Clinical Research Regulation For India and Malawi

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: August 29, 2024

Overview

In accordance with the PMRAAct, the Pharmacy and Medicines Regulatory Authority (PMRA) is responsible for reviewing and approving clinical trial applications for new drugs, generic drugs, and imported drugs to be registered in Malawi. The PMRA has replaced the Pharmacy, Medicines and Poisons Board (PMPB).

The R-HlthResCoord indicates that before submitting a clinical trial application to the PMRA, the sponsor or principal investigator (PI) must obtain full ethical approval from either of the two (2) National Commission for Science and Technology (NCST)-approved ethics committees (ECs)—the National Health Sciences Research Committee (NHSRC) or the College of Medicine Research and Ethics Committee (COMREC). Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.

As per the SciTechOrder, an NCST-issued license is required for research activities involving humans; research involving clinical trials; and research activities of multicentered research. The SciTechOrder does not specify whether the process of obtaining an NCST-issued license is separate from the NHSRC and COMREC approvals. See the Scope of Review section for information on NHSRC and COMREC approvals of the aforementioned research activities.

Clinical Trial Review Process

According to MWI-50, the PMRA receives clinical trial applications through the office of the Director General, and the applicant must submit evidence of ethical clearance from either the NHSRC or COMREC.

Per MWI-34, the guidance in the G-CTARevVacBiol and the G-CTAProcsVacBiol also apply to clinical trials of drugs. The G-CTARevVacBiol and the G-CTAProcsVacBiol indicate that upon receipt of a clinical trial application, the PMRA initially screens the application for completeness and assigns a PMRA reference number to the application. According to the G-CTARevVacBiol, the result of the screening will be communicated, and the screening form will be forwarded by fax, to the applicant. The applicant will forward any outstanding documents to the PMRA. The PMRA’s technical staff then reviews the application or may forward it to an expert, or to an evaluator for scientific review.

The G-CTAProcsVacBiol specifies that the application is evaluated by three (3) PMRA-appointed expert clinical trial reviewers who will provide a written report to the designated registration office, also known as the “Focal Point” division. The Focal Point will then collate and present the expert reviews to the PMRA Clinical Trial Review Committee (CTRC). The CTRC then reviews all the available documentation and provides a recommendation for approval or rejection. The PMRA considers the CTRC’s recommendation and issues a written approval or rejection.

MWI-50 further specifies that the PMRA may grant full or conditional approval depending on the nature of the CTRC’s findings. Depending on the study’s risk profile, the PMRA may conduct post-authorization good clinical practice (GCP) inspections for select clinical trials. Per the G-CTARevVacBiol, if the application is neither approved nor rejected, the PMRA’s technical staff will communicate its recommendation to the applicant. The response from the applicant will be considered at the PMRA’s subsequent scheduled meeting, and the subsequent decision will be communicated to the applicant. If changes must be made to the protocol, investigator’s brochure, or any other document, the amended document should be submitted with the applicant’s response.

The G-CTAProcsVacBiol states that the applicant may appeal a rejection decision, providing additional information, or amending the application to meet the PMRA’s requirements. The appeal will be referred to the CTRC for a final recommendation to the PMRA.

Per MWI-61, the PMRA may conduct GCP inspections during ongoing clinical trials to provide real-time assessment of the investigator’s conduct of the trial and protection of participants. Clinical trial sites may be inspected before regulatory approval, while the trial is ongoing, when participants are being enrolled in a trial, on a routine basis, when triggered by a complaint, or if there is a suspicion of serious non-compliance integrity issues and/or scientific/ethical misconduct. See MWI-61 for more information.

(See the Submission Process and Timeline of Review sections for details on the administrative and technical processing and review timelines. See also the G-CTARevVacBiol and the G-CTAProcsVacBiol for more information on the PMRA’s review procedures.)

1-6

2 and 3

Part II (Sections 4-5) and Part XIII (Section 131)

2.0 and 8.0-8.3

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: August 29, 2024

Pharmacy and Medicines Regulatory Authority

According to the PMRAAct, a person who intends to conduct a clinical trial must apply to the Pharmacy and Medicines Regulatory Authority (PMRA) for a clinical trial certificate upon payment of the prescribed fee.

Per the PMRAFeesRegs, the following fees apply to clinical trials:

Application, review, and registration: 5% of total budget
Annual renewal: $2,200 USD
Amendments: $300 USD

As delineated in the PMRAFeesRegs, a fee equaling 6% of the total invoice value must also be paid for the importation of unregistered medicines or allied substances from authorized sources. The G-ImpExpMP further indicates that this fee is subject to change from time to time.

Payment Instructions

No information is available regarding payment instructions.

National Commission for Science and Technology

No information is available regarding fees for the National Commission for Science and Technology (NCST).

Part VII (Section 75)

10 and 11

3.3

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: August 29, 2024

Overview

Malawi has a centralized registration process for ethics committees (ECs) and EC review. As mandated by the SciTechAct, the National Commission for Science and Technology (NCST) is the governmental body responsible for EC oversight, and for the promotion and coordination of research in Malawi.

As per the G-NHSRC, the G-COMREC, MWI-5, and MWI-50, the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC) are the two (2) NCST-approved ECs responsible for monitoring and evaluating health research studies involving humans. The G-HlthResConduct and the R-HlthResCoord indicate that COMREC, as a subsidiary of the NHSRC, only reviews and approves studies involving or originating from College of Medicine (COM) or Kamuzu College of Nursing (KCN) (now known collectively as the Kamuzu University of Health Sciences (KUHeS), per MWI-62) faculty members and students, and their collaborators/coinvestigators/affiliates. The NHSRC has the sole jurisdiction to review studies with a national interest and multicenter studies, including those from COM and KCN, as well as studies from all other researchers and institutions. Per the R-HlthResCoord, each EC has members representing the other committee in order to facilitate the transfer of information between the ECs. The NHSRC and COMREC report to and are centrally monitored by the NCST.

MWI-25 indicates that as of August 2024, COMREC is operating under KUHeS and will be changing its name to Kamuzu University of Health Sciences Research Committee (KUREC), following approval from the NCST. The COMREC guidance and forms provided in the Malawi profile are still being used.

Ethics Committee Composition

National Health Sciences Research Committee

As per the G-NHSRC, NHSRC must consist of members with varying backgrounds, including the social sciences, to promote complete and adequate research proposal review. The committee should include one (1) lay person, as well as members from the following organizations:

National Research Council of Malawi (one (1) member)
Ministry of Health (MOH) headquarters (two (2) members)
COMREC (two (2) members)
Community Health Sciences Unit (one (1) member)
National AIDS Commission (one (1) member)
Center for Social Research (one (1) member)
Queen Elizabeth Central Hospital (one (1) member)
Zomba Central Hospital (one (1) member)
Lilongwe Central Hospital (one (1) member)
Christian Health Association of Malawi (one (1) member)
Mzuzu University (one (1) member)
Mzuzu Central Hospital (one (1) member)
Nurses and Midwives Council of Malawi (one (1) member)
Ministry of Justice (one (1) member)

The members elect the chairperson and the vice-chairperson.

College of Medicine Research and Ethics Committee

The G-COMREC specifies that COMREC should be multidisciplinary, and its members must have the basic qualifications, experience, and expertise to conduct fair scientific and ethical proposal reviews. The committee must have a maximum membership of 15, and include representatives from the biomedical sciences, research methods, behavioral science, and research ethics areas. Additionally, there must also be representatives from the NCST, the NHSRC, the KCN, and the lay community.

Furthermore, the committee must be diverse, have balanced gender representation, and embody community interests and concerns. Members are also required to sign a confidentiality agreement and refuse projects in which they have a conflict of interest. Members from the COM staff serving on the committee must be a minimum grade of senior lecturer, and preferably have peer reviewed publications.

See the G-NHSRC and the G-COMREC for additional EC membership criteria and qualification requirements.

Terms of Reference, Review Procedures, and Meeting Schedule

National Health Sciences Research Committee

The G-NHSRC states that the MOH’s Research Unit serves as a secretariat for NHSRC, and is responsible for preparing materials and meeting logistics. Research proposals must be distributed to NHSRC members two (2) weeks before the scheduled meetings to allow members time to adequately review the submitted proposals. Half of the NHSRC’s membership constitutes a quorum of any meeting, and the meeting is rescheduled within the following two (2) weeks if a quorum is not reached. Half of the ordinary quorum forms a quorum for the rescheduled meeting if no ordinary quorum is reached. Otherwise, the meeting must be rescheduled.

As delineated by the G-NHSRC, NHSRC decisions are reached by consensus. If there is no consensus, a decision is made by simple majority of members present through an open ballot. In the event of a tie, the chairperson casts a vote.

According to the G-NHSRC, when new NHSRC members have been appointed, they may attend the first one (1) or two (2) meetings as an observer in order to learn about the workings of the NHSRC before being assigned reviewer responsibility. Such members will undergo NHSRC orientation sessions covering guidelines and standard operating procedures (SOPs) of the committee and any practical matters with the secretariat and chairperson. Continuing education for all members in matters of health research ethics and related disciplines in human research protections is also essential, and the chairperson is responsible for fostering local and international networks, links, and partnerships for the purposes of continuing the NHSRC’s education and development.

Per the G-NHSRC, NHSRC members must serve on the committee for three (3) years and are required to renew their appointments if requested by their organizations. The G-NHSRC and the G-HlthResConduct also indicate that the NHSRC meets once every two (2) months.

College of Medicine Research and Ethics Committee

COMREC requires written SOPs to be maintained, and all relevant records (e.g., SOPs, reports, curriculum vitaes (CVs), meeting minutes, and correspondence) to be archived for three (3) years following the study’s completion, as delineated in the G-COMREC. The COMREC secretariat must compile all the relevant documents and materials required for review of a proposal and circulate them to the members at least 14 days before the date of the scheduled meeting. Quorum of any meeting is achieved when a majority of the members attend. The quorum should preferably include members of both genders, a member whose primary area of expertise is in a non-scientific area, and at least one (1) member who is independent of the COM. If the quorum cannot be achieved, the meeting must be rescheduled within two (2) weeks of the failed meeting. If the subsequent meeting does not achieve quorum, then the chairperson must make a decision based on the expertise and number of members present.

The G-COMREC further states that COMREC’s final decision will be reached through a consensus. If there is no consensus, a decision is made through a majority vote.

Per the G-COMREC, COMREC members must receive initial and continuing training regarding the ethics and science of research. The appointment of committee members is valid for three (3) years, and a member may be reappointed to serve another three (3) year term. According to the G-COMREC and the G-HlthResConduct, COMREC meets every month.

1.0, 2.0, 3.1-3.3, 4.0, 5.7-5.8, and 8.0

1 and 7

1.0, 3.1-3.3, and 4.0

Part IV

2.0 and 8.0

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: August 29, 2024

Overview

According to the G-NHSRC and the G-COMREC, the primary scope of information assessed by the two (2) National Commission for Science and Technology (NCST)-approved ethics committees (ECs)—the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC)—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-HlthResConduct states that scientific design; recruitment of research participants; care and protection of research participants; ethical consideration; and community consideration are essential elements that the NHSRC and COMREC must review in a clinical trial application. Per the G-NHSRC, the NHSRC must also pay special attention to reviewing informed consent and to protecting the welfare of certain classes of participants deemed to be vulnerable (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations).

The G-HlthResConduct and the R-HlthResCoord indicate that COMREC, as a subsidiary of NHSRC, only reviews and approves studies involving or originating from the College of Medicine (COM) or Kamuzu College of Nursing (KCN) (now known collectively as the Kamuzu University of Health Sciences (KUHeS), per MWI-62) faculty members and students, and their collaborators/coinvestigators/affiliates. The NHSRC has the sole jurisdiction to review studies with a national interest and multicenter studies, including those from COM and KCN, as well as studies from all other researchers and institutions.

Role in Clinical Trial Approval Process

The R-HlthResCoord indicates that before submitting a clinical trial application to the Pharmacy and Medicines Regulatory Authority (PMRA), the sponsor or principal investigator (PI) must obtain full ethical approval from either the NHSRC or COMREC. Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.

Moreover, as specified in the R-HlthResCoord, for all studies originating outside Malawi, the sponsor or the PI is required to obtain approval from an EC based in their country prior to submitting an application to the NHSRC or COMREC for ethical review and approval.

Per the G-NHSRC and the G-COMREC, the applicable EC will screen submitted applications for completeness, and help determine the type of review to be conducted.

The G-NHSRC states that new studies submitted to the NHSRC are generally reviewed by a fully convened NHSRC meeting. The following studies will be reviewed by the full NHSRC:

All high-risk studies
Studies involving vulnerable populations (including pregnant women, prisoners, mentally incompetent patients, etc.)
Any clinical interventional study that randomly assigns human participants to alternative experimental or placebo groups
Studies involving sensitive information connected to personal identifiers
Studies previously reviewed that require major issues to be addressed

The G-NHSRC and the G-COMREC indicate that following the NHSRC’s or COMREC’s review, the EC will decide to approve the research, stipulate minor changes for approval, or not approve the research. A negative decision on an application must be supported by clearly stated reasons. In addition, the G-NHSRC states that if the NHSRC determines that substantive changes/clarifications must be made before approval may be granted, the study will be deferred for a full NHSRC meeting.

The G-COMREC specifies that the COMREC’s approval of a new application is valid for one (1) year. However, the R-HlthResCoord indicates that EC approval of a study is valid for the period of the study as described in the protocol, which is effective from the date of approval as indicated in the approval letter.

The R-HlthResCoord, the G-NHSRC, and the G-COMREC state that the EC must review and approve any protocol amendments prior to those changes being implemented. See MWI-52 and MWI-44 for the NHSRC and COMREC amendment request forms, respectively. Any changes cannot be implemented until approved by the EC.

The G-COMREC requires that COMREC follow the progress of studies for which a positive decision has been reached and establish a subcommittee responsible for monitoring ongoing studies. The follow-up review intervals are determined by the nature of the research project. However, each protocol should undergo a follow-up review at least once a year. As part of its monitoring process, COMREC conducts inspections of institutions and study sites.

Studies of National Interest

All studies of national interest, as defined in the G-NHSRC, the G-COMREC, and the R-HlthResCoord to include all vaccine trials and stem cell research, should be referred to the NHSRC, regardless of the origin of the protocol. The NHSRC may form a standing committee for that specific project, which will monitor the project through to its conclusion, composed of members to be drawn on the basis of their expertise.

Multicenter Studies

As delineated in the R-HlthResCoord, the NHSRC is designated and mandated to review and approve multicenter clinical trials, including those originating outside Malawi. The NHSRC will conduct a full initial review of the same protocols for a multicenter study submitted by different investigators provided that such protocols are submitted simultaneously. Protocols for the same multicenter trial to be implemented at different institutions may also be merged into one (1) protocol that the NHSRC will treat as a joint submission for review.

Continuing Review

According to the G-NHSRC and the G-COMREC, all approved studies running for more than one (1) year are subject to continuing annual review by the approving EC (the NHSRC or COMREC). If the materials for continuing EC review are not received within one (1) month following the expiration date of the previous approval, then the study will be classified as lapsed and inactive. If a study has lapsed, the EC will order that all study-related operations cease, except those necessary for the welfare of the participants. Per the G-NHSRC, if the PI wants to continue an NHSRC-reviewed study that has lapsed for two (2) months, the PI must submit a new application for NHSRC review and wait for approval before resuming research under the protocol. MWI-53 indicates that the NHSRC follows, at a minimum, the regulations set forth in the Declaration of Helsinki (MWI-42) and the Council for International Organizations of Medical Sciences (CIOMS) guidelines as the criteria for continuing review of a study. The PI is responsible for timely submission of a continuing review application to prevent any lapse in NHSRC approval. NHSRC regulations do not provide for exceptions to the requirement for continuing review. The NHSRC’s continuing review application form is available at MWI-53.

Expedited Review

Per the G-NHSRC and the G-COMREC, research studies that have previously been reviewed by a fully convened committee and require the PI to address minor issues, may be approved through the NHSRC’s or COMREC’s expedited processes. Studies by students may also be considered for expedited review. Expedited review can be considered for continuing review of research previously approved by the NHSRC or COMREC, where the research is permanently closed to the enrollment of new subjects, and all subjects have completed all research related interventions.

Per the G-COMREC, COMREC’s review period for such a resubmission must not exceed 14 days from the date of the resubmission. The G-NHSRC further indicates that the NHSRC will also consider expedited review for continuing review of research previously approved by NHSRC where no subjects have been enrolled and no additional risks have been identified, or where the remaining research activities are limited to data analysis and report writing.

For more information on each EC’s expedited review procedures, see the G-NHSRC and the G-COMREC.

Exemption from Review

As delineated in the G-NHSRC and the G-COMREC, certain types of human participants research may be exempted from NHSRC or COMREC review. Exemption may be considered for research involving the collection or study of existing data, documents, records, program evaluation, pathological specimens, or diagnostic specimens, if the sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified directly or through identifiers linked to the subjects.

Suspension or Termination of Study/Approval

Per the G-NHSRC, the NHSRC chairperson or the convened NHSRC may suspend a study at any time if it is determined that the study requires further review or evaluation. This determination may be made in the event of an adverse event, non-compliance, or other danger to human participants. The study will be reviewed at the next convened meeting to determine if it requires changes. The NHSRC must notify the PI and the sponsor in writing specifying reasons for suspension or termination with a copy to the National Research Council of Malawi (NRCM). The NRCM must be informed of all the suspended or terminated studies with detailed reasons for the decision. In the event of documented serious adverse events and any unanticipated problems as documented by the researcher, the NHSRC must terminate the study and order the investigator to follow up with study participants. In the case of any officially or unofficially reported noncompliance, protocol violation, or deviation by the researcher, the NHSRC must suspend the study to ensure safety of the study participants and carry out an investigation. Upon investigation of the problem prompting the suspension of the study, the convened NHSRC must terminate the study if convinced beyond any reasonable doubt that there was noncompliance, deviation, or violation of the protocol.

The G-COMREC states that COMREC may recommend to COM management suspension or termination of approval of research that is not being conducted in accordance with the guidelines, or that has been associated with unexpected serious harm to participants. Any suspension or termination of approval must include a statement of the reasons for COMREC's action and must be reported promptly to the investigator, appropriate institutional officials, Dean of Postgraduate Studies and Research, and the Principal of the COM. The Principal of the COM must then send a report of suspended or terminated studies with the reasons contained therein to the NCST and the PMRA, or any other government agency responsible for research policy matters.

1.0, 3.2, 3.3, 5.1, 5.4-5.9, 6.0, and 7.0

1, 7, and 9

1.0, 2.0, 3.1, 5.1-5.4, 5.7, 6.2, and 9.2

2.0, 6.0, 7.0, 7.2, 8.1-8.4, 8.6, and 9.0

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: August 29, 2024

National Health Sciences Research Committee

According to MWI-4 and MWI-15, non-Malawian researchers must pay $150 USD or its equivalent in Malawian Kwacha to the National Health Sciences Research Committee (NHSRC) upon submission of a research proposal. Malawian students (Masters and below) are required to pay 5000 Malawian Kwacha.

The G-NHSRC and MWI-5 indicate that following the protocol’s approval, the principal investigator must also pay the Ministry of Health (MOH) a fee of 10% of the total budget indicated in the proposal to cover NHSRC institutional capacity strengthening and administrative operating expenses. MWI-15 further specifies that the fee, referred to as a 10% NHSRC Human Subject Protection (HSP) fee, must be paid by PhD students and above.

MWI-5 clarifies that the NHSRC fee and the Pharmacy and Medicines Regulatory Authority (PMRA)’s Clinical Trial Review Committee (CTRC) fees are included in the 10%. Payment of the 10% fee must be made for all NHSRC-approved research projects prior to commencement of the research study.

Payment Instructions

Per MWI-15, the application fee and the 10% HSP fee may be paid at the MOH Headquarters Cash Office or through the following bank details:

Account Name: NHSRC NCST Review Fees
Account Number: 1010759176
Bank Name: National Bank of Malawi
Bank Address: Capital City Branch, Lilongwe 3, Malawi
Swift Code: NBMAMWMW008

College of Medicine Research and Ethics Committee

As per MWI-5, non-Malawian researchers must pay $150 USD and Malawian researchers must pay 500 Malawian Kwacha to the College of Medicine Research and Ethics Committee (COMREC) upon the submission of a research proposal. COMREC is also mandated to charge a College of Medicine (COM) fee of 10% of the total budget indicated in the proposal. As delineated in MWI-1, the COM’s Dean of Postgraduate Studies and Research can grant waivers for the 10% fee.

However, the G-COMREC states that the COM’s processing fee is $100 USD for each new protocol submission and resubmission for the fourth time, and that eligible investigators may apply to management for exemption from paying the fee.

Payment Instructions

No information is currently available regarding payment instructions for COMREC.

3.3.10

8.0

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: August 29, 2024

Overview

The R-HlthResCoord indicates that the National Commission for Science and Technology (NCST) is the central statutory body responsible for coordinating and regulating all research, science, and technology related activities in Malawi, as mandated by the SciTechAct.

The R-HlthResCoord further specifies that the NCST provides oversight to the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC). The NCST’s core responsibilities in this capacity include:

Participating as an ex-officio member for the NHSRC and COMREC by having a voting representative from the NCST sit on both committees
Reviewing and approving the ethics committees’ (EC) guidelines and standard operating procedures
Monitoring the ECs’ performance and adherence to relevant national policies, laws, regulations, and guidelines

Registration, Auditing, and Accreditation

As stated in the SciTechOrder, an NCST-issued license is required for the accreditation of research institutions and the establishment of an institutional EC. Additional information regarding the NCST-issued license is not available at this time.

Part IV

2.0 and 2.2

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: August 29, 2024

Overview

According to the G-CTARevVacBiol, the R-HlthResCoord, and MWI-50, the Pharmacy and Medicines Regulatory Authority (PMRA) requires the applicant to obtain PMRA approval and ethics committee (EC) approval of a clinical trial application.

The R-HlthResCoord indicates that before submitting a clinical trial application to the PMRA, the sponsor or principal investigator (PI) must obtain full ethical approval from either of the two (2) National Commission for Science and Technology (NCST)-approved ECs—the National Health Sciences Research Committee (NHSRC) or the College of Medicine Research and Ethics Committee (COMREC). Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.

Regulatory Submission

According to MWI-60, an electronic or soft copy of the clinical trial application dossier must be sent to registration@pmra.mw and info@pmra.mw.

As per the G-CTARevVacBiol and MWI-9, applicants must submit three (3) copies of the clinical trial application to the PMRA. MWI-60 further requires that the three (3) dossier hard copies be submitted in a lever arch file to the Director General. Each section of the dossier must be well demarcated for ease of reference by PMRA reviewers. The application may be made by a sponsor or the sponsor’s agent, who must submit a power of attorney (MWI-33) attesting to be a duly appointed agent.

There is no specified language requirement for the clinical trial documents to be submitted to the PMRA.

Ethics Review Submission

National Health Sciences Research Committee

As stated in the G-HlthResConduct and MWI-15, the applicant is required to bind and submit application materials (plus an electronic copy, per MWI-15) to the NHSRC at least three (3) weeks before the date of the review meeting.

MWI-15 states that applications should be submitted to the NHSRC at the following address:

The Chairperson
National Health Sciences Research Committee
Ministry of Health Research Department Area 2/124
P.O. Box 30377
Lilongwe 3, Malawi
Tel: +265 1 789 400

The electronic copy should be submitted at the same time to research@health.gov.mw and mohdoccentre@gmail.com.

MWI-15 indicates that three (3) copies of each item indicated in the NHSRC Checklist (MWI-4) must be submitted in the research proposal package to the NHSRC (See the Submission Content section for a list of these items). Three (3) copies for Malawian student proposals (up to master’s level) must also be submitted to the NHSRC secretariat for expedited review. The submission must be bound in the order indicated by MWI-4 as one (1) PDF document. (See the Submission Content section for more details on the individual elements of the NHSRC research proposal submission.)

According to MWI-15 and MWI-4, the data collection tools and informed consent forms must be provided to the NHSRC in both English and Chichewa (or the appropriate local language).

The R-HlthResCoord indicates that for multicenter trials, sponsors and PIs may plan to hold a pre-clinical trial submission and authorization meeting with the NHSRC, at their own choice and cost. The sponsor or PI must write to the NHSRC secretariat of the review committee to request the meeting’s arrangement at least four (4) weeks in advance of the suggested meeting date. For more information, see the R-HlthResCoord.

College of Medicine Research and Ethics Committee

Per the R-HlthResCoord, COMREC may at its own discretion allow a pre-clinical trial application procedure, where applicable, at the request and cost of the sponsor. As stated in the G-HlthResConduct, the applicant is required to submit application materials to COMREC at least three (3) weeks before the date of the review meeting.

According to MWI-10, protocol submissions to COMREC may be made through the Research Ethics Information Management System (REIMS) (MWI-19). Following submission, the protocol will be reviewed, and feedback will be given through the applicant’s registered email address. All file attachments should be in PDF format with clear, descriptive names. Per MWI-19, ECs in Tanzania, Rwanda, and Kenya also participate in REIMS. See MWI-10 for more information on the REIMS submission portal.

MWI-19 provides the following additional contact information for COMREC:

Tel: +265 888 118 993
Email: comrec@medcol.mw

However, MWI-1 indicates that all documents should be submitted to COMREC by email to comrec@medcol.mw in one (1) PDF file, if the file size does not exceed 5MB. If the file size is over 5MB, then the file should be sent as a compressed zipped file. The data collection tools and informed consent forms must be provided in both English and Chichewa (or the appropriate local language).

3.2

1 and 8

2.0, 7.1, and 8.0-8.3

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: August 29, 2024

Regulatory Authority Requirements

As per the G-CTAProcsVacBiol, the G-CTARevVacBiol, and MWI-60, the following documentation must be submitted to the Pharmacy and Medicines Regulatory Authority (PMRA) in an application to conduct a clinical trial (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Comprehensive table of contents for the entire application, including a complete list of all documents provided in the application. The location of each document should be identified by tab identifiers. In general, the name for the tab identifier should be the name of the document
Cover letter signed by the principal investigator (PI) or sponsor
Proof of payment of the application and registration fees
Signed and stamped Clinical Trial Application (Form CT 8) (MWI-9)
Current version of the study protocol signed and dated by the sponsor and investigator (in the format provided in the International Council for Harmonisation’s (ICH) good clinical practice (GCP) guidelines and/or in line with Attachment 1 of MWI-60)
Investigator’s Brochure (IB), where applicable (in the format provided in the ICH GCP guidelines)
Certificate of Good Manufacturing Practice (GMP) of the investigational product (IP) (also referred to as an investigational medicinal product (IMP) in Malawi) and/or placebo, or evidence of manufacture quality, safety, and consistency
Mock-up labels for the IP
Blank case report forms (CRFs) and serious adverse events (SAEs) reporting form to be used in the study
Investigational Medicinal Product Dossier (IMPD) or alternative as provided in Attachment 2 of MWI-60
Stability data of the IP and auxiliary medicine(s) for climatic zone IVa if not registered in Malawi by the PMRA
Evidence of registration of the IP or auxiliary medicines in a country with Stringent Regulatory Authority (SRA) and/or Certificate of Pharmaceutical Product (CoPP), i.e., if IP/auxiliary medicines are not registered by the PMRA
Summary of Product Characteristics (SmPC) for IP and auxiliary medicines
Pharmacy plan
Report summaries of prior clinical trials with the IP (part of IB if it is in the ICH format)
Capacity building plans including training and updating of staff involved in the trial
Informed consent form (ICF) (in ICH format)
Declaration of intent by the national PI or contact person (MWI-31)
Signed and completed declaration by investigators (MWI-32)
Investigator(s) Curriculum Vitae(s) (CVs), including that of pharmacist(s)
Financial declaration by sponsor and PI (MWI-59)
Ethical clearance certificate from an independent ethics committee (EC) recognized by the laws of Malawi
Certified copy of clinical trial insurance for study participants endorsed by the National Commission for Science and Technology (NCST)
Malpractice insurance for investigators and associated staff endorsed by the NCST
Evidence of accreditation or equivalent of the designated laboratories (see the World Health Organization (WHO)’s guidance on Good Clinical Laboratory Practice (MWI-30))
Completed PMRA Material Transfer Agreement Form on Shipping of Samples (MWI-14)
Description of the site facilities (pictorial presentations may be included)
Evidence of registration of investigators with appropriate bodies
Evidence of registration of pharmacists with the PMRA
Evidence of GCP training by investigators and pharmacists in the last three (3) years
Batch release certificate
Authorization of the clinical trial from the country of origin, if applicable
Full, legible copies of key, peer-reviewed published articles supporting the application
Any other requirement as may be determined by the PMRA

If any above items are not submitted, justification for not submitting the document must be provided. The application may be made by a sponsor or the sponsor’s agent, who must submit a power of attorney (MWI-33) attesting to be a duly appointed agent. See MWI-60 for more details. According to MWI-34, the guidance in the G-CTARevVacBiol and the G-CTAProcsVacBiol also apply to clinical trials of drugs.

Ethics Committee Requirements

National Health Sciences Research Committee

According to the G-NHSRC, MWI-4, and MWI-15, any proposals submitted to the National Health Sciences Research Committee (NHSRC) must be accompanied by the following (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

The NHSRC checklist (MWI-4)
Cover letter from the PI
The NHSRC application form (MWI-15)
Research proposal summary, maximum four (4) pages
Full/main research proposal (see the G-NHSRC, MWI-4, and MWI-15 for details)
Data collection instruments in both English and Chichewa (or other appropriate local language)
Informed consent in both English and Chichewa (or other appropriate local language)
Letter of approval from foreign EC, where applicable (for all students studying in foreign universities)
Support letters from affiliating institutions (e.g., universities, hospitals, research institutions, or companies where the study is going to take place)
A copy of the receipt for the paid application fee
CVs for all the investigators
Proof of funding from the sponsor/funder (where applicable)

MWI-4 requires that if any of the above items are not included in the submission to the NHSRC, an explanation must be provided.

College of Medicine Research and Ethics Committee

MWI-1 indicates that for submissions to the College of Medicine Research and Ethics Committee (COMREC), a single PDF file should include the following information in the following order:

Completed copy of the COMREC checklist (MWI-1)
Cover letter from the PI
Protocol
ICFs in both English and Chichewa for adult participants ages 18 and above, parental consent forms for all minors, and assent forms (in addition to the parental consent forms) for all minors between the ages of 7 and 17
Data collection tools (those that will involve obtaining information from research participants should be translated into Chichewa)
Material transfer agreement forms and documents
Waiver letter for the 10% College of Medicine (COM) overhead fee, if applicable
Information regarding whether the research proposal has been submitted to another EC
Letter of support from COM head of the principal department hosting the research
Letter(s) of support from heads of all other departments and institutions in which any research work will be done
Evidence of current active registration with the Medical Council of Malawi for the PI and other investigators
Investigator(s) CV(s)

MWI-1 further indicates that the proposal should not be submitted unless every item on the checklist is included, or unless a reason can be provided for the absence of any item. The completed checklist must be attached to the front of the submission. See the G-COMREC and MWI-1 for more information.

Clinical Protocol

As delineated in the G-CTAProcsVacBiol, the clinical protocol should comply with the format provided in the ICH's GCP guidelines. Per MWI-25, clinical trials in Malawi are required to follow the ICH's Guideline for Good Clinical Practice E6(R2) (MWI-22). In addition, MWI-60 provides recommended items to address in a clinical trial protocol and related documents, based on SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidance.

Per the G-HlthResConduct, MWI-60, MWI-1, and MWI-22, the following elements should be included in the protocol (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Cover page
General information (protocol title, identifying number, and date; registry name; contact information for the sponsor, medical expert, investigator(s), trial site(s), qualified physician(s), and laboratory and/or institutions involved in the study, along with role responsibilities)
Protocol summary/abstract
Background and justification
Investigator(s) CV(s) and contact information
IP description (See the Investigational Products topic for detailed coverage of this subject)
Form, dosage, route, method, and frequency of administration and treatment period
Summary of potential risks and known benefits to research participants
Hypothesis
Trial objectives and purpose
Study setting
Trial design, random selection method, and blinding level
Work plan/Gantt chart
Participant selection/withdrawal, timeline, and sample size
Participant treatment
Safety and efficacy assessments
Literature review
Adverse event reporting requirements (See the Safety Reporting section for additional information)
Statistics and methods to track trial data
Sponsor specifications for direct access to source data/documents
Quality control/quality assurance procedures and practices
Data monitoring, including composition of a data monitoring committee, and auditing
Ethical considerations, including confidentiality, and plans for seeking EC approval
Plans for communicating important protocol modifications to relevant parties
Data management and recordkeeping
Dissemination of findings
Financing and insurance details
Publication policy
Consent form, and information on who will obtain consent
Plans for collection, laboratory evaluation, and storage of biological specimens

For more detailed protocol requirements and recommendations, refer to MWI-60, MWI-22, MWI-1, and the G-HlthResConduct.

5.0

7 (Checklist of Required Documents)

1, 2, 3.2, and Screening Form

5 and 7

5.1

6

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: August 29, 2024

Overview

As stated in the R-HlthResCoord, one (1) of the two (2) government approved ethics committees (ECs), the National Health Sciences Research Committee (NHSRC) or the College of Medicine Research and Ethics Committee (COMREC), must review and approve a clinical trial application prior to the Pharmacy and Medicines Regulatory Authority (PMRA) initiating its review and approval process. Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.

Regulatory Authority Approval

According to the G-CTARevVacBiol, the PMRA review process takes approximately six (6) weeks.

As per the G-CTARevVacBiol and the G-CTAProcsVacBiol, once the dossier is submitted to the PMRA, the application is screened for completeness. According to the G-CTARevVacBiol, the result of the screening will be communicated to the applicant within 10 working days after receipt of the application, and the screening form will be forwarded by fax. The applicant will have 10 working days to forward any outstanding documents to the PMRA. The PMRA’s technical staff then reviews the application or may forward it to an expert or evaluator for scientific review, with an allocated review period of three (3) weeks.

However, the G-CTAProcsVacBiol specifies that the application is evaluated by three (3) PMRA-appointed expert clinical trial reviewers who will provide a written report within 14 days to the designated registration office, also known as the “Focal Point” division. The Focal Point will then collate and present the expert reviews to the PMRA Clinical Trial Review Committee (CTRC). The CTRC then reviews all the available documentation and provides a recommendation for approval or rejection. The PMRA considers the CTRC’s recommendation and issues a written approval or rejection. (Per MWI-34, the guidance in the G-CTARevVacBiol and the G-CTAProcsVacBiol also apply to clinical trials of drugs.)

As stated in the G-ImpExpMP, the PMRA’s processing time for an import permit application is 10 working days.

Ethics Committee Approval

National Health Sciences Research Committee

The G-NHSRC indicates that in the case of an approval with no changes, the chairperson must inform the investigator in writing within seven (7) days. The NHSRC’s timeline for review of research proposals is not otherwise specified in the requirements.

College of Medicine Research and Ethics Committee

According to the G-COMREC, COMREC must ensure that submitted complete proposals are reviewed in a timely manner, i.e., within the month of submission. A written decision is provided to the applicant within two (2) weeks of the meeting at which the decision was made.

5.1 and 5.9

2-6

1-3

5.4

7.0, 7.2, 8.0-8.2

3.5

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: August 29, 2024

Overview

According to the G-CTARevVacBiol, the R-HlthResCoord, and MWI-50, the Pharmacy and Medicines Regulatory Authority (PMRA) requires the applicant to obtain PMRA approval and ethics committee (EC) approval before initiating a clinical trial.

The R-HlthResCoord indicates that before submitting a clinical trial application to the PMRA, the sponsor or principal investigator (PI) must obtain full ethical approval from either of the two (2) National Commission for Science and Technology (NCST)-approved ECs—the National Health Sciences Research Committee (NHSRC) or the College of Medicine Research and Ethics Committee (COMREC).

In addition, as per the D-ImprtRelIMPs, the sponsor should not supply the investigational product (IP) to be used in the clinical trial until the sponsor obtains all required documentation. As stated in the G-ImpExpMP, IP import permit applications should be made by the pharmacist of record for the trial. (See the Manufacturing & Import section for additional information.)

Clinical Trial Agreement

The G-CTAProcsVacBiol requires the sponsor to sign a letter of agreement with the participating institution(s) before the trial begins. In addition, the investigators and the sponsor or the contract research organization must sign an agreement specific to the clinical trial.

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 indicates that the sponsor should obtain the investigator’s/institution’s agreement to:

Conduct the trial in compliance with good clinical practice (GCP), with the applicable regulatory requirement(s), and with the approved protocol
Comply with procedures for data recording/reporting
Permit monitoring, auditing, and inspection
Retain the trial related essential documents until the sponsor informs the investigator/institution these documents are no longer needed

The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.

Clinical Trial Registration

No clinical trials registry exists at this time and there is no stated requirement to register in an international registry.

3

7 (Checklist of Required Documents (Appendices 1, 8, and 10) and CTA Sections 4 and 8)

1, 3.2, and Screening Form

8.0-8.2

3.7

5.6

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: August 29, 2024

Safety Reporting Definitions

In accordance with the G-SAEs-PMRA, the following definitions provide a basis for a common understanding of Malawi’s safety reporting requirements:

Adverse Event (AE) – Any AE associated with the use of a medicine in humans, and which does not necessarily bear a causal relationship to the treatment. This may include an AE occurring in the following circumstances: during use in professional practice; from an overdose, whether accidental or intentional; from drug abuse; from drug withdrawal; and as a result of any failure of expected pharmacological action.
Adverse Drug Reaction (ADR) – A reaction characterized by the suspicion of a causal relationship between the drug and the occurrence.
Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – An adverse experience occurring at any dose that results in death, is life-threatening, requires or extends patient hospitalization, results in persistent or significant disability, is a birth defect or congenital anomaly; or is an important medical event that, based upon appropriate medical judgment, may jeopardize the participant, and may require intervention to prevent one (1) of the listed outcomes.

Safety Reporting Requirements

As stated in the G-SAEs-PMRA, the sponsor or the investigator(s) is required to report all SAEs that meet the Pharmacy and Medicines Regulatory Authority (PMRA)’s reporting requirements as soon as possible (within 24-72 hours) following site awareness using the SAE Form (MWI-12). All deaths that are assessed as definitely, probably, or possibly related must be reported to the PMRA within 24 hours of site awareness, and the SAE Form (MWI-12) must be submitted within three (3) working days of site awareness. See the G-SAEs-PMRA for additional details on reporting timelines for different reportable SAE situations.

The G-NHSRC indicates that the National Health Sciences Research Committee (NHSRC) requires the investigator to submit a written report for any occurrence of an AE. In the event of documented SAEs and any unanticipated problems as documented by the researcher, the NHSRC must terminate the study and order the investigator to follow up with study participants. Per the G-COMREC, AE and SAE reports must also be submitted to the College of Medicine Research and Ethics Committee (COMREC).

Form Completion & Delivery Requirements

As per the G-SAEs-PMRA, all SAEs that meet reporting requirements must be reported to the PMRA on an SAE Form (MWI-12). The G-SAEs-PMRA indicates that the form must be submitted to the PMRA office by email or hand delivered to the offices at the following address:

The Director General
Pharmacy and Medicines Regulatory Authority
P.O. Box 30241
Lilongwe 3, Malawi
Tel: 265-1755166/165
Email: info@pmra.mw, registration@pmra.mw

According to the G-NHSRC, AE reports submitted to the NHSRC must provide the following details:

Title of protocol
NHSRC assigned reference number
Name of investigator
Local affiliating institution for studies originating from outside Malawi
Subject identifier
Date and site/place of event
Description of event (i.e., nature of injury or other adverse occurrence, assessment of severity, and assessment of relationship of the event to the study)
Action taken by the researcher
Signature of the principal investigator (PI)

See MWI-2 for the NHSRC SAE Reporting Form.

6.0

5.7-5.8

1 and 2

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: August 29, 2024

Interim and Annual Progress Reports

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 notes that the investigator should promptly provide written reports to the sponsor and the institutional ethics committee (EC) on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.

According to the G-NHSRC, the National Health Sciences Research Committee (NHSRC) requires an initial submission of a progress report within three (3) months of approval of the study, and an annual report for medium to long-term studies.

The G-COMREC requires that the College of Medicine Research and Ethics Committee (COMREC) follow the progress of studies for which a positive decision has been reached and establish a subcommittee responsible for monitoring ongoing studies. As part of the monitoring process, every approved study must submit annual reports by November 30, regardless of the date of its approval.

As required in MWI-58, the principal investigator (PI) must submit an annual progress report to the Pharmacy and Medicines Regulatory Authority (PMRA). All sections of the Clinical Trial Annual Progress Reporting Form for Investigators (MWI-58) must be completed in typescript and submitted together with accompanying documents to the PMRA Director General at info@pmra.mw. Both hard and soft (electronic) copies must be submitted.

The G-NHSRC and the G-COMREC further state that all approved studies continuing for more than one (1) year are subject to continuing review by the approving EC. As part of this review, applicant(s) are required to submit a progress report describing the number of participants enrolled, any problems that occurred during the prior approval period, any new knowledge regarding the study, and any procedural changes.

See MWI-54 and MWI-8 for the NHSRC and COMREC report forms, respectively.

Final Report

As required by the G-NHSRC and the G-COMREC, the applicant is required to submit a final report to the approving EC when a study is completed.

According to the G-NHSRC, the investigator must submit three (3) copies of the final technical report when submitting written notice of the completion of the study to NHSRC.

Other Considerations

The G-NHSRC states that all data originating from a research study conducted in Malawi are the property of the Malawi Government irrespective of the source of funds for carrying out the study. Therefore, investigators are required to submit copies of their reports to NHSRC for review prior to submitting for publication within or outside of Malawi. Investigators are expected to have plans for disseminating research findings in Malawi.

5.5 and 6.0

5.1, 5.6, and 11

4.10 and 4.13

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: August 29, 2024

As per the D-ImprtRelIMPs and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MWI-22), a sponsor is defined as an individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial. Per MWI-25, clinical trials in Malawi are required to follow MWI-22. MWI-22 goes on to specify that a sponsor-investigator is an individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a participant. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.

In accordance with MWI-22, a sponsor may 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.

A sponsor may be domestic or foreign. As specified in the R-HlthResCoord, a sponsor that is a foreign company, organization, or individual(s), must first be affiliated with a local Malawian institution that is recognized by the National Commission for Science and Technology (NCST) prior to commencing any operations in the country.

7

10.0

1.53, 1.54, 5.1, and 5.2

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: August 29, 2024

Overview

The G-CTAProcsVacBiol specifies that the investigator(s) must be qualified, experienced, and have specific good clinical practice (GCP) training. The principal investigator (PI) should have acted as a sub-investigator in at least one (1) prior clinical study. The investigator must also commit to complying with the clinical trial protocol, have no conflicts of interest, and have no history of GCP noncompliance.

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 provides the following guidance to sponsors on investigator and site selection:

The sponsor is responsible for selecting the investigator(s)/institution(s). Each investigator should be qualified by training and experience and should have adequate resources to properly conduct the trial for which the investigator is selected. If organization of a coordinating committee and/or selection of coordinating investigator(s) are to be utilized in multicenter trials, their organization and/or selection are the sponsor’s responsibility.
Before entering an agreement with an investigator/institution to conduct a trial, the sponsor should provide the investigator(s)/institution(s) with the protocol and an up-to-date Investigator’s Brochure, and should provide sufficient time for the investigator/institution to review the protocol and the information provided.

As stated in the G-CTAProcsVacBiol, all clinical trials must also be conducted in a laboratory that can provide evidence of accreditation with a recognized control authority to conduct the specified test. In the absence of an accreditation authority, proof of Good Laboratory Practice compliance and validation of assay methods should be provided.

Foreign Sponsor Responsibilities

According to the G-NHSRC, foreign researchers must be affiliated to a local institution and provide a supporting letter from the institution as evidence. Additionally, they must have a local collaborator. The R-HlthResCoord further indicates that any foreign-based institution or organization must first be affiliated with a local Malawian institution that is recognized by the National Commission for Science and Technology (NCST) prior to commencing any operations in the country.

Data and Safety Monitoring Board

Although not specified as a sponsor requirement, the G-CTAProcsVacBiol states that a Data Safety Monitoring Board (DSMB) or a similar body must be established and empowered to regularly assess the trial and to recommend a pause or termination of the trial for safety reasons. MWI-22 notes 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.

Multicenter Studies

As delineated in MWI-22, in the event of a multicenter clinical trial, the sponsor must ensure that:

All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor, and given ethics committee (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

7 (Checklist of Required Documents (Appendices 8 and 10) and CTA Sections 4 and 8)

5.1

10

1.25, 5.5, 5.6, and 5.23

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: August 29, 2024

Insurance

As set forth in the G-CTInsurance-MWI, the G-CTAProcsVacBiol, the G-CTARevVacBiol, and the G-COMREC, the sponsor or the investigator(s) are responsible for providing insurance coverage for any unforeseen injury to research participants. Before a clinical trial begins, the sponsor should also provide insurance or indemnify the investigator and the institution against claims arising from malpractice or negligence. See the G-CTInsurance-MWI, the G-CTAProcsVacBiol, the G-CTARevVacBiol, and the G-COMREC for detailed information on when insurance is required.

As per the G-CTInsurance-MWI, the sponsor or the investigator(s) must provide the participants with a no-fault insurance policy and certificate for the duration of the trial, and for five (5) years following the trial’s completion. “No-fault” is defined as insurance for which proof of negligence or other wrongful conduct need not be established. However, the causal connection between the trial and harm, bodily injury, or death must be proven to trigger the obligation to make a compensation payment. The National Health Sciences Research Committee (NHSRC), the College of Medicine Research and Ethics Committee (COMREC), or the Pharmacy and Medicines Regulatory Authority (PMRA)'s Clinical Trial Review Committee are responsible for determining which clinical trials fall within the scope of this requirement.

Per the G-CTInsurance-MWI, obtaining and submitting insurance is a requirement and a prerequisite to obtaining clinical trial ethics and regulatory approval. The insurance documentation must be included as part of the application package submitted to either the NHSRC or COMREC, and the PMRA. As specified in the G-CTAProcsVacBiol, the sponsor or the investigator(s) must also comply with the insurance and compensation requirements delineated in the Association of the British Pharmaceutical Industry’s guidelines (MWI-21 and MWI-20).

The PMRA’s Indemnity Form for Conducting Clinical Trials (Form CT 10) is available at MWI-18.

Compensation

Injury or Death

As specified in the G-CTInsurance-MWI, the G-CTAProcsVacBiol, and the G-COMREC, 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 MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 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.

As per the G-CTAProcsVacBiol, the sponsor must follow the principles set forth in the Association of the British Pharmaceutical Industry’s guidelines (MWI-21 and MWI-20) to comply with Malawi’s participant compensation and treatment requirements due to trial-related injuries. The guidelines state that the sponsor should furnish written assurance to the investigator that the sponsor will agree to pay compensation to participants and/or the legal heirs in the event of trial-related injuries or death. The investigator, in turn, communicates this information to the relevant ethics committees (ECs).

MWI-21 provides several basic principles to guide sponsors in fulfilling their compensation obligations. Compensation should be paid as follows:

When it can be demonstrated that a causal relationship exists between a participant’s injury and participation in a trial
When a child is injured in utero through participation by the child’s mother in a clinical trial
When the injury results in permanent injury or disability to the participant
When there is an adverse reaction to a medicinal product under trial, and injury is caused by a procedure adopted to deal with that adverse reaction

MWI-21 states that the likelihood of an adverse reaction, or the fact that the participant has freely consented (whether in writing or otherwise) to participate in the trial should not exclude the participant from being eligible for compensation. The amount of compensation paid to the participant should be appropriate to the nature, severity, and persistence of the injury. The compensation should also be generally consistent with the amount of damages commonly awarded for similar injuries.

According to MWI-21, the amount paid in compensation should be abated, or in certain circumstances excluded, in light of the following factors (which will depend on the risk level the participant can reasonably be expected to accept):

The seriousness of the disease being treated
The degree of probability that adverse reactions will occur and any warning given
The risks and benefits of the established treatments relative to those known or suspected of the trial medicines

Per MWI-21, in any case where the sponsor agrees to pay the participant, but the two (2) parties differ on what is the appropriate level of compensation, it is recommended that the sponsor agree to seek the opinion of a mutually acceptable independent expert at the sponsor’s own cost. This opinion should then be made available to the participant(s), and the expert’s opinion should be given substantial weight by the sponsor in reaching a decision on the payment amount.

Additionally, any participant claims pursuant to MWI-21, should be made to the sponsor, preferably via the investigator. The participant should include details on the nature and background of the claim, which the sponsor should review expeditiously. The review process may be delayed if the participant requests an authority to examine any medical records relevant to the claim.

Trial Participation

Per G-BioSampCompense, participants may also be reimbursed for trial-related expenses, if allowed by the EC. However, payments to participants that are construed to affect the voluntary participation of the subjects are not allowed. Furthermore, lump sum payments for research participation are not allowed. Participants who incur direct costs from trial participation must be reimbursed if required by the EC. Such reimbursable expenses include travel and communications costs associated with routine clinical trial evaluations. During review of the protocol, the EC will make a case-by-case determination if the study should provide any form of acceptable recompense.

(b)(ii) and (b)(iii)

9.0

7 (Checklist of Required Documents (Appendix 9), CTA Section 5, CTA Section 9, and Check of Appended Documents (Appendix 9))

1, 2, 3.2, and Screening Form

1.0-3.0 and 7.0

3 and 4

4.8 and 5.8

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: August 29, 2024

Quality Assurance/Quality Control

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 guides sponsors on quality, data, and records management.

Per MWI-22, 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, identification of processes and data that are critical to ensure participant protection and the reliability of trial results
Identification of risks to critical trial processes and data
Evaluation of the identified risks against existing risk controls
Decisions on which risks to reduce and/or which risks to accept
Documentation of quality management activities and communication to those involved in or affected by these activities
Periodic review of risk control measures to ascertain whether the implemented quality management activities are effective and relevant
In the clinical study report, a description of the quality management approach implemented in the trial and a summary of important deviations from the predefined quality tolerance limits and remedial actions taken

Monitoring Requirements

As part of its quality assurance system, the G-CTAProcsVacBiol notes that the sponsor should perform a clinical trial audit. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, standard operating procedures (SOPs), and other applicable regulatory requirements. The sponsor should appoint auditors to review the clinical trial. The sponsor should ensure that the auditors are qualified by training and experience, and the auditor’s qualifications should be documented. The sponsor must also ensure that the audit is conducted in accordance with the sponsor’s own SOPs, the auditor observations are documented, and data are available as needed for the Pharmacy and Medicines Regulatory Authority (PMRA) to review. No specific timeframe is provided for the audit process.

Per MWI-22, 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 on-site monitoring, a combination of on-site 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).

Per MWI-61, the PMRA may conduct good clinical practice (GCP) inspections of clinical trial sites before regulatory approval, while the trial is ongoing, when participants are being enrolled in a trial, on a routine basis, when triggered by a complaint, or if there is a suspicion of serious non-compliance integrity issues and/or scientific/ethical misconduct. In general, the inspectee will be notified one (1) to four (4) weeks prior to the proposed announced inspection date and asked to confirm availability. The notification will identify the study and the proposed sites to be inspected. In relation to triggered inspections, the PMRA may provide a shorter notice period. The inspection dates will be confirmed with the inspectee, who may be required to submit information to the PMRA within 14 days of the receipt of the notice of GCP inspection. The inspection plan is finalized by the PMRA before the inspection. See MWI-61 for more information on PMRA GCP inspections.

Premature Study Termination/Suspension

According to MWI-22, 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 ethics committee (EC) should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor. Refer to MWI-17 for the National Health Sciences Research Committee (NHSRC)’s protocol termination form.

The G-COMREC states that if a study is prematurely suspended/terminated, the applicant should notify the College of Medicine Research and Ethics Committee (COMREC) of the reasons for suspension/termination, and a summary of the results obtained should be communicated to the committee.

6.0

7 (CTA Section 8)

4.0 and 6.2-6.3

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

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: August 29, 2024

Electronic Data Processing System

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). As per MWI-22, 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. 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 system 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 MWI-22 for additional information.

Records Management

As set forth in MWI-22, sponsor-specific essential documents should be retained until at least two (2) years after the last approval of a marketing application, until there are no pending or contemplated marketing applications, or at least two (2) years have elapsed since the formal discontinuation of the investigational product’s clinical development. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.

In addition, MWI-22 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.

According to MWI-15, consent forms must be kept for three (3) years after the completion of the investigation, unless otherwise stipulated by the National Health Sciences Research Committee (NHSRC).

1.65, 5.5, and 8

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: August 29, 2024

Responsible Parties

For the purposes of data protection requirements, as stated in the G-DataPrtct-MWI, the data controller means a natural or legal person who, alone or jointly with another natural or legal person, determines the purpose and means of processing personal data. The data processor means a natural or legal person who processes personal data on behalf of a data controller. The Malawi Communications Regulatory Authority (MACRA) regulates the processing of personal data and is responsible for the enforcement of the G-DataPrtct-MWI.

Data Protection

A data controller and data processor must process personal data lawfully, fairly, and in a transparent manner, as described in the G-DataPrtct-MWI. Additionally, a data controller and data processor must collect personal data for a specific and legitimate purpose and must not process the data in a manner that is incompatible with the purpose for which it was collected. They also must not store personal data for a period that is longer than necessary to achieve the purpose for which the data is processed, except where the data is stored for the purpose of archiving for public interest or for research or statistical purposes. The appropriate technical or organizational security measures must be implemented to guarantee the security of personal data, including protection against unauthorized or unlawful processing and accidental loss, destruction, or damage of the data.

See the G-DataPrtct-MWI for more details on the duties of a data controller and data processor.

Consent for Processing Personal Data

The G-DataPrtct-MWI indicates that a data controller must obtain the consent of a data subject before processing the personal data of the data subject. Where a data controller seeks consent from a data subject on several matters in the form of a written declaration, each matter on which consent is sought must be presented in a clearly distinguishable manner. A data subject may, at any time, withdraw consent given to a data controller and the withdrawal of the consent shall, where practicable, be in the same manner the consent was provided. The withdrawal must not affect the legality of the data processing that occurred before the withdrawal of the consent. Where a question arises on whether consent was freely provided, consideration must be taken of whether the performance of a contract between the data controller and the data subject, or the delivery of a good or a service by the data controller to the data subject, is conditional on provision of the consent.

According to the G-DataPrtct-MWI, a data controller must, at the time of collecting personal data from a data subject, provide the following information to the data subject:

The identity and contact details of the data controller or representative of the data controller
The legal basis for processing the personal data
The purpose for processing the personal data
Where possible, the storage period for the personal data
The existence of automated decision-making, including profiling
The rights of the data subject provided in the G-DataPrtct-MWI (described below)
The right to lodge a complaint with the MACRA
Whether the data controller intends to transfer the personal data to a place outside Malawi

As per the G-DataPrtct-MWI, a data subject has the right to obtain confirmation of whether personal data concerning the data subject is being processed by the data controller or data processor. Where the data controller or data processor confirms the processing of the personal data of the data subject, the data controller or data processor must provide the data subject with a copy of the personal data being processed (i) in a commonly used electronic format; (ii) within 30 days of receipt of the request; and (iii) where practicable, at no expense to the data subject. The data subject also has a right to data portability, rectification of personal data, erasure of personal data, restriction of processing personal data, object to the processing of personal data, and not to be subject to a decision based solely on automated processing. See the G-DataPrtct-MWI for more information on these rights.

Children and Incapacitated Persons

The G-DataPrtct-MWI delineates that where a data subject is a child or any other natural person lacking the legal capacity to exercise the rights of the data subject, a parent or legal representative/guardian of the data subject must exercise the rights of the data subject on behalf of the data subject. A data controller or data processor who intends to process personal data of a data subject who is a child or any other natural person lacking legal capacity to provide consent must obtain the consent from a parent or legal representative/guardian of the data subject. Additionally, the data controller or data processor who obtains such consent must put in place appropriate mechanisms to verify the age of the child or the mental capacity of the other natural person, as well as the identity of the parent or legal representative/guardian providing the consent.

Parts I (2), II (4-5), III (8-17), IV, and V

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: August 29, 2024

Obtaining Consent

In all Malawian clinical trials, a freely given informed consent is required to be obtained from each participant in accordance with the requirements set forth in the G-NHSRC and G-COMREC-IC. The G-BioSampCompense also confirms that a participant’s voluntary informed consent is required. Also, per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22).

As per the G-NHSRC, the G-CTAProcsVacBiol, the G-CTARevVacBiol, the G-COMREC, and MWI-22, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by one (1) of the two (2) National Commission for Science and Technology (NCST)-approved ethics committees (ECs)—the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC)—and provided to the Pharmacy and Medicines Regulatory Authority (PMRA) with the clinical trial application. (See the Required Elements section for details on the contents to be included in the form.)

The G-NHSRC, the G-COMREC-IC, and MWI-22 state that the participant or legal representative/guardian must be provided with detailed research study information. Per the G-NHSRC, the ICF content should be presented orally and in writing, in a manner that is easy to understand, commensurate with the comprehension level of the research participants, and without coercion. When drafting and presenting the ICF, special consideration must be taken with regard to the participant’s culture, traditional values, intelligence, and education.

As per the G-NHSRC and MWI-22, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or the legal representative/guardian to waive or appear to waive the participant’s legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence. The G-BioSampCompense also confirms that researchers must not duly induce participants to participate in any proposed research. Rather, they must design and implement their studies in a manner that calls for the participants’ informed voluntary consent to participate.

Re-Consent

According to MWI-22, the written ICF and any other written information to be provided to participants should be revised whenever important new information becomes available that may be relevant to the participant’s consent. Any revised written ICF and written information should receive the EC's approval/favorable opinion in advance of use. The participant or legal representative/guardian should be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participation in the trial. The communication of this information should be documented, and the participant or legal representative/guardian should receive a copy of the signed and dated ICF updates, including a copy of any amendments to the written information provided to the participants.

Language Requirements

As stated in the G-NHSRC, the G-COMREC, and the G-COMREC-IC, the ICF should be written in English and any other relevant local languages that the participant is able to understand.

Documenting Consent

The G-NHSRC and MWI-22 specify that the participant or legal representative/guardian must sign the ICF. The G-NHSRC indicates that where the participant is illiterate, the NHSRC will permit the participant to provide a thumbprint in the presence of a witness, who must also sign the ICF. NHSRC also permits the participant to provide verbal consent in cases where the participant is illiterate. However, the script or information sheet to be read to the potential participant must be approved by NHSRC and signed for by the participant’s legal representative/guardian.

MWI-22 states that where the participant is illiterate or 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 provided to the participant is read and explained to the participant and the legal representative/guardian
The participant and the 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.

According to MWI-15, consent forms must be kept for three (3) years after the completion of the investigation, unless otherwise stipulated by the NHSRC.

Waiver of Consent

Per the G-NHSRC, the NHSRC may waive the requirement for the investigator to obtain a signed ICF in cases where circumstances warrant such a waiver. The following conditions may be considered for a waiver:

The research presents no more than a minimal risk of harm to the participants and involves no procedures for which written consent is normally required outside of the research context
The research could not practically be carried out without the consent waiver and obtaining informed consent is not practicable
The consent document is the only link between the participant and the research and the principal risk of harm would come from a breach of confidentiality
Waiver is consistent with the individual’s rights

The G-NHSRC indicates that in lieu of a signed ICF, the NHSRC may require the investigator to provide participants with a written statement regarding the research in the form of an information or fact sheet. This statement should contain, at a minimum:

A statement verifying that the project involves research
A description of the level of involvement and amount of time expected from participants
A description of the study
A description of the risks and benefits to the participants
A statement describing the participant’s rights
A description of the compensation to be provided to participants
Contact information for both the investigator and NHSRC chairperson

(b)(i)

5.0

7 (Checklist of Required Documents (Appendix 4), CTA Section 10, and Check of Appended Documents (Appendix 4))

Screening Form

5.1, 6.2, 7.0, and 7.4

2, 4.4, 4.8, 8.2, and 8.3

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: August 29, 2024

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 provides guidance on the elements to include in the informed consent form (ICF). The G-NHSRC and MWI-22 state that information about the research study should be clearly presented in both written and oral form.

Based on the G-NHSRC, the G-COMREC-IC, the G-NHSRC-ICF, MWI-22, and MWI-13, the 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 title, purpose, procedures, and duration
Experimental aspects of the study
The responsibilities and expected duration of the participant's participation
The trial treatment(s) and the probability for random assignment to each treatment
Any expected risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
Any expected benefits to the participant, others, or to the country as a whole that may reasonably be expected from the research
Description of procedures, including data collection, that will be followed
Identification of any experimental procedures
Disclosure of alternate procedures or treatments available to participants that might be advantageous to the participant
Compensation and/or treatment available for the participant in the case of trial-related injury
The anticipated prorated payment, if any, to the participant for participating in the trial
The anticipated expenses, if any, to the participant for participating in the trial
That participation is voluntary, and that the participant can refuse to participate or withdraw from the study at any time without penalty or loss of benefits, including medical treatment, to which the participant is otherwise entitled
That the monitor(s), the auditor(s), the ethics committee (EC), and the regulatory authority(ies) will be granted direct access to the participant's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the participant, to the extent permitted by the applicable laws and regulations and that, by signing a written ICF, the participant or the participant's legally acceptable representative is authorizing such access
The extent to which confidentiality of records identifying the participant will be maintained
Name and contact details of institutions that have approved the study
Contact information for the sponsor and investigator in the event of participant problems or trial-related injuries
EC contact information
Foreseeable circumstances under which the investigator(s) may remove the participant without the participant’s consent
The consequences of a participant’s decision to withdraw from the research, and procedures for orderly withdrawal by the participant
That the participant or legal representative/guardian will be notified in a timely manner if significant new findings develop during the course of the study which may affect the participant's willingness to continue
Any additional costs to the participant that may result from participation in the research
The site of the study
Consent and signature or thumb print, including the last sentence, which should explicitly read “I voluntarily agree”

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

5.1, 6.2, 7.0, and 7.1

4.4 and 4.8

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: August 29, 2024

Overview

Per the G-NHSRC, Malawi’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 MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22), which addresses participant rights.

(See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.)

The Right to Participate, Abstain, or Withdraw

As set forth in the G-NHSRC, the G-COMREC-IC, and MWI-22, the 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 G-NHSRC, the G-COMREC-IC, and MWI-22, 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. (See the Required Elements section for more detailed information regarding participant rights.)

The Right to Privacy and Confidentiality

As per the G-NHSRC, the G-COMREC-IC, and MWI-22, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. 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 G-NHSRC, the G-COMREC-IC, and MWI-22 state that the research participant or legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries and/or to appeal against a violation of the participant’s rights. (See the Required Elements section for more detailed information regarding participant rights.)

The Right to Safety and Welfare

The Malawi government complies with MWI-22 principles that state 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.

2, 6.2, and 7.1

2, 3.1, and 4.8

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: August 29, 2024

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 makes provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by medical emergencies.

Per MWI-22, in an emergency, if the signed informed consent form (ICF) has not been obtained from the research 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 ethics committee (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.

As per the G-NHSRC, a waiver of consent may be justified if the research being conducted could not practically be carried out without the consent waiver, and obtaining informed consent is not practicable. See the Documentation Requirements section for more information on waiver of consent.

7.4

4.8

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: August 29, 2024

Overview

As per the G-NHSRC, in all Malawian 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-NHSRC characterizes vulnerable populations as those who are relatively or absolutely incapable of protecting their own interests due to illiteracy, a lack of education, autonomy, resources, or other necessary attributes. These participants may include children, pregnant women, prisoners, refugees, orphans, sex workers, people living with HIV and AIDS, persons with mental disabilities, and persons in dependent relationships (e.g., some women who culturally must ask their husbands before consenting to participate in a research study).

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 includes the following as vulnerable populations: 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 populations include persons in nursing homes, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

The G-NHSRC specifies that National Health Sciences Research Committee (NHSRC) members must pay special attention to protecting participants who are from vulnerable populations. Consent for those who are not legally, mentally, and physically able should be sought from their legal representative/guardian in the form of a signature or thumbprint.

As per the G-NHSRC, trials involving vulnerable persons require the research to be directly related to the specific conditions of the vulnerable population involved, and that the participants should personally benefit from the research. In addition, the following elements must be considered when studies are conducted using vulnerable populations:

The methods of recruitment, selection, and inclusion/exclusion criteria, as well as informed consent, data confidentiality, and the participant’s willingness to volunteer
Group characteristics such as economic, social, physical, environmental, and cultural conditions
Applicable local laws that bear on the decision-making abilities of potentially vulnerable participants
Research studies involving potentially vulnerable population groups should have adequate procedures in place for assessing and ensuring participants’ capacity, understanding, and informed consent or assent
Safeguards may include NHSRC monitoring of the consent process where possible

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

5.2, 7.0, and 9.2

1.61 and 4.8

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: August 29, 2024

The G-NHSRC states that a minor is a person less than 18 years of age. When the research participant is a minor, assent must be obtained in tandem with permission from the parent/legal guardian.

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 states that when a clinical trial includes minors, the minors should be informed about the trial to the extent compatible with their understanding and, if capable, they should sign and personally date the written informed consent.

Assent Requirements

As per the G-NHSRC, assent must be obtained from a minor who is deemed capable of providing assent. The National Health Sciences Research Committee (NHSRC) bases its assessment of a minor’s ability to assent on the minor’s age, maturity, and psychological state. In certain cases, the NHSRC may regard assent by minors to represent informed consent without requiring the permission of a parent/legal guardian. A typical case is when the minors are emancipated, and may include those that are legally married or are university students under the age of 18.

7.0 and 9.2

4.8

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: August 29, 2024

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 states that 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.

4.8

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: August 29, 2024

No information available regarding consent requirements for prisoners.

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: August 29, 2024

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 states that when a clinical trial includes participants with mental impairment (e.g., those with severe dementia), the participants should be informed about the trial to the extent compatible with their understanding and, if capable, they should sign and personally date the written informed consent.

The G-NHSRC states that consent for those who are not mentally able should be sought from their legal representative/guardian in the form of a signature or thumbprint.

7.0

1.61, 3.1, and 4.8

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: August 29, 2024

As delineated in the D-ImprtRelIMPs and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22), an investigational product (IP) (also referred to as an investigational medicinal product (IMP) in Malawi) is defined as a pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial. This includes a product with a marketing authorization when it is used or assembled (formulated or packaged) in a different way from the approved form, when used for an unauthorized indication, or when used to gain further information about an approved use. Per MWI-25, clinical trials in Malawi are required to follow MWI-22.

7

1.33

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: August 29, 2024

Manufacturing

According to the PMRAAct, the D-ImprtRelIMPs, and the G-CTARevVacBiol, the Pharmacy and Medicines Regulatory Authority (PMRA) is responsible for authorizing the manufacture of investigational products (IPs) (also referred to as an investigational medicinal products (IMPs)) in Malawi.

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 requires IPs to be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP) and used in accordance with the approved protocol. See MWI-11 for the PMRA’s GMP inspection application form.

Import

As stated in the PMRAAct, the D-ImprtRelIMPs, and the G-ImpExpMP, the PMRA is also responsible for authorizing the import of IPs. Per the PMRAAct and the G-ImpExpMP, the PMRA’s authorization is issued as an import permit. The G-ImpExpMP designates the principal investigator of a registered clinical trial as an authorized importer. IP import permit applications should be made by the pharmacist of record for the trial.

As per the G-CTAProcsVacBiol and the G-CTARevVacBiol, the applicant may apply for an import permit at the same time that the clinical trial application is submitted to the PMRA. (Per MWI-34, the guidance in the G-CTAProcsVacBiol and the G-CTARevVacBiol also apply to clinical trials of drugs.)

The G-ImpExpMP further states that upon receipt of an import application, the PMRA will conduct an assessment to verify whether the requirements, as described in the G-ImpExpMP, have been fulfilled. If the application meets the prescribed requirements, the applicant will be required to pay applicable import permit fees (See the Regulatory Fees section) and the PMRA will issue an import permit. In the case that an application has been rejected, the applicant will be issued a rejection letter (see Annex 2 of the G-ImpExpMP) stating clearly reason(s) for rejection. The regulatory processing time for an import permit application is 10 working days. The import permit will be valid for six (6) months, not transferable to any other person, and may be extended for a period not exceeding three (3) months upon successful application to the PMRA. For additional information on general import application requirements, see the G-ImpExpMP.

Per the D-ImprtRelIMPs, shipping of IPs should be conducted according to instructions given by or on behalf of the sponsor in the shipping order. A pre-clearance inspection should be carried out at the port of entry by the PMRA. The sponsor must complete the cover sheet contained in Annex 1 of the D-ImprtRelIMPs for the importation and release of IPs. Please note: Malawi is party to the Nagoya Protocol on Access and Benefit-sharing (MWI-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 MWI-35.

1, 3, 5, and Annex 1

3, 5, and 7 (Checklist of Required Documents (Fees), and Check of Appended Documents (Fees))

2.1 and 3.2

Part II (Section 4), Part V (Section 58), and Part X (Section 96)

1, 3.1, 3.3-3.5, 3.7, and Annex 2

2.12 and 5.13

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: August 29, 2024

Investigator's Brochure

In accordance with the G-CTAProcsVacBiol and the G-CTARevVacBiol, the Malawi government requires the sponsor to provide investigators with an Investigator’s Brochure (IB). Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 specifies that the IB must contain all of the relevant information on the investigational product(s) (IPs) (also referred to as investigational medicinal products (IMPs) in Malawi) obtained through the earlier research phases, including preclinical, toxicological, safety, efficacy, and adverse event data. The sponsor should also update the IB as significant new information becomes available.

As specified in MWI-22, the IB must include the following sections:

Table of Contents
Summary
Introduction
Physical, Chemical, and Pharmaceutical Properties and Formulation
Nonclinical Studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
Effects in Humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; and regulatory and post-marketing experiences)
Summary of Data and Guidance for the Investigator(s)

See MWI-22 for detailed content guidelines.

Quality Management

MWI-60 requires that an Investigational Medicinal Product Dossier (IMPD) or alternative be submitted in the clinical trial application to the Pharmacy and Medicines Regulatory Authority (PMRA). The IMPD must include information on the quality of any IP, the manufacture and control of the IP, and data from non-clinical studies and from its clinical use.

As per the G-CTAProcsVacBiol, the G-CTARevVacBiol, and the D-ImprtRelIMPs, the PMRA requires the following documents to accompany the IP (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Evidence of manufacture under conditions compliant with current good manufacturing practice (GMP)
A release of specifications and tests, including a Certificate of Analysis (CoA) for each batch of IPs, as well as comparator(s), if applicable
A copy of the PMRA’s letter of approval of the clinical trial
Batch release certificate
A copy of a valid Certificate of Manufacture issued by the competent authority in the country of origin
A copy of a valid World Health Organization certificate of a pharmaceutical product issued by the competent authority in the country of origin

The D-ImprtRelIMPs states that the CoA should identify the product name or code; the sponsor/company name; batch numbers; expiration dates; date of issue; signature, qualification, and title of responsible person; and the results of physical and analytical tests. Per MWI-22, the sponsor must maintain a CoA to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.

The sponsor should complete the cover sheet in Annex 1 of the D-ImprtRelIMPs, include it with each IP shipment, and use the checklist in Annex 2 to ensure the required documentation is attached. As delineated in the D-ImprtRelIMPs, the sponsor should also prepare IP shipping instructions, including information about the shipment’s overall physical condition, for PMRA review and approval. The sponsor should provide information on the acceptable storage temperatures and storage conditions.

5, 6, Annex 1, and Annex 2

7 (Checklist of Required Documents (Appendices 2 and 10) and CTA Section 3)

3.2 and Screening Form

5.13, 5.14, 7, and 8.2

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: August 29, 2024

Investigational product (IP) labeling in Malawi must comply with the requirements set forth in the D-ImprtRelIMPs. The D-ImprtRelIMPs states that for an IP to be used in a clinical trial, it must be properly labeled in the official language of the country where the trial is being conducted.

As set forth in the D-ImprtRelIMPs, the following labeling information must be included on the outer packaging or on the immediate packaging when there is no outer packaging:

Wording that clearly indicates the IP is clinical trial material
Product name or unique code
Storage temperature and conditions
Expiration date
Sponsor contact details

Additionally, the G-ImpExpMP provides the following minimum labeling requirements for all imported medicines and/or active pharmaceutical ingredient (API):

The information printed on labels must be indelible, engraved, or embossed on a primary and secondary container
The immediate outer packaging of the medicine or API should be clearly labeled in English
The trade or brand name where applicable should be stated
The International Non-Proprietary Name (INN, generic name) should be clearly stated
State quantities of each API in the given formulation or quantities of the raw material
Date of manufacture and expiry or retest date in case of active raw materials
Batch or lot number
Storage conditions
Name and address of manufacturer
Registration number of the product issued by the Pharmacy and Medicines Regulatory Authority (PMRA) in both outer and inner package of the product(s) where applicable
Enclosed and accompanying literature must be in English
The specification of the API is given according to officially recognized pharmacopoeia, where applicable

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). The D-ImprtRelIMPs and MWI-22 state that the IP must be coded and labeled in a manner that protects the blinding, if applicable.

5.13

4

3.3

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: August 29, 2024

Supply, Storage, and Handling Requirements

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MWI-22). As defined in the D-ImprtRelIMPs and MWI-22, the sponsor must also supply the investigator(s)/institution(s) with the investigational product(s) (IP(s)), including the comparator(s) and placebo, if applicable. The sponsor should not supply either party with the IP(s) until after obtaining Pharmacy and Medicines Regulatory Authority (PMRA) and ethics committee approvals.

The D-ImprtRelIMPs and MWI-22 indicate that IPs must be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage. Additionally, 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):

IP product quality and stability over the period of use
IP is manufactured according to any applicable good manufacturing practice (GMP)
Proper coding, packaging, and labeling of the IP(s)
Records are maintained for document shipment, receipt, disposition, return, and destruction of the IP(s)
Acceptable storage temperatures, conditions, and times for the IP

Timely delivery of the IP(s)
Written procedures are established, including instructions for handling and storage of the IP(s), adequate and safe receipt of the IP(s), dispensing of the IP(s), retrieval of unused IP(s), return of unused IP(s) to the sponsor, and disposal of unused IP(s) by the sponsor
Sufficient quantities of the IP(s) are maintained to reconfirm specifications, should this become necessary

Refer to the D-ImprtRelIMPs for detailed sponsor-related IP requirements.

In addition, the PharmG-InvestDrugs states that the pharmacist at each clinical trial site, designated as the Pharmacist of Record, is the primary individual who is expected to develop and maintain an IP control system, which includes the technical procedures for product ordering, control, dispensing, and accountability. In addition, the Pharmacist of Record is responsible for the establishment of internal policies and procedures for the safe and proper use of IPs. The Pharmacist of Record will perform the day-to-day dispensing and accountability activities. A pharmacy plan must be created by the Pharmacist of Record for each clinical research site, addressing the control and use of IPs. See the PharmG-InvestDrugs for more information.

Record Requirements

In accordance with the D-ImprtRelIMPs, the sponsor is required to maintain a system for retrieving IP(s) and document this retrieval process (e.g., for deficient product recall, reclaim after trial completion, expired product reclaim). The sponsor must also maintain a system for the disposition of unused IP(s) and for the documentation of this disposition. Finally, the sponsor should maintain sufficient quantities of the IP(s) used in the trial to reconfirm specifications, should this become necessary, and maintain records of batch sample analyses and characteristics. Moreover, 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.

G-GMP-MWI requires that for IPs, the batch documentation must be retained for at least five (5) years after the completion or formal discontinuation of the last clinical trial in which the batch was used. Additionally, the G-ImpExpMP indicates that upon issuance of import authorization by the PMRA, the importer is expected to retain such records for five (5) years from the date of importation, either as hard or electronic copies. Stored import records should be easily accessible and availed for review to the PMRA’s inspector/officers for any post-import audit or investigations.

1, 3, 4, and 5

2.2.4

Pharmacy Plan

3.3

2.12, 5.5, 5.12-5.14, and 7

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: August 29, 2024

In Malawi, as per the G-StorExptSpecimens, specimens are defined as human or animal materials, collected directly from humans or animals, including, but not limited to excreta, secreta, blood and its components; tissue and tissue fluid swabs; and body parts being transported for purposes such as research and investigational activities.

Specimens are also referred to as human materials or biological products. The G-StorExptSpecimens defines human material as all biological material of human origin, including organs, tissues, bodily fluids, teeth, hair, nails, and substances extracted from such material as DNA or RNA.

Please refer to G-StorExptSpecimens for more specific definitions for selected terms including genetically modified micro-organisms and infectious substances.

5.4-5.6

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: August 29, 2024

Import/Export

As delineated in the G-CTAProcsVacBiol, MWI-14, and MWI-7, the applicant must obtain approval from the Pharmacy and Medicines Regulatory Authority (PMRA) to import and export human biological specimens into and out of Malawi. The G-CTAProcsVacBiol notes that the applicant may apply to the PMRA for permission to import and/or export materials at the same time that the applicant submits the clinical trial application.

The G-StorExptSpecimens specifies that the sponsor is responsible for shipping specimens, for preparing the required documentation (e.g., nationally authorized import/export permits and dispatch/shipping documents), and for ensuring that the samples collected from research participants are sent through the appropriate carrier to their destination. The sponsor may delegate these functions to the principal investigator (PI). Refer to Annex 1 of the G-StorExptSpecimens for a checklist to be completed by the PI for the proper storage and export of clinical trial samples. As per the G-StorExptSpecimens, the transport of specimens is subject to regulation by the International Air Transport Association.

In cases where investigators are unable to complete all required research tests in Malawi, MWI-14 and MWI-7 state that justification must be provided for the importation and exportation of samples.

Per the G-GenResReqs, the National Health Sciences Research Committee (NHSRC) requires investigators who wish to export biological/genetic materials to apply for a transfer under a material transfer agreement (MTA) that must be reviewed, approved, and signed for by NHSRC. The investigator must provide a satisfactory description of how the privacy and confidentiality of the individuals and communities and the safety of such materials will be maintained. Furthermore, an investigator is not permitted to transfer biological/genetic material to another research group locally and internationally unless NHSRC has approved a collaborative study between the two (2) parties and the material and information provided protects the participants. Additionally, as stated in the SciTechOrder, an NCST-issued license is required for the collection, storage, and use of human samples for research. The SciTechOrder does not specify whether the process of obtaining an NCST-issued license is separate from the NHSRC requirements described above.

Material Transfer Agreement

MWI-14, MWI-16, and MWI-7 indicate that the PMRA, the NHSRC, and the College of Medicine Research and Ethics Committee (COMREC) must ensure a MTA is in place that includes the following:

Intention of the importation and exportation of samples
Duration and location of storage
Appropriate informed consent authorizing the exportation and importation
Person(s) who will have access to the samples
The controlling officer of the samples
Ownership of the samples
Capacity building (only applicable for MWI-7)

See MWI-14, MWI-16, and MWI-7 for the PMRA, NHSRC, and COMREC MTA forms, respectively.

The G-BioSampCompense also confirms that MTAs remain an instrument to be used by a researcher in requesting the approval of an ethics committee (EC) for the transfer of samples for analysis outside of Malawi.

Other Considerations

According to the G-GenResReqs and MWI-6, COMREC and NHSRC-approved samples can be stored for a maximum of five (5) years during which time all tests/analyses approved for that particular study should be concluded. MWI-6 further states that if the sample is to be used beyond five (5) years, an updated authorization must be provided, which will last another five (5) years before it can be renewed. Per G-BioSampCompense, while samples are primarily allowed to be stored as long as they are needed for the initial study, leftover samples are also permitted to be stored as long as needed for a research endeavor. See G-BioSampCompense for additional details regarding EC approval requirements.

(a)(iv) to (ix)

3, 5, and 7 (Checklist of Required Documents (Fees))

4.12

3, 6.4, and Annex 1

Consent for Specimen