Clinical Research Regulation For DRC and India

Last content review/update: November 27, 2024

Overview

According to D-ACOREP, the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention) is the regulatory authority responsible for regulating clinical trials, as well as authorizing and controlling drug imports and exports, in the Democratic Republic of the Congo (DRC). In addition, the G-EthicalEval indicates that an ethics committee (EC) must review the scientific validity and ethical acceptability of any research proposal involving human subjects.

As per the G-EthicalEval, the study protocol must be submitted to the EC for review concurrently with a request to ACOREP for study authorization and registration. Therefore, regulatory and ethics reviews are conducted in parallel. However, ACOREP approval is contingent upon EC approval. Per DRC-12, ACOREP accepts ethics review from any approved local EC.

Clinical Trial Review Process

DRC-12 states that upon receiving a clinical trial application, ACOREP screens it for completeness. The G-EthicalEval indicates that in the event of a favorable opinion from the EC, ACOREP decides whether to approve the trial. If the EC issues an adverse opinion, ACOREP cannot authorize the study.

Per DRC-12, ACOREP issues a decision on approving or denying complete applications within 30 days. The decision is sent to the principal investigator (PI) by email, or the PI can pick up a hard copy of the decision at the secretariat of ACOREP.

Title II (Articles 3-4)

Guidelines 4 and 5

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)

Regulatory Fees

Last content review/update: November 27, 2024

Congolese Pharmaceutical Regulatory Authority (ACOREP)

According to DRC-12, the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention) charges a fee for the submission of a clinical trial application, in accordance with a fee schedule. Applicants should contact ACOREP for the fee schedule.

Payment Instructions

No information is available regarding payment instructions.

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

Ethics Committee

Last content review/update: November 27, 2024

Overview

According to the G-EthicalEval, any research proposal in the Democratic Republic of the Congo (DRC) involving human participants must be submitted for evaluation of its scientific validity and ethical acceptability to an ethics committee (EC). An EC may be established under the auspices of national or local health authorities, national (or centralized) medical research councils, or other national representative bodies. Additionally, the EC must be independent of the research team and approved by the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention).

Order1250-ZKM043 indicates that the purpose of the DRC’s national EC, the National Committee of Health Ethics (Comité National d'Éthique de la Santé (CNES)), is to review proposals for research on human beings based on the ethical principles of respect for the individual, beneficence, and justice. The CNES is also responsible for promoting the creation of and accrediting institutional ECs across the country, among other duties.

Ethics Committee Composition

The G-EthicalEval indicates that an EC should be made up of physicians, scientists, and representatives of other groups, such as nurses, lawyers, ethicists, and non-professionals, who are able to represent the cultural and moral values of the community and uphold the rights of the research participants. An EC must include both men and women.

According to the G-EthicalEval, to ensure the EC is composed of members that have experience as well as new members with a fresh perspective, a certain number of EC members may be renewed periodically. In addition, to ensure the independence of ECs and to avoid any conflict of interest, any members of the committee having special interests, direct or indirect, in a research proposal must exclude themselves from the evaluation of the proposal.

National Committee of Health Ethics (CNES)

As per Order1250-ZKM043, the CNES has 40 members, including:

One (1) delegate per province from institutional ECs
Scientific individuals (at most 10)
Religious individuals (at most five (5))
A delegate from the Order of Physicians
A delegate of the Order of the Pharmacists
A delegate from other health professional associations
A delegate from the Health Administration

Additionally, Order1250-ZKM043 states that CNES members are recruited on the basis of the following criteria:

Proven moral and scientific reputation
Professional experience of at least five (5) years
Practical training in bioethics
Great availability
Community leadership

Order1250-ZKM043 further indicates that CNES’ mandate is five (5) years, which is renewable once. The CNES is governed by an office composed of a president, a vice-president, a secretary-rapporteur, a deputy secretary-general, and a treasurer, all elected by and from among the members. The government’s Public Health authority appoints members of the office.

Terms of Reference, Review Procedures, and Meeting Schedule

The G-EthicalEval states that the EC’s written procedures must define all EC operating standards.

According to the G-EthicalEval, an EC must clearly define the roles necessary for smooth ethical evaluation. The different roles within the EC (such as president and secretary), the requirements of each role, the terms and conditions of attaining a role, and the duties and responsibilities associated with the roles must be detailed in writing.

As per the G-EthicalEval, EC members should receive basic training and access to continuing education on the ethical and scientific aspects of biomedical research. The conditions of appointment should detail the arrangements for providing EC members with initial training on the EC's work, as well as opportunities to strengthen their expertise in conducting an ethics review. These provisions should also include the requirements or expectations for basic and continuing education of EC members. This training can be carried out in the context of cooperation with other ECs in the country or region, and also on other occasions favorable to the basic training and the continuous training of the EC’s members.

The G-EthicalEval indicates that the EC is responsible for establishing well-defined procedures for submitting an application for review. These procedures, as well as any standard forms, must be public and available to applicants. In order to aid researchers, it is desirable that these procedures and forms be harmonized among all the active ECs in the country.

The G-EthicalEval requires that ECs establish specific quorum requirements to review a proposal and make a decision. These requirements must include or specify at least the following:

The minimum number of members required to reach a quorum
The professional qualifications required and distribution of these requirements within the quorum
No quorum shall be composed exclusively of members of the same profession or the same sex
The quorum must include at least one (1) member whose primary area of expertise is not scientific and at least one (1) independent member of the institution or research site

The G-EthicalEval further requires that an EC meet regularly, on scheduled dates announced in advance in a publicly available calendar. The meeting requirements must include or specify at least the following:

Meetings should be scheduled according to a pre-established schedule, which can be modified according to the workload
EC members should have sufficient time, defined before the meeting, to review submitted documents
Meetings must be documented in minutes, and there must be a procedure for approval of the minutes
The applicant, the sponsor, and/or the investigator may be invited to present their proposal or to elaborate on certain specific points
Independent consultants may be invited to the meeting or provide written comments, subject to the confidentiality agreements in force
The EC must send its opinion within 15 days of the meeting

National Committee of Health Ethics (CNES)

According to Order1250-ZKM043, the CNES’ operating mode and the frequency of meetings are determined by internal regulations previously submitted to the Minister of Health for review. The CNES operates in committees and may create, as needed, ad-hoc subcommittees for specific problems. Additionally, the CNES may call upon any resource person whose expertise or experience can be used to resolve or address a problem. The CNES draws up its action plan and activity reports and is subject to the authority of the Ministry of Health, to which it reports.

Guidelines 5, 6, 9, 10, 12, 13, and 15

Title I (Articles 1 and 2), Title II (Article 4), Title III (Articles 6-10), and Title IV (Articles 11-14)

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

Scope of Review

Last content review/update: November 27, 2024

Overview

The G-EthicalEval indicates that the main task of an ethics committee (EC) is to review research proposals and supporting documents, with particular attention to the process of obtaining informed consent, documentation, and the relevance and feasibility of the protocol. The EC must take into account previous scientific and ethical assessments, if any, and the requirements of applicable laws and regulations. An EC may perform its function at the institutional, local, regional, or national level.

According to the G-EthicalEval, ECs are responsible for protecting the rights of research participants, their safety, and their well-being. ECs must act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants; confirming the suitability of the investigator(s), facilities, methods, and scientific design of the study; assessing the participant recruitment process; and verifying the adequacy of confidentiality and privacy safeguards.

Role in Clinical Trial Approval Process

According to the G-EthicalEval, the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention)’s Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) and the EC must approve a clinical trial application for research involving human participants prior to the sponsor or the principal investigator (PI) initiating the clinical trial. The G-EthicalEval further specifies that the PI must submit the request for ethics review. Per DRC-12, ACOREP accepts ethics review from any approved local EC.

As per the G-EthicalEval, the study protocol must be submitted to the EC for review concurrently with a request to ACOREP for study authorization and registration. Therefore, regulatory and ethics reviews are conducted in parallel. The EC must communicate its opinion on the protocol to the PI. A copy of the EC’s opinion should be sent to ACOREP. EC approval of the protocol must be obtained before ACOREP may approve the trial. In the event of a favorable opinion from the EC, ACOREP decides whether to approve the trial. If the EC issues an adverse opinion, ACOREP cannot authorize the study. However, the PI may resubmit the protocol to the EC after modifying the elements that led to the adverse opinion.

According to the G-EthicalEval, ECs must establish procedures for expedited review of research proposals. These procedures must address certain processes, including the nature of the requests, amendments, and other considerations acceptable for expedited review, as well as the quorum requirements for expedited review.

As per the G-EthicalEval, ECs must also establish a procedure for monitoring the progress of all research that has been approved, from the date the decision was made to the end of the research. The follow-up intervals should be determined by the nature of the study and other events, although each protocol should be monitored at least once a year during the recruitment period. The EC must review and approve any protocol amendments prior to those changes being implemented.

The G-EthicalEval also indicates that the PI must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3).

There is no stated expiration date for an EC approval in the G-EthicalEval.

(See the Submission Process section for detailed submission requirements.)

1.25, 4, 5.5

Guidelines 4, 5, 13, 16, 17, 20, 33, and 35

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

Ethics Committee Fees

Last content review/update: November 27, 2024

According to the G-EthicalEval, an ethics committee (EC) may charge a fee for the ethical and scientific evaluation of research protocols, to be directed toward its operating costs. The fee must be a predetermined public rate and should not exceed 2% of research costs, excluding the cost of investment. Applicants should contact ECs individually for specific fees and payment instructions.

Guideline 5

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

Oversight of Ethics Committees

Last content review/update: November 27, 2024

Overview

Order1250-ZKM043 indicates that the Democratic Republic of the Congo’s (DRC) national ethics committee (EC), the National Committee of Health Ethics (Comité National d'Éthique de la Santé (CNES)), is responsible for promoting the creation of and accrediting institutional ECs across the country.

According to Order1250-ZKM043, the CNES coordinates the national network of institutional ECs, both public and private, throughout the country, and mobilizes funds for the functioning of the network of ECs.

Registration, Auditing, and Accreditation

No information is available on registration, auditing, and accreditation responsibilities by the CNES.

Title II (Article 4)

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

Submission Process

Last content review/update: November 27, 2024

Overview

Per D-ACOREP and the G-EthicalEval, the Democratic Republic of the Congo (DRC) requires clinical trial authorization from the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention). According to DRC-12, the sponsor, through the principal investigator (PI), obtains this authorization from ACOREP. In addition, the G-EthicalEval indicates that the PI is required to obtain approval from an ethics committee (EC) for any research proposal involving human subjects. The study protocol must be submitted to the EC for review concurrently with a request to ACOREP for study authorization and registration. Therefore, regulatory and ethics reviews are conducted in parallel. However, ACOREP approval is contingent upon EC approval.

Regulatory Submission

Per DRC-12, ACOREP’s delivery address is:

Ministère de la Santé Publique, Hygiène et Prévention
Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)
4ème niveau, immeubles 5 à sec, boulevard du 30 juin
Kinshasa I, B.P. 11998, République Démocratique du Congo

Ethics Review Submission

The G-EthicalEval indicates that the EC is responsible for establishing well-defined procedures for submitting an application for review, including requirements for language and assembly. These procedures, as well as any standard forms, must be public and available to applicants. In order to aid researchers, it is desirable that these procedures and forms be harmonized between all the active ECs in the country. Applicants should contact ECs individually for specific submission instructions.

According to a subject matter expert as of March 2019, research protocols and relevant materials to be submitted to the national EC, the National Committee of Health Ethics (Comité National d'Éthique de la Santé (CNES)), should be sent to:

National Committee of Health Ethics
Local 5, Immeuble PNMLS, 1er Niveau, Commune of Kasa-Vubu
Kinshasa, Democratic Republic of the Congo

Per a subject matter expert as of March 2019, CNES requires one (1) copy of the dossier, in addition to seven (7) copies of the protocol. Documents submitted to CNES must be in French.

Title II (Articles 3-4)

Guidelines 4, 5, and 13

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)

Submission Content

Last content review/update: November 27, 2024

Regulatory Authority Requirements

Per DRC-12, the following documents are required in a clinical trial application to the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention):

Cover letter
Non-refundable application fee in accordance with ACOREP’s prescribed fee schedule
Application forms completed by ACOREP for the conduct of clinical trials and signed by authorized persons (principal investigator (PI) and authorized representative of the sponsor)
Clinical trial protocol
Proof of enrollment in a clinical trial registry
Investigator's brochure (IB)
Investigational product (IP) dossier
Certificate of good manufacturing practice (GMP)
Certificate of good clinical practice (GCP) and PI curriculum vitae (CV) for each site
Ethics committee (EC) approval
Insurance cover
Financial statement
Data and Safety Monitoring Board (DSMB) information and signed charter
Sponsor/PI contractual agreement
Informed consent and assent forms (if applicable)
Statistical analysis plan (SAP)
Material transfer agreement (if applicable)
Labeling materials

According to DRC-12, applications submitted to ACOREP should also comply with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3).

Ethics Committee Requirements

As specified in the G-EthicalEval, the PI must file the request for ethics review. The requirements for the submission must be clearly described in the EC’s application procedures. These requirements must include or specify at least the following:

Name(s) and address(es) of the secretary of the EC or the member(s) to whom the application is to be filed
Application form(s), made available by the EC, with a list of the documentation requested by the EC
Format of the application, clearly referring to the title, date, and version of the protocol
Documentation, the study protocol, the informed consent form (ICF), the IB, the PI's CV, and the certificate of insurance obtained
Language(s) in which the (essential) documents are to be filed
Number of copies to be filed
Application deadlines, based on review dates (15 days prior to the meeting)
Means by which the receipt of applications will be acknowledged, including communication regarding incomplete applications
Deadline for notification of the decision after examination (within 15 days)
Time limit in case the EC requests additional information or changes to the documents from the PI
Application examination fee, if applicable
Standard procedure for requesting amendments to the protocol

As per the G-EthicalEval, the following documentation must be submitted to the EC for the proposed research:

Application form dated and signed by the PI
Proposed research protocol (clearly identified and dated), describing objectives, data collection procedures, ethical considerations, and details of the research process
Supporting documents for information not detailed in the protocol
When the research involves a product under study (such as a drug or medical device), an adequate summary of all available safety, pharmacological, pharmaceutical, and toxicological data available on the product being evaluated, as well as a summary of the clinical experience gained to date on this product
Current CVs of the investigator(s), dated and signed
Planned means (including classified advertising) for the recruitment of potential research participants, if not described in the protocol
Description of the procedure to obtain the informed consent of the subjects according to the degree of instruction, if not sufficiently described in the protocol
Information pamphlet (clearly identified and dated) and other forms of information for potential participants, in the language(s) understood by them and, if necessary, in other languages
ICF (clearly identified and dated) in the language(s) understood by potential participants and, if necessary, in other languages
Statement regarding possible compensation for research subjects, for their participation (including reimbursement of expenses and access to medical care), if not sufficiently described in the protocol
Description of arrangements made, if any, for compensation for injury, if not sufficiently described in the protocol or certificate of insurance
A copy of the sponsor’s insurance policy, for the insurance coverage of the participants (if in a language other than French, a translation into French must also be provided)
Statement by the investigator committing to respect the ethical principles set out in the applicable guidelines, if not sufficiently described in the protocol
Any significant prior decisions made by other ECs or regulatory authorities regarding the research in question (whether in the same research site or another) and an indication of the change(s) made to the protocol in this regard (reasons for previous adverse decisions must be provided)
Any other information, such as the establishment of a Tolerance Data Monitoring Committee, also known as DSMB or Independent Committee

Clinical Protocol

According to the G-EthicalEval, the protocol should be prepared by the researcher(s) and contain a summary of the project, general information, a brief justification of the project, bibliographical references, and a documentary review. The protocol should describe the goals and objectives of the study, as well as its design and the methodology used. In addition, the protocol should address safety or tolerability considerations, monitoring, statistical data management and analysis, quality assurance, expected results and dissemination, and publication policy.

The G-EthicalEval further requires that the protocol provide guidance on the duration of the project and anticipated problems, project management and ethical considerations, the documents used to gather informed consent from subjects, the budget and funding agencies, and collaborators. Finally, the protocol should attach the CV of each researcher, listing all the projects in which the researcher is currently participating, and the percentage of time to be devoted to the project. Possible financing or insurance arrangements should also be specified in documents presented to the EC.

Additionally, DRC-3 requires the following protocol contents:

General information (protocol title, identifying number, and date; contact information for the sponsor, medical expert, investigator(s), trial site(s), qualified physician(s), and laboratory and/or institutions involved in the study)
Background information
Objectives and purpose
Trial design
Selection, withdrawal, and treatment of participants
Assessment of efficacy
Assessment of safety
A description of the statistical methods to be used in the trial
Direct access to source data and documents
Quality control and quality assurance
Ethical considerations
Data handling and recordkeeping
Publication policy

6

Guidelines 4, 5, 13, and Glossary

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)

Timeline of Review

Last content review/update: November 27, 2024

Overview

As per D-ACOREP, the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention) is the regulatory authority responsible for regulating clinical trials in the Democratic Republic of the Congo (DRC).

The G-EthicalEval indicates that for research involving human subjects, the study protocol must be submitted to an ethics committee (EC) for review concurrently with a request to ACOREP for study authorization and registration. Therefore, regulatory and ethics reviews are conducted in parallel. However, the principal investigator (PI) must obtain the EC’s approval of the protocol before ACOREP may approve the trial.

Regulatory Authority Approval

No official timelines are specified in the available regulatory documentation.

Ethics Committee Approval

As per the G-EthicalEval, the EC must communicate its opinion on the protocol to the PI within 15 days of making a decision, and send a copy to ACOREP.

The G-EthicalEval further requires that ECs establish procedures for expedited review of research proposals. These procedures must address certain processes, including the nature of the requests, amendments, and other considerations acceptable for expedited review, as well as the quorum requirements for expedited review.

There is no stated expiration date for an EC approval in the regulatory resources referenced for the DRC.

Title II (Articles 3-4)

Guidelines 4, 5, 13, and 17

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

Initiation, Agreements & Registration

Last content review/update: November 27, 2024

Overview

As per D-ACOREP and the G-EthicalEval, the Democratic Republic of the Congo (DRC) requires clinical trial authorization from the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention). According to DRC-12, the sponsor, through the principal investigator (PI), obtains this authorization from ACOREP. As stated in the G-EthicalEval, for research proposals involving human participants, the PI must also obtain approval from an ethics committee (EC) before ACOREP can approve the trial. Per DRC-12, ACOREP accepts ethics review from any approved local EC.

According to DRC-12, an import license is required for the shipment of the investigational product (IP) to be used in the trial. The sponsor may apply for IP import approval through ACOREP’s Digital Platform (DRC-13). (See the Manufacturing & Import section for additional information).

Clinical Trial Agreement

The G-EthicalEval states that before submitting a clinical trial application, a memorandum of understanding must be developed between the sponsor or PI and the partner research institutions. The PI must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3).

As per DRC-3, the sponsor should obtain the investigator's/institution's agreement to:

Conduct the trial in compliance with 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

As per DRC-12, proof of enrollment in a clinical trial registry is a required element of a clinical trial application to ACOREP.

5.6

Title II (Articles 3-4)

Guidelines 4 and 5

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)

Safety Reporting

Last content review/update: November 27, 2024

Safety Reporting Definitions

As delineated in the G-PV, the following definitions provide a basis for a common understanding of the Democratic Republic of the Congo’s (DRC) safety reporting requirements:

Adverse Event (AE) – Any medical event occurring after the administration of a drug to a patient or subject of a clinical trial, without necessarily being caused by that drug. This includes any harmful and unwanted reaction such as a clinical or paraclinical sign or symptom, or a disease associated with taking a drug
Adverse Drug Reaction (ADR) – Any response to the administration of a drug that is harmful and undesirable. An ADR may result from the use of a drug at therapeutic doses, overdose, misuse, or medication error
Serious Adverse Event (SAE) – Any adverse reaction that causes death, is life-threatening, requires hospitalization or prolongation of hospitalization, leads to significant or persistent disability, or causes congenital malformation
Unexpected Adverse Event (UAE) – Any adverse event that does not match the known information on the drug in nature, severity, or outcome

According to the G-PV, the requirements in the G-PV are based on the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). The G-EthicalEval further indicates that before the start of the trial, the principal investigator (PI) must ensure adequate safety reporting procedures in accordance with DRC-3 and the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10).

Order1250-SP013 states that the DRC’s National System of Pharmacovigilance, implemented by the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention), aims to identify as early as possible all of the adverse effects of health products, especially those that are serious and unexpected. The National System of Pharmacovigilance includes the National Pharmacovigilance Center, which is responsible for collecting information from manufacturers, health professionals, and other individuals on the adverse effects of health products; establishing accountability; and assessing the relative risk.

Safety Reporting Requirements

The G-PV indicates that it is mandatory to report any AE, even when it is the result of abuse or misuse. All providers are required to systematically report AEs.

According to G-PV, all AEs that are both serious and unexpected must be reported through the expedited notification process. Any serious and unexpected AE that is fatal or life-threatening, including those occurring during a clinical trial, should be notified to the National Pharmacovigilance Center as soon as the notifier becomes aware of it, within seven (7) calendar days. Updated information may be provided within an additional period not exceeding 15 calendar days. All other serious and unexpected AEs should be reported immediately, but no later than 15 calendar days after becoming aware of them. All other AEs must be reported within 90 calendar days.

In addition, according to DRC-12, SAEs must be reported to the national ethics committee (EC), the National Committee of Health Ethics (Comité National d’Éthique de la Santé (CNES)), or to the EC that approved the study.

Form Completion & Delivery Requirements

As per the G-PV, all AEs must be reported on a form (See Annex I of G-PV) and submitted in a sealed envelope or via internet to the National Pharmacovigilance Center:

Clinical Pharmacology Unit
Faculty of Medicine and Pharmaceutical Sciences
University of Kinshasa
Tel: 0998110172 / 0813261360 / 0993547926 / 0815171991 / 0815171766
Email: cnpvrdc@yahoo.fr and pharmacoclinique@unikin.ac.cd

5.16-5.17

Guideline 35

Introduction, I (I.1), III (III.2 and III.5), and Annex I

Chapter I (Article 2), Chapter III (Article 6), and Chapter VII (Article 18)

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

Progress Reporting

Last content review/update: November 27, 2024

Interim and Annual Progress Reports

The G-EthicalEval also indicates that the principal investigator (PI) must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3).

DRC-3 notes that the investigator should submit written summaries of the trial status to the institutional ethics committee (EC) annually, or more frequently, if requested by the EC. The investigator should also promptly provide written reports to the sponsor and the institutional EC on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.

As per the G-EthicalEval, the EC must establish a procedure for monitoring the progress of all research that has been approved, from the date the decision was made to the end of the research. The follow-up intervals should be determined by the nature of the study and other events, although each protocol should be monitored at least once a year during the recruitment period.

Final Report

According to the G-EthicalEval, the PI must notify the EC of the closure of a study, and the EC should receive a copy of the final summary or final report of the research.

The G-EthicalEval further requires that community leaders receive an adapted report specifically for their understanding, with the relevant information. The results of the clinical trial should be shared with the participants based on the context and budgetary constraints.

4.10 and 4.13

Guidelines 20, 35, and 36

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

Definition of Sponsor

Last content review/update: November 27, 2024

As per the G-EthicalEval, the sponsor is defined as the person, company, institute, or organization responsible for launching, managing, and/or financing a clinical trial, as well as legally responsible for the trial. In non-commercial research, it is often the case that the sponsor and the funding agency are different entities. In this case, the legal responsibility rests with the sponsor.

The G-EthicalEval indicates that for biomedical research on humans, the sponsor is the person who initiates, manages, and verifies the funding of the research.

The G-EthicalEval also indicates that the principal investigator (PI) must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 specifies 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.

DRC-3 also notes that a sponsor may transfer any or all 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.

According to the G-EthicalEval, a sponsor may be domestic or foreign.

1.53, 1.54, 5.1, and 5.2

Guideline 35 and Glossary

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)

Site/Investigator Selection

Last content review/update: November 27, 2024

Overview

According to the G-EthicalEval, the principal investigator (PI) must be a qualified and experienced person in the relevant field of research, with an understanding of the concepts and research activities, the drug, its toxicity, and its safety. The PI reports to the sponsor, as well as to the regulatory authorities and the ethics committees (ECs).

Per the G-EthicalEval, before a trial begins, the PI must:

Be based in the Democratic Republic of the Congo (DRC), with some exceptions
Ensure that the approval of a recognized EC and regulatory authority are obtained, and that the information package developed by the sponsor regarding clinical trials has been read and accepted
Have a good knowledge of the protocol, related documents, and regulatory requirements of the regulatory authority or other regulatory body
Have read, understood, and agreed to work in accordance with the protocol, the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), or other applicable legal and regulatory documents
Use the investigational product (IP) only for the purpose of the study as described in the protocol
Take responsibility for the IP
Document the sequence of events to be followed in the conduct of the clinical trial, including the timeline, roles, and responsibilities
Ensure the availability of all necessary infrastructure, equipment, and finances for the conduct of the test or study
Develop any appropriate mechanism to obtain informed consent from the participant
Accept the involvement of the instructors to review and verify the quality control procedures and the conduct of the data
Accept the possibility of an audit and/or inspection by an independent auditor engaged by the sponsor, the regulator, or the EC
Obtain the right to publish (it is unethical for the sponsor to reserve the right to publish the research data)
Ensure adequate safety reporting procedures, etc. (see DRC-3 and DRC-10)

As per DRC-3, 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 the organization of a coordinating committee and/or the 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 the sponsor should provide sufficient time for the investigator/institution to review the protocol and the information provided.

Foreign Sponsor Responsibilities

The G-EthicalEval requires that if a sponsor is a foreign person or entity, the sponsor must work closely with the PI(s) from the partner institution(s) with which the sponsor has signed a memorandum of understanding. Each PI, who must be based in the DRC, in turn works with one (1) or more local investigators at their site.

Data and Safety Monitoring Board

The G-EthicalEval indicates that, as appropriate, the EC should evaluate the adequacy of the arrangements made for monitoring and auditing research, including setting up a Data and Safety Monitoring Board (DSMB). Any information regarding the establishment of a DSMB should also be included in the documentation submitted to the EC in the clinical trial application packet. Per DRC-12, any DSMB information must also be included in the clinical trial application to the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention).

DRC-3 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 DRC-3, 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 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

The G-EthicalEval also states that a coordinating investigator should be appointed to coordinate activities of PIs at each site of a multicenter trial.

1.25, 4, 5.5, 5.6, and 5.23

Guidelines 13, 16, and 35

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)

Insurance & Compensation

Last content review/update: November 27, 2024

Insurance

As per the G-EthicalEval, the sponsor is required to carry a valid insurance policy to cover research participants. A copy of the sponsor’s insurance policy must be submitted to the ethics committee (EC) as part of the application for ethics review of the proposed research. If the insurance policy is in a language other than French, a French translation must also be provided.

Per DRC-12, insurance cover documentation must also be included in the clinical trial application to the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention).

Compensation

The G-EthicalEval indicates that the principal investigator (PI) must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 provides guidance for sponsors on providing compensation to research participants.

Injury or Death

The G-EthicalEval indicates that the clinical trial application packet submitted to the ethics committee (EC) must include a description of arrangements made, if any, for compensation for injury, if not sufficiently described in the protocol or certificate of insurance.

DRC-3 states that the sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries.

Trial Participation

As per the G-EthicalEval, the application packet submitted to the EC must also include a statement regarding possible compensation for research subjects for their participation (including reimbursement of expenses and access to medical care), if not sufficiently described in the protocol.

4.8 and 5.8

Guidelines 13 and 35

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

Risk & Quality Management

Last content review/update: November 27, 2024

Quality Assurance/Quality Control

The G-EthicalEval indicates that the principal investigator (PI) must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 provides guidance for sponsors on clinical trial quality management.

Per DRC-3, the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:

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

Monitoring Requirements

Per DRC-3, 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).

Premature Study Termination/Suspension

The G-EthicalEval indicates that in the event of suspension or premature termination of a trial, the PI must inform the ethics committee (EC) of the reasons for the decision. A summary of the results up to that point must then be submitted to the EC.

According to DRC-3, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the EC should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor.

5.0, 5.1, 5.2, 5.5, 5.18, 5.19, 5.21, and 6.10

Guidelines 20 and Glossary

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)

Data & Records Management

Last content review/update: November 27, 2024

Electronic Data Processing System

The G-EthicalEval indicates that the principal investigator (PI) must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 provides guidance for sponsors on clinical trial data and records management.

As per DRC-3, 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 DRC-3 for additional information.

Records Management

According to the G-EthicalEval, the research protocol should address monitoring, statistical data management and analysis, quality assurance, expected results and dissemination, and publication policy.

As set forth in DRC-3, 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, DRC-3 states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.

1.65, 5.5, and 8

Guidelines 20 and Glossary

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)

Personal Data Protection

Last content review/update: November 27, 2024

Responsible Parties

As per the DigiCode, the data controller is a natural or legal person, public authority, agency, or other body which, alone or jointly with others, determines the purposes and means of the processing of personal data. The representative of the data controller is a natural or legal person permanently established in the territory of the country, who replaces the data controller in fulfilling the obligations provided for in the DigiCode. Additionally, the data controller must appoint a data protection officer to ensure that any processing of personal data is not likely to infringe on the rights and freedoms of the data subjects. The data protection officer is responsible for ensuring, in an independent manner, the internal application of the provisions of the DigiCode, and for keeping a register of the processing carried out by the data controller.

Additionally, the DigiCode provides for the establishment of the Data Protection Authority (APD), which will be responsible for monitoring compliance with the DigiCode provisions related to the processing of public and personal data hosted in the Democratic Republic of Congo (DRC). As of November 2024, there is no information available on the establishment of the APD. See the DigiCode for more information on the APD.

Data Protection

As stated in the DigiCode, personal data must be treated confidentially and protected, in particular when the processing involves transmissions of data over a network. The personal data must be kept in a form that permits identification of the persons concerned for a period not exceeding that necessary to achieve the purposes for which they are collected or for which they are processed. Personal data may be kept for longer periods to the extent that they will be processed exclusively for archival purposes in the public interest, for scientific or historical research purposes, or for statistical purposes, provided that the appropriate technical and organizational measures are implemented to guarantee the rights and freedoms of the person concerned. The personal data collected must be reliable, adequate, relevant, accurate, complete, and not excessive. All appropriate measures must be taken to ensure that data that is inaccurate or incomplete, in relation to the purposes for which it was collected or for which it is subsequently processed, is erased or rectified.

According to the DigiCode, the processing of personal data is subject to a prior declaration to the APD. The declaration, which includes an undertaking that the processing meets the requirements of the DigiCode, is made by the data controller or their representative. Additionally, the processing of personal data relating to genetic and medical data, as well as scientific research in these areas, requires prior authorization from the APD before any implementation. The intended transfer of personal data to a third country also requires prior authorization. The request for authorization is submitted by the data controller or their representative. See the DigiCode for more information on declarations and authorizations.

The DigiCode indicates that the request for declaration or authorization may be sent to the APD electronically, by post, or by any other means where the receipt is acknowledged by the APD. The APD will make a decision within 30 days of receipt of the request for declaration or authorization. This period may be extended once by 30 days upon reasoned decision of the APD. If the declaration or authorization requested from the APD is not made within the prescribed period, the silence of the APD will be deemed to be acceptance. In the event of refusal by the APD, the data controller may appeal within 15 days of notification of the refusal decision.

The DigiCode states that the processing of personal data is carried out within the framework of respect for human dignity, privacy, and public freedoms. The processing of personal data, whatever its origin or form, must not infringe the rights of persons protected by the laws and regulations in force and it is, in all cases, prohibited to use this data to harm persons or their reputation. Additionally, the personal data must be processed in a manner that ensures appropriate security, including protection against unauthorized or unlawful processing and against accidental loss, destruction or damage, using appropriate technical or organizational measures.

See the DigiCode for more information on the responsibilities of the data controller and the data protection officer.

Consent for Processing Personal Data

The DigiCode indicates that the processing of personal data will be lawful only to the extent that the data subject has consented to the processing of their personal data or if the processing is necessary for the performance of a legal obligation to which the controller is subject. If the data subject is incapable of giving consent, consent is governed by the principle of common law.

Per the DigiCode, where processing is based on consent, the controller must be able to demonstrate that the data subject has given consent for the processing of their personal data. Where the data subject's consent is given in the context of a written statement which also concerns other matters, the request for consent must be completed in a form which clearly distinguishes it from these other matters, in a comprehensible and easily accessible manner, and formulated in clear and simple terms. The data subject has the right to withdraw consent at any time, by the same means used to give it. Withdrawal of consent will not affect the lawfulness of processing based on consent prior to its withdrawal. The data subject must be informed of this before giving consent. Withdrawal should be as simple as giving consent. When determining whether consent is freely given, the utmost regard should be given, among other things, to whether the performance of a contract (including the provision of a service) is subject to consent for personal data processing, but such processing is not necessary for the performance of that contract.

According to the DigiCode, the data subject may request from the controller:

Information allowing them to know and contest the processing of their personal data
Confirmation as to whether or not personal data concerning them are being processed, as well as information on the purposes of the processing; the categories of data to which it relates and the categories of recipients to whom the data is communicated; the recipients or categories of recipients to whom the personal data have been or will be communicated, where possible; and the existence of automated decision-making, including profiling, and, at least in those cases, meaningful information about the logic involved, as well as the significance and envisaged consequences of such processing for the data subject
The communication in intelligible form of personal data concerning them, as well as any available information as to the origin of such data
Where applicable, information relating to the transfers of personal data envisaged to a third party, after consultation with APD
Where possible, the envisaged period for which the personal data will be retained or, where this is not possible, the criteria used to determine that period
The existence of the right to request from the controller rectification or erasure of personal data, or restriction of processing of personal data concerning the data subject, or to object to such processing
The right to lodge a complaint with the competent authority
Any available information as to their source, where the personal data are not collected from the data subject

See the DigiCode for additional details on data subject rights.

Preliminary Book (Article 2), Book I (Articles 15-18), and Book III – Digital Content (Articles 187, 189-194, 196, 209-216, 222, and 262-270)

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

Documentation Requirements

Last content review/update: November 27, 2024

Obtaining Consent

For any biomedical research involving humans in the Democratic Republic of the Congo (DRC), the investigator must obtain the free and informed consent of the prospective participant in accordance with the requirements set forth in the G-EthicalEval, the Declaration of Helsinki (DRC-11), the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), and the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10).

As per the G-EthicalEval and DRC-3, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an ethics committee (EC). The G-EthicalEval further states that when reviewing the informed consent process, the EC should review the arrangements for receiving and responding to requests and complaints from research participants or their representatives during the course of a study. (See the Required Elements section for details on what should be included in the form.)

In addition, DRC-3 states that that the participant or legal representative/guardian must be provided with detailed research study information. None of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or to appear to waive their 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-EthicalEval indicates that in the process of obtaining informed consent, sponsors and investigators must refrain from unjustified deception, attempts to exert undue influence, or intimidation. The sponsor and investigator may solicit consent only after making sure that the potential participant understands the details of participation and has been given time to consider it.

Re-Consent

The G-EthicalEval indicates that when material changes occur in the modalities or procedures of a study, or periodically for long-term studies, the investigator must again seek the informed consent of the participants. Sponsors and investigators have a duty to obtain the informed consent of each participant in the event of a significant change in the terms and conditions of the research, or if new information emerges that may affect the willingness of the participants to continue. For example, new pieces of information may have emerged from the study or from other sources (other studies or pharmacovigilance) about the risks or benefits of the products being investigated or about products to replace them. If it changes the risk, then this information must be promptly communicated to the participants. However, the results of the study will be disclosed at the end of the research after analysis of the data.

The sponsor and investigator must also seek renewed informed consent for each participant in long-term studies at predetermined intervals, even if there is no change in the design or objectives of the research.

Language Requirements

The G-EthicalEval requires that the ICF be provided in the language(s) understood by potential participants and, if necessary, in other languages. The investigator must convey the information in the informed consent process, orally and in writing, in a language that corresponds with the level of understanding of the participant. The investigator should also consider that the participant’s ability to understand the information required to express informed consent depends on the maturity, comprehension ability, level of education, and belief system of the participant.

Documenting Consent

According to the G-EthicalEval and DRC-3, the participant or legal representative/guardian must sign the ICF. The G-EthicalEval states that it is advisable to give participants information sheets to keep that may be similar to ICFs, but do not require a signature. The EC must approve the content of the informed consent material. When consent has been obtained orally, investigators are required to provide documentation or evidence of consent.

The G-EthicalEval indicates that if the participant is illiterate, an independent witness must sign the consent. DRC-3 further specifies that where the participant is illiterate or the legal representative/guardian is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:

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

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

Waiver of Consent

The G-EthicalEval states that the EC may authorize, in extraordinary cases, the waiver of a signed consent form, such as in a case where the existence of a signed consent form would constitute an unreasonable threat to the privacy of the participant.

2, 4.4, 4.8, 8.2, and 8.3

Guidelines 13, 16, 24-26, and 35

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

Required Elements

Last content review/update: November 27, 2024

The G-EthicalEval indicates that the principal investigator must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 provides guidance on the elements to include in the informed consent form (ICF) and states that information about the research study should be clearly presented in both written and oral form.

The G-EthicalEval and DRC-3 state that before seeking the consent of a person to participate in research, the investigator must indicate the following to the person using language or any other form of intelligible communication (Note: the sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each):

That the person is invited to participate in the research as a subject, the reasons for which the person is eligible, and that participation is voluntary
That the person is free to refuse to participate and may at any time terminate participation without being penalized or losing any advantage to which the person would normally have been entitled
The purpose of the research and the procedures to be used by the investigator and the participant, and how the research departs from the usual medical care
For controlled trials, the modalities of the research (randomization, double-blind, etc.) and that the participant will only be informed of the assigned treatment once the study has been completed and the double-blind procedure has ended
The expected duration of participation (including the number and duration of visits to the research center and the resulting total duration) and the possibility of early termination of the trial or participation in the trial
Whether money or other types of material gratuity will be given in return for participation and, if so, their nature and amount
The anticipated expenses, if any, to the participant for participating in the trial
That, after completion of the study, the participant will be informed of the findings of the research in general terms and will be individually informed of any findings regarding the participant’s personal health status
That the participant will be able to access, upon request, data concerning the participant even if these data have no immediate clinical utility
That the participant or legal representative/guardian will be informed in a timely manner if information becomes available that may be relevant to the participant's willingness to continue participation in the trial
All risks, pain, or discomfort foreseeable for the participant (or other persons) arising from participation in the research, including risks to the health or well-being of the spouse or partner of the participant
The reasonably foreseeable risks or inconveniences to the participant and, when applicable, to an embryo, fetus, or nursing infant
Where appropriate, the direct benefits that the participant can expect from participation in the research
The expected benefits of research for the community or society, or the contributions of this research to scientific knowledge
If, when, and how any of the products or interventions that research has shown to be safe and effective will most likely be made available to the participant after ending participation in the research
Any intervention or alternative treatment currently available
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 legal representative/guardian is authorizing such access
The arrangements that will be made to ensure the participant’s privacy and the confidentiality of the files where the participant is identified
The legal or other limitations of the investigators' ability to maintain confidentiality and the potential consequences of breaches of confidentiality
The rules applicable to the use of genetic test results and family genetic information, and the precautions taken to prevent the disclosure of genetic test results of a participant to the close family or to third parties without the participant’s consent
The proponents of the research, the institution to which the investigators report, and the nature and sources of funding for the research
Possible uses, direct or secondary, of the participant’s medical record and biological samples collected as part of clinical care
If it is anticipated that the biological samples taken from the research will be destroyed when the research is completed, and if not, a detailed description of how they will be preserved (where, how, for how long, and how it will be disposed of) and the future uses envisaged, and whether the participant has the right to decide on these future uses, to refuse the conservation, and to demand the destruction of the material in question
Whether commercial products can be derived from biological samples, and whether the participant will receive pecuniary or other benefits from the development of such products
If the investigator's sole function is to be an investigator, or both an investigator and the treating physician of the participant
The extent of the investigator's responsibility for providing medical benefits to the participant
That treatment will be provided free of charge for specified types of physical injury related to research or for research-related complications, the nature and duration of such treatment, the name of the organization or individual treatment, and if there are uncertainties about the funding of the treatment
How and by which organization the participant or family, or dependents of the participant, will be compensated for any disability or death resulting from such bodily injury (or, if applicable, that nothing is provided for this purpose)
That an EC has approved or authorized the research protocol (name and date)
Foreseeable circumstances under which the investigator(s) may remove the participant without the participant’s consent
Approximate number of participants involved in the study
The person(s) to contact for further information regarding the trial and the rights of trial participants, and whom to contact in the event of trial-related injury

The G-EthicalEval further indicates that this list is not exhaustive, and it is recommended to follow the latest edition of DRC-11, DRC-10, and DRC-3.

4.4 and 4.8

Guidelines 25 and 35

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)

Participant Rights

Last content review/update: November 27, 2024

Overview

As delineated in the G-EthicalEval, a participant’s rights must be clearly addressed in the informed consent form (ICF) and during the informed consent process.

In addition, the G-EthicalEval states that the principal investigator (PI) should closely follow the guidelines provided by the Declaration of Helsinki (DRC-11), the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the Council for International Organizations of Medical Sciences’ (CIOMS) International Ethical Guidelines for Biomedical Research Involving Human Subjects (DRC-2).

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

The Right to Participate, Abstain, or Withdraw

As set forth in the G-EthicalEval and DRC-3, the participant should be informed that participation is voluntary, and that the participant may withdraw from the research study at any time without being penalized or losing any advantage to which the participant would normally have been entitled.

The Right to Information

As delineated in the G-EthicalEval and DRC-3, a potential research participant has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, and any potential benefits, risks, or constraints. (See the Required Elements section for more detailed information regarding participant rights.)

The G-EthicalEval further states that information collected during the study should be shared with the indigenous community in the research community. Researchers must consider community input and allow dissenting voices to speak in public if differences of opinion were not resolved earlier.

The Right to Privacy and Confidentiality

According to the G-EthicalEval and DRC-3, the participant should be informed of arrangements that will be made to ensure the participant’s privacy and the confidentiality of the files where the participant is identified.

The Right of Inquiry/Appeal

DRC-3 states 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 G-EthicalEval states that the PI is responsible for the well-being and integrity of the participants. In addition, the principles in DRC-3 state that a research participant’s right to safety and the protection of the participant’s health and welfare must take precedence over the interests of science and society.

2, 3.1, and 4.8

Guidelines 25, 35, and 36

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

Emergencies

Last content review/update: November 27, 2024

According to the G-EthicalEval, the principal investigator must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 makes provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by emergencies.

Per DRC-3, 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 must approve the protocol in advance. The participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

4.8

Guideline 35

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

Vulnerable Populations

Last content review/update: November 27, 2024

Overview

In all clinical trials in the Democratic Republic of the Congo (DRC), research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process in accordance with the G-EthicalEval. Vulnerable populations, which have a limited ability to give informed consent, include children and adolescents, adults with serious mental or behavioral disorders, people with reduced levels of consciousness, pregnant women, prisoners, and socio-economically disadvantaged individuals. Research on these populations must be justified in detail, and efforts must be made to obtain the consent of the legal guardian(s) of these participants.

In addition, the G-EthicalEval requires principal investigators to work in accordance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 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.

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

Indigenous Peoples

According to the G-EthicalEval, special provisions must also be made for research related to the traditional or sacred knowledge of an indigenous community, or its members as indigenous people. The researcher should consult with community leaders and obtain their consent before approaching members individually. After obtaining the consent of the community, the researcher must still make sure to have the prior free and informed consent of each participant.

The G-EthicalEval further states that it is advisable to establish an informed consent process for communities and individual participants early in the research process or authorization, which should take into account the legitimate decision-making processes of communities at all stages of the process.

1.61 and 4.8

Guidelines 24, 28, and 35, and Glossary

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

Children/Minors

Last content review/update: November 27, 2024

According to the FamilyCodeMemo, the age of majority is 18 years old in the Democratic Republic of the Congo (DRC).

The G-EthicalEval recommends that children be included in the decision to participate in research based on their physical, psychological, and social developmental abilities. In addition, the G-EthicalEval requires principal investigators to work in accordance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), which 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, should sign and personally date the written informed consent.

Assent Requirements

As per the G-EthicalEval, a child's ability to give informed assent to participate in research is globally established at the minimum age of 13. The research team should consider the complexity of the research and other aspects to raise this age, but never go below it. A minor’s parent/legal guardian must provide consent for the minor to participate in the research. Once the minor reaches the minimum age of 13, the minor must also give assent. It is therefore necessary to first obtain the consent of the parent/legal guardian, and then the assent of the child.

The G-EthicalEval further indicates that the refusal of the parent/legal guardian or child constitutes dissent and precludes the child's participation in the research.

4.8

Guidelines 27 and 35

Book II (Section 3)

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)

Pregnant Women, Fetuses & Neonates

Last content review/update: November 27, 2024

While G-EthicalEval lists pregnant women as a vulnerable population, there are no relevant provisions regarding any special consent procedures for pregnant women, fetuses, or neonates.

However, the G-EthicalEval requires principal investigators to work in accordance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), which 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

Guidelines 24 and 35, and Glossary

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)

Prisoners

Last content review/update: November 27, 2024

While G-EthicalEval lists prisoners as a vulnerable population, there are no relevant provisions regarding any special consent procedures for them.

Guideline 24 and Glossary

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

Mentally Impaired

Last content review/update: November 27, 2024

While G-EthicalEval lists adults with serious mental or behavioral disorders as a vulnerable population, there are no relevant provisions regarding any special consent procedures for them.

However, the G-EthicalEval requires principal investigators to work in accordance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), which 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.

1.61, 3.1, and 4.8

Guidelines 24 and 35, and Glossary

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)

Definition of Investigational Product

Last content review/update: November 27, 2024

As delineated in the G-PV and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), an investigational product (IP) is defined as a pharmaceutical form of an active ingredient being studied or used as a reference in a clinical trial. This includes products already authorized but used or formulated and packaged in a different way from the authorized version, when used for an unauthorized indication, or when used to gain further information about an approved use.

The G-EthicalEval indicates that the principal investigator must agree to work in accordance with DRC-3.

1.33

Guideline 35

I (I.1)

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)

Manufacturing & Import

Last content review/update: November 27, 2024

As per D-ACOREP and DRC-15, the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention), in collaboration with the relevant foreign trade ministry, is responsible for authorizing and controlling drug manufacture and imports in the Democratic Republic of the Congo (DRC).

The G-EthicalEval requires that the principal investigator agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 requires investigational products (IPs) to be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP) and used in accordance with the approved protocol.

According to DRC-12, an import license is required for the shipment of the IP to be used in the trial. The sponsor may apply for IP import approval through ACOREP’s Digital Platform (DRC-13).

Please note: DRC is party to the Nagoya Protocol on Access and Benefit-sharing (DRC-1), 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 DRC-7.

2.12 and 5.13

Title II (Article 4)

Guidelines 2 and 35

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)

Quality Requirements

Last content review/update: November 27, 2024

Investigator’s Brochure

The G-EthicalEval indicates that the principal investigator must agree to work in accordance with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (DRC-3), which provides detailed Investigator’s Brochure (IB) requirements. DRC-3 specifies that the IB must contain all of the relevant information on the investigational product(s) (IP(s)) 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 DRC-3, 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 DRC-3 for detailed content guidelines.

Quality Management

In accordance with the G-EthicalEval, an applicant must provide the ethics committee (EC) with the following IP information in the clinical trial application submission:

An adequate summary of all safety, pharmacological, pharmaceutical, and toxicological data available on the IP to be evaluated
A summary of the clinical experience to date with this IP (e.g., recent IB, publication(s), and summarized product characteristics)

Per DRC-3, the sponsor must maintain a Certificate of Analysis (CoA) to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.

5.13, 5.14, 7, and 8.2

Guidelines 13 and 35

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

Labeling

Last content review/update: November 27, 2024

The G-EthicalEval requires that the principal investigator agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 provides guidance on labeling of investigational products, stating that they should be coded and labeled in a manner that protects the blinding, if applicable. Per DRC-12, labeling materials must be included in the clinical trial application to the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention).

5.13

Guidelines 2 and 35

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

Product Management

Last content review/update: November 27, 2024

Supply, Storage, and Handling Requirements

The G-EthicalEval requires that the principal investigator agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3).

Per DRC-3, the sponsor must supply the investigator(s)/institution(s) with the investigational product(s) (IP(s)). The sponsor should not supply either party with the IP(s) until the sponsor obtains all required documentation. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

The sponsor must ensure the following:

IP product quality and stability over the period of use
IP manufactured according to any applicable Good Manufacturing Practice (GMP)
Proper coding, packaging, and labeling of the IP(s)
Records maintained for document shipment, receipt, disposition, return, and destruction of the IP(s)
Acceptable storage temperatures, conditions, and times for the IP(s)
Timely delivery of the IP(s)
Written procedures 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
Maintain sufficient quantities of the IP(s) to reconfirm specifications, should this become necessary

Record Requirements

Per DRC-3, the sponsor should comply with the following records requirements:

Maintain records that document shipment, receipt, disposition, return, and destruction of the IP(s)
Maintain a system for retrieving IPs and documenting this retrieval (e.g., for deficient product recall, reclaim after trial completion, and expired product recovery)
Maintain a system for the disposition of unused IP(s) and for the documentation of this disposition

2.12, 5.5, and 5.12-5.14

Guidelines 2 and 35

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

Definition of Specimen

Last content review/update: November 27, 2024

In the G-EthicalEval, a specimen is referred to as a “biological sample.” The G-EthicalEval does not define biological samples, but indicates that they should be considered a loan made to the investigator, unless otherwise specified in the research agreement. This requirement is inspired by the philosophies of the Bantu community on “bodily integrity,” according to which every product and part of the human body is an essential and sacred component of the person. The investigator should therefore be considered the guardian of the samples, rather than the owner.

Guideline 34

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

Specimen Import & Export

Last content review/update: November 27, 2024

Import/Export

In accordance with the G-EthicalEval, the transfer of data or biological samples to a third party requires the consent of the researcher, the participant concerned, and the community. If the data or biological samples are transferred abroad, the applicable authorities often need to be given the Materials Transfer Agreement.

Guideline 33

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

Consent for Specimen