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
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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: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2), Chapter II (3), Chapter V (19 and 21-22), Second Schedule (1), and Third Schedule (1)
(2) (Legislation and Implementing Regulations) 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)
(3) (Guidance) Handbook for Applicants & Reviewers of Clinical Trials of New Drugs in India (Hdbk-ClinTrial) (January 2017)
Indian Council of Medical Research, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: Preface, 5.1, 5.2, and Appendix 8.3
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 Additional Resource (A), CDSCO functions under the Directorate General of Health Services (DGHS), which is part of the Ministry of Health and Family Welfare (MOHFW). Per Additional Resources (A) and (B), 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 DCGI is advised by the Drug Technical Advisory Board (DTAB) and the Drug Consultative Committee (DCC). Additional Resources (C) and (D) state 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 in the event the DCGI constitutes one (1) or more of these expert committees or group of experts to evaluate scientific and technical drug-related issues, the committee/group may submit its recommendations within 60 days from the date of the request.

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
(A) (Website) SUGAM - An e-Governance Solution for CDSCO (Current as of June 30, 2019)
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: About Us
(B) (Website) Central Drugs Standard Control Organization - About Us (Current as of June 30, 2019)
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Suresh, S; Puranik, SB; and Patel, P; Research and Reviews: Journal of Pharmacy and Pharmaceutical Science
Relevant Sections: The Regulatory Process of India
Gupta, M. et al; WHO Drug Information
Relevant Sections: Regulatory System
(E) (Website) Central Drugs Standard Control Organization - Contact Us (Current as of June 30, 2019)
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
(F) (Website) Central Drugs Standard Control Organization - Who’s Who (Current as of June 30, 2019)
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
(G) (Article) Indian Regulatory Update: January – March 2018 (July-September 2018)
Bhave, Amita; Perspect Clin Res
Relevant Sections: Office Order Regarding Setting Up of Public Relation Office at CDSCO (HQ)
Regulatory Authority > Scope of Assessment
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2), Chapter II (3), Chapter V (19-25, and 28), Chapter XIII (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, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
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 (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 7.0 and 7.1
(4) (Circular) Requirement of NOC from DCGI for Addition of New Clinical Trial Site or Investigator (C-NOCDCGIreq) (August 3, 2016)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare
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 (IND), and imported drugs to be registered in India. Additionally, per the 2019 CTRules, the ICMR Guidelines, and Additional Resource (A), 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 investigational new drug and new drug clinical trials, global clinical trials, and post marketing studies (Phases I – IV).

The 2019 CTRules and Additional Resource (A) 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 Additional Resource (A), 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 Additional Resource (A), has not been approved as a drug for marketing in any country.

In addition, according Additional Resources (A), (B), (C), and (D), 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 Additional Resources (A), (E), and (F), 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 Additional Resource (A), 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 Additional Resource (A) 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

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 CT Rules states that these applications shall 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 Additional Resources (F) and (G), 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 Additional Resource (A) 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) shall remain valid for two (2) years from the date of its issue, unless extended by the DCGI as noted in the 2019 CTRules and Additional Resource (A).

According to Additional Resource (H), the DCGI’s (CDSCO’s) review and approval process operates as a three-tiered system. Clinical trial applications and new drugs are initially evaluated by the Subject Expert Committee (SEC) or IND committees. At the second level, the SEC’s/IND’s recommendations are reviewed by the Technical Committee (TC), which consists of experts from various therapeutic areas. At the third level, the Apex Committee conducts the final review and approves the application based on the TC’s recommendations. Upon receipt of the Apex Committee’s approval, the DCGI then issues final approval to the sponsor (applicant).

With the publication of the Hdbk-ClinTrial in 2017, the three-tier review process was slightly altered. Per the CDSCO/SEC review processes described in the Hdbk-ClinTrial, unless the sponsor (applicant) specifically requests additional TC review, only the SEC’s recommendations are required for the DCGI (CDSCO) to issue a final decision to the Apex Committee.

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 the SEC for further technical review. Once the SEC has completed its review, the committee sends its comments via email to CDSCO. CDSCO will then compile any written SEC comments requiring sponsor (applicant) clarification or modification and sent 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 TC 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.

Additionally, in accordance with Additional Resources (I), (J), and (K), the Apex Committee recommended removal of the three-tier review process for global clinical trial (GCT) applications in June 2017.

The Hdbk-ClinTrial specifies that SECs usually consist of six (6) medical experts including pharmacologists/clinical pharmacologists, and medical specialists.

The Hdbk-ClinTrial and the 2019 CTRules state that 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

The 2019 CTRules and the Hdbk-ClinTrial also mention:

  • Safety/dosage/investigational tests (e.g. pharmacogenetic tests), and
  • Any additional information or study(ies) needed before marketing approval for inclusion in package insert/ summary product characteristic (SmPC) post marketing

Another development in 2015, per the C-NOCDCGIreq, is that only institutional EC approval of sponsor (applicant) proposals is required to add site(s) and investigator(s) to an existing clinical trial. The sponsor (applicant), however, should inform the DCGI of these changes. If no objection is received, then the sponsor (applicant) may assume that these changes are acceptable to the DCGI. (See the Clinical Trial Lifecycle topic, Submission Process, Submission Content, and Timeline of Review subtopics for detailed submission content and timeline requirements.)

Additional Resources
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 2-3, 7, 10-11, 18, 22, 25, 31-33, 38, and 79
(B) (Article) Regulatory Timelines in the Asia-Pacific (August 22, 2016)
George Clinical; Pharmaphorum
Relevant Sections: India
Davis, Sanish et al
Relevant Sections: Introduction
Sharma, Hitt and Parekh, Sameer; Pharmaceutical Regulatory Affairs: Open Access
Relevant Sections: Regulatory Bodies, Framework and Procedures
(E) (Article) India: The New Drugs And Clinical Trial Rules, 2019 (Last Modified April 16, 2019)
Singh & Associates
Relevant Sections: Clinical Trial of New drugs
(F) (Article) New Clinical Trials Rules will Help Patients — Here’s How (Last Modified April 8, 2019)
The Financial Express
Vaidyanathan, Gayathri; Nature
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 1, 2, 3, and 11
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: Item 02
Koul, Rahul; BioVoice News
Novotech
Relevant Sections: New Changes to Streamline Process and Reduce Timelines Even Further
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Regulatory Authority > Regulatory Fees
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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 and Additional Resources (A) and (B), 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 Additional Resource (A) 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 Additional Resource (A), payment shall 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 Additional Resource (B).

In addition, according to Additional Resources (A) and (B), electronic payment is made via the SUGAM Portal (Additional Resource (C)). 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).

Additional Resources (A) and (B) also specify that the online payment will take two (2) to three (3) days to be credited to the Government 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).

Refer to Additional Resources (A) and (B) for detailed fee requirements and online payment instructions via SUGAM.

Note to users: Although the fees listed in Additional Resource (A) are correct, the SUGAM website and associated documentation as well as CDSCO’s Pre-Screening Checklist 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
(A) (Manual) User Manual for SUGAM Online Payment (Version 1.1) (March 29, 2019)
Centre for Development of Advanced Computing and Central Drugs Standard Control Organization
(B) (Manual) User Manual For e-Governance Solution for CDSCO (Version 1.0) (Date Unavailable)
Centre for Development of Advanced Computing and Central Drugs Standard Control Organization
Relevant Sections: 1 and 6
(C) (Website) SUGAM - An e-Governance Solution for CDSCO (Current as of June 30, 2019)
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Ethics Committee > Ethics Committee
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Chapters 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 (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 2.1, 2.8, 4.0-4.2, 4.10, Tables 4.1 and 4.2, and Annex 1
Summary

Overview

As delineated in the 2019 CTRules and Additional Resource (A), 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 (biomedical and health research or clinical trial focused) are based at either institutions/organizations, or function independently, and must meet the requirements set forth in the 2019 CTRules and the ICMR Guidelines. 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. (Note to users: Chapter IV of the 2019 CTRules comes into force September 15, 2019.)

EC Composition

Pursuant to the 2019 CTRules and the ICMR Guidelines, an institutional/independent EC should be multidisciplinary and multi-sectorial, representing a mixed gender and age composition.

The 2019 CTRules and the ICMR Guidelines 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 ICMR Guidelines, preferably 50% of the members should also be non-affiliated or from outside the institution.

As per the 2019 CTRules and the ICMR Guidelines, 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:

Terms of Reference, Review Procedures, and Meeting Schedule

As delineated in the 2019 CTRules and the ICMR Guidelines, EC members should be made aware of their roles and responsibilities as committee members. 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 ICMR Guidelines, 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 ICMR Guidelines indicates the term of membership is generally two (2) to three (3) years, and may be extended.

In terms of training, the ICMR Guidelines 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 ICMR Guidelines, 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 ICMR Guidelines 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 ICMR Guidelines, 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 ICMR Guidelines.

Additional Resources
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 32-33
(B) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 6
Ethics Committee > Scope of Review
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2), Chapter III (7 and 11), Chapter V (19-20, 25, and 28), and Third Schedule (1 and 3)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 2.1, 2.8, 4, Tables 4.1 and 4.2, and Annex 1
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (ICMR Guidelines-Children) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 3.1
(4) (Circular) Restriction of Conducting Three Clinical Trials Per Investigator (C-NoCTLimit) (August 2, 2016)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare
(5) (Guidance) Handbook for Applicants & Reviewers of Clinical Trials of New Drugs in India (Hdbk-ClinTrial) (January 2017)
Indian Council of Medical Research, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
(6) (Circular) Requirement of NOC from DCGI for Addition of New Clinical Trial Site or Investigator (C-NOCDCGIreq) (August 3, 2016)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare
Summary

Overview

The primary scope of information assessed by the ethics committee (EC) relates to maintaining and protecting the rights, safety, and well-being of all trial participants, especially those in vulnerable populations, in accordance with the requirements set forth in the 2019 CTRules, the ICMR Guidelines, the ICMR Guidelines-Children, the Declaration of Helsinki, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum). (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 ICMR Guidelines also state that ECs must ensure an independent, timely, and competent review of all ethical aspects of the clinical trial protocol. 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 ICMR Guidelines or detailed ethical review guidelines. Per the ICMR Guidelines-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.

 In addition, according to the C-NoCTLimit, the EC should make the determination about how many trials an investigator can undertake based on its assessment of the risk and complexity of the trials.

Role in Clinical Trial Approval Process

As per the 2019 CTRules, the ICMR Guidelines, and Additional Resource (C), 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 Additional Resource (C) 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 Additional Resource (C), 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.

As specified in the 2019 CTRules, the Hdbk-ClinTrial, and Additional Resource (C), 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 Additional Resource (C) 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 Additional Resource (C), the EC of each site should notify the DCGI of its approval and provide a copy within 15 working days of making this decision.

In addition, according Additional Resources (C), (D), (E), and (F), 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.

The ICMR Guidelines further states that the EC must review and approve any protocol amendments prior to those changes being implemented. In addition, the EC has a continuing responsibility to monitor the approved trial(s) to ensure ethical compliance throughout the study duration.

As per the C-NOCDCGIreq, only EC approval of sponsor (applicant) proposals to add site(s) and investigator(s) to an existing clinical trial is required. The sponsor (applicant), however, should inform the DCGI of these changes. If no objection is received, the sponsor (applicant) may assume these changes are acceptable to the DCGI.

As delineated in the ICMR Guidelines, in a multicenter clinical trial, the participating sites usually follow a common protocol, and may decide to use a common EC from a participating site designated as the main EC for primary review. This EC should be based in India and registered with the DCGI. However, local site requirements (e.g., informed consent (IC) process) may be implemented by the local EC.

Per the ICMR Guidelines, 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

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 ICMR Guidelines for additional participating site requirements when a primary EC is selected for common EC review.

There is no stated expiration date for an EC approval in the 2019 CTRules or the ICMR Guidelines. 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.

Additional Resources
(A) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.27 and 3.1
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 2, 11, and 31-35
(D) (Article) Regulatory Timelines in the Asia-Pacific (August 22, 2016)
George Clinical; Pharmaphorum
Relevant Sections: India
Davis, Sanish et al
Relevant Sections: Introduction
Sharma, Hitt and Parekh, Sameer; Pharmaceutical Regulatory Affairs: Open Access
Relevant Sections: Regulatory Bodies, Framework and Procedures
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 6
Ethics Committee > Ethics Committee Fees
Last content review/update: July 01, 2019
Requirements
(1) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 4.14
Summary

Overview

As indicated in the ICMR Guidelines, 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: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Chapter III (6, 8-11, and 14), Chapter IV (17), and Chapter V (19-20, and 25), Third Schedule (Table 1), and Eighth Schedule (Form CT-01 and CT-02)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 4.1 and 4.15
Summary

Overview

In accordance with the 2019 CTRules, the ICMR Guidelines, and Additional Resource (A), all ethics committees (ECs) are required to register with the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), prior to reviewing and approving a clinical trial protocol. (Note to users: Chapter IV of the 2019 CTRules comes into force September 15, 2019.)

Registration Provisions

As specified in the 2019 CTRules, every EC must submit an application to register with the DCGI using Form CT-01 (found in the 2019 CTRules). 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 (found in the 2019 CTRules). The EC registration shall remain valid for a period of five (5) years from the date of issue, unless suspended or cancelled sooner. The EC may submit an application for registration renewal via Form CT-01 and 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.

In addition, the ICMR Guidelines specifies that the 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 ICMR Guidelines 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
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 32-33
Clinical Trial Lifecycle > Submission Process
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
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 (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 4.0-4.2, 4.8, and 4.10
(4) (Notice) Dated 15 Jan 2018 Regarding Implementation of Online Submission of Application (Notice15Jan18) (January 15, 2018)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare
(5) (Notice) Dated 05-10-2016 Regarding Submission of Online Applications for Global Clinical Trials (Notice5Oct16) (October 5, 2016)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare
Summary

Overview

In accordance with the 2019 CTRules, the Hdbk-ClinTrial, the ICMR Guidelines, and Additional Resource (A), 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 Additional Resources (A), (B), (C), and (D), the DCGI review and approval process may be conducted at the same time as the EC review for each clinical trial site.

In addition, per the 2019 CTRules and Additional Resource (A), non-regulatory academic/research clinical trials only require EC approval. The 2019 CTRules and Additional Resource (A), 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 Additional Resource (A), 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.

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

Delivery Information for Clinical Trial Application

As indicated in the Notice15Jan18, effective February 1, 2018, all clinical trial application submissions must be submitted electronically via CDSCO’s online portal, SUGAM (Additional Resource (E)). 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
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 10-11 and 31-33
(B) (Article) Regulatory Timelines in the Asia-Pacific (August 22, 2016)
George Clinical; Pharmaphorum
Relevant Sections: India
Davis, Sanish et al
Relevant Sections: Introduction
Sharma, Hitt and Parekh, Sameer; Pharmaceutical Regulatory Affairs: Open Access
Relevant Sections: Regulatory Bodies, Framework and Procedures
(E) (Website) SUGAM - An e-Governance Solution for CDSCO (Current as of June 30, 2019)
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Taylor, Nick Paul; Regulatory Focus
Clinical Trial Lifecycle > Submission Content
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
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 (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 4.0-4.2, 4.8, and 4.10
Summary

Overview

As set forth in the 2019 CTRules, the Hdbk-ClinTrial, the ICMR Guidelines, and Additional Resource (A), 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 Additional Resources (A), (B), (C), and (D), 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. 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, and Additional Resource (E), 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.

From the 2019 CTRules, the Hdbk-ClinTrial, and Additional Resource (E):

  • 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
  • Regulatory status in other countries
  • Prescribing information
  • Testing protocol(s) for quality control testing
  • Clinical study protocol
  • Investigator’s Brochure (IB)
  • 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

From the 2019 CTRules and Additional Resource (E):

  • Active ingredient information (for INDs and global clinical trials)
  • Formulation data (for INDs and global clinical trials)
  • Therapeutic class (for INDs and global clinical trials)

From the Hdbk-ClinTrial:

  • Dosage form
  • Justification and schematic diagram/flow chart proposed study and design (for INDs and global clinical trials)
  • Number of patients globally (for global clinical trials) and number of patients to be enrolled from India (for INDs and global clinical trials)

From the Hdbk-ClinTrial:

  • 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 Appendix Il of Schedule Y and International Conference on Harmonisation (ICH) Common Technical Document (CTD)
  • Protocol safety measures per toxicological studies; early clinical studies, approved product insert for marketed product, and published literature

From Additional Resource (E):

  • Investigational Medicinal Products Dossier (IMPD) (for global clinical trials)
  • Affidavit stating the IB information is correct and based on facts (for global clinical trials)
  • Source of bulk drugs (for INDs and global clinical trials)
  • Treasury Challan with Form CT-16 (Import license application) (for global clinical trials)
  • Applicant name (for INDs and global clinical trials)
  • Sponsor name (for global clinical trials)
  • Sponsor authorization letter (for global clinical trials)
  • Study drug name (for INDs and global clinical trials)
  • Details of biological specimens to be exported and application (for global clinical trials) (See Specimens topic for more information)
  • Drug status in India and other countries (for global clinical trials)
  • Proposed study status in other participating countries and any approvals, withdrawals, discontinuation of approval, etc. (for global clinical trials)
  • Affidavit stating study has not been discontinued in any country (for global clinical trials)

See the 2019 CTRules, the Hdbk-ClinTrial, and Additional Resource (E) 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 Additional Resource (A) 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 ICMR Guidelines, 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 (Additional Resource (F))
  • 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 ICMR Guidelines 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 (Additional Resource (F)) 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 ICMR Guidelines, the clinical study protocol should include the following elements:

  • Title page
  • Table of contents
  • Brief summary (ICMR Guidelines)
  • Study rationale
  • Study objective
  • Study design and methodology
  • Study population
  • Justification of inclusion/exclusion of vulnerable populations (ICMR Guidelines)
  • 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 ICMR Guidelines 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 ICMR Guidelines.

Additional Resources
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 10-11 and 31-33
(B) (Article) Regulatory Timelines in the Asia-Pacific (August 22, 2016)
George Clinical; Pharmaphorum
Relevant Sections: India
Davis, Sanish et al
Relevant Sections: Introduction
Sharma, Hitt and Parekh, Sameer; Pharmaceutical Regulatory Affairs: Open Access
Relevant Sections: Regulatory Bodies, Framework and Procedures
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 1 (INDs) and 3 (Global Clinical Trials)
(F) (Form) Application Form for Initial Review (Version 1) (Date Unavailable)
Indian Council of Medical Research, Department of Health and Family Welfare, Ministry of Health and Family Welfare
Clinical Trial Lifecycle > Timeline of Review
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2), Chapter II (3), Chapter V (19-25, and 28), Chapter XIII (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, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
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 (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 4.1, 4.2, 4.8, and 4.10  
Summary

Overview

Based on the 2019 CTRules, the Hdbk-ClinTrial, the ICMR Guidelines, and Additional Resource (A), 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 the Additional Resources (A) and (B), 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 Additional Resources (A), (C), and (D), 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 Additional Resource (A), 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 Additional Resource (A) 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

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 CT Rules states that these applications shall 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 Additional Resources (D) and (E), 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 Additional Resource (A) 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 shall remain valid for two (2) years from the date of its issue, unless extended by the DCGI as noted in the 2019 CTRules and Additional Resource (A).

Per Additional Resource (F), the DCGI’s review and approval process operates as a three-tiered system. The Subject Expert Committee (SEC) or investigational new drug (IND) committees initially evaluate clinical trial applications and new drugs. At the second level, the SEC’s/IND’s recommendations are reviewed by the Technical Committee (TC), which consists of experts from various therapeutic areas. At the third level, the Apex Committee conducts the final review and approves the application based on the TC’s recommendations. Upon receipt of the Apex Committee’s approval, the DCGI then issues final approval to the sponsor (applicant).

Per the Hdbk-ClinTrial, the three (3)-tier review process has been slightly altered. Per the Central Drugs Standard Control Organization (CDSCO)/SEC review processes described in the Hdbk-ClinTrial, unless the sponsor (applicant) specifically requests additional TC review, only the SEC’s recommendations are required for the DCGI (CDSCO) to issue a final decision to the Apex Committee.

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 the SEC for further technical review. Once the SEC has completed its review, 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 them 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 TC 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.

Additionally, in accordance with Additional Resources (G), (H), and (I), the Apex Committee recommended removal of the three-tier review process for global clinical trial (GCT) applications in June 2017.

EC Approval

As per Additional Resource (J), 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 ICMR Guidelines 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
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 10-11, 18, 22, 25, 31-33, 38, and 79
Davis, Sanish et al
Relevant Sections: Introduction
(C) (Article) India: The New Drugs And Clinical Trial Rules, 2019 (Last Modified April 16, 2019)
Singh & Associates
Relevant Sections: Clinical Trial of New drugs
(D) (Article) New Clinical Trials Rules will Help Patients — Here’s How (Last Modified April 8, 2019)
The Financial Express
Vaidyanathan, Gayathri; Nature
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 1, 2, 3, and 11
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: Item 02
Koul, Rahul; BioVoice News
Novotech
Relevant Sections: New Changes to Streamline Process and Reduce Timelines Even Further
(J) (Article) Regulatory Timelines in the Asia-Pacific (August 22, 2016)
George Clinical; Pharmaphorum
Relevant Sections: India
Clinical Trial Lifecycle > Trial Initiation
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
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 (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 4.1, 4.2, 4.8, and 4.10
(4) (Guidance) Guidelines for Good Clinical Laboratory Practices (GCLP) (2008)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
(5) (Circular) Restriction of Conducting Three Clinical Trials Per Investigator (C-NoCTLimit) (August 2, 2016)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare
Summary

Overview

As set forth in the 2019 CTRules, the Hdbk-ClinTrial, the ICMR Guidelines, and Additional Resource (A), 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 Additional Resource (A), 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 Additional Resource (A), 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 ICMR Guidelines for Good Clinical Laboratory Practices and Additional Resource (A) for additional laboratory requirement information, and Additional Resources (B) and (C) for international Good Laboratory Practice guidelines. According to the C-NoCTLimit, the EC should make the determination about how many trials an investigator can undertake based on its assessment of the risk and complexity of the trials.

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 ICMR Guidelines, and Additional Resource (A), 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) 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 Additional Resource (E), 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 Additional Resource (F), 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 Indian Council of Medical Research (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
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 10-11, 23-24, 32-33, 37, 64-67, and 71-75
(C) (Document) OECD Principles on Good Laboratory Practice (GLPs) (as revised in 1997) (1998) (OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring – Number 1)
Environment Directorate, Organisation for Economic Co-operation and Development
(D) (Website) Clinical Trials Registry - India (Current as of June 30, 2019)
National Institute of Medical Statistics, Indian Council of Medical Research, Ministry of Health and Family Welfare
National Institute of Medical Statistics, Indian Council of Medical Research, Ministry of Health and Family Welfare
Sabrang India
Kaul, Rhythma; Hindustan Times
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 1 (INDs), 2 (New Drugs), 5 (Test License), and 7 (New Drug Formulation)
Clinical Trial Lifecycle > Safety Reporting
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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 (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 2.6, 5.3, 7.1, and Glossary
Summary

Overview

In accordance with the 2019 CTRules and the ICMR Guidelines, 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.
  • 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 (ICMR Guidelines)

Reporting Requirements for AEs/ADRs

Investigator Responsibilities

As indicated in the 2019 CTRules and the ICMR Guidelines, 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, shall then be forwarded by the investigator to the DCGI, the Chairperson of the ethics committee, 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.

The ICMR Guidelines further states that the investigator may report SAEs/SADRs through email or fax communication (including on non-working days). Per the ICMR Guidelines, the investigator must also 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 subjects 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 shall forward their SAE/SADR reports to the DCGI within 14 days of knowledge of this occurrence. 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 the Sponsorship topic, Compensation subtopic for additional information on sponsor compensation requirements.

Safety Reporting Data Elements

The 2019 CTRules outlines the data elements required for reporting SAEs/SADRs that occur during a clinical trial. More detailed information on these data elements is available in the 2019 CTRules.

Additional Resources
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 14
(B) (Press Release) Notification on Clinical Trials (August 30, 2013)
Press Information Bureau, Ministry of Health and Family Welfare
Clinical Trial Lifecycle > Progress Reporting
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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 Additional Resource (A), 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 online portal, SUGAM (Additional Resource (B)). 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.

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.

Additional Resources
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 36
(B) (Website) SUGAM - An e-Governance Solution for CDSCO (Current as of June 30, 2019)
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Sponsorship > Definition of Sponsor
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Chapter I (2)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 4.0-4.2, 4.8, and 4.10
Summary

Overview

As per the, 2019 CTRules and the ICMR Guidelines, 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 ICMR Guidelines 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).

Additional Resources
No additional resources
Sponsorship > Trial Authorization
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 4.0-4.2, 4.8, and 4.10
(3) (Guidance) Handbook for Applicants & Reviewers of Clinical Trials of New Drugs in India (Hdbk-ClinTrial) (January 2017)
Indian Council of Medical Research, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: Objective
Summary

Overview

In accordance with the 2019 CTRules, and the ICMR Guidelines, the Hdbk-ClinTrial, and Additional Resource (A), 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 Additional Resources (A), (B), (C), and (D), 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 Additional Resource (A), 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.

Additional Resources
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 10-11, 14, and 31-33
(B) (Article) Regulatory Timelines in the Asia-Pacific (August 22, 2016)
George Clinical; Pharmaphorum
Relevant Sections: India
Davis, Sanish et al
Relevant Sections: Introduction
Sharma, Hitt and Parekh, Sameer; Pharmaceutical Regulatory Affairs: Open Access
Relevant Sections: Regulatory Bodies, Framework and Procedures
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 1 and 3
Sponsorship > Insurance
Last content review/update: July 01, 2019
Requirements
(1) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 2.6.2, 4.8, Box 4.4(a), and 7.1
(2) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Third Schedule (Table 1)
Summary

Overview

The ICMR Guidelines specifies that the sponsor should provide insurance coverage or a provision in the budget for possible compensation for trial-related injuries. The ICMR Guidelines 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. Additional Resource (A) 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, Additional Resource (A) 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 Additional Resource (A) for additional information on policy types and coverage limits.

With regard to indemnity coverage, the ICMR Guidelines 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
Faculty of Clinical Research, Institute of Good Manufacturing Practices India
Relevant Sections: Current Scenario of Liability and Indemnity in India and Other Countries
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Sponsorship > Compensation
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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 (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
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 ICMR Guidelines, 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 ICMR Guidelines, 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 ICMR Guidelines), 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, shall 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 ICMR Guidelines 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 Additional Resource (A) 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 shall have no liability for post-trial use of the IP

In addition, the ICMR Guidelines 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 ICMR Guidelines, 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 ICMR Guidelines, 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 Additional Resource (A), 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 Additional Resource (A) 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 shall 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 shall 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, shall 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 shall, 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 ICMR Guidelines 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 ICMR Guidelines 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
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 12, 39-41, and 61
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 14
Faculty of Clinical Research, Institute of Good Manufacturing Practices India
Sponsorship > Quality, Data & Records Management
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 11 and Third Schedule
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 4.2.3, 4.10, and 6.1 (Table 6.1)
Summary

Overview

In accordance with the 2019 CTRules and the ICMR Guidelines, 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.

Electronic Data Processing System

No information is currently available on electronic data processing systems.

Audit Requirements

As part of its QA system, the 2019 CTRules notes that investigator(s) may provide periodic study progress reports, 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.

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.

Multicenter Studies

Per the ICMR Guidelines, in a multicenter clinical trial, the participating sites usually follow a common protocol, and may decide to use a common EC from a participating site designated as the main EC for primary review. This EC should be based in India and registered with the DCGI. However, local site requirements (e.g., informed consent (IC) processes) may be implemented by the local EC.

See the ICMR Guidelines 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
(A) (Document) GCP Inspection Checklist (February 9, 2018)
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Sponsorship > Site/Investigator Selection
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Third Schedule
(2) (Circular) Requirement of NOC from DCGI for Addition of New Clinical Trial Site or Investigator (C-NOCDCGIreq) (August 3, 2016)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare
(3) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 4.2.3 and 4.10
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 the C-NOCDCGIReq, only institutional ethics committee (EC) approval of sponsor (applicant) proposals is required to add site(s) and investigator(s) to an existing clinical trial. The sponsor (applicant), however, should inform the Drugs Controller General of India (DCGI) of these changes. If no objection is received, then the sponsor (applicant) may assume that these changes are acceptable to the DCGI.

Further, per the ICMR Guidelines, 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
No additional resources
Informed Consent > Documentation Requirements
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Chapter III (11) and Third Schedule (2-3 and Tables 1 and 3)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 2.2, 4.4, 4.8, 5.0, 5.2-5.4, and 5.8
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (ICMR Guidelines-Children) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 3.1
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 ICMR Guidelines, and the ICMR Guidelines-Children.

As per the 2019 CTRules and the ICMR Guidelines, 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 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 ICMR Guidelines, and the ICMR Guidelines-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 ICMR Guidelines, 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 ICMR Guidelines 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.

Re-Consent

According to the ICMR Guidelines and the ICMR Guidelines-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 ICMR Guidelines and the ICMR Guidelines-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 ICMR Guidelines and the ICMR Guidelines-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 ICMR Guidelines, the ICF should be written in English and/or in the vernacular language that the participant is able to understand.

Documentation Copies

The ICMR Guidelines and the ICMR Guidelines-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 ICMR Guidelines, if the participant and/or his/her legal representative(s) or guardian(s) cannot sign, a thumb impression must be obtained. Also, the investigator(s) who administer the consent should also sign and date the ICF. As stated in the ICMR Guidelines and the ICMR Guidelines-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 ICMR Guidelines, the ICF may also be administered and documented electronically, as long as the EC approves the process first.

As described in the ICMR Guidelines, 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 ICMR Guidelines and the ICMR Guidelines-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 ICMR Guidelines-Children, the investigator should also keep a signed copy of the ICF.

Additional Resources
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
Informed Consent > Required Elements
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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 (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 2.2, 5.0- 5.3, and 6.11
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (ICMR Guidelines-Children) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 3.1
Summary

Overview

As delineated in the 2019 CTRules and the ICMR Guidelines, 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 ICMR Guidelines and the ICMR Guidelines-Children state that information about the research study should be presented in easily understandable and unambiguous language.

No Coercion

As per the ICMR Guidelines, 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 ICMR Guidelines, and the ICMR Guidelines-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 ICMR Guidelines and the ICMR Guidelines-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 ICMR Guidelines and the ICMR Guidelines-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) shall 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 ICMR Guidelines, and the ICMR Guidelines-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 Specimens subtopic for further information.

Additional Resources
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
Informed Consent > Compensation Disclosure
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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 (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 2.5, 5.1 (Box 5.1)
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (ICMR Guidelines-Children) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 5.1 and 5.2
Summary

Overview

In accordance with the 2019 CTRules, the ICMR Guidelines, and the ICMR Guidelines-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 ICMR Guidelines, 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 ICMR Guidelines and the ICMR Guidelines-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 ICMR Guidelines, 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 ICMR Guidelines 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 ICMR Guidelines, and the ICMR Guidelines-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
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 14
Faculty of Clinical Research, Institute of Good Manufacturing Practices India
Informed Consent > Participant Rights
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Chapter III (7 and 11), Chapter V (28) and Third Schedule (3)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 1.0, 1.1, 2.2, 2.3, 4.0, 5.0-5.2, and 7.1
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (ICMR Guidelines-Children) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 3.1
Summary

Overview

In accordance with the 2019 CTRules and the ICMR Guidelines, India’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The ICMR Guidelines upholds the Declaration of Helsinki. The 2019 CTRules, the ICMR Guidelines, and the ICMR Guidelines-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 ICMR Guidelines, and the ICMR Guidelines-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.

The Right to Information

As per the 2019 CTRules, the ICMR Guidelines, and the ICMR Guidelines-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 ICMR Guidelines, and the ICMR Guidelines-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, ICMR Guidelines, and the ICMR Guidelines-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 ICMR Guidelines 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
(A) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
Informed Consent > Special Circumstances/Emergencies
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Third Schedule (2)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Box 5.2, 5.7, and 5.8
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (ICMR Guidelines-Children) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 3.1 and 6.5
Summary

Overview

The 2019 CTRules, the ICMR Guidelines, and the ICMR Guidelines-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 ICMR Guidelines-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 Management 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 ICMR Guidelines, the ICMR Guidelines-Children, and Additional Resource (A), 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 ICMR Guidelines, an attempt should be made to obtain the participant’s consent as soon as possible.

Moreover, per the ICMR Guidelines-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 ICMR Guidelines, the ICMR Guidelines-Children, and Additional Resource (A), 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.

As described in Additional Resource (A), a waiver provision should only be used when alternative mechanisms for ensuring participant protection are acceptable and in place. The waiver request must be applied for in advance to the Technical Review Committee and communicated to the EC. The request should also contain the reason the sponsor believes a waiver is justified; and, a description of the alternative mechanism(s) for participant protection the sponsor intends to use in the community. Written information translated into the participant’s local language should also be provided to the participant explaining the implications. Please refer to Additional Resource (A) for detailed conditions under which a wavier may be granted.

The ICMR Guidelines-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
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 2
(B) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
Informed Consent > Vulnerable Populations
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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 (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 1.1, 2.9, 6.0. 6.1, 6.2, 6.6, 6.7, 6.9, and 6.10
Summary

Overview

As set forth in the 2019 CTRules and the ICMR Guidelines, 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 ICMR Guidelines 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 ICMR Guidelines, 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 ICMR Guidelines, specify that ethics committees (ECs) must pay special attention to protecting participants who are from vulnerable populations. See the ICMR Guidelines for detailed safeguards that must be complied with when trials involving vulnerable populations are conducted. The ICMR Guidelines 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.

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 ICMR Guidelines, 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 ICMR Guidelines 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 ICMR Guidelines, 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 ICMR Guidelines, 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
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
Informed Consent > Children/Minors
Last content review/update: July 01, 2019
Requirements
(1) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 6.5
(2) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: First Schedule (3) and Third Schedule (2)
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (ICMR Guidelines-Children) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 1.5, 2, 3.1-3.3, 4.1, and 6.1
Summary

Overview

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

As stated in the ICMR Guidelines, the 2019 CTRules, and the ICMR Guidelines-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 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 ICMR Guidelines, 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 ICMR Guidelines-Children should be consulted for detailed EC assessment criteria to be used to evaluate research studies involving children.

Assent Requirements

As delineated in the ICMR Guidelines, the 2019 CTRules, and the ICMR Guidelines-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 ICMR Guidelines, mature minors are those from age seven (7) up to age 18.

The ICMR Guidelines-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 ICMR Guidelines-Children.

Additional Resources
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: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: First Schedule (3)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 6.4 and 7.18
(3) (Guidance) National Ethical Guidelines for Biomedical Research Involving Children (ICMR Guidelines-Children) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 6.1
Summary

Overview

As per the 2019 CTRules and the ICMR Guidelines, 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 ICMR Guidelines:

  • 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 ICMR Guidelines-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
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
Informed Consent > Prisoners
Last content review/update: July 01, 2019
Requirements
(1) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 6.9
Summary

Overview

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

The ICMR Guidelines 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: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Third Schedule (2)
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 5.3, 5.4, 6.3, 6.5, and 6.8
Summary

Overview

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

The ICMR Guidelines 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 ICMR Guidelines also states that the presence of a mental disorder is not synonymous with incapacity of understanding or inability to provide informed consent.

Per the ICMR Guidelines, 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
(A) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare
Relevant Sections: 13
Investigational Products > Definition of Investigational Product
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Chapter V (25), Chapter VIII (52), Chapter IX (67), Chapter X (75), Chapter XIII (13), Second Schedule (1), Sixth Schedule, Eighth Schedule (Forms CT-10, CT-16, and CT-18)
(2) (Legislation and Implementing Regulations) 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
Summary

Overview

As specified in the 2019 CTRules and Additional Resource (A), the Drugs Controller General of India (DCGI) is responsible for authorizing the manufacture or import of investigational products (IPs) (also referred to as new drugs or investigational new drugs) in India. The DCGI approves the manufacture or import of IPs as part of the clinical trial application review and approval process. Applicants must apply for permission using Forms CT-10, CT-16, and CT-18 located in the 2019 CTRules.

In addition, per the 2019 CTRules and Additional Resource (A), the sponsor (applicant) is required to obtain an import license for the purpose of examination, testing, or analysis from the DCGI for the shipment of the IP to be used in the trial using Form CT-16. (See Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics; and Regulatory Authority topic, Regulatory Fees subtopic for detailed clinical trial application requirements). Refer to Additional Resources (B) and (C) for detailed fee requirements and online payment instructions via SUGAM.

According to the 2019 CTRules, the sponsor must submit a fee of 5000 Indian National Rupees (INRs) per product with an application for permission to manufacture or import a new drug or investigational new drug for a clinical trial.

The sponsor must ensure that imported IPs are manufactured in accordance with Good Manufacturing Practices (GMP) as laid down in the DCA-DCR. Refer to Schedule M of the DCA-DCR to review the GMP requirements.

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 Additional Resources (E) and (F), 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.

The 2019 CTRules and Additional Resource (A) 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 to establish the new drug’s safety and efficacy per the DCGI-approved formulation

In addition, per the 2019 CTRules and Additional Resource (A), 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.

Additional Resources
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 64-67, 71-75, and 79
(B) (Manual) User Manual for SUGAM Online Payment (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
(C) (Manual) User Manual For e-Governance Solution for CDSCO (Version 1.0) (Date Unavailable)
Centre for Development of Advanced Computing and Central Drugs Standard Control Organization
Relevant Sections: 1, 4, and 6
(D) (Website) SUGAM - An e-Governance Solution for CDSCO (Current as of June 30, 2019)
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
(E) (Article) New Clinical Trials Rules will Help Patients — Here’s How (Last Modified April 8, 2019)
The Financial Express
Vaidyanathan, Gayathri; Nature
Investigational Products > IMP/IND Quality Requirements
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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)
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).

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 Additional Resource (A), 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 Additional Resource (B) 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 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.

Additional Resources
Raghavan, Prabha; The Economic Times
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 79
Investigational Products > Labeling & Packaging
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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 Additional Resource (A), 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
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 70
Investigational Products > Product Management
Last content review/update: July 01, 2019
Requirements
(1) (Regulation) New Drugs and Clinical Trials Rules, 2019 (2019 CTRules) (Effective March 19, 2019)
Department of Health, 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 Additional Resource (A), 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 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
New Drugs Division, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare
Relevant Sections: 68
Specimens > Definition of Specimen
Last content review/update: July 01, 2019
Requirements
(1) (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
(2) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: Chapter III, Review Procedures, Section 3
Summary

Overview

In India, per the G-XBiolMat and the ICMR Guidelines, 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 and the ICMR Guidelines, 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

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: July 01, 2019
Requirements
(1) (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
(2) (Notification) 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)
Directorate General of Foreign Trade, Department of Commerce, Ministry of Commerce and Industry
(3) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 3.8 and 11.4
(4) (Guidance) Guidance for International Collaboration of Transfer of Biological Material (G-IntlCollab-BioMat) (Last Updated September 6, 2018)
International Health Division, Indian Council of Medical Research
Relevant Sections: Health Ministry’s Screening Committee (HMSC)
Summary

Overview

As specified in the G-XBiolMat, the HumBiol_ImprtExprt, and Additional Resource (A), 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 Additional Resource (A), 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 Government of India (GOI’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 ICMR Guidelines indicate that the export of all biological materials is to be covered under existing GOI and ethics guidelines. The ICMR Guidelines 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 Additional Resources (C) and (D) for detailed information on the HMSC.

Per the ICMR Guidelines, 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 ICMR Guidelines and the G-IntlCollab-BioMat, 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 ICMR Guidelines also indicates that an appropriate MoU should be in place to safeguard mutual country interests and ensure compliance.

Refer to the G-XBiolMat, the ICMR Guidelines, and the G-IntlCollab-BioMat 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.

Additionally, per Additional Resource (E), following the DCGI’s approval of a study, the DGFT is to be contacted to obtain approvals for the export of blood samples out of India. DGFT approval typically takes two (2) to four (4) weeks.

Additional Resources
(A) (Website) Transfer of Biological Material (Last Updated September 1, 2018)
Indian Council of Medical Research, International Health Division, Ministry of Health and Family Welfare
Directorate General of Health Services, Central Drugs Standard Control Organization, Ministry of Health and Family Welfare
Seth, Sandeep; Journal of the Practice of Cardiovascular Sciences
National Institutes for Allergy and Infectious Diseases, National Institutes of Health
(E) (Website) Clinical Research in India (Current as of June 30, 2019)
Criterium
Relevant Sections: An Overview of the Indian Regulation Process for of Clinical Trials
Specimens > Consent for Specimen
Last content review/update: July 01, 2019
Requirements
(1) (Guidance) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (ICMR Guidelines) (October 2017)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare
Relevant Sections: 4.0, 5.1 (Box 5.1), and 10.4
Summary

Overview

In accordance with the ICMR Guidelines a 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 ICMR Guidelines, 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 ICMR Guidelines require investigator(s) to communicate the following information to participants in 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 ICMR Guidelines 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 ICMR Guidelines, 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 ICMR Guidelines 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

Additionally, per the ICMR Guidelines, in the case of population or community-based studies, group consent must 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 ICMR Guidelines, 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 ICMR Guidelines 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).

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