatment, admission, or personal assistance
Appreciate any reasonably foreseeable consequence of a decision or lack of decision on the treatment, admission, or personal assistance, or
Communicate the decision by means of speech, expression, gesture, or any other means

Per MHA2017, information must be provided to a person with mental illness using simple and understandable language, sign language, visual aids, or any other means to enable the person to understand the information. In the case in which a person makes a decision regarding one’s mental healthcare or treatment that is perceived by others as inappropriate or wrong, that by itself, must not be interpreted as the person not having the capacity to make such a decision, as long as the person has the capacity to meet the above stated requirements.

MHA2017 further delineates that every person with mental illness who is not a minor must have the right to appoint a nominated representative. The nomination must be made in writing on plain paper with the person’s signature or thumb impression. The person appointed as nominated representative must not be a minor, be competent to discharge the duties or perform the assigned functions under the MHA2017, and give consent in writing to the mental health professional to discharge the person’s duties and perform the assigned functions. A person who has appointed an individual as the nominated representative may revoke or alter the appointment at any time. The appointment of a nominated representative, or the inability of a person with mental illness to appoint a nominated representative, must not be construed as the lack of capacity of the person to make decisions about mental healthcare or treatment. All persons with mental illness must have the capacity to make mental healthcare or treatment decisions but may require varying levels of support from their nominated representative to make decisions. When fulfilling responsibilities, the nominated representative must have the right to give or withhold consent for research under circumstances.

Pursuant to MHA2017, professionals conducting research must obtain free and informed consent from all persons with mental illness for participation in any research that involves interviewing the person, or any research that involves psychological, physical, chemical, or medicinal interventions. In the case of research involving psychological, physical, chemical, or medicinal interventions to be conducted on a person who is unable to give free and informed consent, but does not resist participation in such research, permission to conduct such research must be obtained from the appropriate State Authority. The State Authority may allow the research to proceed based on informed consent being obtained from the person’s nominated representative if the State Authority is satisfied that the following criteria are met:

The proposed research cannot be performed on persons who are capable of giving free and informed consent
The proposed research is necessary to promote the mental health of the population represented by the person
The purpose of the proposed research is to obtain knowledge relevant to the particular mental health needs of persons with mental illness
A full disclosure of the interests of the persons and organizations conducting the proposed research is made and there is no conflict of interest involved, and,
The proposed research follows all the national and international guidelines and regulations concerning the conduct of such research, and ethical approval has been obtained from the institutional EC where such research is to be conducted

A research-based study of the case notes of a person who is unable to give informed consent will be permitted so long as the anonymity of the person is secured. In addition, the person with mental illness or the nominated representative who gives informed consent for participation in any research under MHA2017 may withdraw consent at any time during the research period.

5.3-5.4, 6.3, 6.5, and 6.8

Chapter I (Section 4), Chapter IV (Sections 14 and 17), and Chapter XI (Section 99)

Last content review/update: July 2, 2024

As per the G-ECBiomedRes and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), an ethics committee (EC) within the relevant institution must approve the participation of adult research participants who are incapable by reason of physical and mental capacity to give consent. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

In addition, as delineated in the G-ECBiomedRes, a research study may involve participants with mental incapacities or behavioral disorders under the following conditions:

Such research could not be carried out equally well with individuals who are in possession of their full mental faculties
The knowledge gained would be relevant to the health needs of persons with mental or behavioral disorders
The participant’s consent has been obtained to the extent of the participant’s capabilities, and a prospective participant’s refusal to participate is always respected
In the case of incompetent individuals, informed consent shall be obtained from a legal guardian or other duly authorized person
The degree of risk attached to the intervention not intended to benefit the individual participant is low and commensurate with the importance of knowledge to be gained
Interventions that are intended to provide therapeutic benefit are likely to be at least as advantageous to the individual participant as any alternative

1.61 and 3.1

4.2

1.48 and 1.63

Definition of Investigational Product

Last content review/update: June 21, 2024

As delineated in the 2019-CTRules, an investigational product (IP) is defined as the pharmaceutical formulation of an active ingredient or a placebo (including the comparator product) being tested or used as a reference in a clinical trial.

The 2019-CTRules further defines an investigational new drug as a new chemical or biological entity or a product having a therapeutic indication, but which has never been tested before on human participants.

Chapter I (2)

Last content review/update: July 2, 2024

The G-KenyaCT defines an investigational product (IP) as any pharmaceutical product, including a new product or existing product for a new indication, in the form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use.

Glossary of Terms, 1.48, and 1.63

Manufacturing & Import

Last content review/update: June 21, 2024

Manufacturing

As specified in the 2019-CTRules and IND-31, the Drugs Controller General of India (DCGI) is responsible for authorizing the manufacture of investigational products (IPs) in India. The DCGI approves the manufacture of IPs as part of the clinical trial application review and approval process. The DCGI is head of the Central Drugs Standard Control Organization (CDSCO) and is commonly referred to as the Central Licensing Authority in the Indian regulations.

To obtain permission to manufacture an IP for clinical trial purposes, the 2019-CTRules explains that applicants must apply to the DCGI using the Application for Grant of Permission to Manufacture New Drug or Investigational New Drug for Clinical Trial or Bioavailability or Bioequivalence Study or for Examination, Test and Analysis (CT-10). Per Notice16Jan24, applicants may access this form via the National Single Window System (NSWS) portal (IND-3).

Per IND-73, once users have completed the NSWS portal (IND-3) registration process, they can search for their required approval applications/registrations using the NSWS Central Approvals webpage (IND-23), or by selecting the Know Your Approvals (KYA) module (IND-12) via the NSWS portal (IND-3).

IND-73 explains that the NSWS Central Approvals webpage (IND-23) allows users to filter their search by ministry/department to obtain a complete list of approval applications (e.g., the Ministry of Health and Family Welfare (MOHFW) filter would pull up a complete list of MOHFW/CDSCO approval applications.) When an approval application link is selected, users can review additional details about the approval including who can apply, applicability, related acts and rules, period of validity, and learn whether the application can be submitted via the NSWS portal (IND-3). Users may also choose to add the application to their “Dashboard” of approvals in order to complete the application process. See the IND-11 for guidance additional instructions on submitting CDSCO approvals via IND-3. Also, please note that, at this time, per Notice1Jan24 and Notice16Jan24, only a few CDSCO steps and processes (e.g., medical device related registration, manufacturing/import applications, and drug manufacturing/import applications) have been moved to the NSWS portal (IND-3).

Per the 2019-CTRules, after reviewing CT-10 and any supplemental information, the DCGI will either grant permission to manufacture the IP via Form CT-11 or reject the application, for reasons to be recorded in writing, within 90 working days from the date of application receipt. If applicable, the DCGI must inform the applicant of deficiencies in the application within 90 working days. If the applicant chooses to rectify the deficiencies within the specified period and provide the required information and documents, the DCGI must review the application again. Based on the review, the DCGI will either grant manufacturing permission to the applicant or reject the application within a period of 90 working days from the date the required information and documents were provided. In the case of rejection, the applicant may request the DCGI reconsider the application within a period of 60 working days from the rejection date along with payment of the specified fees in the 2019-CTRules and submission of the required information and documents. Refer to the 2019-CTRules for additional timeline information and the applicable forms. See also IND-23 for additional approval details on CT-10.

In addition, while applications are now required to be submitted via IND-3, Notice18Feb20 still provides clarifying information in IND-31 concerning where to mail CT-10 applications. For biological drugs, applications should be sent to CDSCO Headquarters (HQ) at FDA Bhavan, New Delhi; for drugs other than biologicals, applications should be sent to the appropriate zonal office/sub-zonal office for pure chemical testing, and the zonal office/sub-zonal office or CDSCO HQ for clinical trials or BA/BE studies. Furthermore, if the applicant obtains permission to manufacture new drugs/IPs for a clinical trial or BA/BE study, the applicant should automatically consider the approval as permission to conduct other chemical/physical testing and analysis on these new drugs/IPs. Refer to IND-58 for detailed CDSCO HQ, zonal office/sub-zonal office contact information. Notice18Feb20 also states that applicants must clearly mention the site where the product will be manufactured in their applications using the following statement: M/s. [name and address of the firm] having manufacturing premises for test and analysis at [name and address of the manufacturing site for test and analysis]. Refer to Notice18Feb20 for additional information.

Per Notice16Jan24, applicants who intend to manufacture an unapproved active pharmaceutical ingredient (API) to develop a pharmaceutical formulation for clinical trial purposes should submit the following to the DCGI via the NSWS portal (IND-3) along with any supplemental information:

If applying as a pharmaceutical formulation manufacturer, use the Application for Grant of Permission to Manufacture Formulation of Unapproved Active Pharmaceutical Ingredient for Test or Analysis or Clinical Trial or Bioavailability or Bioequivalence study (CT-12)
If applying as an API manufacturer, use the Application for Grant of Permission to Manufacture Unapproved Active Pharmaceutical Ingredient for Development of Formulation for Test or Analysis or Clinical Trial or Bioavailability or Bioequivalence Study (CT-13)

As stated in the 2019-CTRules, after reviewing the submission and conducting further inquiry, if needed, the DCGI will grant permission to the applicant to manufacture the unapproved API in Form CT-15 and permission to the manufacturer of the pharmaceutical formulation in Form CT-14 within 90 working days. If dissatisfied, the DCGI will reject the application, for reasons to be recorded in writing, within a period of 90 working days from the application submission date. Refer to the 2019-CTRules for additional timeline information and the applicable forms. See also IND-23 for additional approval details on CT-12 and CT-13. Refer to the instructions provided in the preceding paragraphs to submit CT-12 and CT-13 via the NSWS portal (IND-3).

Per Notice13Mar20, when the application is solely to conduct a clinical trial, the DCGI also requires the sponsor (also known as applicant) to submit the international non-proprietary name (INN) or generic name, drug category, dosage form, and data supporting IP stability in the intended container-closure system for the duration of the clinical trial. See the 2019-CTRules (Second Schedule, Table 1) for detailed data requirements. Additionally, for Phase III clinical trial batches, process validation data requirements may not be required; however, this requirement will vary depending on the IP’s complexity (biological, high tech, etc.). If approved, the DCGI will grant permission for a period of three (3) years to both manufacturers of new drugs or investigational new drugs and manufacturers of unapproved APIs. In exceptional circumstances, the DCGI may extend the period of permission for an additional year. See the 2019-CTRules and IND-31 for more detailed information on manufacturing application submission requirements.

Import

As delineated in the 2019-CTRules and IND-31, the DCGI is responsible for authorizing the import of IPs in India. The DCGI approves the import of IPs as part of the clinical trial application review and approval process.

Per the 2019-CTRules and IND-31, the sponsor is required to obtain a license from the DCGI using the Application for Grant of License to Import New Drug or Investigational New Drug for Clinical Trial or Bioavailability or Bioequivalence Study or for Examination, Test and Analysis (CT-16) to import an IP (new drug or investigational new drug) for clinical trial purposes. Additionally, as explained in IND-31, the Application to Import Drugs for the Purposes of Examination, Test or Analysis (Form 12) should be used to obtain permission to import a drug that is not a new drug as required by the DCA-DCR. See also IND-23 for additional approval details on CT-16 and Form 12. Refer to the instructions provided above to submit CT-16 and Form 12 via the NSWS portal (IND-3).

Per the 2019-CTRules, the sponsor must also ensure that the imported IPs are manufactured in accordance with Good Manufacturing Practices (GMPs) as laid down in the DCA-DCR. Refer to Schedule M of the DCA-DCR to review the GMP requirements. See also the Second Schedule in the 2019-CTRules for the data requirements to be included in the DCGI’s import application.

The 2019-CTRules and IND-31 further state that the DCGI will grant an import license within 90 working days of receipt of the application. Once approved, the import license must remain valid for three (3) years from the date of issue, unless suspended or cancelled. In exceptional circumstances, the DCGI may extend the license for an additional year. (See the Submission Process and Submission Content sections for detailed clinical trial application requirements). See also IND-35 for a checklist of manufacturing and import related forms to be included in a global clinical trial application submission. See Regulatory Fees section for information on manufacturing and import fees. Refer to IND-43 and IND-42 for detailed fee requirements and online payment instructions via the SUGAM portal (IND-59).

As explained in IND-25, the DCGI does not require a drug import license to be obtained when an ethics committee (EC) has granted approval for the conduct of an academic clinical trial that will be using a permitted drug formulation with a new indication, a new route of administration, a new dose, or a new dosage form. A copy of the EC approval for the trial must be provided to the Port office at the time of import along with a letter of undertaking that specifies the quantity of the drug being imported and states that it will be used exclusively for the academic clinical trial.

In addition, per the 2019-CTRules and IND-31, the DCGI will relax, abbreviate, omit, or defer clinical and non-clinical data requirements to import or manufacture new drugs already approved in other countries on a case-by-case basis for life threatening or serious/rare diseases and drugs intended to treat diseases of special relevance to the Indian population, unmet medical needs in India, and in disaster or special defense use (e.g., hemostatic and quick wound healing, enhancing oxygen carrying capacity, radiation safety, or drugs to combat chemical, nuclear, or biological conditions). This decision will vary depending on the specific clinical trial phase proposed and the clinical parameters related to the study drug.

Please note: India is party to the Nagoya Protocol on Access and Benefit-sharing (IND-29), which may have implications for studies of investigational products developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see IND-45.

64-67, 71-75, and 79

1.6

1, 4, and 6

Foreword, Step 1, Step 2, and Step 5

CT-10, CT-12, CT-13, CT-16, and Form 12

DCR, 1945 – Rule 34, Form 12, and Schedule M

65 and 123

Chapter V (25), Chapter VIII (52-54, 59-61, and 64), Chapter IX (67-70), Chapter X (75), Chapter XIII (101), Second Schedule (1 and Table 1), Sixth Schedule, Eighth Schedule (Forms CT-10, CT-11, CT-12, CT-13, CT-14, CT-15, and CT-16)

Last content review/update: July 2, 2024

Manufacturing

According to the PPA and the G-KenyaCT, the Pharmacy and Poisons Board (PPB) is responsible for authorizing the manufacture of all drug products, including investigational products (IPs) in Kenya. Per the CTRules and the G-KenyaCT, an IP must be manufactured in accordance with the requirements of good manufacturing practice (GMP). The CTRules requires a sponsor to immediately notify the PPB in writing when a pharmaceutical or chemical alteration may affect the quality, safety, or efficacy of the IP product during an ongoing clinical trial. The G-KenyaCT states that the sponsor must submit the IP dossier directly to the PPB or may submit it through the principal investigator. The IP dossier must be prepared as per the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), which is required per G-KenyaCT. The manufacture of IPs may be subject to GMP inspection by the PPB in the same way as in the case of marketed drug products. See the G-KenyaCT for detailed chemistry and manufacturing information to be provided to the PPB if the IP has not been registered with the PPB.

KEN-14 also requires IPs to be manufactured, handled, and stored in accordance with applicable GMPs and used in accordance with the approved protocol.

Per the PPA, the PPB is authorized to regulate the manufacturing of medicine, including:

Ensure that all medicinal products manufactured in, imported into, or exported from the country conform to prescribed standards of quality, safety, and efficacy
Ensure that the personnel, premises, and practices employed in the manufacture, storage, marketing, distribution, and sale of medicinal substances comply with the defined codes of practice and other prescribed requirements
Grant or revoke licenses for the manufacture, importation, exportation, distribution, and sale of medicinal substances
Inspect and license all manufacturing premises, importing and exporting agents, wholesalers, distributors, pharmacies (including those in hospitals and clinics), and other retail outlets

See the KenyaGMP, for PPB’s compilation of recommended World Health Organization GMP guidelines to help comply with GMP requirements and prepare for an inspection, including for manufacture of IPs.

Import

Per the PPA and the ImpExp, the PPB is authorized to regulate the import and export of health products and technologies, including IPs. As per the ImpExp and the G-KenyaCT, to obtain an import permit for a clinical trial, the sponsor or investigator must submit an application online to the Kenya Trade Network Agency’s Kenya TradeNet Single Window System (KEN-28). The following documents must be submitted (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

The proforma invoice or invoice
The ethics committee favorable opinion letter
The Expert Committee on Clinical Trials approval letter from the PPB
Registration of the institution where the research is being undertaken

The G-KenyaCT states that the sponsor must submit to the PPB a copy of the endorsed clinical trial import permit and/or evidence of delivery to the approved investigator(s)/trial center(s) on importation and supply of each consignment of the product. The product must only be supplied to the investigator(s) at the trial site(s) named in the clinical trial import license application for the purpose and use as stated in the said application. Prior PPB notification and approval is required for changes in the investigator, trial site, or protocol. The sponsor must inform PPB of any change in information, or any information received that casts doubt on the continued validity of the data, which was submitted with, or in connection with the application for the import permit. The sponsor must also inform the PPB of any decision to discontinue the trial to which the permit relates and state the reason for the decision. See KEN-8 for additional details on the procedures for obtaining an import license.

Per the CTRules, the import of an IP must comply with the applicable regulatory requirements to ensure integrity and accountability of the products. The PPB may revoke or suspend an import permit if the IP was manufactured in conditions not consistent with GMP; if the clinical trial was discontinued; or if the sponsor provided false information.

Please note: Kenya is party to the Nagoya Protocol on Access and Benefit-sharing (KEN-3), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see KEN-15.

2.12 and 5.13

Glossary of Terms, 2.0, 5.1.7, and 6.0-6.3

Legal Framework, 1.24-1.26, 1.48, 1.63, 1.215-1.240, 1.346-1.354, and 1.542-1.551

Part 1 (3B), Part IIIA (35A and 35B), and Part IV (44)

Part IV (14)

Quality Requirements

Last content review/update: June 21, 2024

Investigator's Brochure

The 2019-CTRules requires the Investigator’s Brochure (IB) to contain the version number, release date, and the following sections:

Contents
Summary
Introduction
Physical, Chemical, and Pharmaceutical Properties and Formulation
Non-clinical studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
Effects in humans (Pharmacokinetics and Product Metabolism in Humans, Safety and Efficacy, and Marketing Experience)
Summary of Data and Guidance for the Investigator

Refer to the 2019-CTRules for detailed content guidelines.

Per the 2019-CTRules, the licensee is responsible for ensuring the products are manufactured in accordance with the principles of Good Manufacturing Practice (GMP). (See the Product Management section for additional information on investigational product (IP) supply, storage, and handling requirements).

Additionally, per Notice13Mar20, when the application is solely to conduct a clinical trial, the DCGI also requires the sponsor (also known as applicant) to submit the international non-proprietary name (INN) or generic name, drug category, dosage form and data supporting IP stability in the intended container-closure system for the duration of the clinical trial (see the Second Schedule, Table 1 in the 2019-CTRules for detailed data requirements). Additionally, for Phase III clinical trial batches, process validation data requirements may not be required; however, this requirement will vary depending on the IP’s complexity (biological, high tech, etc.).

Quality Documentation

As noted in the 2019-CTRules the applicant is required to provide the following:

A free sale certificate from country of origin
Certificate(s) of analysis of IP shipped

Per IND-75, the Central Drugs Standard Control Organization (CDSCO) determined that the Certificate of Pharmaceutical Product (COPP) should be issued under the World Health Organization (WHO) GMP Certification Scheme and extended the validation period from two (2) to three (3) years subject to the condition that the manufacturing facility GMP status be monitored per WHO guidelines through periodic inspections.

Further, per the 2019-CTRules, the submission of requirements related to pre-clinical/toxicological animal studies may be modified or relaxed in the case of new drugs approved or marketed for several years in other countries if the DCGI determines there is adequate published evidence regarding a drug’s safety.

See IND-35 for a checklist of global clinical trial (GCT) documentation requirements.

Chapter VIII (55 and 63), Chapter IX (70), Chapter X (75), Chapter XIII (101), Second Schedule (Table 1), Third Schedule (Table 7), and Eighth Schedule (Forms CT-10, CT-12, and CT-16)

1

Last content review/update: July 2, 2024

Investigator’s Brochure

In accordance with the CTRules and the G-KenyaCT, the sponsor must provide an up-to-date investigator’s brochure (IB). An updated IB and Drug Safety Update Report (DSUR) must be submitted whenever available but at least once year as a notification to the Pharmacy and Poisons Board (PPB) or when there are substantial changes to the previous version.

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). As specified in the G-KenyaCT and KEN-14, the IB must provide coverage of the following areas:

Physical, chemical, and pharmaceutical properties
The pharmacological aspects including its metabolites in all animal species tested
The pharmacokinetics and metabolism including its biological transformation in all animal species tested
Toxicological effects in any animal species tested under a single dose study, a repeated dose study, or a special study
Results of clinical pharmacokinetic studies
Information regarding safety, pharmacodynamics, efficacy, and dose responses that were obtained from previous clinical trials in humans

The G-KenyaCT indicates that the sponsor must also follow the guidance contained in KEN-14.

Quality Management

In accordance with the G-KenyaCT, a good manufacturing practice (GMP) certificate must be provided by a competent authority from the country of manufacture to the PPB in the clinical trial application. At a minimum, the GMP certificate should include the competent authority’s name and contact details, address of the manufacturing site, date of inspection, and validity period. Certificates of Analysis (CoAs) must also be provided to the PPB for all investigational products (IPs) and comparator products. Per KEN-14, the sponsor must maintain a CoA to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.

See the G-KenyaCT for detailed chemistry and manufacturing information to be provided to the PPB if the IP has not been registered with the PPB. In addition, see Cert-Emrgcy for information about good clinical practice (GCP) and GMP certifications during emergencies.

(See Product Management section for additional information on sponsor requirements).

7

Glossary of Terms, 1.13-1.29, 1.48, 1.63-1.88, 1.213-1.240, 1.340-1.354, and 1.542-1.551

Part III (8)

Labeling

Last content review/update: June 21, 2024

Per the 2019-CTRules and IND-31, the labeling of any new drug or investigational new drug product manufactured or imported for the purpose of conducting a clinical trial or for testing and analysis should include the following items:

The drug name or code number
Batch number or lot number
Manufacture date
Use before date
Storage conditions
Name of institution/organization/center where the clinical trial or testing and analysis is proposed to be conducted
Manufacturer name and address
Purpose for which the investigational product is being imported

Chapter VIII (66) and Chapter IX (73)

70

Last content review/update: July 2, 2024

Per the G-KenyaCT, investigational products (IPs) used in Kenyan clinical trials must be properly labelled. A final copy/version of the labelling must be submitted to the Pharmacy and Poisons Board (PPB) for approval and should contain the following minimum information:

Statement indicating that the product is for “clinical trial purpose only”
Recommended storage conditions
Protocol code or identification
Name, address, and telephone number of the sponsor, contract research organization, or investigator (the main contact for information on the product, clinical trial, and emergency unblinding)
Pharmaceutical dosage form, route of administration, quantity of dosage units, and in the case of open trials, the name/identifier and strength/potency
The batch and/or code number to identify the contents and packaging operation
A trial reference code allowing identification of the trial, site, investigator, and sponsor, if not given elsewhere
The trial participant identification number/treatment number and, where relevant, the visit number
The name of the investigator (if not included above)
Directions for use (reference may be made to a leaflet or other explanatory document intended for the trial participant or person administering the product)
Period of use (use-by date, expiry date, or re-test date as applicable), in month/year format and in a manner that avoids any ambiguity
The complete physical address of the manufacturing site

As indicated in the G-KenyaCT, it is recommended that an IP is not re-labeled wherever possible. It is, however, accepted that in certain cases it is necessary to re-label and the PPB will review applications for the extension of expiration dates based on sufficient evidence being provided by the applicant that an extended expiration date is warranted. A written justification and evidence should be provided to the PPB. Any re-labelling of remaining IPs from previously manufactured batches must be performed in accordance with good manufacturing practice (GMP) principles and is limited to an extension of the expiration date where sufficient evidence is available to support such extension. Any request for re-labelling should be accompanied by a certificate of analysis of the product from a PPB-recognized laboratory or World Health Organization (WHO) prequalified laboratories (KEN-18). After approval, the re-labelling must be carried out under the supervision of a pharmaceutical inspector on the ground. In case of use-date extension, an additional label should be affixed to the IP to indicate the new use date and repeat the batch number. It may be superposed on the old use date, but not on the original batch number. PPB will not approve re-labelling of a product if the proposed additional label obscures the original labelling. At all times, the original label should be visible. This operation may be performed onsite by the clinical trial monitor(s) or the clinical trial site pharmacist, in accordance with specific and standard operating procedures. The operation should be checked by a second person. Documented evidence of this additional labelling should be available in the trial documentation and in the batch records. KEN-34 indicates that all documents submitted to the PPB in a clinical trial application should be in English, including a pictorial sample of the IP with the labeling text.

The International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (KEN-14), which the G-KenyaCT requires following, states that the IP must be coded and labeled in a manner that protects the blinding, if applicable. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

5.13

1.48, 1.63, 1.307-1.317

Product Management

Last content review/update: June 21, 2024

Supply, Storage, and Handling Requirements

According to the 2019-CTRules and IND-31, in the event that a new drug or investigational new drug manufactured for clinical trial or testing and analysis purposes is left over, remains unused, incurs damage, has an expired shelf life date, or has been found to be of sub-standard quality, the drug must be destroyed and the action taken should be recorded.

Per the 2019-CTRules, the investigational product (IP) section of the protocol submitted as part of the clinical trial application must include the following:

IP description and packaging (i.e., IP ingredients and formulation, and placebos used, if applicable)
Dosing required during study
Packaging, labeling, and blinding method
Method of assigning treatments to participants and identification code numbering system to be used
Storage conditions
Accountability (e.g., instructions for receipt, storage, dispensation, and return of IPs)
Policy and procedure for handling unused IPs

Record Requirements

No information is currently available on IP record requirements.

Chapter VIII (55) and Third Schedule (Tables 2 and 7)

68

Last content review/update: July 2, 2024

Supply, Storage, and Handling Requirements

Per the PPA, the Pharmacy and Poisons Board (PPB) is responsible for the regulation of investigational products (IPs), including all matters relating to the safety, packaging, and distribution of medicines. The PPB must ensure that all medicinal products manufactured in, imported into, or exported from the country conform to prescribed standards of quality, safety, and efficacy. Further, the PPB must ensure that the personnel, premises, and practices employed in the manufacture and storage of IPs complies with prescribed requirements.

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). As defined in the G-KenyaCT and KEN-14, the sponsor must ensure the following (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Timely delivery of IPs to the investigator(s)
Records that document shipment, receipt, disposition, return, and destruction of the IPs are maintained
A system for retrieving IPs and documenting that this retrieval is maintained
A system for the disposition of unused IPs is maintained
Steps taken to ensure that the IPs are stable over the period of use
Sufficient quantities of the IPs used in the trials are maintained

To the extent stability permits, samples should be retained either until the analyses of the trial data are complete or as required by the applicable regulatory requirement(s), whichever represents the longer retention period.

As defined in the G-KenyaCT and KEN-14, the sponsor must also supply the investigator(s)/institution(s) with the IPs, including the comparator(s) and placebo, if applicable. The sponsor or the representative should not supply either party with the IP(s) until approval from the PPB and a favorable opinion letter from the local and national ethics committees (ECs) are obtained. In addition, the G-KenyaCT requires the following supply, storage, and handling processes:

Analysis or evaluation of samples is performed in accordance with the protocol and, where applicable, the contract/agreement, the work instruction, and associated methods
Adherence to the laboratories, policies, and standard operating procedures (SOPs)
Prior to the initiation of sample analysis or evaluation, it is often necessary to prepare a work instruction detailing the procedures, which will be used to conduct the analysis or evaluation
Have automated equipment for routine hematology, biochemistry, and serology tests
Have procedures for analyzer calibration and quality control
Regularly maintain all the equipment, including point-of-care equipment
Have a procedure for transporting samples safely and quickly from clinical areas to the laboratory
Have written procedures for all assays, and validate the assays
Have a stock control procedure to make sure that reagents and consumables are used within their expiry dates
Keep records, including source documents and final reports
Have a laboratory information management system, and validate and backup the system
Provide protective clothing and safety equipment for staff
Have a central alarm system for all fridges and freezers
Have an internal audit program

The G-KenyaCT also states that the sponsor must submit to the PPB a copy of the endorsed Clinical Trial Import License and/or evidence of delivery to the approved investigator(s)/institution(s) upon importing and supplying each product consignment. In addition, the IP must only be supplied to the investigator(s)/institution(s) named in the application for the Clinical Trial Import License/Clinical Trial Exemption for the purpose and use specified. The sponsor must inform the PPB in the event of any information changes including:

Information the sponsor receives that casts doubt on the continued validity of the submitted data
Information associated with the Clinical Trial Import License

See the G-KenyaCT for additional information on principal investigator requirements relating to the Clinical Trial Import License.

Record Requirements

As per the G-KenyaCT, the sponsor is required to maintain records that document IP(s) shipment, receipt, disposition, return, and destruction. The sponsor must also maintain a system for retrieving IPs and documenting this retrieval, and maintain a system for the disposition of unused IPs.

According to the G-KenyaCT, IP manufacturers or importers must also retain samples for each batch of bulk product, and the packaging components used for each finished batch, for at least two (2) years following the trial. The sponsor should maintain sufficient samples from each batch and keep a record of their analyses and characteristics for reference so that, if necessary, an independent laboratory could reconfirm the same data.

5.5, 5.12-5.14, and 7

Glossary of Terms, 1.13-1.29, 1.48, 1.63-1.88, 1.213-1.214, 1.307-1.317, 1.355-1.372. 1.491, 1.507-1.511, and 1.542-1.551

3B

Definition of Specimen

Last content review/update: June 21, 2024

In India, per the G-XBiolMat, the G-ICMR, and the G-StemCellRes, a specimen is referred to as “human biological material,” “human biological sample,” “biological material,” or “biospecimen.” The G-XBiolMat defines a specimen as human material with the potential for use in biomedical research. According to the G-XBiolMat, the G-ICMR, and the G-StemCellRes, this material specifically includes (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Organs and parts of organs
Cells and tissue
Blood (e.g., cord blood and dried blood spots)
Gametes (e.g., sperm, ova, and oocytes)
Embryos and fetal tissue
Blastocysts
Somatic cells

The G-XBiolMat definition also includes the following:

Sub-cellular structures and cell products
Wastes (e.g., urine, feces, sweat, hair, epithelial scales, nail clippings, placenta, etc.)
Cell lines from human tissues

As per the G-XBiolMat, these biological specimens or human material samples may be obtained from the following sources:

Patients following diagnostic or therapeutic procedures (e.g., dental, labor, etc.)
Autopsy specimens
Organ or tissue donation from living or dead persons
Fetal tissue
Body waste
Abandoned tissue
Tissue banks

Chapter III, Review Procedures, Section 3

15.0

Definition

Last content review/update: July 2, 2024

Specimens are not defined in the Kenyan regulations. However, per KEN-26, the Kenya Medical Research Institute (KEMRI) identifies biological samples and specimens as including, but not limited to, blood samples, saliva, breast milk samples, mosquito parts samples, biological cultures, tissue and tissue samples, hair samples, human stool, and environmental samples used in human health research.

Submission Forms (Shipping)

Specimen Import & Export

Last content review/update: June 21, 2024

Import/Export

As specified in the G-XBiolMat, the HumBiol-ImprtExprt, and IND-55, the applicable import/export guidelines for human biological materials/specimens in India are determined by whether the materials are to be used for biomedical research or for commercial purposes. According to IND-55, the G-XBiolMat should be followed to import/export human biological material for biomedical research purposes, and the HumBiol-ImprtExprt is to be used to import/export human biological samples for commercial purposes.

Biomedical Research

According to the G-XBiolMat, the following guidelines should be considered for requests to transfer biological material abroad for research/diagnostic purposes, and for requests to transfer biological material from abroad to Indian institutions for research purposes:

Exchange of material for diagnostic or therapeutic purposes for individual cases may be done without restriction, if this exchange is considered necessary by the doctor(s) in charge of the patient
Exchange of material from and to recognized laboratories such as the World Health Organization (WHO)’s Collaborating Centres may be allowed as part of routine activities relating to quality control, quality assurance, comparison with reference material, etc., without having to seek permission from any authority
Where exchange of material is envisioned as part of a collaborative research project, the project proposal as a whole must be routed through the appropriate authorities for evaluation and clearance (see International Research Collaboration section below for additional information)
The availability of facilities within India for carrying out certain investigations need not prevent collaboration with scientists in other countries from conducting the same investigations, including transfer of human material, if required
For the technology transfer/training of Indian scientists abroad/training of foreign scientists and students in India, and visits by foreign collaborators to their Indian partners’ laboratories to work with Indian material, there should be no restrictions on the visits of scientists to the laboratories concerned. However, any fieldwork to be undertaken in the community and other sensitive issues would have to be regulated according to the National Portal of India’s rules

International Research Collaboration

In the case of international research collaboration involving human biological material transfer, the G-XBiolMat and the G-ICMR indicate that the export of all biological materials is to be covered under existing Government of India and ethics guidelines. The G-ICMR further specifies that all biomedical and health research proposals relating to foreign assistance and/or collaboration should be submitted to the Indian Council of Medical Research (ICMR) for a technical review. Next, the ICMR submits the project to the Health Ministry’s Screening Committee (HMSC) for review and approval through its International Health Division that serves as the HMSC’s secretariat. Refer to IND-74 for detailed information on the HMSC.

Per the G-ICMR, the ethics committee (EC) may review research proposals requiring biological material transfer on a case-by-case basis. The exchange of human biological material from and to WHO Collaborating Centres for specific purposes, as well as for individual cases of diagnosis or therapeutic purposes, may not require permission. However, Indian participating center(s) must have appropriate regulatory approval and registration to receive foreign funds for research.

See IND-1 for the application form to request a no objection certificate (NOC) to export biological samples. Refer to the G-XBiolMat, the G-ICMR, IND-74, and IND-27 for additional information.

Commercial Purposes

According to the HumBiol-ImprtExprt, per the Directorate General of Foreign Trade (DGFT) within India’s Ministry of Commerce and Industry, the import of human biological samples by Indian diagnostic laboratories/Indian clinical research centers for laboratory analysis/research and development testing, or, for exporting these materials to foreign laboratories, should be permitted by customs authorities at the port of entry/exit without prior approvals (import license/export permit) from any other government agency. In these cases, the concerned Indian company/agency should submit a statement that it is following all the applicable rules, regulations, and procedures for the safe transfer and disposal of biological samples being imported/exported. For more information, see the HumBiol-ImprtExprt.

Additionally, per Notice11Mar24, the export policy for human biological samples has been revised to permit the export of items containing human biological materials, samples, and products subject to obtaining an NOC from CDSCO. To this end, as indicated in IND-55 and IND-77, the ICMR has developed the Transfer of Human Biological Material (THBM) online portal (IND-67) to enable applicants to obtain the necessary NOC for the export of human biological material for commercial purposes and for contract research by Indian companies and organizations.

Material Transfer Agreement

Per the G-ICMR and IND-74, any research involving the exchange of biological materials with collaborative institutions outside India must sign a Material Transfer Agreement (MTA). The MTA must justify the purpose and quantity of the sample being collected; the type of investigation(s) to be conducted using the material; the names/addresses of institution(s)/scientist(s) to whom the material is to be sent; and address confidentiality issues, data sharing, post-analysis handling of remaining biological materials, safety norms, etc. The G-ICMR also indicates that an appropriate memoranda of understanding (MoU) should be in place to safeguard mutual country interests and ensure compliance.

Per the G-XBiolMat, the collaborating partners (India and foreign) should enter into an MoU and/or MTA for requests to transfer biological material abroad for research/diagnostic purposes, and for requests to transfer biological material from abroad to Indian institutions for research purposes.

Section 11

Some Important points for Consideration by PIs

3.8 and 11.4

Definition, Transfer, Mechanism, and Exchange of Biological Material for Commercial Purposes

Last content review/update: July 2, 2024

Import/Export

Per the G-ECBiomedRes, biological material must not be imported nor exported without proper justification and authorization, which includes a signed material transfer agreement (MTA) approved by the relevant institutions and deposited with the National Commission for Science, Technology and Innovation (NACOSTI). For exports, a Kenyan investigator must be included in the team that is conducting the research in the recipient country. All biological samples and data collected during research belong to the local participating institutions and country.

In addition, KEN-37 has indicated that Kenya’s Pharmacy and Poisons Board (PPB) will approve of an export for overseas research if the following requirements are met:

PPB initial approval letter or annual approval letter
Ethics committee (EC) approval letter
MTA
Study protocol with a summary justification for the participants' sample exportation
Informed consent form that highlights the areas where study participants are informed about the exportation of their samples

The G-KenyaCT states that in the case of transfer of materials during research involving children, the sponsor or the representative or the principal investigator should provide to the EC an MTA including, but not limited to, the following information:

Identification of the provider and recipient
Definition of the trial and how the material will and will not be used
Maintenance of confidentiality of background of supporting data or information, if any
Indemnification and insurance

In addition, KEN-26 provides an example of the Kenya Medical Research Institute (KEMRI)'s procedures for handling requests to ship biological samples or specimens. KEN-17 also provides an example of an MTA form from the Kenyatta National Hospital-University of Nairobi (KNH-UoN) Ethics and Research Committee.

KNH-UoN ERC Material Transfer Request Form

Submission Forms

4.1 and 4.2

Glossary of Terms and 1.172

Consent for Specimen