Clinical Research Regulation For India
Regulatory Authority
Regulatory Authority
Scope of Assessment
Regulatory Fees
Ethics Committee
Ethics Committee
Scope of Review
Ethics Committee Fees
Authorizing Body
Clinical Trial Lifecycle
Submission Process
Submission Content
Timeline of Review
Trial Initiation
Safety Reporting
Progress Reporting
Sponsorship
Definition of Sponsor
Trial Authorization
Insurance
Compensation
Quality, Data & Records Management
Site/Investigator Selection
Informed Consent
Documentation Requirements
Required Elements
Compensation Disclosure
Participant Rights
Special Circumstances/Emergencies
Vulnerable Populations
Children/Minors
Pregnant Women, Fetuses & Neonates
Prisoners
Mentally Impaired
Investigational Products
Definition of Investigational Product
Manufacturing & Import
IMP/IND Quality Requirements
Labeling & Packaging
Product Management
Specimens
Definition of Specimen
Specimen Import & Export
QUICK FACTS
Clinical trial application language English
Regulatory authority & ethics committee review may be conducted at the same time Yes
Clinical trial registration required Yes
In-country sponsor presence/representation required Yes
Age of minors Under 18
Specimens export allowed Yes
Regulatory Authority > Regulatory Authority
Last content review/update: March 25, 2021
Requirements
(1) (Legislation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA-DCR) (Amended through December 31, 2016)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: DCA, 1940: Chapter II (5 and 7)
(2) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2), Chapter II (3), Chapter V (19 and 21-22), Chapter XIII (100), Second Schedule (1), and Third Schedule (1)
(3) (Guidance) Handbook for Applicants & Reviewers of Clinical Trials of New Drugs in India (Hdbk-ClinTrial) (January 2017)
Indian Council of Medical Research and Central Drugs Standard Control Organization
Relevant Sections: Preface, 5.1, 5.2, and Appendix 8.3
(4) (Order) Order Regarding Approved Subject Expert Committees (Order13Jan20) (January 13, 2020)
Central Drugs Standard Control Organization
Summary

Overview

As set forth in the 2019-CTRules and the Hdbk-ClinTrial, the Central Drugs Standard Control Organization (CDSCO) is the regulatory authority responsible for clinical trial oversight, approval, and inspections in India. In accordance with the provisions of the 2019-CTRules, the Drugs Controller General of India (DCGI) heads CDSCO, and is responsible for granting permission for clinical trials to be conducted and for regulating the sale and importation of drugs for use in clinical trials. The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.

According to IND-59, CDSCO functions under the Directorate General of Health Services (DGHS), which is part of the Ministry of Health and Family Welfare (MOHFW). Per IND-59 and IND-47, as the Central Drug Authority, CDSCO is responsible for approving new drugs, conducting clinical trials, establishing drug standards, overseeing the quality of imported drugs, providing expert advice, and coordinating the state licensing authorities who regulate the manufacture, sale, and distribution of drugs.

Per the DCA-DCR, the Drugs Technical Advisory Board (DTAB) and the Drug Consultative Committee (DCC) advise the DCGI. IND-16 states that the DTAB, a statutory board, is composed of technical experts who advise the central and state governments on technical drug matters and on making rules. The DCC, a statutory committee, consists of central and state drug control officials who advise the central and state governments and the DTAB to ensure drug control measures are enforced throughout India.

In addition, as indicated in the Hdbk-ClinTrial, Subject Expert Committees (SECs) comprise experts representing the relevant therapeutic areas that are responsible for reviewing the submitted clinical trial applications, investigators’ brochures, and study protocols. 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. In accordance with the 2019-CTRules, with the approval of the MOHFW, Order13Jan20 establishes the terms of reference that CDSCO will use to constitute the SECs from the groups/panels of approximately 550 medical experts with specialization in relevant fields, including the existing members of the SECs from various government medical colleges and institutions. Refer to Regulatory Authority topic, Scope of Assessment subtopic for additional information on the therapeutic areas to be reviewed by the SECs.

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.

Contact Information

Drugs Controller General of India
Central Drugs Standard Control Organization
Directorate General of Health Services
Ministry of Health and Family Welfare
Government of India
FDA Bhavan
ITO
Kotla Road
New Delhi 110002
India
Phone: +91-11-23216367 / 23236975
Fax: +91-11-23236973
E-mail: dci@nic.in

Public Relations Office
Central Drugs Standards Control Organization
Headquarters - Ground Floor
FDA Bhawan
Kotla Road
New Delhi 110002
India
Phone (Toll free for in-country callers): 1 800 11 1454
Email: startupinnov@cdsco.nic.in

Additional Resources
(1) (Article) Indian Regulatory Update: January – March 2018 (IND-4) (July-September 2018)
Bhave, Amita; Perspectives in Clinical Research
Relevant Sections: Office Order Regarding Setting Up of Public Relation Office at CDSCO (HQ)
(2) (Article) Medicines Regulation: Regulatory Systems in India (IND-16) (2017)
Gupta, M. et al; WHO Drug Information
Relevant Sections: Regulatory System
(3) (Document) Nagoya Protocol on Access and Benefit-sharing (IND-29) (2011)
Convention on Biological Diversity, United Nations
(4) (Webpage) Central Drugs Standard Control Organization - About Us (IND-47) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
(5) (Webpage) Central Drugs Standard Control Organization - Contact Us (IND-58) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
(6) (Webpage) Central Drugs Standard Control Organization - Who's Who (IND-62) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
(7) (Webpage) Country Profile: India (IND-45) (Current as of March 25, 2021)
Access and Benefit-sharing Clearing-house, Convention on Biological Diversity, United Nations
(8) (Webpage) SUGAM Portal (IND-59) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
Relevant Sections: About Us
Regulatory Authority > Scope of Assessment
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2), Chapter II (3), Chapter III (11), Chapter V (19-25, and 28), 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)
(2) (Guidance) Handbook for Applicants & Reviewers of Clinical Trials of New Drugs in India (Hdbk-ClinTrial) (January 2017)
Indian Council of Medical Research and Central Drugs Standard Control Organization
Relevant Sections: Preface, 4.0, 5.0, 5.1, 5.2, 5.22, 8.2, and Appendix 8.3
(3) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 4.8 (Table 4.2), 7.0, and 7.1
(4) (Guidance) National Guidelines for Gene Therapy Product Development and Clinical Trials (G-GeneThrpy) (November 2019)
Indian Council of Medical Research, Central Drug Standards Control Organisation, and Ministry of Science and Technology
Relevant Sections: 7.11, and Annexures I, II, and III
(5) (Guidance) National Guidelines for Stem Cell Research (G-StemCellRes) (2017)
Indian Council of Medical Research, Ministry of Science and Technology
Relevant Sections: 4, 11.2, and Annexures I and II
(6) (Notice) Notice Regarding the New Drugs and Clinical Trial Rules 2019 FAQs (Notice18Feb20) (February 18, 2020)
Central Drugs Standard Control Organization
Relevant Sections: 1
(7) (Order) Order Regarding Approved Subject Expert Committees (Order13Jan20) (January 13, 2020)
Central Drugs Standard Control Organization
Summary

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 initiating the trial, except in the case of non-regulatory academic/research clinical trials that only require EC approval. Refer to the Ethics Committee topic, Scope of Review subtopic for detailed information on non-regulatory academic/research clinical requirements.

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.

The 2019-CTRules and IND-31 define 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, 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.

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 and IND-13, 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 Ethics Committee topic, Scope of Review subtopic for more information.)

Clinical Trial Review Process

As specified in the 2019-CTRules, and according to IND-31, IND-17, and IND-18, upon receipt of a clinical trial application (see the 2019-CTRules for Form CT-04), the DCGI has 90 calendar days to evaluate the application for drugs developed outside India and 30 days for drugs discovered, researched, and manufactured in India. If the DCGI does not respond within 30 days to applications for drugs developed in India, the sponsor (applicant) may conclude that permission to conduct the trial has been granted.

In addition, per 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. The waiver will be considered for applications submitted to conduct a trial with a new drug already approved in certain countries, as specified in periodic orders.

The 2019-CTRules and IND-31 further explain that the DCGI will consider a local clinical trial waiver for approval of a new drug already approved in other countries if the following conditions are met:

  • The new drug is approved and marketed in countries to be specified by the DCGI and no major unexpected serious adverse events have been reported, or
  • The DCGI has already granted permission to conduct a GCT 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, 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

Per the 2019-CTRules, the DCGI plans to issue periodic orders to specify the countries that may be eligible for this waiver. 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. Although the 2019-CTRules does not delineate the countries that may be eligible for a waiver, according to IND-18 and IND-19, the United States, the United Kingdom, the European Union, Canada, Australia, and Japan are the countries that will no longer be required to complete local clinical trials for already approved and marketed new drugs. Refer to the Investigational Products topic, Manufacturing & Import subtopic for detailed information on import requirements for new drugs already approved outside of India.

The 2019-CTRules and IND-31 further specify that once the sponsor (applicant) obtains approval, he/she must inform CDSCO prior to initiating the clinical trial via Form CT-4A (found in the 2019-CTRules). 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. The DCGI’s permission to initiate a clinical trial granted via either Form CT-06 (found in the 2019-CTRules) or as an automatic approval via Form CT-4A (found in the 2019-CTRules) must 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.

As delineated in the Hdbk-ClinTrial, CDSCO coordinates the clinical trial application process. Upon receipt of an application, a CDSCO official is responsible for conducting 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 his/her 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 (applicant) 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.

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 (applicants) 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. The committee/group may submit its recommendations within 60 days from the date of the request. Additionally, per Order13Jan20, SECs will evaluate and advise 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 (applicant) clarification or modification and sends this feedback to the sponsor (applicant) within one (1) week of receipt. The sponsor (applicant) must submit a written reply to CDSCO within four (4) weeks of receiving the comments, and his/her comments will, in turn, be sent to the SEC for review.

Once the sponsor (applicant)’s response is received, 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 (applicant)’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 (applicant)’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 (applicant) to communicate this decision. Refer to the Hdbk-ClinTrial for additional timeline information.

The Hdbk-ClinTrial and the 2019-CTRules further state 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

In addition, per the 2019-CTRules, an investigator should not implement any deviations from or changes to the 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 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 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 be notified of administrative or logistical changes or minor amendments in the protocol within 30 days.

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

(See the Clinical Trial Lifecycle topic, Submission Process, Submission Content, and Timeline of Review subtopics for detailed submission content and timeline requirements.)

Additional Resources
(1) (Article) Ethics Committees and the Changed Clinical Research Environment in India in 2016: A Perspective! (IND-13) (Jan-Mar 2017)
Davis, Sanish et al
Relevant Sections: Introduction
(2) (Article) India's Clinical-Trial Rules to Speed up Drug Approvals (IND-19) (April 3, 2019)
Vaidyanathan, Gayathri; Nature
(3) (Article) India: The New Drugs And Clinical Trial Rules, 2019 (IND-17) (April 16, 2019)
Singh & Associates
Relevant Sections: Clinical Trial of New drugs
(4) (Article) India’s New Drugs and Clinical Trials Rules: An Industry Perspective (IND-6) (July 19, 2019)
Jain, Parveen and Chauhan, Rahul; Regulatory Focus
Relevant Sections: Revising New Drug Definition and Waivers of Local Clinical Trial Data
(5) (Article) New Clinical Trials Rules will Help Patients - Here's How (IND-18) (Last Updated April 8, 2019)
The Financial Express
(6) (Document) Frequently Asked Questions (FAQs) on Clinical Trials (IND-24) (Date Unavailable)
Central Drugs Standard Control Organization
(7) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 2-3, 7, 10-11, 18, 22, 25, 31-33, 38, and 79
(8) (Document) Global Clinical Trial (GCT) Application Checklist (IND-35) (Date Unavailable)
Central Drugs Standard Control Organization
(9) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 1, 2, 3, and 11
(10) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (IND-41) (Step 4 Version) (November 9, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Regulatory Authority > Regulatory Fees
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter V (21), Chapter XIII (102), Sixth Schedule, and Eighth Schedule (Form CT-04)
Summary

Overview

As per the 2019-CTRules, IND-43, and IND-42, a sponsor (applicant) is responsible for a paying a fee to the Drugs Controller General of India (DCGI) to submit a clinical trial application.

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

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).

Instructions for Payment of Clinical Trial Application Fees

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 SBI ePay payment gateway. 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.

In addition, according to IND-43 and IND-42, electronic payment is made via the SUGAM portal (IND-59). Once 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 on the SUGAM portal 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 the Central Drugs Standard Control Organization (CDSCO).

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.

Refer to IND-43 and IND-42 for detailed fee requirements and online payment instructions via the SUGAM portal.

(Note: Although the fees listed in IND-43 are correct, the SUGAM portal 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.)

Additional Resources
(1) (Document) Frequently Asked Questions (FAQs) on Clinical Trials (IND-24) (Date Unavailable)
Central Drugs Standard Control Organization
(2) (Document) User Manual For e-Governance Solution for CDSCO (IND-42) (Version 1.0) (Date Unavailable)
Centre for Development of Advanced Computing and Central Drugs Standard Control Organization
Relevant Sections: 1 and 6
(3) (Document) User Manual for SUGAM Online Payment (IND-43) (Version 1.1) (March 29, 2019)
Centre for Development of Advanced Computing and Central Drugs Standard Control Organization
(4) (Document) [Pre-Screening Checklist - Clinical Trial and New Drug Applications] (IND-32) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 1 (INDs) and 3 (Global Clinical Trials)
(5) (Webpage) SUGAM Portal (IND-59) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
Ethics Committee > Ethics Committee
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapters I, III- IV, Chapter V (19-20, and 25), Third Schedule (1 and Table 1), and Eighth Schedule (Forms CT-01 and CT-02)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 2.1, 2.8, 4.0-4.4, 4.10, Tables 4.1-4.3, Glossary, and Annex 1
(3) (Notice) Notice Regarding Registration of Ethics Committees for Biomedical and Health Research Involving Human Participants (Notice15Sept19) (Effective September 15, 2019)
Central Drugs Standard Control Organization
Summary

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), also commonly referred to as the Central Licensing Authority.

In addition, the 2019-CTRules established a separate registration and monitoring system for ECs that oversee biomedical and health research studies. 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. The G-ICMR further describes clinical research as studies that directly involve a particular person or group of people to study the effect of interventions, or uses materials/data from humans indirectly, such as their behavior or samples of their tissue for the prevention, treatment, and diagnosis of a disease condition/health disorder. Clinical trials, by comparison, are defined by the 2019-CTRules and the G-ICMR as systematic studies of new drugs (or investigational new drugs per the 2019-CTRules) in human participants to generate data for discovering and/or verifying the clinical, pharmacological (including pharmacodynamic and pharmacokinetic), and/or adverse effect(s) with the objectives of determining the safety and/or efficacy of a new drug.

Per Notice15Sept19 and chapter IV of the 2019-CTRules, any institution/organization that plans to conduct biomedical and health research involving human participants is now required to have an EC to review and oversee the conduct of such research before the study is initiated and throughout its duration. 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). See the Ethics Committee topic, Authorizing Body subtopic for detailed registration requirements. As is true for ECs that oversee clinical trials, ECs that monitor biomedical and health research studies are also required to comply with the 2019-CTRules and the G-ICMR.

EC 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.

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 also be non-affiliated or from outside 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; and honorarium to members, 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, and these must be recorded, however, the experts would not have any voting rights; only members independent of the trial and the trial sponsor 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 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 his/her 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 and the G-ICMR.

Additional Resources
(1) (Article) Highlights of Indian Council of Medical Research National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (IND-5) (May-June 2019)
Mathur, Roli et al; Indian J Pharmacology 51(3): 214–221
Relevant Sections: Section II (Ethics Committee Membership and Review)
(2) (Article) Indian Council of Medical Research's National Ethical Guidelines for Biomedical and Health Research Involving Human Participants: The Way Forward from 2006 to 2017 (IND-3) (July 12, 2019)
Behera, Sapan Kumar et al; Perspectives in Clinical Research
Relevant Sections: Sections 1-4
(3) (Article) India’s New Drugs and Clinical Trials Rules: An Industry Perspective (IND-6) (July 19, 2019)
Jain, Parveen and Chauhan, Rahul; Regulatory Focus
Relevant Sections: Ethics Committees (ECs)
(4) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 32-33
(5) (Document) Handbook on National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (IND-27) (2018)
Indian Council of Medical Research
Relevant Sections: Sections 1-4
(6) (Document) ICMR Policy on Research Integrity and Publication Ethics (IND-28) (2019)
Indian Council of Medical Research
(7) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 6
(8) (International Guidance) Declaration of Helsinki (IND-63) (October 19, 2013)
World Medical Association
(9) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (IND-41) (Step 4 Version) (November 9, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(10) (Webpage) Department of Health Research – About Us (IND-50) (Current as of March 25, 2021)
Ministry of Health and Family Welfare
Relevant Sections: Registration of Ethics Committees reviewing Biomedical & Health Research
Ethics Committee > Scope of Review
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter I, Chapter III (7 and 11), Chapter IV (15-17), Chapter V (19-20, 25, and 28), and Third Schedule (1, 3, and Table 4)
(2) (Guidance) Handbook for Applicants & Reviewers of Clinical Trials of New Drugs in India (Hdbk-ClinTrial) (January 2017)
Indian Council of Medical Research and Central Drugs Standard Control Organization
Relevant Sections: Preface, 4.0, 5.0-5.2, 5.22, 8.2, and Appendix 8.3
(3) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 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, Glossary, and Annex 1
(4) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (G-Children) (October 2017)
Indian Council of Medical Research
Relevant Sections: 3.1
(5) (Guidance) National Guidelines for Gene Therapy Product Development and Clinical Trials (G-GeneThrpy) (November 2019)
Indian Council of Medical Research, Central Drug Standards Control Organisation, and Ministry of Science and Technology
Relevant Sections: 7.11, and Annexures I, II, and III
(6) (Guidance) National Guidelines for Stem Cell Research (G-StemCellRes) (2017)
Indian Council of Medical Research, Ministry of Science and Technology
Relevant Sections: 4, 11.2, and Annexures I and II
(7) (Notice) Notice Regarding Registration of Ethics Committees for Biomedical and Health Research Involving Human Participants (Notice15Sept19) (Effective September 15, 2019)
Central Drugs Standard Control Organization
Summary

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 Informed Consent topic, and the subtopics of Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired 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. See the G-ICMR or detailed ethical review guidelines. 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.

Per the 2019-CTRules, ECs also have a continuing responsibility to monitor the 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.

Role in Clinical Trial Approval Process

As per the 2019-CTRules, the G-ICMR, and IND-31, the Drugs Controller General of India (DCGI) (also known as the Central Drugs Authority) and a DCGI-registered EC must approve a clinical trial application prior to the sponsor initiating the trial, except in the case of non-regulatory academic/research clinical trials that only require EC approval.

The 2019-CTRules and IND-31 state that an academic/research trial intended to study a new indication or route of administration, or, new dose or dosage of an already approved drug formulation 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

Per the 2019-CTRules and IND-31, the EC should inform the DCGI about the academic trials it has approved and about 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. 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 Investigational Products topic, Manufacturing & Import subtopic for detailed information.

As specified in the 2019-CTRules, the Hdbk-ClinTrial, and IND-31, 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 the responsible EC and the associated clinical trial site should be located within the same city or within a radius of 50 kilometers of the primary clinical 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.

In addition, according to IND-31 and IND-13, 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.

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 logistic changes or minor amendments in the protocol within 30 days.

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

Role in Biomedical and Health Research Approval Process

As discussed in Notice15Sept19 and chapter IV of the 2019-CTRules, any institution or organization that intends to conduct biomedical and health research is required to have an EC to review and oversee the conduct of such research before the study is initiated and throughout its duration. 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). According to IND-50, the DHR’s Office for Ethics Committee Registration was established to coordinate and monitor EC registrations and related activities to provide transparency, accountability, and structure to regulate and monitor biomedical and health research in India.

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. 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 IC 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 located 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.

Additional Resources
(1) (Article) Ethics Committees and the Changed Clinical Research Environment in India in 2016: A Perspective! (IND-13) (Jan-Mar 2017)
Davis, Sanish et al
Relevant Sections: Introduction
(2) (Article) Indian Council of Medical Research's National Ethical Guidelines for Biomedical and Health Research Involving Human Participants: The Way Forward from 2006 to 2017 (IND-3) (July 12, 2019)
Behera, Sapan Kumar et al; Perspectives in Clinical Research
Relevant Sections: Sections 1-4
(3) (Article) India’s New Drugs and Clinical Trials Rules: An Industry Perspective (IND-6) (July 19, 2019)
Jain, Parveen and Chauhan, Rahul; Regulatory Focus
Relevant Sections: Regulations on Biomedical and Health Research (BHR) and Academic Trials
(4) (Document) Additional FAQ on New Drugs and Clinical Trial Rules, 2019 (IND-25) (August 23, 2019)
Central Drugs Standard Control Organization
(5) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 2, 11, and 31-35
(6) (Document) Handbook on National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (IND-27) (2018)
Indian Council of Medical Research
Relevant Sections: Introduction and Sections 1-4, and 6
(7) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 6
(8) (Form) ICMR EC Application Form for Clinical Trials (Annexure 8) (IND-36) (Version 2.0) (Date Unavailable)
Indian Council of Medical Research
(9) (International Guidance) Declaration of Helsinki (IND-63) (October 19, 2013)
World Medical Association
(10) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (IND-41) (Step 4 Version) (November 9, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.27 and 3.1
(11) (Webpage) Common Forms for Ethics Committee Review (IND-52) (Current as of March 25, 2021)
Indian Council of Medical Research
(12) (Webpage) Department of Health Research – About Us (IND-50) (Current as of March 25, 2021)
Ministry of Health and Family Welfare
Relevant Sections: Registration of Ethics Committees reviewing Biomedical & Health Research
Ethics Committee > Ethics Committee Fees
Last content review/update: March 25, 2021
Requirements
(1) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 4.14
Summary

Overview

As indicated in the G-ICMR, the ethics committee (EC) 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.

Additional Resources
No additional resources
Ethics Committee > Authorizing Body
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: 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) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 4.1 and 4.15
(3) (Notice) Notice Regarding Ethics Committee Registration through SUGAM Portal (Notice1Aug18) (August 1, 2018)
Central Drugs Standard Control Organization
(4) (Notice) Notice Regarding Registration of Ethics Committees for Biomedical and Health Research Involving Human Participants (Notice15Sept19) (Effective September 15, 2019)
Central Drugs Standard Control Organization
Summary

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.

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.

Registration Provisions for Clinical Trial ECs

As specified in the 2019-CTRules and Notice1Aug18, ECs that intend to review clinical trial research protocols must submit an electronic application via the SUGAM portal (IND-59) to register with the DCGI using Form CT-01. 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. 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 submit an electronic application for registration renewal via the SUGAM portal 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.

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 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 ECs

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. 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. Once the NECRBHR verifies the application and approves the account registration, the applicant will receive an email that will allow him/her to login to the DHR’s NAITIK portal (IND-54) to submit an application electronically. 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 submit an application 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 ECs

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 Strategic Initiative for Developing Capacity in Ethical Review (SIDCER), 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.

Additional Resources
(1) (Article) DCGI Kickstarts Online Registration of ECs Reviewing Biomedical and Health Research for Effective Regulation (IND-2) (October 3, 2019)
Nautiyal, Shardul; Pharmabiz.com
(2) (Document) Checklist for Ethics Committee Registration for Biomedical and Health Research (IND-66) (Date Unavailable)
Ministry of Health and Family Welfare
(3) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 32-33
(4) (Document) Handbook on National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (IND-27) (2018)
Indian Council of Medical Research
(5) (Document) User Manual For e-Governance Solution for CDSCO (IND-42) (Version 1.0) (Date Unavailable)
Centre for Development of Advanced Computing and Central Drugs Standard Control Organization
Relevant Sections: 1 and 6
(6) (Document) User Manual for SUGAM Online Payment (IND-43) (Version 1.1) (March 29, 2019)
Centre for Development of Advanced Computing and Central Drugs Standard Control Organization
(7) (Form) EC Applicant Registration Form (IND-38) (Current as of March 25, 2021)
National Ethics Committee Registry for Biomedical and Health Research, Ministry of Health and Family Welfare
(8) (Webpage) Department of Health Research – About Us (IND-50) (Current as of March 25, 2021)
Ministry of Health and Family Welfare
Relevant Sections: Registration of Ethics Committees reviewing Biomedical & Health Research
(9) (Webpage) Ethics Committee Re-Registration Data (IND-48) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
(10) (Webpage) Ethics Committee Registration Data (IND-49) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
(11) (Webpage) NAITIK Portal (IND-54) (Current as of March 25, 2021)
National Ethics Committee Registry for Biomedical and Health Research, Ministry of Health and Family Welfare
(12) (Webpage) National Ethics Committee Registry for Biomedical and Health Research (NECRBHR) (IND-51) (Last Updated January 31, 2020)
Department of Health Research, Ministry of Health and Family Welfare
(13) (Webpage) Registration of Ethics Committees Reviewing Biomedical and Health Research with Department of Health Research (IND-53) (Current as of March 25, 2021)
Indian Council of Medical Research
(14) (Webpage) SUGAM Portal (IND-59) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
Clinical Trial Lifecycle > Submission Process
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2), Chapter II (3), Chapter V (19-22, 25, and 28), Second Schedule (1), Third Schedule (1 and Tables 3 and 7), and Eighth Schedule (Forms CT-04, CT-4A, and CT-06)
(2) (Guidance) Handbook for Applicants & Reviewers of Clinical Trials of New Drugs in India (Hdbk-ClinTrial) (January 2017)
Indian Council of Medical Research and Central Drugs Standard Control Organization
Relevant Sections: 5.0, 5.1, 5.2, and Appendix 8.3
(3) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 4.0-4.2, 4.8, and 4.10
(4) (Guidance) National Guidelines for Gene Therapy Product Development and Clinical Trials (G-GeneThrpy) (November 2019)
Indian Council of Medical Research, Central Drug Standards Control Organisation, and Ministry of Science and Technology
Relevant Sections: 7.11, and Annexures I, II, and III
(5) (Guidance) National Guidelines for Stem Cell Research (G-StemCellRes) (2017)
Indian Council of Medical Research, Ministry of Science and Technology
Relevant Sections: 4, 11.2, and Annexures I and II
(6) (Notice) Notice for Filing of Application for Clinical Trial, Marketing Authorization, Registration Certificate and Import License for r-DNA Derived Drugs in SUGAM Portal (Notice15Jan18) (January 15, 2018)
Central Drugs Standard Control Organization
Summary

Overview

In accordance with the 2019-CTRules, the Hdbk-ClinTrial, the G-ICMR, and IND-31, India requires the sponsor (applicant) to obtain clinical trial authorization from the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), and the investigator to obtain ethics committee (EC) approval from a DCGI-registered EC prior to initiating a study. In addition, according to IND-31, the DCGI review and approval process may be conducted in parallel with the EC review for each clinical trial site.

In addition, per the 2019-CTRules and IND-31, non-regulatory academic/research clinical trials only require EC approval. The 2019-CTRules and IND-31, state that an academic/research trial intended to study a new indication or route of administration, or, new dose or dosage of an already approved drug formulation 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

As explained in the 2019-CTRules and IND-31, the EC should inform the DCGI about the academic trials it has approved and about cases where there could be an overlap between the 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. 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 Investigational Products topic, Manufacturing & Import subtopic for detailed information.

See the Ethics Committee topic, Scope of Review subtopic for additional information on EC protocol review requirements.

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

Delivery Information for Clinical Trial Application

As indicated in the Notice15Jan18, all clinical trial application submissions must be submitted electronically via CDSCO’s SUGAM portal (IND-59). CDSCO no longer accepts hard copies of the clinical trial application.

Clinical Trial Application Language Requirements

While there is no specified language requirement in the regulatory requirements for documents submitted to CDSCO, since the SUGAM portal is in English, it is reasonable to conclude that clinical trial application submissions should be in English as well.

Additional Resources
(1) (Article) CDSCO to Stop Accepting Offline Clinical Trial, Marketing Applications (IND-14) (January 16, 2018)
Taylor, Nick Paul; Regulatory Focus
(2) (Article) Ethics Committees and the Changed Clinical Research Environment in India in 2016: A Perspective! (IND-13) (Jan-Mar 2017)
Davis, Sanish et al
Relevant Sections: Introduction
(3) (Document) Additional FAQ on New Drugs and Clinical Trial Rules, 2019 (IND-25) (August 23, 2019)
Central Drugs Standard Control Organization
(4) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 10-11 and 31-33
(5) (Document) SUGAM Portal Approval Process for Global Clinical Trials (IND-22) (Date Unavailable)
Central Drugs Standard Control Organization
(6) (Webpage) Clinical Trials Toolkit India (IND-46) (Current as of March 25, 2021)
Clinical Development Services Agency (CDSA), MRC Clinical Trials Unit, University College London, and Translational Health Science and Technology Institute (THSTI)
(7) (Webpage) SUGAM Portal (IND-59) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
Clinical Trial Lifecycle > Submission Content
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2), Chapter II (3), Chapter V (19-22, 25, and 28), 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)
(2) (Guidance) Handbook for Applicants & Reviewers of Clinical Trials of New Drugs in India (Hdbk-ClinTrial) (January 2017)
Indian Council of Medical Research and Central Drugs Standard Control Organization
Relevant Sections: Preface, 3, 5.0, 5.1, 5.2, and Appendix 8.3 and 8.4
(3) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 4.0-4.2, 4.8, and 4.10
Summary

Overview

As set forth in the 2019-CTRules, the Hdbk-ClinTrial, the G-ICMR, and IND-31, India requires an sponsor (applicant) to obtain clinical trial authorization from the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), and the investigator to obtain ethics committee (EC) approval from a DCGI-registered EC prior to initiating a study. In addition, according to IND-31 and IND-13, the DCGI review and approval process may be conducted in parallel as the EC review for each clinical trial site, except in the case of non-regulatory academic/research clinical trials that only require EC approval. 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.

DCGI Requirements

As per the 2019-CTRules, the Hdbk-ClinTrial, IND-32, and IND-35, specific documentation must be submitted to DCGI as part of the approval process for investigational new drugs (INDs). The data required 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: The regulatory sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.)

  • Form CT-04 (the clinical trial application form including 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 EC and investigator names) (See Form CT-04 in the 2019-CTRules for additional details)
  • 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 Conference on 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 Form CT-16 (import license application) (for GCTs)
  • Sponsor authorization letter (for GCTs)
  • Details of biological specimens to be exported and the online application for export NOC for biological samples on the SUGAM portal (IND-59) (for GCTs) (See Specimens topic for more information)
  • Case Report Form (CRF)
  • Informed consent form (ICF) and patient information sheet (See Informed Consent topic, Required Elements subtopic 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.

The 2019-CTRules and the Hdbk-ClinTrial further note that the nature and extent of information to be included in the application may vary based on type of application, phase of the study, stage in drug development process, and study objective. 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.

EC 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 (IC) 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, 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, date of commencement and date of expiry of coverage of risk (if applicable)
  • Any additional document(s), as required by EC (such as other EC clearances for multicentric studies)
  • Protocol

The G-ICMR also specifies that investigators should submit research proposals as soft or hard copies to the Secretariat for review in the prescribed format and required documents as per EC SOPs.

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 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 (G-ICMR)
  • Study rationale
  • Study objective
  • Study design and methodology
  • Study population
  • Justification of inclusion/exclusion of vulnerable populations (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 mention 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
  • IC procedure and sample of the patient/participant information sheet and IC forms including audiovisual recording, if applicable, and IC 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.

Additional Resources
(1) (Article) Ethics Committees and the Changed Clinical Research Environment in India in 2016: A Perspective! (IND-13) (Jan-Mar 2017)
Davis, Sanish et al
Relevant Sections: Introduction
(2) (Document) Frequently Asked Questions (FAQs) on Clinical Trials (IND-24) (Date Unavailable)
Central Drugs Standard Control Organization
(3) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 10-11 and 31-33
(4) (Document) Global Clinical Trial (GCT) Application Checklist (IND-35) (Date Unavailable)
Central Drugs Standard Control Organization
(5) (Document) [Pre-Screening Checklist - Clinical Trial and New Drug Applications] (IND-32) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 1 (INDs) and 3 (Global Clinical Trials)
(6) (Form) Application Form for Initial Review (IND-39) (Version 1) (Date Unavailable)
Indian Council of Medical Research
(7) (International Guidance) ICH Guideline: The Common Technical Document for the Registration of Pharmaceuticals for Human Use (M4) (IND-68) (Step 5 Versions) (Modules range from 2002-2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(8) (Webpage) Clinical Trials Toolkit India (IND-46) (Current as of March 25, 2021)
Clinical Development Services Agency (CDSA), MRC Clinical Trials Unit, University College London, and Translational Health Science and Technology Institute (THSTI)
(9) (Webpage) SUGAM Portal (IND-59) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
Clinical Trial Lifecycle > Timeline of Review
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: 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 Eighth Schedule (Forms CT-04, CT-4A, and CT-06)
(2) (Guidance) Handbook for Applicants & Reviewers of Clinical Trials of New Drugs in India (Hdbk-ClinTrial) (January 2017)
Indian Council of Medical Research and Central Drugs Standard Control Organization
Relevant Sections: 5.0, 5.1, 5.2, and Appendix 8.3
(3) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 4.1, 4.2, 4.8, and 4.10
Summary

Overview

Based on the 2019-CTRules, the Hdbk-ClinTrial, the G-ICMR, and IND-31, the Drugs Controller General of India’s (DCGI) review and approval of an application to conduct a clinical trial is dependent upon obtaining ethics committee (EC) approval from a DCGI-registered EC prior to initiating a study. In addition, according to IND-31 and IND-13, 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/research clinical trials that only require EC approval.

DCGI Approval

As specified in the 2019-CTRules, and according to IND-31, IND-17, and IND-18, upon receipt of a clinical trial application (Form CT-04 found in the 2019-CTRules), the DCGI has 90 calendar days to evaluate the application for drugs developed outside India and 30 days for drugs discovered, researched, and manufactured in India. If the DCGI does not respond within 30 days to applications for drugs developed in India, the sponsor (applicant) may conclude that permission to conduct the trial has been granted.

In addition, per 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. The waiver will be considered for applications submitted to conduct a trial for a drug already approved in certain countries as specified in periodic orders.

The 2019-CTRules and IND-31 further explain that the DCGI will consider a local clinical trial waiver for approval of a new drug already approved in other countries if the following conditions are met:

  • The new drug is approved and marketed in countries to be specified by the DCGI and no major unexpected serious adverse events have been reported, or,
  • The DCGI has already granted permission to conduct a global clinical trial (GCT) 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, 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

Per the 2019-CTRules, the DCGI plans to issue periodic orders to specify the countries that may be eligible for this waiver. 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. Although the 2019-CTRules does not delineate the countries that may be eligible for a waiver, according to IND-18 and IND-19, the United States, the United Kingdom, the European Union, Canada, Australia, and Japan are the countries that will no longer be required to complete local clinical trials for already approved and marketed new drugs. Refer to the Investigational Products topic, Manufacturing & Import subtopic for detailed information on import requirements for new drugs already approved outside of India.

The 2019-CTRules and IND-31 further specify that once the sponsor (applicant) obtains approval, he/she must inform the Central Drugs Standard Control Organization (CDSCO) prior to initiating the clinical trial via Form CT-4A (found in the 2019-CTRules). 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. The DCGI’s permission to initiate a clinical trial granted via either Form CT-06 (found in the 2019-CTRules) or as an automatic approval via Form CT-4A must 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.

As delineated in the Hdbk-ClinTrial, CDSCO coordinates the clinical trial application process. Upon receipt of an application, a CDSCO official is responsible for conducting 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 his/her 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 (applicant) 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.

Per the Hdbk-ClinTrial, SECs are comprised of experts representing various therapeutic areas that 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 (applicants) 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 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.

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 (applicant) clarification or modification and send this feedback to the sponsor (applicant) within one (1) week of receipt. The applicant must submit a written reply to CDSCO within four (4) weeks of receiving the comments, and his/her comments will, in turn, be sent to the SEC for review. Once the sponsor (applicant)’s response is received, 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 (applicant)’s request for reconsideration, CDSCO will review the resubmitted application and send to the SEC again, or, to the Technical Committee  per the sponsor (applicant)’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 (applicant) to communicate this decision. Refer to the Hdbk-ClinTrial for additional timeline information.

EC 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.

Additional Resources
(1) (Article) Ethics Committees and the Changed Clinical Research Environment in India in 2016: A Perspective! (IND-13) (Jan-Mar 2017)
Davis, Sanish et al
Relevant Sections: Introduction
(2) (Article) India's Clinical-Trial Rules to Speed up Drug Approvals (IND-19) (April 3, 2019)
Vaidyanathan, Gayathri; Nature
(3) (Article) India: The New Drugs And Clinical Trial Rules, 2019 (IND-17) (April 16, 2019)
Singh & Associates
Relevant Sections: Clinical Trial of New drugs
(4) (Article) New Clinical Trials Rules will Help Patients - Here's How (IND-18) (Last Updated April 8, 2019)
The Financial Express
(5) (Article) Regulatory Timelines in the Asia-Pacific (IND-9) (August 22, 2016)
George Clinical; Pharmaphorum
Relevant Sections: India
(6) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 10-11, 18, 22, 25, 31-33, 38, and 79
(7) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 1, 2, 3, and 11
Clinical Trial Lifecycle > Trial Initiation
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2), Chapter II (3), Chapter V (19-22, 25, and 28-29), 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)
(2) (Guidance) Handbook for Applicants & Reviewers of Clinical Trials of New Drugs in India (Hdbk-ClinTrial) (January 2017)
Indian Council of Medical Research and Central Drugs Standard Control Organization
Relevant Sections: 5.0, 5.1, 5.2, and Appendix 8.3
(3) (Guidance) ICMR Guidelines for Good Clinical Laboratory Practices (GCLP) (2021)
Indian Council of Medical Research
(4) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 4.1, 4.2, 4.8, and 4.10
(5) (Guidance) National Guidelines for Gene Therapy Product Development and Clinical Trials (G-GeneThrpy) (November 2019)
Indian Council of Medical Research, Central Drug Standards Control Organisation, and Ministry of Science and Technology
Relevant Sections: 7.11, and Annexures I, II, and III
(6) (Guidance) National Guidelines for Stem Cell Research (G-StemCellRes) (2017)
Indian Council of Medical Research, Ministry of Science and Technology
Relevant Sections: 4, 11.2, and Annexures I and II
Summary

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 (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 Ethics Committee topic, Scope of Review subtopic for additional details). There is no waiting period required following the sponsor (applicant)’s receipt of these approvals.

In addition, per the 2019-CTRules and IND-31, the sponsor (applicant) 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 Investigational Products topic, Manufacturing & Import subtopic for additional information.)

As stated in the 2019-CTRules, all investigators must possess appropriate qualifications, training, and experience, and should conduct the trials in compliance with the Good Clinical Practices (GCPs) and Good Laboratory Practices. (See GCLP for the G-ICMR for Good Clinical Laboratory Practices, IND-31 for additional laboratory requirement information, and IND-40 and IND-30 for international Good Laboratory Practice guidelines.)

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 in the 2019-CTRules.

As per the 2019-CTRules, before the trial begins, the sponsor (applicant) must permit clinical trial site inspections by DCGI authorized officers.

EC Confirmation of Review and Approval

While the 2019-CTRules require ethics committee review and approval before a clinical trial can commence, there are no stated requirements related to the investigator providing confirmation to the sponsor.

See Ethics Committee topic, Scope of Review subtopic for detailed information on the institutional EC review and approval process.

Clinical Trial Registration

Per the 2019-CTRules, the G-ICMR, and IND-31, it is mandatory for all sponsors (applicants) 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 Ethics Committee topic, Scope of Review subtopic and the Clinical Trial Lifecycle topic, Submission Process subtopic for further information on academic trials.

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

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.

Additional Resources
(1) (Article) Mandatory to Register Clinical Trials Before Tests Begin (IND-12) (October 25, 2017)
Kaul, Rhythma; Hindustan Times
(2) (Article) UN Standards on Clinical Trials to be Implemented by ICMR (IND-10) (May 20, 2017)
Sabrang India
(3) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 10-11, 23-24, 32-33, 37, 64-67, and 71-75
(4) (Document) Global Clinical Trial (GCT) Application Checklist (IND-35) (Date Unavailable)
Central Drugs Standard Control Organization
(5) (Document) OECD Principles on Good Laboratory Practice (GLPs) (as revised in 1997) (IND-30) (1998) (OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring – Number 1)
Organisation for Economic Co-operation and Development
(6) (Document) [Pre-Screening Checklist - Clinical Trial and New Drug Applications] (IND-32) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 1 (INDs), 2 (New Drugs), 5 (Test License), and 7 (New Drug Formulation)
(7) (International Guidance) Handbook - Good Laboratory Practice (GLP): Quality Practices for Regulated Non-clinical Research and Development (IND-40) (2nd Edition) (2009)
World Health Organization
(8) (Webpage) Clinical Trials Registry - India (IND-57) (Current as of March 25, 2021)
Indian Council of Medical Research
(9) (Webpage) Clinical Trials Registry - India: Important Notice for all Trial Registrants (IND-56) (Current as of March 25, 2021)
Indian Council of Medical Research
(10) (Webpage) Clinical Trials Toolkit India (IND-46) (Current as of March 25, 2021)
Clinical Development Services Agency (CDSA), MRC Clinical Trials Unit, University College London, and Translational Health Science and Technology Institute (THSTI)
Clinical Trial Lifecycle > Safety Reporting
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2), Chapter V (25), Chapter VI (42), and Third Schedule (2-3 and Tables 4-5)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 2.6, 5.3, 7.1, and Glossary
(3) (Notice) Notice Regarding Online Submission of SAE Reports in SUGAM Portal (Notice25Feb21) (Effective March 14, 2021)
Central Drugs Standard Control Organization
Summary

Overview

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 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 (IC)/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)

Reporting Requirements for AEs/ADRs

Investigator Responsibilities

As indicated in the 2019-CTRules, the G-ICMR, and IND-42, the investigator must report all SAEs/SADRs to the Drugs Controller General of India (DCGI), the sponsor or his/her representative, and the ethics committee (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, he/she is required to provide reasons for the delay to the DCGI along with the SAE/SADR report for the DCGI’s approval. The report, after due analysis, must then be forwarded by the investigator to the DCGI, the Chairperson of the EC, and the head of the institution where the trial has been conducted within 14 days of the occurrence of the incident. 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, per the G-ICMR, the investigator must submit a report to the DCGI on 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.

Sponsor Responsibilities

As delineated in the 2019-CTRules, the sponsor (applicant) must forward any SAE/SADR report, after due analysis, within 14 days of the occurrence to the DCGI, the EC Chairman, and the head of the institution where the trial is being conducted.

In the event of an SAE/SADR resulting in death, per the 2019-CTRules, the sponsor or his/her representative and the investigator must forward his/her 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 his/her 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 Sponsorship topic, Compensation subtopic for additional information on sponsor compensation requirements.

Form Completion & Delivery Requirements

As per Notice25Feb21, the investigator, the sponsor or his/her representative, and the EC must report all SAEs electronically via the SUGAM portal (IND-59), effective March 14, 2021. Paper submissions will no longer be accepted. However, follow-up reports pertaining to previously submitted SAE reports 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 the SUGAM portal.

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’s (ICMR) EC Serious Adverse Event Reporting Format (Clinical Trials).

Additional Resources
(1) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 14
(2) (Document) User Manual For e-Governance Solution for CDSCO (IND-42) (Version 1.0) (Date Unavailable)
Centre for Development of Advanced Computing and Central Drugs Standard Control Organization
Relevant Sections: Chapter 8
(3) (Form) ICMR EC Serious Adverse Event Reporting Format (Clinical Trials) (Annexure 9) (IND-37) (Version 2.0) (Date Unavailable)
Indian Council of Medical Research
(4) (Webpage) SUGAM Portal (IND-59) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
Clinical Trial Lifecycle > Progress Reporting
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter III (11), Chapter V (25), First Schedule (6), and Third Schedule (3 and Table 6)
Summary

Overview

As indicated in the 2019-CTRules, investigators and sponsors share responsibility for submitting clinical trial progress reports and final reports upon the trial’s completion.

Interim/Progress Reports

As described in the 2019-CTRules and IND-31, the Drugs Controller General of India (DCGI) requires the sponsor (applicant) to submit a six (6)-month status report of each clinical trial electronically via the Central Drugs Standard Control Organization (CDSCO)’s SUGAM portal (IND-59). The report should clarify whether the trial is ongoing, completed, or terminated. In 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.

Annual Reports

As delineated in the 2019-CTRules, sponsors are required to submit an annual status report on the clinical trial to the Drugs Controller General of India (DCGI).

The 2019-CTRules also 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 (applicant) 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 also IND-35 for a checklist of documentation requirements to be included in a global clinical trial application pertaining to end of clinical trial notification.

Additional Resources
(1) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 36
(2) (Document) Global Clinical Trial (GCT) Application Checklist (IND-35) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: Checklist of Notification for Annual Status Report; Checklist for Notification for End of GCT
(3) (Webpage) SUGAM Portal (IND-59) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
Sponsorship > Definition of Sponsor
Last content review/update: March 25, 2021
Requirements
(1) (Legislation) Information Technology (Amendment) Act, 2008 (ITActAmend) (February 5, 2009)
Parliament of India
Relevant Sections: Part II (22)
(2) (Legislation) Information Technology Act, 2000 (ITAct) (Effective October 17, 2000)
Parliament of India
Relevant Sections: Chapter IX (43A)
(3) (Regulation) Information Technology (Reasonable Security Practices and Procedures and Sensitive Personal Data or Information) Rules, 2011 (IT-SPDIRules) (April 11, 2011)
Ministry of Communications and Information Technology
Relevant Sections: 2, 4, and 5
(4) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2)
(5) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 4.0-4.2, 4.8, and 4.10
Summary

Overview

As per the 2019-CTRules and the G-ICMR, a sponsor 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).

For the purposes of data protection requirements, 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 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). For more information on the sponsor’s role in data protection, see Quality, Data & Records Management subtopic.

Additional Resources
(1) (Webpage) Clinical Trials Toolkit India (IND-46) (Current as of March 25, 2021)
Clinical Development Services Agency (CDSA), MRC Clinical Trials Unit, University College London, and Translational Health Science and Technology Institute (THSTI)
Sponsorship > Trial Authorization
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2), Chapter II (3), Chapter V (19-22, 25, and 28), Second Schedule (1 and Tables 1-4), Third Schedule (1 and Tables 1-4 and 6-7), and Eighth Schedule (Forms CT-04, CT-4A, and CT-06)
(2) (Guidance) Handbook for Applicants & Reviewers of Clinical Trials of New Drugs in India (Hdbk-ClinTrial) (January 2017)
Indian Council of Medical Research and Central Drugs Standard Control Organization
Relevant Sections: Objective
(3) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 4.0-4.2, 4.8, and 4.10
(4) (Guidance) National Guidelines for Gene Therapy Product Development and Clinical Trials (G-GeneThrpy) (November 2019)
Indian Council of Medical Research, Central Drug Standards Control Organisation, and Ministry of Science and Technology
Relevant Sections: 7.11, and Annexures I, II, and III
(5) (Guidance) National Guidelines for Stem Cell Research (G-StemCellRes) (2017)
Indian Council of Medical Research, Ministry of Science and Technology
Relevant Sections: 4, 11.2, and Annexures I and II
Summary

Overview

In accordance with the 2019-CTRules, the G-ICMR, the Hdbk-ClinTrial, and IND-31, the sponsor (applicant) or his/her contract research organization (CRO) is required to submit the clinical trial application to the Drugs Controller General of India (DCGI).

In addition, according to IND-31 and IND-13, the DCGI review and approval process may be conducted at the same time as a DCGI-registered ethics committee (EC) review for each clinical trial site.

Per the 2019-CTRules, non-regulatory academic/research clinical trials only require EC approval. However, per the 2019-CTRules and the Hdbk-ClinTrial, the DCGI must confirm the EC approvals for each participating site have been obtained per the protocol prior to approving the initiation of the study.

As specified in the 2019-CTRules and IND-31, to complete the clinical trial application package, the sponsor (applicant) must use Form CT-04 found in the 2019-CTRules. In addition to the completed application form, the submission package should include, but is not limited to, the clinical study protocol, a draft of the informed consent document, a list of proposed investigators who have agreed to participate in the trial, and background information about the drug in accordance with the 2019-CTRules.

See the Clinical Trial Lifecycle topic, Submission Content subtopic for detailed submission requirements.

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

Additional Resources
(1) (Article) Ethics Committees and the Changed Clinical Research Environment in India in 2016: A Perspective! (IND-13) (Jan-Mar 2017)
Davis, Sanish et al
Relevant Sections: Introduction
(2) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 10-11, 14, and 31-33
(3) (Document) Global Clinical Trial (GCT) Application Checklist (IND-35) (Date Unavailable)
Central Drugs Standard Control Organization
(4) (Document) [Pre-Screening Checklist - Clinical Trial and New Drug Applications] (IND-32) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 1 and 3
Sponsorship > Insurance
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Third Schedule (Table 1)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 2.6.2, 4.8, Box 4.4(A), and 7.1
Summary

Overview

The G-ICMR specifies that the sponsor 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. IND-60 provides a table of the different policy types available in India including the no fault compensation, the claims-made policy, and the premium rating policy. Regarding coverage limits, IND-60 further indicates there is no set rule for establishing coverage limits or minimums in India, however, the consensus in the insurance community is that a clinical trials liability policy should carry a minimum limit of $1 million and can have upper limits of $10 million through $20 million or more. See IND-60 for additional information on policy types and coverage limits.

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.

See the Sponsorship topic, Compensation subtopic and Informed Consent topic, Compensation Disclosure subtopic for specific details related to sponsorship compensation obligations.

Additional Resources
(1) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
(2) (Webpage) Liability and Indemnity in Clinical Trials and its Global Complexities (IND-60) (Last Updated December 12, 2018)
Institute of Good Manufacturing Practices India
Relevant Sections: Current Scenario of Liability and Indemnity in India and Other Countries
Sponsorship > Compensation
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2), Chapter V (25 and 27), Chapter VI (39-40, and 42), Third Schedule (3 and Table 3), and Seventh Schedule
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 2.5-2.7, 4.7, 4.8, 7.1, and 7.16
Summary

Overview

In accordance with the 2019-CTRules and the G-ICMR, the sponsor (applicant), whether a pharmaceutical company, an institution, an investigator, or his/her representative, 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.

As specified in the 2019-CTRules and the G-ICMR, the sponsor (applicant) 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 ethics committee (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 his/her 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 his/her representative to conduct any further clinical trial or take any other action for such period deemed appropriate for this case.

The G-ICMR similarly states that the investigator should ensure free treatment for research-related injury (e.g., disability, chronic life-threatening disease and congenital anomaly or birth defect).

The 2019-CTRules and IND-31 further explain that the investigator may recommend the sponsor (applicant) 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 and/or his/her legal representative(s) or guardian(s) 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

In addition, 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 those that are research related including patient work-ups, or interventions associated with treatment, and, if applicable, participants may receive additional medical services at no further cost.

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 EC.

As noted in the 2019-CTRules, the sponsor (applicant) is responsible for compensating the research participant and/or his/her 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 IP
  • Any trial procedures involved in the study
  • A violation of the approved protocol, scientific misconduct, or negligence by the sponsor, his/her 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 effect (SAE)/serious adverse drug reaction (SADR)

According to IND-31, compensation and medical management requirements are also applicable in the case of injury or death occurring during an academic trial.

Payment Procedures and Requirements

In the case of a trial-related injury, the 2019-CTRules and IND-31 state that the sponsor (applicant) 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 (applicant) is also required to provide compensation to the participant or his/her legal representative(s) or guardian(s) within 30 days of receiving the DCGI’s order.

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 his/her 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 his/her 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 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 of receiving the expert committee’s report specifying the quantum of compensation that the sponsor or his/her representative is required to pay. As earlier stated, the sponsor or his/her representative must then pay this compensation within 30 days of receiving the order.

In the case of an SAE/SADR resulting in permanent disability or any other injury other than death, the 2019-CTRules indicates that the sponsor or his/her 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 determine the quantum of compensation to be paid by the sponsor or his/her representative and issue this order within 90 days of receiving the report. As earlier noted, the sponsor or his/her representative must pay the compensation 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 his/her representative fails to provide compensation to a research participant for trial-related injuries, or to his/her 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 his/her representative from conducting any further clinical trials in India or taking any other action deemed fit given the circumstances.

The G-ICMR also indicates that the EC is responsible for determining the quantum and type of assistance to be provided to participants based on a review of the various aspects of the study including the research type and the extent of injury.

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

(See Informed Consent topic, Compensation Disclosure subtopic for additional information on the participant’s right to compensation)

Additional Resources
(1) (Article) Asia Regulatory Roundup: India Drops Interim Compensation Requirements From Proposed Clinical Trial Rules (IND-20) (April 3, 2019)
Taylor, Nick Paul; Regulatory Focus
(2) (Article) India’s New Drugs and Clinical Trials Rules: An Industry Perspective (IND-6) (July 19, 2019)
Jain, Parveen and Chauhan, Rahul; Regulatory Focus
Relevant Sections: Post-Trial Access
(3) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 12, 39-41, and 61
(4) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 14
Sponsorship > Quality, Data & Records Management
Last content review/update: March 25, 2021
Requirements
(1) (Legislation) Information Technology (Amendment) Act, 2008 (ITActAmend) (February 5, 2009)
Parliament of India
Relevant Sections: Part II (22)
(2) (Legislation) Information Technology Act, 2000 (ITAct) (Effective October 17, 2000)
Parliament of India
Relevant Sections: Chapter IX (43A)
(3) (Regulation) Information Technology (Reasonable Security Practices and Procedures and Sensitive Personal Data or Information) Rules, 2011 (IT-SPDIRules) (April 11, 2011)
Ministry of Communications and Information Technology
Relevant Sections: 2 and 5
(4) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: 55, 70, and Third Schedule
(5) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 4.2.3, 4.10, and 6.1 (Table 6.1)
Summary

Overview

In accordance with the 2019-CTRules and the G-ICMR, the sponsor 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, and all applicable laws and regulations.

Data Protection

Data protection in India is currently regulated by the ITAct, the ITActAmend, and the IT-SPDIRules. Per the IT-SPDIRules, the “body corporate,” or any other person on its behalf, responsible for collecting, receiving, possessing, storing, dealing with, or handling provider information must provide a privacy policy for the handling of or dealing with this personal information including sensitive personal data or information. (Note: In ClinRegs, the “body corporate” is referred to as “sponsor,” but the requirements may apply to other parties as well). 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.

Electronic Data Processing System

No information is currently available on electronic data processing systems.

Record Management

Per the 2019-CTRules, the sponsor (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 applicant 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.

Audit Requirements

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 where he/she agrees to maintain adequate and accurate records and to make those records available for audit or inspection by the sponsor, the EC, the Central Licencing Authority, or their authorised representatives, in accordance with regulatory provisions and the Good Clinical Practices guidelines. The investigator must agree to fully cooperate with any study-related audit conducted by regulatory officials or authorised representatives of the sponsor.

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

Premature Study Termination/Suspension

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.

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

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 ECs. 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 Ethics Committee topic, Scope of Review subtopic for additional details.

Additional Resources
(1) (Article) India - Data Protection Overview (IND-65) (January 2021)
Chacko, Mathew and Misra, Aadya; OneTrust DataGuidance
(2) (Article) Privacy and Data Protection - India Wrap 2020 (IND-67) (January 15, 2021)
Kittane, Purushotham et al; The National Law Review
(3) (Article) The Personal Data Protection Bill, 2019 (IND-64) (Date Unavailable)
PRS Legislative Research
(4) (Document) GCP Inspection Checklist (IND-34) (February 9, 2018)
Central Drugs Standard Control Organization
(5) (Document) Global Clinical Trial (GCT) Application Checklist (IND-35) (Date Unavailable)
Central Drugs Standard Control Organization
Sponsorship > Site/Investigator Selection
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter III (11), Third Schedule (1, 3, and Table 4)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 4.2.3, 4.8 (Table 4.2.3), and 4.10
(3) (Notice) Notice Regarding List of Approved Clinical Trial Sites and Investigators (Notice2Dec19) (December 2, 2019)
Central Drugs Standard Control Organization
Summary

Overview

The 2019-CTRules states that the investigator should possess appropriate qualifications, training, and experience and have access to investigational and treatment facilities as relevant to the protocol. Prior to entering into an agreement with the investigator(s)/institution(s) to conduct a study, the sponsor 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 which includes an Excel spreadsheet of sites and investigators involved in global clinical trials has been uploaded to the CDSCO website and is available in IND-26).

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, good clinical practices, standard operating procedures (SOPs), and study protocols. (See the Sponsorship topic, Quality, Data & Records Management subtopic for additional multicenter study requirements.)

Foreign Sponsor Responsibilities

No information is currently available on foreign sponsor responsibilities.

Data and Safety Monitoring Board

No information is currently available on data and safety monitoring boards.

Additional Resources
(1) (Document) Global Clinical Trial (GCT) Application Checklist (IND-35) (Date Unavailable)
Central Drugs Standard Control Organization
(2) (Document) ICMR Policy on Research Integrity and Publication Ethics (IND-28) (2019)
Indian Council of Medical Research
(3) (Document) List of Approved Clinical Trial Sites & Investigators for Global Clinical Trials (IND-26) (December 2, 2019)
Central Drugs Standard Control Organization
Informed Consent > Documentation Requirements
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) Information Technology (Reasonable Security Practices and Procedures and Sensitive Personal Data or Information) Rules, 2011 (IT-SPDIRules) (April 11, 2011)
Ministry of Communications and Information Technology
Relevant Sections: 3 and 5
(2) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter III (11) and Third Schedule (2-3 and Tables 1 and 3)
(3) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 2.2, 4.4, 4.8, 5.0, 5.2-5.4, and 5.8
(4) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (G-Children) (October 2017)
Indian Council of Medical Research
Relevant Sections: 3.1
(5) (Guidance) National Guidelines for Gene Therapy Product Development and Clinical Trials (G-GeneThrpy) (November 2019)
Indian Council of Medical Research, Central Drug Standards Control Organisation, and Ministry of Science and Technology
Relevant Sections: 7.11 and Annexures I, II, and III
(6) (Guidance) National Guidelines for Stem Cell Research (G-StemCellRes) (2017)
Indian Council of Medical Research, Ministry of Science and Technology
Relevant Sections: 4, 11.2, and Annexures I and II
Summary

Overview

In all Indian clinical trials, a freely given, informed written 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, the informed consent form (ICF) and patient information sheet are viewed as essential documents that must be reviewed and approved by the ethics committee (EC) and supplied to the Drugs Controller General of India (DCGI), prior to beginning a clinical trial. The ICF and patient information sheet are ultimately integrated into one (1) document referred to as the ICF. (See the Informed Consent topic, Required Elements subtopic for details on what should be included in the form.)

The 2019-CTRules, the G-ICMR, and the G-Children, specify that investigator(s) should provide detailed study information to the research participant and/or his/her legal representative(s) or guardian(s). 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 and/or his/her legal representative(s) or guardian(s), should be given adequate time to consider whether to participate.

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 (IC) process for vulnerable participants in clinical trials of new chemical entity or new molecular entity, including the procedure of providing information to the participant and his/her 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 IC process. The investigator(s) is also required to retain the audio recording for his/her records.

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

In addition, 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.

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. (Note: In ClinRegs, the “body corporate” is referred to as “sponsor,” but the requirements may apply to other parties as well). The IT-SPDIRules 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

Re-Consent

According to the G-ICMR and the G-Children, investigator(s) are required to renew the IC 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 his/her 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, who had suffered loss of mental competence and regains ability to understand the research implications
  • A child becomes an adult during the course of the study or the legal representative(s) or guardian(s) 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 the vernacular language that the participant is able to understand.

Documentation Copies

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

Per the G-ICMR, if the participant and/or his/her legal representative(s) or guardian(s) cannot sign, a thumb impression must be obtained. In addition, the investigator(s) who administer 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 his/her legal representative(s) or guardian(s). Per the G-Children, the investigator should also keep a signed copy of the ICF.

Additional Resources
(1) (Article) Highlights of Indian Council of Medical Research National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (IND-5) (May-June 2019)
Mathur, Roli et al; Indian J Pharmacology 51(3): 214–221
Relevant Sections: Section II (Informed Consent)
(2) (Article) Indian Council of Medical Research's National Ethical Guidelines for Biomedical and Health Research Involving Human Participants: The Way Forward from 2006 to 2017 (IND-3) (July 12, 2019)
Behera, Sapan Kumar et al; Perspectives in Clinical Research
Relevant Sections: Section 5
(3) (Document) Frequently Asked Questions (FAQs) on Clinical Trials (IND-24) (Date Unavailable)
Central Drugs Standard Control Organization
(4) (Document) Handbook on National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (IND-27) (2018)
Indian Council of Medical Research
Relevant Sections: 5
(5) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
(6) (Webpage) Clinical Trials Toolkit India (IND-46) (Current as of March 25, 2021)
Clinical Development Services Agency (CDSA), MRC Clinical Trials Unit, University College London, and Translational Health Science and Technology Institute (THSTI)
Informed Consent > Required Elements
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Second Schedule (1) and Third Schedule (2-3 and Tables 1, and 3-4)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 2.2, 5.0-5.3, and 6.11
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (G-Children) (October 2017)
Indian Council of Medical Research
Relevant Sections: 3.1
(4) (Guidance) National Guidelines for Gene Therapy Product Development and Clinical Trials (G-GeneThrpy) (November 2019)
Indian Council of Medical Research, Central Drug Standards Control Organisation, and Ministry of Science and Technology
Relevant Sections: 7.11, and Annexures I, II, and III
(5) (Guidance) National Guidelines for Stem Cell Research (G-StemCellRes) (2017)
Indian Council of Medical Research, Ministry of Science and Technology
Relevant Sections: 4, 11.2, and Annexures I and II
Summary

Overview

As delineated in 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 written informed consent form (ICF) and any other information being provided to the research participant and/or his/her legal representative(s) or guardian(s).

The G-ICMR and the G-Children state that information about the research study should be presented in easily understandable and unambiguous language.

No Coercion

As per the G-ICMR, the consent should be given voluntarily and not be obtained under duress or coercion of any sort or by offering any inducements.

ICF Required Elements

Requirements listed in the 2019-CTRules, the G-ICMR, and the G-Children include:

  • The study involves research and an explanation of its nature and purpose
  • The expected duration of the participant's participation
  • Any benefits to the participant or others reasonably expected from the research; 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 his/her participation

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 his/her 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

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

  • 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 his/her consent
  • The consequences of a participant’s decision to withdraw from the research, and procedures for orderly withdrawal by the participant
  • The participant and/or his/her legal representative(s) or guardian(s) will be notified in a timely manner if significant new findings develop during the course of the study which may affect the participant's willingness to continue
  • 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

The 2019-CTRules, the G-ICMR, and the G-Children also require the approximate number of participants enrolled in the study to be provided.

See the Informed Consent topic, Compensation Disclosure and Vulnerable Populations subtopics and the Specimens topic, Consent for Specimen subtopic for further information.

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

Additional Resources
(1) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
Informed Consent > Compensation Disclosure
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Third Schedule (3 and Table 3)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 2.5, 5.1 (Box 5.1)
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (G-Children) (October 2017)
Indian Council of Medical Research
Relevant Sections: 5.1 and 5.2
Summary

Overview

In accordance with the 2019-CTRules, the G-ICMR, and the G-Children, the informed consent form (ICF) should contain a statement describing the compensation or medical treatment the participant can receive for participating in a clinical trial.

Compensation for Participation in Research

As described in the 2019-CTRules and the G-ICMR, the ICF should contain a statement with a description of the anticipated prorated payment to the participant(s) that is reasonably expected for participation in the trial, such as travel. The G-ICMR and the G-Children further state that the participant may also be paid for the inconvenience and time spent, reimbursed for expenses incurred, and receive free medical services in connection with his/her participation.

Per the G-ICMR, participants should also not be required to pay for any expenses incurred beyond routine clinical care and that are research related (e.g., patient work-up and/or associated treatment). The G-ICMR explains that when legal representative(s) or guardian(s) give consent on a participant’s behalf, payment should not become an inducement and should be reviewed carefully by the ethics committee (EC).

Compensation for Injury

As per the 2019-CTRules, the G-ICMR, and the G-Children, the ICF should include a statement advising the participant that compensation and medical treatment is available in the event of any trial-related injury.

(See Sponsorship topic, Compensation subtopic for more information on payment procedures and requirements.)

Additional Resources
(1) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 14
Informed Consent > Participant Rights
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) Information Technology (Reasonable Security Practices and Procedures and Sensitive Personal Data or Information) Rules, 2011 (IT-SPDIRules) (April 11, 2011)
Ministry of Communications and Information Technology
Relevant Sections: 5
(2) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter III (7 and 11), Chapter V (28) and Third Schedule (3)
(3) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 1.0, 1.1, 2.2, 2.3, 4.0, 5.0-5.2, and 7.1
(4) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (G-Children) (October 2017)
Indian Council of Medical Research
Relevant Sections: 3.1
Summary

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 (IC) process.

The Right to Participate, Abstain, or Withdraw

As stated in the 2019-CTRules, the G-ICMR, and the G-Children, the participant and/or his/her legal representative(s) or guardian(s) should be informed that participation is voluntary, he/she 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.

Per the IT-SPDIRules, within the context of data protection legislation, the “body corporate” or its representative, must provide an option to the information provider to withhold his/her requested data or information prior to the collection of information including sensitive personal data or information. (Note: In ClinRegs, the “body corporate” is referred to as “sponsor,” but the requirements may apply to other parties as well). The information provider must, at any time, have the option to withdraw its consent given earlier to the sponsor or its representative. This withdrawal of consent must be sent in writing.

The Right to Information

As per the 2019-CTRules, the G-ICMR, and the G-Children, a potential research participant and/or his/her legal representative(s) or guardian(s) 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 and/or his/her legal representative(s) or guardian(s) 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 his/her rights.

The Right to Safety and Welfare

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

See the Informed Consent topic, and the subtopics of Required Elements and Vulnerable Populations for additional information regarding requirements for participant rights.

Additional Resources
(1) (Document) Handbook on National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (IND-27) (2018)
Indian Council of Medical Research
Relevant Sections: Sections 1 and 5
(2) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
(3) (International Guidance) Declaration of Helsinki (IND-63) (October 19, 2013)
World Medical Association
Informed Consent > Special Circumstances/Emergencies
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Third Schedule (2)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: Box 5.2, 5.7, and 5.8
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (G-Children) (October 2017)
Indian Council of Medical Research
Relevant Sections: 3.1 and 6.5
Summary

Overview

The 2019-CTRules, the G-ICMR, and the G-Children make provisions to protect the rights of a research participant during the informed consent (IC) process when special circumstances complicate the procedure. Special circumstances can include medical emergencies or a mentally incapacitated participant.

Medical Emergencies

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 EC(s) 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 situation, deferred consent is suggested. Deferred consent involves giving minimum information verbally, followed by full details and formal consent later. If the legal representative(s) or guardian(s) are 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 Informed Consent topic, Children/Minors subtopic for additional IC pediatric requirements.

Per the G-ICMR and the G-Children, the EC may specifically grant consent for a waiver for research conducted during humanitarian emergencies and disasters, when the participant may not be in a position to give consent. However, per the G-ICMR, an attempt should be made to obtain the participant’s consent as soon as possible.

Moreover, per the G-Children, if a child’s legal representative(s) or guardian(s) refuses to give consent once their child is stabilized, he/she 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 legal representative(s)’s or guardian(s)’s permission.

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

The G-Children explains that following EC approval of the protocols listed below, the IC requirement may be waived:

  • 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
Additional Resources
(1) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 2
(2) (International Guidance) Declaration of Helsinki (IND-63) (October 19, 2013)
World Medical Association
Informed Consent > Vulnerable Populations
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: First Schedule (3) and Third Schedule (3)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 1.1, 2.9, 6.0. 6.1, 6.2, 6.6, 6.7, 6.9, and 6.10
(3) (Guidance) National Guidelines for Gene Therapy Product Development and Clinical Trials (G-GeneThrpy) (November 2019)
Indian Council of Medical Research, Central Drug Standards Control Organisation, and Ministry of Science and Technology
Relevant Sections: 7. 11, and Annexures I, II, and III
(4) (Guidance) National Guidelines for Stem Cell Research (G-StemCellRes) (2017)
Indian Council of Medical Research, Ministry of Science and Technology
Relevant Sections: 4, 11.2, and Annexures I and II
Summary

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 (IC) 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.

The 2019-CTRules and the G-ICMR, specify that ethics committees (ECs) must pay special attention to protecting participants who are from vulnerable populations. 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.

See the Informed Consent topic, and the subtopics of Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired for additional information about these vulnerable populations.

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

Geriatrics

Permission to conduct clinical trials in geriatric patients must comply with the requirements listed in the Informed Consent topic, Required Elements subtopic. According to 2019-CTRules, geriatric patients should be included in Phase II and Phase III clinical trials at the sponsor’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

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.

Tribal Populations

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.

Persons in Subordinate or Dependent Groups

As indicated in the G-ICMR, while reviewing protocols involving participants who are engaged in subordinate or dependent relationships, the 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

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
Additional Resources
(1) (Article) Highlights of Indian Council of Medical Research National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (IND-5) (May-June 2019)
Mathur, Roli et al; Indian J Pharmacology 51(3): 214–221
Relevant Sections: Section II (Vulnerable Groups)
(2) (Article) Indian Council of Medical Research's National Ethical Guidelines for Biomedical and Health Research Involving Human Participants: The Way Forward from 2006 to 2017 (IND-3) (July 12, 2019)
Behera, Sapan Kumar et al; Perspectives in Clinical Research
Relevant Sections: Sections 5-6
(3) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
Informed Consent > Children/Minors
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: First Schedule (3) and Third Schedule (2)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 6.5
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (G-Children) (October 2017)
Indian Council of Medical Research
Relevant Sections: 1.5, 2, 3.1-3.3, 4.1, and 6.1
Summary

Overview

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, the participants are legally unable to provide written informed consent, and are dependent on their legal representative(s) or guardian(s) 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 legal representative(s) or guardian(s); 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 legal representative(s)’s or guardian(s)’s opinion, a pediatric patient’s welfare would be jeopardized by his/her failing to participate in the study. In this situation, continued legal representative(s) or guardian(s) 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.

Assent Requirements

As delineated in the G-ICMR, the 2019-CTRules, and the G-Children, if the pediatric participant has the capacity for assent, his/her 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 seven (7) and 11 years, oral assent must be obtained in the presence of their legal representative(s) or guardian(s). For children between 12 and 18 years, written assent must be obtained.

A child’s dissent or refusal to participate must always be respected, and he/she must be informed in an understandable manner that he/she may withdraw his/her assent 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.

Additional Resources
(1) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
Informed Consent > Pregnant Women, Fetuses & Neonates
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: First Schedule (3)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 6.4 and 7.18
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (G-Children) (October 2017)
Indian Council of Medical Research
Relevant Sections: 6.1
Summary

Overview

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 his research participation, 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.

If one (1) of the parents is a minor, then consent should not be taken from her/him. 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.

Additional Resources
(1) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
Informed Consent > Prisoners
Last content review/update: March 25, 2021
Requirements
(1) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 6.9
Summary

Overview

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 her/his care
  • Mechanisms to avoid coercion due to being part of an institution or hierarchy should be described in the protocol
Additional Resources
No additional resources
Informed Consent > Mentally Impaired
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Third Schedule (2)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 5.3, 5.4, 6.3, 6.5, and 6.8
Summary

Overview

As per the 2019-CTRules and the G-ICMR, informed consent should be obtained from the legal representative(s) or guardian(s) of participants.

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 (e.g., Braille for the visually impaired). 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.

Per the G-ICMR, 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.

Additional Resources
(1) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (IND-33) (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
(2) (International Guidance) Declaration of Helsinki (IND-63) (October 19, 2013)
World Medical Association
Investigational Products > Definition of Investigational Product
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2)
Summary

Overview

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.

Additional Resources
No additional resources
Investigational Products > Manufacturing & Import
Last content review/update: March 25, 2021
Requirements
(1) (Legislation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA-DCR) (Amended through December 31, 2016)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: DCR, 1945: Schedule M
(2) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: 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)
(3) (Notice) Notice Regarding Grant of Permission in Form CT-11/ CT-14/CT-15/ CT-17 Under New Drugs and Clinical Trials Rules 2019 (Notice20Feb20) (February 20, 2020)
Central Drugs Standard Control Organization
(4) (Notice) Notice Regarding Process Validation Report Requirement for Permission to Conduct Clinical Trials/BA-BE Studies (Notice13Mar20) (March 13, 2020)
Central Drugs Standard Control Organization
(5) (Notice) Notice Regarding the New Drugs and Clinical Trial Rules 2019 FAQs (Notice18Feb20) (February 18, 2020)
Central Drugs Standard Control Organization
Relevant Sections: 65 and 123
Summary

Overview

As specified in the 2019-CTRules and IND-31, the Drugs Controller General of India (DCGI) is responsible for authorizing the manufacture or import of investigational products (IPs) in India. The DCGI approves the manufacture or import of IPs as part of the clinical trial application review and approval process.

The 2019-CTRules explains that applicants must apply to the DCGI using Form CT-10 to obtain permission to manufacture an IP for clinical trial purposes. After reviewing the information and documents accompanying the application in Form CT-10, the DCGI will, if satisfied, grant permission to manufacture the IP by providing Form CT-11 within 90 working days from the date of application receipt. If dissatisfied, the DCGI will reject the application, for reasons to be recorded in writing, within a period of 90 working days from the date the application was submitted. In the case where the DCGI indicates there are some deficiencies in the application that may be rectified, the applicant must be informed of these deficiencies within a period of 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, and if satisfied, grant manufacturing permission to the applicant. If still dissatisfied, the DCGI will 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.

Applicants who intend to manufacture an unapproved active pharmaceutical ingredient (API) to develop a pharmaceutical formulation for clinical trial purposes should submit to the DCGI either Form CT-12, if applying as a pharmaceutical formulation manufacturer, or Form CT-13, if applying as an API manufacturer. These forms are available in the 2019-CTRules. After reviewing the information and documents accompanying the application in Form CT-12 or CT-13, and conducting further inquiry, if any is required, 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 date the application was submitted. Refer to the 2019-CTRules for additional timeline information.

In addition, Notice18Feb20 clarifies information provided in IND-31 concerning where applications should be sent to obtain permission to manufacture trial batches of new drugs or IPs for testing and analysis, clinical trials, or bioavailability and bioequivalence (BA/BE) studies. 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, he/she 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. Notice20Feb20 further specifies that applications sent to either CDSCO HQ or the appropriate zonal office/sub-zonal office will be processed within seven (7) working days of receipt.

Notice18Feb20 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 Notice13Mar20, when the application is solely to conduct a clinical trial, the DCGI also requires the sponsor 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.

In addition, per the 2019-CTRules and IND-31, the sponsor (applicant) is required to obtain a license from the DCGI using Form CT-16 to import an IP (new drug or investigational new drug) for clinical trial purposes. 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 its issue, unless suspended or cancelled. In exceptional circumstances, the DCGI may extend the license for an additional year. (See Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics and Regulatory Authority topic, Regulatory Fees subtopic 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. According to the 2019-CTRules, the sponsor must submit a fee of 5,000 Indian National Rupees (INRs) per product with an application for permission to manufacture or import the IP to be used in a clinical trial. 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.

As per the 2019-CTRules, for new drugs already approved outside India, the results of local clinical trials may not be necessary to submit along with the application to import or manufacture a new drug if the DCGI decides to grant permission on the basis of data available from countries to be specified in a future DCGI order. Although the 2019-CTRules does not delineate the countries that may be eligible for a waiver, according to IND-18 and IND-19, the United States, the United Kingdom, the European Union, Canada, Australia, and Japan are the countries that will no longer be required to complete local clinical trials for already approved and marketed new drugs. See Regulatory Authority topic, Scope of Assessment subtopic for detailed waiver requirements.

The 2019-CTRules and IND-31 further explain that the DCGI will consider a local clinical trial waiver for approval of a new drug already approved in other countries if the following conditions are met:

  • The new drug is approved and marketed in countries to be specified by the DCGI 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, 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

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.

Additional Resources
(1) (Article) India's Clinical-Trial Rules to Speed up Drug Approvals (IND-19) (April 3, 2019)
Vaidyanathan, Gayathri; Nature
(2) (Article) New Clinical Trials Rules will Help Patients - Here's How (IND-18) (Last Updated April 8, 2019)
The Financial Express
(3) (Document) Additional FAQ on New Drugs and Clinical Trial Rules, 2019 (IND-25) (August 23, 2019)
Central Drugs Standard Control Organization
(4) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 64-67, 71-75, and 79
(5) (Document) Global Clinical Trial (GCT) Application Checklist (IND-35) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 1.6
(6) (Document) Nagoya Protocol on Access and Benefit-sharing (IND-29) (2011)
Convention on Biological Diversity, United Nations
(7) (Document) User Manual For e-Governance Solution for CDSCO (IND-42) (Version 1.0) (Date Unavailable)
Centre for Development of Advanced Computing and Central Drugs Standard Control Organization
Relevant Sections: 1, 4, and 6
(8) (Document) User Manual for SUGAM Online Payment (IND-43) (Version 1.1) (March 29, 2019)
Centre for Development of Advanced Computing and Central Drugs Standard Control Organization
Relevant Sections: Foreword, Step 1, Step 2, and Step 5
(9) (Webpage) Central Drugs Standard Control Organization - Contact Us (IND-58) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
(10) (Webpage) Country Profile: India (IND-45) (Current as of March 25, 2021)
Access and Benefit-sharing Clearing-house, Convention on Biological Diversity, United Nations
(11) (Webpage) SUGAM Portal (IND-59) (Current as of March 25, 2021)
Central Drugs Standard Control Organization
Investigational Products > IMP/IND Quality Requirements
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter VIII (55 and 63), Chapter IX (70), Chapter X (75), Chapter XIII (101), Second Schedule (Table 1) and Third Schedule (Table 7), and Eighth Schedule (Forms CT-10, CT-12, and CT-16)
(2) (Notice) Notice Regarding Process Validation Report Requirement for Permission to Conduct Clinical Trials/BA-BE Studies (Notice13Mar20) (March 13, 2020)
Central Drugs Standard Control Organization
Summary

Overview

In accordance with the 2019-CTRules, the sponsor is responsible for providing the investigators with an Investigator’s Brochure (IB).

IB Content Requirements

The 2019-CTRules requires the 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 Investigational Products topic, Product Management subtopic for additional information on 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 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.).

Certificate of Analysis and Drug Manufacturing Certificate Requirements

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

According to IND-8, the Central Drugs Standard Control Organization (CDSCO) increased the validation period of its World Health Organization GMP certificate from two (2) to three (3) years to improve its ability to conduct business.

In addition, the 2019-CTRules and IND-31 explain that the DCGI will consider a local clinical trial waiver for approval of a new drug already approved in other countries if the following conditions are met:

  • The new drug is approved and marketed in countries to be specified by the DCGI and no major unexpected serious adverse events have been reported, or
  • The DCGI has already granted permission to conduct a global clinical trial (GCT) 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, 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 to establish the new drug’s safety and efficacy per the DCGI-approved formulation

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 GCT documentation requirements.

Additional Resources
(1) (Article) CDSCO Increases WHO GMP Certificate to Three Years for Ease of Doing Business (IND-8) (May 8, 2018)
Raghavan, Prabha; The Economic Times
(2) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 79
(3) (Document) Global Clinical Trial (GCT) Application Checklist (IND-35) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 1
Investigational Products > Labeling & Packaging
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter VIII (66) and Chapter IX (73)
Summary

Overview

Investigational product (IP) labeling in India must comply with the requirements set forth in the 2019-CTRules. Per the 2019-CTRules and IND-31, the labeling of any new drug or investigational new drug 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 IP is being imported
Additional Resources
(1) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 70
Investigational Products > Product Management
Last content review/update: March 25, 2021
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019-CTRules - Hindi and English) (Effective March 19, 2019)
Ministry of Health and Family Welfare
Relevant Sections: Chapter VIII (55) and Third Schedule (Tables 2 and 7)
Summary

Overview

In accordance with the 2019-CTRules, the sponsor is responsible for providing the investigator(s) with an Investigator’s Brochure (IB).

Investigational Product 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.

The 2019-CTRules also describes investigational product (IP) management requirements in the context of proposed protocol contents to be submitted as part of the clinical trial application submission. Per the 2019-CTRules, the IP section of the protocol 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.

Additional Resources
(1) (Document) Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials (IND-31) (Date Unavailable)
Central Drugs Standard Control Organization
Relevant Sections: 68
Specimens > Definition of Specimen
Last content review/update: March 25, 2021
Requirements
(1) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: Chapter III, Review Procedures, Section 3
(2) (Guidance) National Guidelines for Stem Cell Research (G-StemCellRes) (2017)
Indian Council of Medical Research, Ministry of Science and Technology
Relevant Sections: 15.0
(3) (Guidance) Office Memorandum: Guidelines for Exchange of Human Biological Material for Biomedical Research Purposes (G-XBiolMat) (November 19, 1997)
Ministry of Health and Family Welfare
Relevant Sections: Definition
Summary

Overview

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:

  • 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

(Note: The regulatory sources provide overlapping and unique elements so each of the items listed above will not necessarily be in each source.)

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
Additional Resources
No additional resources
Specimens > Specimen Import & Export
Last content review/update: March 25, 2021
Requirements
(1) (Guidance) Guidelines for International Collaboration/Research Projects in Health Research; MoUs & HMS Procedure (G-IntlResProj) (Last Updated January 22, 2021)
Indian Council of Medical Research
Relevant Sections: Health Ministry’s Screening Committee (HMSC)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 3.8 and 11.4
(3) (Guidance) Office Memorandum: Guidelines for Exchange of Human Biological Material for Biomedical Research Purposes (G-XBiolMat) (November 19, 1997)
Ministry of Health and Family Welfare
Relevant Sections: Definition, Transfer, Mechanism, and Exchange of Biological Material for Commercial Purposes
(4) (Notice) Import/Export Policy for Human Biological Samples for Commercial Purposes: Amendment Schedule–1 (Import Policy) and Schedule–2 (Export Policy) of ITC (HS), 2012 (HumBiol-ImprtExprt – Hindi and English) (August 4, 2016)
Ministry of Commerce and Industry
Summary

Overview

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.

Import/Export for 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 Import/Export for 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
  • To protect the rights of Indian study participants as well as Indian scientists/organizations, a memoranda of understanding (MoU) and/or material transfer agreements (MTAs) should be entered into between the collaborating partners (Indian and foreign)

Import/Export for 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 GOI 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-15 and IND-44 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.

Per the G-ICMR and the G-IntlResProj, any research involving the exchange of biological materials with collaborative institutions outside India must sign an 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 MoU should be in place to safeguard mutual country interests and ensure compliance.

Refer to the G-XBiolMat, the G-ICMR, and the G-IntlResProj for additional information.

Import/Export for 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.

Additional Resources
(1) (Article) Health Ministry’s Screening Committee (Indian Council of Medical Research) (IND-15) (January 2015)
Seth, Sandeep; Journal of the Practice of Cardiovascular Sciences
(2) (Document) Guidance for Investigators for Collaborative Biomedical Research in India (IND-44) (Date Unavailable)
National Institutes for Allergy and Infectious Diseases, National Institutes of Health
(3) (Document) Handbook on National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (IND-27) (2018)
Indian Council of Medical Research
Relevant Sections: Section 11
(4) (Form) Application Format for the Obtaining of Export NOC of Biological Samples of Clinical Trial for Testing (Annexure) (IND-1) (July 20, 2012)
Central Drugs Standard Control Organization
(5) (Webpage) Transfer of Biological Material (IND-55) (Last Updated April 29, 2020)
Indian Council of Medical Research
Specimens > Consent for Specimen
Last content review/update: March 25, 2021
Requirements
(1) (Guidance) ICMR Guidelines for Good Clinical Laboratory Practices (GCLP) (2021)
Indian Council of Medical Research
Relevant Sections: 8.4
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (G-ICMR) (October 2017)
Indian Council of Medical Research
Relevant Sections: 4.0, 5.1 (Box 5.1), and 10.4
(3) (Guidance) National Guidelines for Gene Therapy Product Development and Clinical Trials (G-GeneThrpy) (November 2019)
Indian Council of Medical Research, Central Drug Standards Control Organisation, and Ministry of Science and Technology
Relevant Sections: 7.11 and Annexures I, II, and III
(4) (Guidance) National Guidelines for Stem Cell Research (G-StemCellRes) (2017)
Indian Council of Medical Research, Ministry of Science and Technology
Relevant Sections: 4, 11.2, and Annexures I and II
Summary

Overview

In accordance with the G-ICMR, prior to collecting, storing, or using a research participant’s human biological material, consent must be obtained from the participant and/or his/her legal representative(s) in writing. In addition, per the G-ICMR, it is necessary for all health research involving human participants and their biological material and data to be reviewed and approved by an appropriately constituted ethics committee (EC).

In addition to the informed consent form (ICF) required elements listed in the Informed Consent topic, the G-ICMR require investigator(s) to communicate the following information to participants in the ICF regarding the use of their biological samples:

  • The participant’s right to prevent the use of his/her biological sample (e.g., DNA, cell-line, etc.) and related data at any time during the conduct of the research
  • The risk of discovery of biologically sensitive information and provisions to safeguard confidentiality

The GCLP further indicates that prior to specimen collection, appropriate counseling should be completed and written consent obtained. Attention should also be paid to the participant’s sensibilities during the entire process.

The G-ICMR also require the following information:

  • The storage period of the sample/data and probability of the material being used for secondary purposes
  • A statement clearly indicating whether material is to be shared with others
  • If research on biological material and/or data leads to commercialization, a statement describing post-research plan/benefit sharing
  • The publication plan, if any, including photographs and pedigree charts
  • A provision for pre-test and post-test counseling, if there is the possibility that the research could lead to any stigmatizing condition (e.g., HIV and genetic disorders)

Human Genetic Research Consent Requirements

As stated in the G-ICMR, investigator(s) must comply with stringent norms and exercise caution in conducting the consent process with participants for genetic research purposes. The following considerations must be taken into account during this process:

  • For routine genetic diagnostic testing, written consent may or may not be needed as per institutional policies; however, it is required for any research
  • Written informed consent is essential for procedures such as pre-symptomatic testing, next generation sequencing (NGS), prenatal testing, genomic studies, and carrier status, etc.
  • The investigator(s) should emphasize that consent for screening or a subsequent confirmatory test does not imply consent to any specific treatment, or termination of a pregnancy, or for research
  • If the research or testing involves a child, appropriate age-specific assent (verbal/oral/written) should be obtained along with parental consent

The G-ICMR further specifies that the ICF for genetic research testing should address the following additional points:

  • The nature and complexity of information that would be generated
  • The nature and consequences of returning results and the choice offered to the participant as to whether to receive that information and incidental findings, if any
  • Direct/indirect benefits and their implications, including if there are no direct benefits to the participants
  • How the data/samples will be stored, for how long, and procedures involved in anonymisation, sharing, etc.
  • Choice to opt out of testing/withdraw from research at any time
  • Whether the affected individual or the participant at the starting point of the study (proband) would like to share her/his genetic information with family members who may benefit from it
  • Issues related to ownership rights, intellectual property right concerns, commercialization aspects, and benefit sharing

Per the G-ICMR, in the case of population or community-based studies, group consent must also be taken from the community head and/or the culturally appropriate authority due to the potential of the genetic research to generate information applicable to the community/populations from which the participants are drawn. However, even if group consent is taken, it will not be a replacement for individual consent.

In addition, as indicated in the G-ICMR, the transfer of human biological material to be stored at a biorepository or a biobank, or another institution, must be communicated to the participant. The participant owns the biological sample and data collected from her/him, and could therefore withdraw both the biological material donated to the biobank and the related data unless the latter is required for outcome measurement, and is mentioned accordingly in the initial informed consent document. Please refer to Section 11 of the G-ICMR for detailed consent requirements associated with storing human biological materials in a biorepository or a biobank. (See the Informed Consent topic, Required Elements and Participant Rights subtopics for additional information on informed consent).

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

Additional Resources
(1) (Article) Highlights of Indian Council of Medical Research National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (IND-5) (May-June 2019)
Mathur, Roli et al; Indian J Pharmacology 51(3): 214–221
Relevant Sections: Section I (Broad Consent)
(2) (Article) Indian Council of Medical Research's National Ethical Guidelines for Biomedical and Health Research Involving Human Participants: The Way Forward from 2006 to 2017 (IND-3) (July 12, 2019)
Behera, Sapan Kumar et al; Perspectives in Clinical Research
Relevant Sections: Sections 10-11
(3) (Document) Handbook on National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (IND-27) (2018)
Indian Council of Medical Research
Relevant Sections: Sections 5 and 10-11
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