Regulatory Authority
Regulatory Authority
Scope of Assessment
Regulatory Fees
Ethics Committee
Ethics Committee
Scope of Review
Ethics Committee Fees
Authorizing Body
Clinical Trial Lifecycle
Submission Process
Submission Content
Timeline of Review
Trial Initiation
Safety Reporting
Progress Reporting
Sponsorship
Definition of Sponsor
Trial Authorization
Insurance
Compensation
Quality, Data & Records Management
Site/Investigator Selection
Informed Consent
Documentation Requirements
Required Elements
Compensation Disclosure
Participant Rights
Special Circumstances/Emergencies
Vulnerable Populations
Children/Minors
Pregnant Women, Fetuses & Neonates
Prisoners
Mentally Impaired
Investigational Products
Definition of Investigational Product
Manufacturing & Import
IMP/IND Quality Requirements
Labeling & Packaging
Product Management
Specimens
Definition of Specimen
Import & Export
Consent for Specimens
India
QUICK FACTS
Clinical trial application languageEnglish
Parallel regulatory and ethical review permittedYes
Clinical trial registration requiredYes
In-country sponsor presence/representation requiredYes
Age of minorsUnder 18
Specimens export allowedYes
Regulatory Authority > Regulatory Authority
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
In India, the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), is the regulatory authority responsible for clinical trial oversight, approval and inspections. The DCGI grants permission for clinical trials to be conducted in India in accordance with the provisions of the DCA, 1940/DCR, 1945 and Schedule Y. The DCGI is also commonly referred to as the Licensing Authority in the Indian regulations.

CDSCO is India’s central regulatory body for pharmaceuticals and medical devices. The DCGI, who directs CDSCO, handles the drug and device regulatory process; he/she is also responsible for registering all imported drugs and new drugs and for overseeing clinical trials. CDSCO functions under the Directorate of General Health Services (DGHS) which is part of the Ministry of Health and Family Welfare (MOHFW).

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: +91-11-23236965 / 23236975
Fax: +91-11-23236973
E-mail: dci@nb.nic.in
Staff Directory: http://www.cdsco.nic.in/forms/contentpage1.aspx?lid=1441

ADDITIONAL RESOURCES

(A) (Website) Central Drugs Standard Control Organization – Contact Us (Current as of December 8, 2016)
Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India

(B) (Website) Central Drugs Standard Control Organization – About Us (Current as of December 8, 2016)
Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: The Drugs and Cosmetics Rules, Part IV (Sections 21 & 22)

(2) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: Section 2 (1)

Regulatory Authority > Scope of Assessment
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
India’s review and approval process has been undergoing significant transformation over the past few years. As of July 2014, the New Drug Advisory Committees (NDACs) established in 2011 were renamed Subject Expert Committees (SECs). According to the OrderNDAC, SEC members will be drawn randomly from a pool of experts.

As per Order5Sept14, all new clinical trial applications in India must be evaluated in regard to the following parameters:

  • Assessment of risk versus benefit to the patients
  • Innovation vis-à-vis existing therapeutic option
  • Unmet medical need in the country

The Drugs Controller General of India (DCGI)’s review and approval process within the Central Drugs Standard Control Organization (CDSCO) operates as a three-tiered system. Clinical trial applications and new drugs are initially evaluated by the SECs, and their recommendations are then reviewed by the Technical Review Committee (TRC) that has been constituted under the Directorate General of Health Services (DGHS). The TRC consists of experts from various therapeutic areas. The DCGI will grant clinical trial application and new drug approvals based on the TRC’s recommendations. As per the OrderPlaceboCT, the SEC is also responsible for ensuring that only those placebo controlled clinical trials with appropriate, efficient, and ethical designs be considered for approval.

In addition, as per Additional Resources (B), (C), and (D), effective January 2013, the Honorable Supreme Court of India mandated a system be established to supervise clinical trials by constituting an Apex Committee under the Chairmanship of the Secretary of Health and Family Welfare.

Both the DCGI and ethics committee (EC) approvals are mandatory for a sponsor to initiate a clinical trial, except in the case of clinical trials for academic/research purposes that are non-regulatory in nature. (See Clinical Trial Review Process below.)

According to Additional Resource (E), the Ministry of Health and Family Welfare (MOHFW) also constituted an Expert Committee under the chairmanship of Professor Ranjit Roy Chaudhury in February 2013 to formulate policy, guidelines, and standard operating procedures to approve new drugs, including biologicals, clinical trials and the banning of drugs. The Expert Committee is responsible for proposing several actions that have been finalized as Orders by the MOHFW in July 2014.

Definition of New Drugs/Investigational New Drugs
The scope of the DCGI assessment includes a review of applications to conduct clinical trials for new drugs and investigational new drugs. According to the DCA, 1940/DCR, 1945, a “new drug” may be defined as:

  • a bulk drug substance which 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 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.

An investigational new drug in turn is defined by the DCA, 1940/DCR, 1945 as a new chemical entity or a product having therapeutic indication, but which has never been tested before on human participants. The IN-GCPs, similarly, defines an investigational product as a pharmaceutical product (including the comparator product) being tested or used as a reference in a clinical study.

Clinical Trial Review Process
The DCGI’s review of a clinical trial drug protocol is described in Schedule Y as the “systematic study of new drug(s) in human subject(s) to generate data for discovering and/or verifying the clinical, pharmacological (including pharmacodynamic and pharmacokinetic) and/or adverse effects with the objective of determining safety and/or efficacy of the new drug.”((1) section G.S.R. 32(E))

In India, a clinical study includes clinical trials (Phase I to Phase III) and bioavailability/bioequivalence studies; both study types follow the same application process. The DCGI reviews a clinical trial application submitted by the sponsor using Form 44. The DCGI, in turn, grants permission to the sponsor using Form 45, 45-A, 45 or 46-A. (See the Clinical Trial Lifecycle topic, Submission Process subtopic for detailed submission requirements.)

The DCGI review and approval process is conducted in parallel with the EC review, except in the case of clinical trials for academic/research purposes that are non-regulatory in nature.

According to DCR-SecondAmdmt-2016, a clinical trial intended for academic purposes that studies a new indication or route of administration or new dose or dosage of an already approved drug formulation does not require DCGI approval so 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 licensing authority (DCGI)

As per DCR-SecondAmdmt-2016, the EC shall 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 shall be presumed that DCGI permission is not required.

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

ADDITIONAL RESOURCES

(A) (Website) Central Drugs Standard Control Organization – Recommendations of New Drugs Advisory Committee (NDAC) and Medical Devices Advisory Committee (MDAC) (Current as of May 2, 2014)
Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India

(B) (Presentation) Impact of Recent Regulatory Changes for Conducting Clincial Trials in India (October 9, 2013)
Singh, Surinder, National Institute of Biologicals, Ministry of Health and Family Welfare, Government of India

(C) (Document) Major Achievements of CDSCO (January 2012 to February 2014) (March 1, 2014)

(D) (Article) Indian Regulatory Update 2013 (October-December 2013)
Suvarnapathaki, Kedar
Perspectives in Clinical Research

Relevant Section: 237-238

(E) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: *G.S.R. 32(E), 1, 2 (1, 6, 7, 8), 5 and Appendices I, II, III, IV and X

(2) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Part XA (Sections 122-A, 122-B, 122-DA, 122-DB, 122-DC, and 122-E)

(3) (Regulation) Notice: Expansion of Panel of Experts for Evaluation of Applications of New Drugs, Clinical Trials & Medical Devices – Regarding (Notice) (August 28, 2012)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(4) (Regulation) Order: Constitution of New Drugs Advisory Committee (NDAC) to advise Drugs Controller General (India) {DCG(I)} in matters for Review of Applications of New Drugs and Clinical Trials – Regarding (March 31, 2011)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(5) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: Definitions

(6) (Regulation) Order: Procedure for Review of Applications of Clinical Trials and New Drugs – Regarding (OrderNDAC) (July 3, 2014)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(7) (Regulation) Order: Placebo Controlled Trials – Regarding (OrderPlaceboCT) (July 3, 2014)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(8) (Regulation) Order Dated 5 September 2014 (Order5Sept14) (September 5, 2014)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(9) (Regulation) Drugs and Cosmetics (Second Amendment) Rules, 2016 (DCR-SecondAmdmt-2016) (March 16, 2016)
Department of Health and Family Welfare, Ministry of Health and Family Welfare, Government of India

Relevant Section: Rule 122 DA (4)

(10) (Guidance) Circular: Requirement of NOC from DCGI for Addition of New Clinical Trial Site or Investigator – Regarding (C-NOCreq) (November 10, 2015)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

Regulatory Authority > Regulatory Fees
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Official Fees
As per Rule 122-DA under Part XA in the DCA, 1940/DCR, 1945, a clinical trial application form (Form 44) should be accompanied by one of the following officially mandated fees:

  • 50,000 Rupees ($1,020 USD) for Phase I (human) clinical trials
  • 25,000 Rupees ($510 USD) for Phase II (exploratory) clinical trials
  • 25,000 Rupees ($510 USD) for Phase III (confirmatory) clinical trials

Additional Provisions
In accordance with Rule 122-DA under Part XA in the DCA, 1940/DCR, 1945:

  • If the clinical trials are being conducted for academic or research purposes, no fee is required to be paid along with the clinical trial application when the Central Government of India or one of India’s state government institute(s) is sponsoring the clinical research.

Instructions for Payment of Clinical Trial Application Fees
As per Additional Resources (A) and (B), clinical trial application payments should be made using a Treasury Challan form. Treasury Challan is the remittance slip for making a payment to a government account. See Additional Resource (B) for example of form.

Payments should be sent to:

Bank Name: Bank of Baroda
Address: Bank of Baroda, Kasturba Gandhi Marg, New Delhi – 110 001
Swift Code: Swift mode of transfer is not yet functional
Payment Mode: Through Challan or Electronic Clearance System
Beneficiary Code: 0210 – Medical and Public Health, 04 – Public Health, 104 – Fees and Fines

ADDITIONAL RESOURCES

(A) (ebook) Global Clinical Trials: Effective Implementation and Management (June 6, 2011)
Chin, Richard and Bairu, Menghis, eds., Academic Press

Relevant Section: Chapter 7, Section 7.8.2.

(B) (Website) Treasury Challan Form (Current as of July 3, 2012)
National Portal of India, Government of India

REQUIREMENTS

(1) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: The Drugs and Cosmetics Rules, Part IV (Section 122-DA)

Ethics Committee > Ethics Committee
Back to Top
Email section Share    Print section Print
Last content review/update: July 11, 2017. Submit updates or comments.
SUMMARY

Overview
India has a decentralized process for the ethical review of clinical trial applications, and requires ethics committee (EC) approval for each trial site. The majority of ECs are based at clinical or academic institutions and hospitals. There are also independent ECs that function outside institutions for those researchers who have no institutional attachments or who work in institutions with no EC.

EC Composition
The EC should be multidisciplinary and multisectorial in composition. As per the IN-GCPs, the ICMR Guidelines, and DCR-3rdAmdmt, an EC should have at least seven (7) members and appoint from among its members a chairperson (from outside the institution) and a member secretary (generally from inside the institution to conduct committee business). The other members should be a mix of medical/non-medical and scientific/non-scientific persons, including the lay public, to represent differing viewpoints.

The composition should be as follows:

  1. Chairperson
  2. One (1) to two (2) basic medical scientists (preferably one (1) pharmacologist)
  3. One (1) to two (2) clinicians from various institutions
  4. One (1) legal expert or retired judge
  5. One (1) social scientist/representative of non-governmental voluntary agency
  6. One (1) philosopher/ethicist/theologian
  7. One (1) lay person from the community
  8. Member secretary

Additionally, ECs are required to comply with the following composition:

  • Must include at least one (1) member whose primary area of interest/specialization is non-scientific and at least one (1) member who is independent of the institution/trial site
  • Should have as its members, individuals from other institutions/communities, as required
  • Members should be familiar with key clinical regulatory requirements as delineated in the IN-GCPs, the ICMR Guidelines, Schedule Y, DCR-3rdAmdmt, the Declaration of Helsinki, and the International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs)
  • Members representing basic medical science/clinical research should have post-graduate qualifications and experience in their fields and be aware of their roles/responsibilities as committee members
  • Based on the research area requirement (e.g., HIV AIDS, genetic disorders, etc.), it is desirable to include a member from specific patient groups in the EC as much as possible. If required, subject experts could be invited to offer their views, but would not have any voting rights
  • There should be appropriate gender and age representation on the EC
  • There should be no conflict of interest. Members should voluntarily withdraw from the EC while making a decision on an application that evokes a conflict of interest. This should be documented in writing to the chairperson prior to the review and recorded in the minutes
  • Only those EC members who are independent of the clinical trial and the sponsor of the trial should vote/provide opinions in study related matters

Terms of Reference
As delineated in the IN-GCPs and the ICMR Guidelines, EC members should be made aware of their roles and responsibilities as committee members. Any change in the regulatory requirements should be brought to their attention, and they should be kept abreast of all national/international developments in this regard. The terms of reference should also include a statement on terms of appointment with reference to the term duration; policy for removal/replacement; resignation procedure; meeting frequency; payment of processing fee to EC for review; and honorarium to members, invited experts, etc. Each committee should specify these terms in its own standard operating procedures (SOPs) which should be made available to each member.

Review Process and Meeting Schedule
The ICMR Guidelines require the EC Member Secretary to screen the clinical trial applications for their completeness and categorize them into three (3) types according to risk level: exemption from review, expedited review, or full review. An investigator cannot decide that his/her protocol falls in the exempted category without an EC review.

As per the IN-GCPs, the ICMR Guidelines, and Schedule Y, the EC review should be conducted through formal meetings and should not resort to decisions through a circulation of proposals. The committee should meet at regular intervals and should not keep a decision pending for more than 3-6 months, which should be defined in the SOP.

The EC(s) should conduct, at appropriate intervals, ongoing reviews of the trials for which they review protocol(s). Such a review may be based on:

  • periodic study progress reports furnished by the investigators, and/or
  • monitoring and internal audit reports furnished by the sponsor, and/or
  • by visiting the study sites
ADDITIONAL RESOURCES

(A) (Article) Advisory – Notice: Unless an Ethics Committee is Accredited, It Should Not Function (October 20, 2012)
Chaudrury, Ranjit Roy. Express Pharma

(B) (ICH Guidance) International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Conference on Harmonisation
Geneva, Switzerland

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.4.2 and Appendix V

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Chapter II

(3) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2 (1), 5, and Appendix VIII

(4) (Regulation) Drugs and Cosmetics (3rd Amendment) Rules, 2013 (DCR-3rdAmdmt – English and Hindi/Hindī) (February 8, 2013)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Ethics Committee > Scope of Review
Back to Top
Email section Share    Print section Print
Last content review/update: July 11, 2017. Submit updates or comments.
SUMMARY

Overview
The primary scope of information assessed by the ethics committee (EC) centers on verifying the protection of the rights, safety, and well-being of all trial participants, especially those in vulnerable populations, in accordance with the requirements set forth in the IN-GCPs, the ICMR Guidelines, Schedule Y, the Declaration of Helsinki, and the International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs). In addition, as per OrderPlaceboCT, the EC is required to ensure that the design used in a placebo controlled clinical trial is appropriate, efficient, and ethical. (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 EC should also ensure that a scientific evaluation has been completed by a designated scientific review committee prior to initiating an ethical review.

The EC is responsible for:

  • Ensuring a competent review of all ethical aspects of the clinical trial protocol
  • Evaluating the possible risks and expected benefits to participants
  • Confirming the suitability of the investigator(s), facilities, and methods, including investigators and sites added throughout study duration
  • Confirming that sufficient information is used to obtain and document participant informed consent (IC) (See the Informed Consent topic for detailed coverage of this subject).
  • Verifying the adequacy of confidentiality safeguards

Additionally, 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.

In the case of clinical trial related injury or death, the EC should also review and make recommendations for compensation to be paid by the sponsor in a stipulated manner and time period (See the Sponsorship topic, Compensation subtopic and the Informed Consent topic, Compensation Disclosure subtopic for additional compensation requirements).

Role in Clinical Trial Approval Process
Both regulatory authority (Drugs Controller General of India (DCGI)) and EC approvals of a clinical trial application are mandatory for a sponsor to initiate a clinical trial, except in the case of clinical trials for academic/research purposes that are non-regulatory in nature, which only require EC approval.

The EC review is conducted in parallel with the DCGI review process. The EC must review and approve both the proposed and final trial protocols in order for the sponsor to receive DCGI approval. The EC also has a continuing responsibility to regularly monitor the approved trial(s) to ensure ethical compliance throughout the study duration.

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

If a multicenter trial is being conducted and the same clinical protocol is being used for all the sites, an EC that approves one (1) trial site may also grant approval to another site within the study. However, the approving EC must also be willing to accept responsibility for overseeing the studies at each of the approved sites. Furthermore, the site must be willing to accept the EC’s oversight role in this arrangement. (See Schedule Y for more details).

According to DCR-SecondAmdmt-2016, a clinical trial intended for academic purposes that studies a new indication or route of administration or new dose or dosage of an already approved drug formulation does not require DCGI approval so 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 licensing authority (DCGI)

As per DCR-SecondAmdmt-2016, the EC shall however 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 shall be presumed that DCGI permission is not required.

There is no stated expiration date for an EC approval in the IN-GCPs, the ICMR Guidelines, or Schedule Y. However, in the event that an EC revokes its approval accorded to 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.

Clinical Protocol Documentation Requirements
The EC must review the submitted clinical trial application along with the clinical trial protocol. (See the Clinical Trial Lifecycle topic, Submission Content subtopic for details on the clinical trial application and the clinical trial protocol).

ADDITIONAL RESOURCES

(A) (Article) Advisory – Notice: Unless an Ethics Committee is Accredited, It Should Not Function (October 20, 2012)
Chaudrury, Ranjit Roy, Express Pharma

(B) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

(C) (ICH Guidance) International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Conference on Harmonisation
Geneva, Switzerland

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.4.2 and Appendix V

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Chapter II

(3) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2 (1), 5, and Appendix VIII

(4) (Regulation) Drugs and Cosmetics (3rd Amendment) Rules, 2013 (DCR-3rdAmdmt – English and Hindi/Hindī) (February 8, 2013)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

(5) (Regulation) Order: Placebo Controlled Trials – Regarding (OrderPlaceboCT) (July 3, 2014)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(6) (Regulation) Drugs and Cosmetics (Second Amendment) Rules, 2016 (DCR-SecondAmdmt-2016 Hindi/Hindī and English) (March 16, 2016)
Department of Health and Family Welfare, Ministry of Health and Family Welfare, Government of India

Relevant Section: Rule 122 DA (4)

(7) (Guidance) Circular: Requirement of NOC from DCGI for Addition of New Clinical Trial Site or Investigator – Regarding (C-NOCreq) (November 10, 2015)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(8) (Regulation) Circular: Restriction of Conducting Three Clinical Trials Per Investigator - Regarding (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, Government of India

Ethics Committee > Ethics Committee Fees
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
There is no official standard fee assessed by an ethics committee (EC) for reviewing a clinical trial application. The ICMR Guidelines state that reasonable fees may be charged to cover the expenses related to review and administrative processes. EC members may also be given reasonable compensation for their time reviewing the clinical protocols. Basically, every institution should allocate adequate funds to ensure the smooth functioning of the EC.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Chapter II

Ethics Committee > Authorizing Body
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
The Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), is the licensing authority that must approve the registration of an ethics committee (EC) in accordance with the requirements described in DCR-3rdAmdmt. The EC must submit an application for registration to the DCGI.

The DCGI may reject an application if he/she is not satisfied, and shall inform the applicant of the reasons for the rejection and the conditions which must be satisfied before registration can be granted.

Registration Provisions
As specified in DCR-3rdAmdmt, EC registration is valid for a period of three (3) years from the date of issue, unless suspended or cancelled sooner. If the EC fails to comply with any of the registration conditions, the DCGI may, after giving the EC an opportunity to show cause 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 within 90 days to the Government of India (also known as the Central Government) who may confirm, reverse, or modify such an order.

The EC must 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.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Regulation) Drugs and Cosmetics (3rd Amendment) Rules, 2013 (DCR-3rdAmdmt – English and Hindi/Hindī) (February 8, 2013)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Clinical Trial Lifecycle > Submission Process
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
The Drugs Controller General of India (DCGI) review and approval process is conducted in parallel with the ethics committee (EC) review and approval process except in the case of clinical trials for academic/research purposes that are non-regulatory in nature. The sponsor must submit the clinical trial application to both the DCGI and the EC. The EC must grant a separate approval for each trial site to be used, and the DCGI must be informed of each approval. The process for submitting the clinical trial application to the DCGI is outlined below, whereas each EC has its own process.

For clinical trials for academic/research purposes that are non-regulatory in nature, per the DCR-SecondAmdmt-2016, institutional EC approval is required, but DCGI approval is not required. (See the Ethics Committee topic, Scope of Review subtopic for more information).

Delivery Address for Clinical Trial Application
As indicated in Additional Resource (A), all clinical trial applications and subsequent correspondence should be sent to the following address:

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

E-mail: dci@nb.nic.in

Responses to clarification requests issued by the DCGI should also be sent directly to the above address.

Assembly and Number of Copies
Currently, electronic submissions of clinical trial applications have not yet been fully implemented in India. As delineated in the G-CTA, applicants should submit two (2) hard copies and two (2) soft copies (i.e., CDs in PDF format) of the clinical trial application.

Hard copies: Must be well labeled with document number, name of the firm, submission date, etc. The number of volumes should be labeled as Volume Number/Total Number of volumes (e.g., if there are five volumes, volume three will be labeled as Volume: 3/5).

Soft copies: Must be well labeled with document number, name of the firm, submission date, etc. Scanned copies of only signed documents, such as test reports, will be acceptable as soft copies. The table of contents under each heading should be linked to the file(s) or relevant document(s) for easy tracking in the CDs.

The applicant should preserve/maintain one (1) hard copy and one (1) soft copy of the submitted documents for future reference.

Clinical Trial Application Language Requirements
As per Additional Resources (B) and (C), clinical trial application submissions must be in English and all EC documents are also required to be in English.

ADDITIONAL RESOURCES

(A) (Website) Central Drugs Standard Control Organization – Contact Us (Current as of December 8, 2016)
Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India

(B) (ebook) Global Clinical Trials: Effective Implementation and Management (June 6, 2011)
Chin, Richard and Bairu, Menghis, eds., Academic Press

Relevant Section: Chapter 7, Section 7.8.3.

(C) (Article) Practical Aspects of Conducting a Clinical Trial in India (February 2009)
Kumar, Mukesh, Regulatory Focus

Relevant Section: pages 30-37

REQUIREMENTS

(1) (Guidance) Guidance for Industry on Submission of Clinical Trial Application for Evaluating Safety and Efficacy (General Considerations for Conducting Clinical Trial as per Drugs and Cosmetics Act 1940 and Rules 1945) (G-CTA) (2008) (Version 1.1)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: Objective

(2) (Regulation) Drugs and Cosmetics (Second Amendment) Rules, 2016 (DCR-SecondAmdmt-2016Hindi/Hindī and English) (March 16, 2016)
Department of Health and Family Welfare, Ministry of Health and Family Welfare, Government of India

Relevant Section: Rule 122 DA (4)

Clinical Trial Lifecycle > Submission Content
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
In accordance with the DCA, 1940/DCR, 1945, Schedule Y, the IN-GCPs, and the ICMR Guidelines, an applicant must obtain approval from the Drugs Controller General of India (DCGI) and the respective ethics committee(s) (ECs) to conduct a clinical trial. As per Order5Sept14, all applications for clinical trials of new drugs in India should provide information on the following:

  • Assessment of risk versus benefit to the patients
  • Innovation vis-à-vis existing therapeutic option
  • Unmet medical need in the country

As part of the approval process, the following documentation must be submitted.

DCGI Requirements

  • Form 44 (the clinical trial application form) and Treasury Challan demonstrating payment of corresponding fee
  • Clinical study protocol
  • EC approvals (if already available)
  • Form 12 (Import license application) and Treasury Challan demonstrating payment of corresponding fee (to obtain a test license for permission to import drugs for the purpose of examination, testing or analysis) (See G-Form 11 for additional information).
  • Informed consent form (ICF) and Patient information sheet (See Informed Consent topic, Required Elements subtopic for additional information).
  • Case Report Form (CRF)
  • Investigator’s Brochure (IB) – duly supported by an affidavit stating that the summarized information submitted is based on facts
  • Investigator(s) undertakings
  • Details of biological specimens to be exported (if applicable) (See Specimens topic for more information).
  • Sponsor authorization letter if submitted by a contract research organization

EC Requirements

  • Cover letter
  • Copy of the clinical trial application
  • Clinical study protocol and amendments
  • Certificate of Analysis for the drug sample and comparator drug to be used in the trial
  • IB
  • ICF and patient information sheet
  • Sample CRF
  • Investigator agreements
  • Investigator curriculum vitae(s)
  • List of centers and investigators
  • Proposed financial agreement
  • Indemnity insurance
  • Any other patient information to be used in the study (e.g., patient diaries)

Form 44 Content
As per the DCA, 1940/DCR, 1945 and Schedule Y, an applicant uses Form 44 to apply for a grant of permission from the DCGI to conduct a clinical trial. The form should include a brief description of the drug and therapeutic class, and be accompanied by the following data in accordance with Schedule Y’s appendices:

  • chemical and pharmaceutical information (Appendix I (App I), item 2)
  • animal pharmacology data (App I, item 3 and Appendix IV (App IV)): (a) specific pharmacological actions (App I, item 3.2); (b) general pharmacological actions (App I, item 3.3 and App IV, item 1.2); (c) pharmacokinetic data related to the absorption, distribution, metabolism and excretion of the test substance (App I, item 3.5)
  • animal toxicology data (App I, item 4 and Appendix III (App III))
  • human clinical pharmacology data (App I, items 5, 6, and 7) and the appendix sections listed in the details below.

The human clinical pharmacology data requirements are dependent upon what phase of clinical trial the applicant is requesting permission to initiate and where the drug is originating from:

  • New drug substances discovered in India: clinical trials are required to be carried out in India from phase I and data should be submitted as required (App I, items 1, 2, 3, 4, 5 (data, if any, from other countries), and 9). As discussed in Additional Resource (C), initial phase I trials of new drugs may only be approved for drugs developed in India.
  • New drug substances discovered in countries other than India: Phase I trial of new drugs from other countries is only possible as a repeat of an earlier phase I trial already conducted outside of India. Phase I data should be submitted as required (App I, items 1, 2, 3, 4, 5 (data from other countries) and 9). After phase I data generated outside India is submitted to the DCGI, permission may be granted to repeat phase I trials and/or to conduct phase II trials, and subsequently, to conduct phase III trials concurrently with other global trials for that drug. Phase III trials are required to be conducted in India before permission to market the drug in India is granted. (For detailed information on human clinical pharmacology data requirements, see Schedule Y).

As per the DCR-SeventhAmdmt-2015, which amends what must be included on Form 44 in regards to new chemical entity and global clinical trial, the following must be provided:

  • Assessment of risk versus benefit to the patients
  • Innovation vis-à-vis existing therapeutic option
  • Unmet medical need in the country

Clinical Protocol
As delineated in Appendix X of Schedule Y and the IN-GCPs, the clinical study protocol should include the following elements:

  • Title page
  • Study synopsis (1 to 2 pages)
  • Statement of compliance with the IN-GCPs
  • List of abbreviations and definitions
  • Table of contents
  • Ethical considerations 
  • Study team
  • Study rationale
  • Study objective(s)
  • Study design
  • Trial participants
  • Study conduct
  • Study drug supplies/administration
  • Study monitoring/supervision
  • Investigational product management (See Investigational Products topic for detailed coverage of this subject).
  • Efficacy evaluation
  • Safety evaluation
  • Adverse Event/Adverse Drug Reaction management responsibilities
  • Discussion and overall conclusion
  • List of references
  • Appendices

For detailed information on these elements, see Schedule Y and the IN-GCPs.

ADDITIONAL RESOURCES

(A) (ebook) Global Clinical Trials: Effective Implementation and Management (June 6, 2011)
Chin, Richard and Bairu, Menghis, eds., Academic Press

Relevant Section: Chapter 7, Section 7.8.2.

(B) (Website) Treasury Challan Form (Current as of July 3, 2012)
National Portal of India, Government of India

(C) (Article) Regulatory Considerations for Conducting Clinical Trials in India (March 2007)
Kumar, Mukesh and Kher, Surinder, RA Focus

Relevant Section: pages 26-31

(D) (Document) Global Clinical Trial Checklist (January 2014)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Part XA (Sections 122A, 122B, 122D, 122-DA, and 122-E) and Part XIX (Forms 12 and 44)

(2) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.3, Appendix II to Schedule Y, and section 1(2)

(3) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Chapter IV, Specific Principles and Section I

(4) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 1 (1 & 2) and Appendices I, I-A, III, IV, V, VI, VII, VIII, X, and XI

(5) (Guidance) Guidance Document on Grant of Licence in Form 11 (Test Licence) for the Purpose of Examination Testing and Analysis as per Rule 33 of Drugs and Cosmetics Acts and Rules 1945 (G-Form 11) (May 30, 2011)
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India

Relevant Sections: A, B, B.1, B.2, and B.3

(6) (Regulation) Order Dated 5 September 2014 (Order5Sept14) (September 5, 2014)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(7) (Regulation) Drugs and Cosmetics (Seventh Amendment) Rules, 2015 (DCR-SeventhAmdmt-2015 – English and Hindi/Hindī) (October 30, 2015)
Department of Health and Family Welfare, Ministry of Health and Family Welfare, Government of India

Relevant Section: Schedule A (Form 44) and Schedule Y (Appendix I)

Clinical Trial Lifecycle > Timeline of Review
Back to Top
Email section Share    Print section Print
Last content review/update: July 11, 2017. Submit updates or comments.
SUMMARY

Overview
The Central Drugs Standard Control Organization (CDSCO) does not provide official review and approval timelines on its website or in its regulatory documentation. However, Additional Resources (A), (B), and (C), state that the typical timeline for the Drugs Controller General of India (DCGI) and the ethics committee(s) (ECs) to conduct a parallel review and approval of a clinical trial application is on average eight (8) to 12 weeks. This is true of clinical trial applications submitted for all trial phases (I-III).

DCGI Approval
As per Additional Resources (A), (B), and (C), the DCGI review and approval of a clinical trial application is generally within 45 working days for the first response or for approval. However, this timeline may vary based upon a number of factors.

EC Approval
As per Additional Resources (A) and (B), the EC review and approval process, which occurs in parallel to the DCGI review and approval, generally takes from four (4) to eight (8) weeks.

ADDITIONAL RESOURCES

(A) (ebook) Global Clinical Trials: Effective Implementation and Management (June 6, 2011)
Chin, Richard and Bairu, Menghis, eds., Academic Press

Relevant Section: Chapter 7, Section 7.8.3.

(B) (Article) Clinical Trial Regulations in India: Inundation of Global Clinical Trials (January 2011)
Desai, Shubhangi and Naik, Savitha, Modern Pharmaceuticals

Relevant Section: pages 60-62

(C) (Article) Regulatory Considerations for Conducting Clinical Trials in India (March 2007)
Kumar, Mukesh and Kher, Surinder, RA Focus

Relevant Section: pages 26-31

(D) (Presentation) Clinical Trials New Horizon – India (March 26, 2009)
Singh, Surinder, Drugs Controller General of India, Central Drugs Standard Controller Organization, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India

(E) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

No applicable regulatory requirements

Clinical Trial Lifecycle > Trial Initiation
Back to Top
Email section Share    Print section Print
Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY

Overview
As per Rule 122-DA under Part XA of the DCA, 1940/DCR, 1945 and Schedule Y, a clinical trial can only commence in India after the applicant receives permission from the Drugs Controller General of India (DCGI) and approval from the respective ethics committees (ECs). According to the DCR-SecondAmdmt-2016, for clinical trials for academic/research purposes that are non-regulatory, only institutional EC approval is required. (See the Ethics Committee topic, Scope of Review subtopic for more information). There is no waiting period required following the applicant’s receipt of these approvals.

All investigators must possess appropriate qualifications, training, and experience. As per the C-NoCTLimit, there is no limit on the number of trials an investigator may conduct at the same time. The three (3) trial limit outlined in the OrderCTLimit has been removed. However, 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. The trials should be conducted in compliance with the IN-GCPs, the ICMR Guidelines, and Schedule Y. In addition to complying with the IN-GCPs, all clinical trials must be conducted in a laboratory complying with Good Laboratory Practices.

Clinical Trial Agreement
As delineated in the IN-GCPs, before the trial begins, the sponsor or his/her CRO must sign a formal legal agreement or contract with each participating institution(s). If no institutions are involved, the individual investigator signature is required. The contract should define the relationship between the sponsor and the investigator(s)/institution(s) in terms of financial support, fees, honorarium, and payments in kind. The sponsor or his/her CRO must also agree to:

  • Conduct the trial in compliance with the IN-GCPs, the applicable regulatory requirements, and the clinical trial protocol agreed to by the sponsor and approved by the EC
  • Comply with the procedures for data recording and reporting
  • Retain the trial-related essential documents until he/she informs the investigator(s)/institution(s) in writing that these documents are no longer needed

As per the IN-GCPs and the DCR-2ndAmdmt, the sponsor must also permit clinical trial site inspections by DCGI authorized officers.

EC Confirmation of Review and Approval
The IN-GCPs mandate that the sponsor obtain confirmation of EC review and approval from the investigator(s) and/or the institutions. The sponsor must receive the following information prior to the trial’s commencement:

  • EC member profiles (names, addresses, qualifications and experience)
  • Documented approval of EC’s favorable opinion
  • Copy of EC recommendations in case it has based its approval on change(s) in any aspect of the study (e.g., protocol modifications, written informed consent form, or any other written information and/or other procedures)
  • Copy of EC documents relating to re-evaluations/reapprovals with favorable opinions, and of any withdrawals or suspensions of approval/favorable opinion

(See Ethics Committee topic, Scope of Review subtopic and Clinical Trial Lifecycle topic, Submission Content subtopic for additional details on EC review process)

Clinical Trial Registration
Effective 2009, it is mandatory for all applicants to register their clinical trials with the Indian Council of Medical Research Indian Clinical Trial Registry before initiation of the study.

ADDITIONAL RESOURCES

(A) (Article) Clinical Trial Registration Gains Momentum in India (July 2009)
Pandey, A. Aggarwal, A., Maulik, M. & Seth, S.D.
Indian J Med Res 130

Relevant Section: pages 85-86

(B) (Handbook) Handbook –Good Laboratory Practices (GLP): Quality Practices for Regulated Non-clinical Research and Development (2009) (2nd Edition)
World Health Organization

(C) (Website) Indian Council of Medical Research - Clinical Trial Registry-India (Current as of December 8, 2016)
National Institute of Medical Statistics, Indian Council of Medical Research, Ministry of Health and Family Welfare, Government of India

(D) (Notice) Registration of Clinical Trial in ICMR Clinical Trial Registry – www.ctri.in –reg (2009)
Drugs Controller General of India (New Drug Division), Directorate General of Health Services, Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

(E) (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

(F) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Part XA (Section 122-DA)

(2) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: 3.1.2

(3) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Chapters I-III, IV (Section I)

(4) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: 1 (1)

(5) (Guidance) Guidelines for Good Clinical Laboratory Practices (GCLP) (2008)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

(6) (Regulation) Order: Limiting Number of Clinical Trials an Investigator can Undertake at a Time – Regarding (OrderCTLimit) (July 3, 2014)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(7) (Regulation) Drugs and Cosmetics (Second Amendment) Rules, 2016 (DCR-SecondAmdmt-2016Hindi/Hindī and English) (March 16, 2016)
Department of Health and Family Welfare, Ministry of Health and Family Welfare, Government of India

Relevant Section: Rule 122 DA (4)

(8) (Regulation) Drugs and Cosmetics (2nd Amendment) Rules, 2013 (DCR-2ndAmdmt – English and Hindi/Hindī) (February 1, 2013)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Rule 122 DAC – Clause 2 (g and h)

(9) (Regulation) Circular: Restriction of Conducting Three Clinical Trials Per Investigator - Regarding (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, Government of India

Clinical Trial Lifecycle > Safety Reporting
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
In accordance with the IN-GCPs, 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 out-patients), 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.


Reporting Requirements for AEs/ADRs
Investigator Responsibilities
The investigator is responsible for the medical management of all AEs/ADRs, and the protocol must designate these AE/ADR management responsibilities which must be submitted to the ethics committee (EC) for approval. As set forth in the DCA, 1940/DCR, 1945, the ICMR Guidelines, Schedule Y, and the DCR–1stAmdmt, an unexpected AE/ADR requires expedited review by the EC.

According to the DCR–1stAmdmt and the DCR-6thAmdmt, the investigator should report all SAEs/SADRs to the DCGI, the sponsor, and the EC that accorded approval to the study protocol within 24 hours.  

As per the DCR-6thAmdmt, which amends the DCR–1stAmdmt, after due analysis, the investigator(s) is required to forward any SAE/SADR report to the DCGI, the EC Chairman, and the head of the institution where the trial is being conducted within 14 days of the SAE/SADR occurrence. If the investigator fails to report any SAE/SADR within the stipulated period, he must furnish the reason for the delay to the DCGI along with a copy of the SAE/SADR report.

Sponsor Responsibilities
The DCR-6thAmdmt, indicates that the sponsor must report, after due analysis, any SAEs/SADRs during a clinical trial within 14 days of the SAE/SADR occurrence to the DCGI and the EC that accorded approval to the study protocol.  

In addition, the IN-GCPs require the sponsor to provide the AE/ADR reporting forms to the investigator(s) and institution(s). The sponsor is also responsible for expediting the reporting of all unexpected SAEs/SADRs to all concerned parties (including the EC and the DCGI).

The DCR-6thAmdmt further states that the EC must forward its report on the SAE/SADR, 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 SAE/SADR occurrence.

According to the ICMR Guidelines, at the end of the trial, all adverse events, whether related to the trial or not, are to be listed, evaluated, and discussed in detail in the final report. The study protocol must also include a financial plan (including insurance, if necessary) to manage the AEs/ADRs and compensation for trial-related injury (See Sponsorship topic, Compensation subtopic for additional information).

Safety Reporting Data Elements
Appendix XI of Schedule Y and G-CTA outline the data elements required for reporting SAEs/SADRs that occur during a clinical trial. More detailed information on these data elements is available in Schedule Y and the G-CTA.

ADDITIONAL RESOURCES

(A) (Article) Regulatory Considerations for Conducting Clinical Trials in India (March 2007)
Kumar, Mukesh and Kher, Surinder, RA Focus

Relevant Section: pages 26-31

(B) (Press Release) Notification on Clinical Trials (August 30, 2013)
Press Information Bureau, Ministry of Health and Family Welfare, Government of India

(C) (Document) System of Pre-screening for Submission of Reports of SAEs to CDSCO (F.No. 12-01/13-DC (Pt-13A)
New Drugs Division, Office of Drugs Controller General (India), Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

(D) (Article) Amendment Made to 122 DAB – Recently Notified by CDSCO (Current as of Decmber 8, 2016)
Faculty of Clinical Research,  Institute of Good Manufacturing Practices India

REQUIREMENTS

(1) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Schedule M and  Schedule Y (Section 1(1.3))

(2) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2 (2), Section 3 (2), and Appendix XI

(3) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Definitions and Section 3.1.10, 3.1.11, and 3.1.12

(4) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Chapter IV (Section I)

(5) (Guidance) Guidance for Industry on Submission of Clinical Trial Application for Evaluating Safety and Efficacy (General Considerations for Conducting Clinical Trial as per Drugs and Cosmetics Act 1940 and Rules 1945) (G-CTA) (2008) (Version 1.1)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Objective and Part 2: Appendix XI to Schedule Y

(6) (Regulation) Drugs and Cosmetics (1st Amendment) Rules, 2013 (DCR-1stAmdmt – English and Hindi/Hindī) (January 30, 2013)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2: Clause 2 (c and e) and Appendix XII (6)

(7) (Regulation) Drugs and Cosmetics (Sixth Amendment) Rules, 2014 (DCR-6thAmdmt – English and Hindi/Hindī) (December 12, 2014) (Effective date: June 12, 2015)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 1 and 2

Clinical Trial Lifecycle > Progress Reporting
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
Under the DCA, 1940/DCR, 1945, Schedule Y, and the IN-GCPs, investigators and sponsors share responsibility for submitting interim and annual reports on the status of a clinical trial. The investigator must prepare the interim reports and the sponsor is required to submit the annual reports.

Interim Reports
The progress reports section of the IN-GCPs states that the investigator should submit written summaries of the study status at the period specified in the clinical protocol to the person(s)/organization(s) to whom he/she is reporting. Further, all investigator reportings should identify the participants by unique code numbers assigned to the study participants rather than by the participant’s name(s), personal identification number(s), and/or addresses.

Annual Reports
As delineated in the DCA, 1940/DCR, 1945, Schedule Y, and the IN-GCPs, sponsors are required to submit to the Drugs Controller General of India (DCGI) an annual status report on each clinical trial.

Schedule Y 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), a summary report should be submitted by the sponsor within three 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 IN-GCPs state that the sponsor must ensure the preparation and appropriate approval(s) of a comprehensive final clinical study report suitable for regulatory and/or marketing purposes, whether or not the study has been completed. In addition, the final clinical trial reports submitted by the sponsor must ensure that the investigator has duly signed the report within a stipulated time period.

All final reports prepared should comply with the format and content guidelines listed in Appendix II of Schedule Y, the IN-GCPs, and the DCA, 1940/DCR, 1945. The guidelines are as follows:

  • Title page
  • Study synopsis (1 to 2 pages) 
  • List of abbreviations and definitions
  • Table of contents
  • Ethics committee 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 Schedule Y, the IN-GCPs, and the DCA, 1940/DCR, 1945 for more detailed information on preparing these reports.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Schedule Y (Section 1(1.3); Section, 1(9); Appendix II)

(2) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2 (2) and Appendix II

(3) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Definitions; 3.1.12; 3.3.8; Schedule Y (Section 1 (3) and (9); Appendix I)

Sponsorship > Definition of Sponsor
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
As per the Definitions section of the IN-GCPs, 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. Further, an investigator who independently initiates and takes full responsibility for a trial automatically assumes the role of a sponsor.

A sponsor may be domestic or foreign. A foreign sponsor must appoint a local representative or contract research organization (CRO) to fulfill the appropriate local responsibilities as delineated by the Drugs Controller General of India (DCGI). The sponsor may transfer any or all of his/her study related duties and functions to a CRO. However, he/she is ultimately responsible for the study data’s quality and integrity.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: Definitions, 3.1.17

Sponsorship > Trial Authorization
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
A sponsor or his/her designated contract research organization (CRO) is responsible for filing a clinical trial application with the Drugs Controller General of India (DCGI) except when the trial is for academic/research purposes that are non-regulatory in nature. To complete the clinical trial application package, a sponsor must use Form 44 and include a 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 Schedule Y and the DCA, 1940/DCR, 1945. In addition, as per OrderPlaceboCT, the sponsor or his/her CRO is required to ensure that the design used in a placebo controlled clinical trial is appropriate, efficient, and ethical. (See Clinical Trial Lifecycle topic, Submission Contents subtopic for detailed application submission requirements.)

As per the DCR-SecondAmdmt-2016, clinical trials for academic/research purposes that are non-regulatory in nature only require institutional EC approval. (See the Ethics Committee topic, Scope of Review subtopic for more information). 

Indian Council of Medical Research Indian Clinical Trial Registry
A sponsor or his/her designated CRO has the primary responsibility for ensuring that the clinical trial is registered with the Indian Council of Medical Research Indian Clinical Trial Registry prior to enrolling the first research participant. A sponsor may permit the principal investigator to register on his/her behalf. (See the Clinical Trial Lifecycle topic, Trial Initiation subtopic for additional information).

ADDITIONAL RESOURCES

(A) (Notice) Registration of Clinical Trial in ICMR Clinical Trial Registry – www.ctri.in –reg (2009)
Drugs Controller General of India (New Drug Division), Directorate General of Health Services, Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

(B) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 1 (1) and Appendices I, I-A, III, IV, V, VI, VII, VIII, IX, X, and XI

(2) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Part XA, Section 122-DA; Part XIX, Forms 12 and 44; and Schedule Y

(3) (Regulation) Order: Placebo Controlled Trials – Regarding (OrderPlaceboCT) (July 3, 2014)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(4) (Regulation) Drugs and Cosmetics (Second Amendment) Rules, 2016 (DCR-SecondAmdmt-2016Hindi/Hindī and English) (March 16, 2016)
Department of Health and Family Welfare, Ministry of Health and Family Welfare, Government of India

Relevant Section: Rule 122 DA (4)

Sponsorship > Insurance
Back to Top
Email section Share    Print section Print
Last content review/update: July 11, 2017. Submit updates or comments.
SUMMARY

Overview
As set forth in the IN-GCPs and the ICMR Guidelines, the sponsor, whether a pharmaceutical company, or an institution, is responsible for providing insurance coverage for any unforeseen injury to research participants. Before the clinical trial begins, the sponsor is obligated to address indemnity and insurance issues in the clinical trial agreement between the sponsor or its contract research organization (CRO) and the institution and/or investigator(s). Appendix VIII of Schedule Y states that the ethics committee also requires a copy of the insurance as part of its submission review process. (See the Clinical Trial Lifecycle topic, Submission Content subtopic for additional submission requirements)

Indemnity Agreement and Clinical Trial Insurance Certificate
As per Additional Resource (A), a sponsor typically signs an indemnity agreement with the contract research organization (CRO), investigator or institution to cover any risks related to study-related participant injuries arising out of any act, omission, negligence or misconduct by the CRO, investigator or institution. The sponsor, in turn, also needs to obtain insurance coverage to cover any costs that may be incurred as a result of providing this indemnification. Specific details related to sponsorship compensation obligations to participants are available in the Sponsorship topic, Compensation subtopic and Informed Consent topic, Compensation Disclosure subtopic.

Although most Indian subsidiaries of multinational pharmaceutical companies tend to seek protection under master insurance programs arranged by their parent company, it is also necessary for these subsidiaries to obtain the locally issued insurance certificate because insurance policies issued abroad are deemed to be illegal in India (See Additional Resource (C) for further information on this subject).

ADDITIONAL RESOURCES

(A) (Article) Issues & Concerns in Conducting Clinical Trials in India (2011)
Antani, M. and Gokhale, Gowree, PharmaFocus Asia

(B) (Article) Clinical Trials in India – Boon or Bane? (September 4, 2008)
Tharu, Reeja, Medindia

(C) (Article) Managing the Complex Challenges of a Global Insurance Program: Foreign Clinical Trials Case Study (Fall 2009)
Farrow, Lee W. and Gaffney, Robert J., The John Liner Review, Vol. 23, No. 3

Relevant Section: pages 28-33

 

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: 2.4.7.1

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Chapter III, Section VI

(3) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: Appendix VIII

Sponsorship > Compensation
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
In accordance with the IN-GCPs, the ICMR Guidelines, the DCR-1stAmdmt, the DCR-2ndAmdmt, and the DCR-6thAmdmt, a sponsor, whether a pharmaceutical company, or an institution, must agree in a clinical trial agreement before the study begins, to provide medical treatment as well as financial compensation to research participants for any physical or mental injury which they may suffer during the clinical trial. In addition, in the case of study-related death, the participant’s legal heir(s) is/are entitled to material compensation. A child injured in-utero because of a parent’s participation in a trial must also be compensated. The DCR-6thAmdmt states that medical treatment should be provided for as long as required, or until such time it is established that the injury is not related to the clinical trial, whichever is earlier. In addition, in cases where the participant suffers no permanent injury, the quantum of compensation should be commensurate with the nature of the non-permanent injury and loss of wages.

As per the OrderCTCompensation, the sponsor also is required to provide compensation to the trial participant and/or his/her legal heir(s) when a drug-related anomaly is identified at a later stage of the study, and is accepted to be drug-related and resulting in injury or death. In addition, the OrderAncillaryCare states that the sponsor should provide ancillary care to participants suffering from any other brief illness during the trial at the same hospital or trial site, whenever required.

As per the DCR-1stAmdmt and the DCR-6thAmdmt, the sponsor is responsible for compensating the research participant and/or his/her legal heir(s) if the injury or death has occurred due to any of the following reasons:

  • adverse effects of investigational product(s) (IPs)
  • any clinical trial procedures involved in the study
  • violation from approved protocol, scientific misconduct or negligence by the investigator/sponsor/CRO, or other responsible parties
  • failure of an IP to provide intended therapeutic effect where, the standard care, though available, was not provided to the participant as per trial protocol
  • use of a placebo in a placebo-controlled trial where, the standard care, though available, was not provided to the participant as per trial protocol
  • adverse effects due to concomitant medication administered as per the approved protocol
  • injury to the child in-utero due to a parent’s participation in a clinical trial

The participant may be paid for the inconvenience and time spent, reimbursed for expenses incurred, and receive free medical services in connection with his/her participation as long as required. The sponsor is also required to provide ancillary care to participants suffering from any other brief illness during the trial at the same hospital or trial site. (See Informed Consent topic, Compensation Disclosure subtopic for additional information on participant right to compensation).

Foreign Sponsors
In the case of a foreign sponsor, he/she must appoint a local representative or a contract research organization (CRO) to fulfill the appropriate responsibilities as governed by the Indian regulations. The foreign sponsor must also enter into an agreement with his/her local representative stating that as the sponsor, he/she will be responsible for medical treatment expenses as well as financial compensation in the case of trial-related injury or death of trial participants.

Payment Procedures and Requirements
The DCR-1stAmdmt indicates that the sponsor should provide financial compensation and medical treatment as per the recommendations of the ethics committee (EC), the Expert Committee (constituted by the Drugs Controller General of India (DCGI)), where applicable), and ultimately the DCGI.

The DCR-6thAmdmt, which amends the DCR–1stAmdmt, indicates that the sponsor must report, after due analysis, any serious adverse events (SAEs)/serious adverse drug reaction (SADRs) during a clinical trial within 14 days of the SAE/SADR occurrence to the DCGI and the EC(s) that accorded approval to the study protocol. The EC then submits its report with financial compensation recommendations within 30 days to the DCGI. Within 150 days of the occurrence of the adverse event, the DCGI must determine the cause of injury or death and make the final decision on the quantum of compensation to be paid by the sponsor or his/her representative. According to the DCR–1stAmdmt, the sponsor or his/her representative is required to pay the compensation to the participant or his/her legal heirs (in the case of death) within 30 days of receipt of the DCGI order. The G-CompDeath provides the compensation formula in the case of death. The OrderCompInjury provides the compensation formula for SAEs other than death.

In the event that a sponsor 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 may, 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 and restrict the sponsor/CRO/local representative of a foreign sponsor from conducting any further clinical trials in India, or take any other action deemed fit under the rules.

ADDITIONAL RESOURCES

(A) (Article) Issues & Concerns in Conducting Clinical Trials in India (2011)
Antani, M. and Gokhale, Gowree, PharmaFocus Asia

(B) (Press Release) Notification on Clinical Trials (August 30, 2013)
Press Information Bureau, Ministry of Health and Family Welfare, Government of India

(C) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

(D) (Article) Amendment Made to 122 DAB – Recently Notified by CDSCO (Current as of December 8, 2016)
Faculty of Clinical Research, Institute of Good Manufacturing Practices India

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.4.7.1 and 3.1.6

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Chapter III, Section VI and Chapter IV, Section I

(3) (Regulation) Drugs and Cosmetics (1st Amendment) Rules, 2013 (DCR-1stAmdmt – English and Hindi/Hindī) (January 30, 2013)
Department of Health, Ministry of Health and Family Welfare, Government of India

(4) (Regulation) Drugs and Cosmetics (2nd Amendment) Rules, 2013 (DCR-2ndAmdmt – English and Hindi/Hindī) (February 1, 2013)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section:  Rule 122 DAC – Clause 2 (f)

(5) (Regulation) Formula to Determine the Quantum of Compensation in the Cases of Clinical Trial Related Serious Adverse Events (SAES) of Deaths Occurring During Clinical Trials (G-CompDeath) (2013)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

(6) (Regulation) Order: Clinical Trial – Compensation in Case of Injury or Death Discerned at a Later Stage – Regarding (OrderCTCompensation) (July 3, 2014)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(7) (Regulation) Order: Providing Ancillary Care to the Clinical Trial Subjects – Regarding (OrderAncillaryCare) (July 3, 2014)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(8) (Regulation) Order: Formulae to Determine the Quantum of Compensation in Case of Clinical Trial Related Injury (Other than Death) (OrderCompInjury) (December 15, 2014)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(9) (Regulation) Drugs and Cosmetics (Sixth Amendment) Rules, 2014 (DCR-6thAmdmt – English and Hindi/Hindī) (December 12, 2014) (Effective date: June 12, 2015)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 1 and 2

Sponsorship > Quality, Data & Records Management
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
As part of the sponsor’s role as clinical trial oversight manager, he/she must prepare standard operating procedures (SOPs) to ensure compliance with the IN-GCPs, Schedule Y, and the DCA, 1940/DCR, 1945. The SOPs and the clinical trial protocol should be signed by both the sponsor and the investigator(s) to confirm their agreement.

The IN-GCPs state that the sponsor must also secure a clinical trial agreement from all involved parties on the designation of protocol-related and other responsibilities including:

  • Access to trial related sites, source data, documents and reports for inspection, monitoring and auditing by authorized parties and national/foreign regulatory authorities
  • Data processing
  • Decoding participant database treatment codes 
  • Statistical analysis 
  • Study report preparation
  • Preparation and submission of materials to the ethics committee (EC), the Drugs Controller General of India (DCGI), and other review bodies
  • Adverse drug reaction(s)/adverse event(s) reporting to the EC
  • Quality Assurance (QA)/Quality Control (QC) systems with written SOPs to ensure study compliance with the clinical protocol and relevant regulatory guidelines

The sponsor should also seek the opinion of an EC regarding the protocol’s suitability, the adequacy of the informed consent (IC) documentation, and the methods and documents to be used to recruit trial participants. In addition, he/she must ensure the safekeeping of all trial related documents and materials for a period of three (3) years following the study’s completion, or submission of data to the DCGI, whichever is later.

In addition, the IN-GCPs indicate that the sponsor must appoint adequately trained monitors or a contract research organization (CRO) to supervise an ongoing study.

Electronic Data Processing System
The sponsor must ensure that the electronic data processing system conforms to the specific documented requirements for completeness, accuracy, reliability, and consistency of intended performance, and that he/she maintains SOPs for using these systems.

Independent Data Monitoring Committee
The sponsor is permitted to establish an Independent Data Monitoring Committee (IDMC) to assess the study’s progress. The IDMC would review safety data and critical efficacy endpoints at various intervals, and would recommend to the sponsor whether to continue, modify, or stop a trial. The IDMC should also have written SOPs and maintain written records of all its meetings.

Audit Requirements
As part of its QA system, the sponsor should perform a clinical trial audit. The audit should be conducted separately and independently from other routine monitoring or QC functions. It should evaluate study conduct and compliance with the protocol, the SOPs, the IN-GCPs, Schedule Y, and the DCA, 1940/DCR, 1945. The sponsor may appoint individuals qualified by training and experience to conduct audits, their qualifications must be documented, and the auditors must be independent of the parties involved in the study. The sponsor must also ensure that the audit is conducted in accordance with his/her own SOPs, that the auditor observations are archived, and that data is available as needed for DCGI review. No specific timeframe is provided for the audit process.

If the auditor discovers that any party involved has failed to comply with the IN-GCPs, the SOPs, the protocol, and/or any applicable regulatory requirements, the sponsor should initiate prompt action. Further, if auditing identifies serious and/or persistent non-compliance, the sponsor should terminate the defaulting party’s study participation and immediately notify the DCGI. For additional QA system details, see Sections 3.1.14 and 4.8 of the IN-GCPs.

Premature Study Termination/Suspension
If the sponsor chooses, or is required to terminate prematurely or suspend a study, he/she must notify the investigator(s), institution(s), the EC, and the DCGI accordingly. The notification should document the reason(s) for the termination/suspension.

Multicenter Studies
In the event of a multicenter clinical trial, the sponsor must make special administrative arrangements for the conduct of these studies by several investigators at different institutions who are following the same protocol. Some of the administrative tasks requiring special consideration include:

  • Ensuring strict adherence to the protocol and applicable IN-GCPs
  • Assuming responsibility for study commencement and overall performance
  • Supervising the data
  • Monitoring ADRs/AEs
  • Facilitating communication between investigators at various sites
  • Obtaining written acceptance of the protocol and its annexes from each of the investigator(s)/institution(s) involved

Additional details on how to handle this type of study are available in Section 3.1.15 of the IN-GCPs.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.3.1.10, 3.1.3, 3.1.5, 3.1.14, 3.1.15, 3.1.16, 4.3, 4.4, and 4.8

(2) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

(3) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Sponsorship > Site/Investigator Selection
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
As per the IN-GCPs, the sponsor is responsible for selecting the investigator(s) and institution(s) for the clinical trial, taking into account the appropriateness and availability of the study site and facilities. The sponsor must also be assured of the investigator(s) qualifications and availability for the study duration. 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.

Further, if a multicenter trial is going to be conducted, the sponsor must organize a coordinating committee or select coordinating investigators. The sponsor must also conduct training of investigators in ethics, good clinical practices, standard operating procedures, and study protocols.

In addition, the IN-GCPs indicate that the sponsor must appoint adequately trained monitors or a contract research organization (CRO) to supervise an ongoing study.

Foreign Sponsor Responsibilities
A sponsor that is a foreign company, organization, or individual(s), must appoint a local representative or CRO to fulfill the appropriate local responsibilities as delineated by the Drugs Controller General of India (DCGI). The sponsor may transfer any or all of his/her study related duties and functions to a CRO. However, he/she is ultimately responsible for the study data’s quality and integrity. Any study related duties, functions or responsibilities transferred to and assumed by a local representative or CRO must be specified in writing. Other duties, functions, or responsibilities not specifically transferred shall be deemed to have been retained by the sponsor. Additional foreign sponsor requirements are listed in Section 3.1.17 of the IN-GCPs.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 3.1.1, 3.1.14, 3.1.13, and 3.1.17

Informed Consent > Documentation Requirements
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
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 laid down in the IN-GCPs, the ICMR Guidelines, and Schedule Y.

As per the IN-GCPs, the ICMR Guidelines, and Schedule Y, 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 licensing authority, 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 investigator(s) should provide study information to the participant and/or his/her legal representative(s) or guardian(s) as well as to an impartial witness. The ICF content should be brief and clearly presented, without coercion or unduly influencing a potential participant to enroll in the clinical trial.

Participant information should be presented in both written and oral form, whenever possible, and in nontechnical and understandable terms. When written consent as a signature or thumb impression is not possible, verbal consent may be taken after ensuring its documentation by an impartial witness, or through audio/video means.

Effective July 31, 2015, the DCR-5thAmdmt states that 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, any change in the ICF due to a protocol modification or an alteration in treatment modality, procedures, or site visits, should be approved by the EC, and submitted to the DCGI before such changes are implemented. The participant and/or his/her legal representative(s) or guardian(s) will also be required to re-sign the revised ICF. (See the Informed Consent topic, Special Circumstances/Emergencies subtopic for additional re-consent information.)

Language Requirements
As stated in the IN-GCPs, the ICMR Guidelines, and Schedule Y, the ICF should be written in English and in the vernacular language that the participant is able to understand. The document should be scientifically accurate as well as sensitive to the participant’s social and cultural context.

Documentation Copies
The IN-GCPs states that the ICF should be signed and personally dated by the participant and the investigator(s). If the participant is incapable of giving an informed consent, his/her legal representative(s) or guardian(s) should sign and date the ICF.

In cases where the participant and/or his/her legal representative(s) and/or guardian(s) is illiterate, an impartial witness, who should be present during the entire informed consent discussion, should sign and date the ICF. By signing the consent form, the witness attests that the ICF and any other written information provided, was accurately explained to, and understood by, the participant and/or his/her legal representative(s) and/or guardian(s), and that informed consent was freely given by the participant and/or his/her legal representative(s) and/or guardian(s).

A copy of the signed ICF should be retained by the investigator(s), and one (1) copy should be given to the participant for his/her record.

ADDITIONAL RESOURCES

(A) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.4.3.1, 3.3.4, 3.3.7, 4.5, and Appendix II (1 (3))

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Chapter III (I)

(3) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2 (4) and Appendix V

(4) (Regulation) Drugs and Cosmetics (Fifth Amendment) Rules, 2015 (DCR-5thAmdmt – English and Hindi/Hindī) (July 31, 2015)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Informed Consent > Required Elements
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
As delineated in the IN-GCPs and Schedule Y, prior to beginning a research study, the investigator(s) is required to obtain ethics committee (EC) approval for the written informed consent form (ICF), and for all information being provided to the research participant and/or his/her legal representative(s) or guardian(s) as well as an impartial witness. The ICF and patient information sheet should provide adequate information about the research study in easily understandable and unambiguous language in both written and oral form, whenever possible. The potential research participant and/or his/her legal representative(s) or guardian(s) should be given sufficient time to inquire about the details of the research study and have all questions answered to his/her satisfaction.

No Coercion
None of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant and/or his/her legal representative(s) and/or guardian(s) to waive or to appear to waive his/her legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

ICF Required Elements
Based on Schedule Y's informed consent essential elements checklist, the IN-GCPs, the ICMR Guidelines, and the DCR-5thAmdmt, the ICF should include the following statements or descriptions, as applicable:

  • The study involves research and an explanation of its nature and purpose
  • The expected duration of the participant's participation
  • The procedures to be followed
  • Any reasonably foreseeable risks or discomforts to the participant resulting from his/her participation, and whether the project involves more than minimal risk
  • 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
  • Any benefits or prorated payment 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
  • Clinical trial treatment schedule(s) and the probability for random assignment to each treatment
  • The policy on compensation and/or medical treatment(s) available to the participant in the event of a trial-related injury, disability, or death
  • Principal investigator (PI) and co-investigator(s) contact information
  • EC contact information
  • The participant’s responsibilities in participating in the trial
  • 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
  • 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
  • If genetics and/or HIV testing is to be conducted, counseling prior to consent for testing must be given as per national guidelines
  • The storage period of biological sample and related data with a choice offered to the participant regarding future use of the sample, refusal for storage, and receipt of its results
  • The participant’s right to prevent the use of his/her biological sample (DNA, cell-line, etc.) at any time during the conduct of the research
  • The participant should be informed about any publication of his/her medical information, including photographs and pedigree charts

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

ADDITIONAL RESOURCES

(A) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee , Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.4.3.1, 2.4.3.2, 2.4.4, and Appendix I

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Chapter III, (I and V)

(3) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: 2 (4) and Appendix V

(4) (Regulation) Drugs and Cosmetics (Fifth Amendment) Rules, 2015 (DCR-5thAmdmt – English and Hindi/Hindī) (July 31, 2015)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Informed Consent > Compensation Disclosure
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
In accordance with the IN-GCPs, the ICMR Guidelines, and Schedule Y, the informed consent form (ICF) should contain a statement describing the compensation or benefits the participant may receive for participating in a clinical trial.

Compensation for Participation in Research
As per the IN-GCPs, the ICMR Guidelines, and Schedule Y, 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. The ICF should also contain a statement indicating whether any compensation and medical treatment will be made available if injury occurs. 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. However, payments should not be so large or medical services so excessive, as to induce a prospective participant to consent to participate in a clinical trial against his/her better judgment. The ethics committee (EC) should approve all payments, reimbursement, and medical services to be provided to the research participant.

The IN-GCPs and the ICMR Guidelines also include the following compensation requirements:

  • When a legal representative or guardian is asked to give consent on behalf of an incompetent participant, no remuneration should be offered except to refund out-of-pocket expenses
  • When a participant has withdrawn from research for medical reasons related to the clinical trial, he/she should get the benefit for full participation
  • When a participant withdraws for any other reasons, he/she should be paid in proportion to the amount of participation.

Compensation for Injury
As per the IN-GCPs, the ICMR Guidelines, and Schedule Y, the ICF should include a statement advising the participant that compensation and/or treatment(s) are available in the event of any temporary or permanent clinical trial-related injury or disability. The DCR–1stAmdmt also mandates that a quantum of financial compensation and free medical treatment be provided to the participant in the case of trial-related injury. In the case of the participant’s death, his/her legal heirs are entitled to financial compensation. Both instances are subject to review by the EC, an Expert Committee (constituted by the Drugs Controller General of India (DCGI), where applicable), and ultimately the DCGI. The DCR-6thAmdmt further states that medical treatment should be provided for as long as required, or until such time it is established that the injury is not related to the clinical trial, whichever is earlier. In addition, in cases where the participant suffers no permanent injury, the quantum of compensation should be commensurate with the nature of the non-permanent injury and loss of wages.

As per the OrderCTCompensation, the sponsor is also required to provide compensation to the trial participant and/or his/her legal heir(s) when a drug-related anomaly is identified at a later stage in the study, and is accepted to be a drug-related anomaly resulting in injury or death. In addition, the OrderAncillaryCare states that the sponsor should provide ancillary care to patients suffering from any other brief illness during the trial at the same hospital or trial site, whenever required. (See Sponsorship topic, Compensation subtopic for more information on payment procedures and requirements.)

ADDITIONAL RESOURCES

(A) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

(B) (Article) Amendment Made to 122 DAB – Recently Notified by CDSCO (Current as of December 8, 2016)
Faculty of Clinical Research, Institute of Good Manufacturing Practices India

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.4.3.2, 2.4.5, and 2.4.7

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Chapter III (I and II)

(3) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: Appendix V

(4) (Regulation) Drugs and Cosmetics (1st Amendment) Rules, 2013 (DCR-1stAmdmt – English and Hindi/Hindī) (January 30, 2013)
Department of Health, Ministry of Health and Family Welfare, Government of India

(5) (Regulation) Order: Clinical Trial – Compensation in Case of Injury or Death Discerned at a Later Stage – Regarding (OrderCTCompensation) (July 3, 2014)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(6) (Regulation) Order: Providing Ancillary Care to the Clinical Trial Subjects – Regarding (OrderAncillaryCare) (July 3, 2014)
Central Drugs Standard Control Organization, Directorate General of Health Services, Office of Drugs Controller General, Ministry of Health and Family Welfare, Government of India

(7) (Regulation) Drugs and Cosmetics (Sixth Amendment) Rules, 2014 (DCR-6thAmdmt – English and Hindi/Hindī) (December 12, 2014) (Effective date: June 12, 2015)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 1 and 2

Informed Consent > Participant Rights
Back to Top
Email section Share    Print section Print
Last content review/update: July 11, 2017. Submit updates or comments.
SUMMARY

Overview
In accordance with the principles set forth in the Declaration of Helsinki, the IN-GCPs, and the ICMR Guidelines, India’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The informed consent form (ICF) must clearly address the rights of research participants during the informed consent process. Below are the basic rights for participants in research studies. (See the Informed Consent topic, and the subtopics of Required Elements; Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired for additional information regarding requirements for participant rights.)

The Right to Participate, Abstain, or Withdraw
The participant and/or his/her legal representative(s) or guardian(s) should be informed that participation is voluntary, that he/she may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information
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 for participation or injury/treatment, and any significant new information regarding the research study. (See the Informed Consent topic, Required Elements subtopic for more detailed information regarding participant rights.)

The Right to Privacy and Confidentiality
Participants have the right to privacy and confidentiality. All participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. It is the responsibility of the investigator(s) to safeguard the confidentiality of research data to protect the identity and records of research participants.

The Right of Inquiry/Appeal
The 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 to address clinical trial- related queries, in the event of any injury and/or to appeal against a violation of his/her rights. (See the Informed Consent topic, Required Elements subtopic for more detailed information regarding participant rights.)

The Right to Safety and Welfare
The IN-GCPs and the Declaration of Helsinki clearly state that a research participant’s right to safety and the protection of his/her health and welfare must take precedence over the objectives of biomedical research.

ADDITIONAL RESOURCES

(A) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Foreword, 2.4.1, 2.4.3.2, 2.4.4, and Appendix I

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Chapter I, Chapter II, and Chapter III, (I and IV)

(3) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: Appendix V

Informed Consent > Special Circumstances/Emergencies
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
Schedule Y, the ICMR Guidelines, and the IN-GCPs make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by special circumstances such as medical emergencies, or if a research participant is mentally incapacitated.

Medical Emergencies
Consent in special circumstances, such as medical emergencies, is addressed by India’s doctrine of emergency which corresponds to the IPC-92. The code states that treating a research participant without his/her consent is permissible if the participant is unconscious, mentally ill, or gravely sick, and no one who is authorized to provide consent is directly attending the participant. It is implied that the procedure is performed to save the life of the participant. If possible, proxy consent should be taken.

Schedule Y and the ICMR Guidelines similarly state that when a participant is unable to give his/her informed consent, and it is considered essential that research be conducted on this person, his/her legal representative(s) or guardian(s) is permitted to provide consent on his/her behalf. The ethics committee (EC) will make the final decision on the form of consent to be taken or its waiver based on the degree of risk that may be involved.

Waiver of Consent
Although voluntary informed consent is always a requirement for every research proposal, this obligation can be waived by the EC, if such studies have protections in place for both privacy and confidentiality, and do not violate the rights of the participants. In addition to the preceding requirements, a waiver may be justified if the research being conducted meets one of the following conditions:

  • It involves only minimal risk
  • The participant and the researcher do not come into contact
  • It is necessitated in emergency situations where no proxy consent can be taken

Re-Consent
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 clearly explained in the informed consent form. (See the Informed Consent topic, Documentation Requirements subtopic for other conditions in which re-consent is appropriate.)

ADDITIONAL RESOURCES

(A) (Article) Informed Consent (2007)
Krishnan, N.R. and Kasthuri, A.S.
Medical Journal Armed Forces India

Relevant Section: 63:164-166

(B) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.4.3.1, 2.4.6.3, and Appendix I

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Chapter III (I and IV)

(3) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: 2 (4)

(4) (Regulation) The Indian Penal Code, 1860 (IPC-92) (October 6, 1860)
Government of India

Relevant Section: 92

Informed Consent > Vulnerable Populations
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
In all Indian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. According to the IN-GCPs and the ICMR Guidelines, vulnerable populations are characterized as research participants who have diminished autonomy including those with incurable diseases, in nursing homes, in detention, unemployed or impoverished, in emergency rooms, homeless persons, nomads, refugees, prisoners, students, service personnel, and any ethnic or racial minority groups.

The mode of consent for these participants must be carefully considered and approved by the ethics committee (EC). Additional criteria that must be met to comply with the terms of proxy consent are as follows:

  • Vulnerable groups should not be included unless the research is necessary to promote the health of the population represented, and this research cannot instead be performed on legally competent participants
  • Research should be done only if the physical/mental condition that prevents obtaining informed consent is a necessary characteristic of the research population. Specific reasons for involving participants with a condition that renders them unable to give informed consent should be stated in the protocol for EC review and approval. The protocol should state that consent to remain in the study should be obtained as soon as possible from the participant and/or his/her legal representative(s) or guardian(s)


See the Informed Consent topic, and the subtopics of Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired for additional information about these vulnerable populations. Information on the other vulnerable populations specified by Schedule Y is provided below.

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 Schedule Y, 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
ADDITIONAL RESOURCES

(A) (Article) Medical Consent in India–Ethical and Legal Issues (July 1, 2007)
Kohli, A.
Anil Aggrawal's Internet Journal of Forensic Medicine and Toxicology

Relevant Section: 8 (2)

(B) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.4.2.9, 2.4.3.1, 2.4.6.1, 2.4.6.2, 2.4.6.3, and Appendix I

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Chapter III (IV)

(3) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 3 (1, 2, and 3)

Informed Consent > Children/Minors
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
As per the ICMR Guidelines, the legal age of consent for a minor in India is generally understood to be 18 years or younger. However, legislation regarding the age of consent for medical treatment is still under examination.

In accordance with Schedule Y, pediatric participants are legally unable to provide written, informed consent, and are dependent upon their legal representative(s) or guardian(s) to assume responsibility for their participation in a research study. All pediatric participants, however, should be informed to the fullest extent possible about the study in language and terms that they are easily able to understand. A pediatric participant’s refusal to participate in a study must always be respected unless there is no medically acceptable alternative to the therapy available and his/her welfare is in jeopardy. In this situation, continued legal representative(s) or guardian(s) consent should be sufficient to allow participation in the study.

Assent Requirements
As delineated in the IN-GCPs, the ICMR Guidelines, and Schedule Y, if the pediatric participant has the capacity for assent, his/her affirmative assent is required to participate in a study. 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 following additional criteria must be met to conduct clinical trials with minors:

  • The research purpose is to obtain knowledge relevant to children’s health needs
  • Children will not be involved in research that could be carried out equally well in adults
  • For a new drug clinical evaluation, the pediatric research study should always be carried out after the Phase III clinical trial in adults, unless the drug has a therapeutic value in a disease primary to children
  • Research should be conducted in settings in which the child and parent can obtain adequate medical and psychological support
  • Interventions intended to provide direct diagnostic, therapeutic, or preventive benefit for the pediatric participant must be justified in relation to the anticipated risks involved in the research study and the anticipated benefits to society
  • Interventions designed to provide therapeutic benefit are likely to be at least as advantageous to the pediatric participant as any available alternative interventions
  • Risks presented by interventions not intended to benefit the pediatric participant are low when compared to the importance of the knowledge that is to be gained
ADDITIONAL RESOURCES

(A) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.4.2.9, 2.4.3.1, 2.4.6.1, 2.4.6.2, 2.4.6.3, and Appendix I

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Chapter III (IV)

(3) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 3 (1, 2, and 3)

Informed Consent > Pregnant Women, Fetuses & Neonates
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
As per the IN-GCPs, the ICMR Guidelines, and Schedule Y, any Indian clinical studies involving pregnant or nursing women and fetuses require additional safeguards to ensure that the research conforms to appropriate ethical standards and upholds societal values. The following conditions are required for research to be conducted involving pregnant or nursing women or fetuses:

  • 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
  • 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

Informed consent requirements for conducting clinical trials with pregnant or nursing women or fetuses follow the general requirements listed in the Informed Consent topic, Required Elements subtopic.

ADDITIONAL RESOURCES

(A) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.4.2.9, 2.4.3.1, 2.4.6.1, 2.4.6.2, 2.4.6.3, and Appendix I

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Chapter III, Section IV, Sections i, ii, and iii

(3) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 3 (1, 2, and 3)

Informed Consent > Prisoners
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

No relevant provisions

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

No applicable regulatory requirements

Informed Consent > Mentally Impaired
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
As per the IN-GCPs, the ICMR Guidelines, and Schedule Y, appropriate proxy consent from a participant’s legal representative(s) or guardian(s) should be taken on behalf of mentally challenged and mentally differently able participants who are incapable of giving informed consent, or those with behavioral disorders. This consent should only be provided once the legal representative(s) or guardian(s) is well informed about the research study, the need for participation, the risks and benefits involved, and the privacy and confidentiality procedures. The entire consent process should be properly documented. (See the Informed Consent topic, Required Elements subtopic and the Informed Consent topic, Documentation Requirements subtopic for detailed information on informed consent form (ICF) requirements/elements and documentation requirements.)

ADDITIONAL RESOURCES

(A) (Document) Report of the Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of New Drugs, Clinical Trials and Banning of Drugs (July 2013)
Prof. Ranjit Roy Chaudhury Expert Committee, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (December 21, 2004)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.4.2.9, 2.4.3.1, 2.4.6.1, 2.4.6.2, 2.4.6.3, and Appendix I

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Chapter III (IV)

(3) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 3 (1, 2, and 3)

Investigational Products > Definition of Investigational Product
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
As delineated in the IN-GCPs, an investigational product is defined as a pharmaceutical product (including the comparator product) being tested or used as a reference in a clinical study. An investigational product can be either an active chemical entity or a formulated dosage form.

Rule 122-DA under Part XA of the DCA, 1940/DCR, 1945 and the DCR-SeventhAmdmt-2015, define an investigational new drug as a new chemical entity or a product having a therapeutic indication, but which has never been tested before on human participants.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (December 21, 2004)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: Definitions

(2) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Part XA, Section 122-DA

(3) (Regulation) Drugs and Cosmetics (Seventh Amendment) Rules, 2015 (DCR-SeventhAmdmt-2015 – Hindi/Hindī and English) (October 30, 2015)
Department of Health and Family Welfare, Ministry of Health and Family Welfare, Government of India

Relevant Section: Rule 122-DA (3)

Investigational Products > Manufacturing & Import
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
According to the DCA, 1940/DCR, 1945, Schedule Y, and the IN-GCPs, the Drugs Controller General of India (DCGI) is responsible for authorizing the manufacture of investigational products in India. Applicants must apply for permission using Forms 44 and 12.

The DCGI is also responsible for authorizing the import of investigational products. Rule 34-A of the DCA, 1940/DCR, 1945 requires that an application for a license to import drugs for the purpose of examination, testing or analysis be made on Form 12 (See G-Form 11 for additional information on test licensing requirements). (See Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics; and Regulator Authority topic, Regulatory Fees subtopic for detailed application requirements). The NDA Cklist and the Form11 Cklist may also be referenced to ensure compliance with all applicable requirements. In addition, the sponsor must ensure that imported investigational products are manufactured in accordance with Good Manufacturing Practices as laid down in Schedule M of the DCA, 1940/DCR, 1945.

As per the DCR-SecondAmdmt-2016, for new drugs already approved outside India, pre-clinical/toxicological animal studies do not have to be repeated in India in order to obtain DCGI approval to import/manufacture the new drug in India unless specific concerns are recorded in writing.

ADDITIONAL RESOURCES

(A) (Checklist) Pre-screening Checklist for the Submission of New Drug Applications Submitted to CDSCO (NDA Cklist) (2013)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: Applications for Investigational New Drugs

(B) (Checklist) Pre-screening for Test Licence in Form-11 (Form11 Cklist) (Current as of December 8, 2016)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

REQUIREMENTS

(1) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Part XA, Section 122-DA; Part XIX, Forms 11, 12, 44, 45, 45A, and 46; Schedule M; and Schedule Y

(2) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 1 (1 and 2) and Appendices I and I-A

(3) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (December 21, 2004)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Appendix II (Schedule Y), Appendix I to Schedule Y

(4) (Guidance) Guidance Document on Grant of Licence in Form 11 (Test Licence) for the Purpose of Examination Testing and Analysis as per Rule 33 of Drugs and Cosmetics Acts and Rules 1945 (G-Form 11) (May 30, 2011)
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India

Relevant Sections: A, B, B.1, B.2, and B.3

(5) (Regulation) Drugs and Cosmetics (Second Amendment) Rules, 2016 (DCR-SecondAmdmt-2016Hindi/Hindī and English) (March 16, 2016)
Department of Health and Family Welfare, Ministry of Health and Family Welfare, Government of India

Relevant Section: Schedule Y (Appendix I)

Investigational Products > IMP/IND Quality Requirements
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
In accordance with Appendix IV of the IN-GCPs, the sponsor is responsible for preparing the Investigator’s Brochure (IB) which is a compilation of the clinical and non-clinical data on the investigational product(s) (IPs). The IB provides the investigator(s) and other parties involved in the clinical trial with information on the rationale to facilitate compliance with the key features of the protocol (i.e., dosing, dose frequency/intervals, methods of administration, and safety monitoring procedures). It also serves as background information to support the clinical management of the trial participants. The IB should be written in a concise, simple, objective, balanced and non-promotional format that will afford investigator(s) an unbiased risk-benefit assessment of the appropriateness of the proposed trial.

The IB must be revised whenever necessary to comply with sponsor guidelines, the stage of development, and when any new information is generated. New information that is considered to be important must be immediately communicated to the investigator(s), ethics committee(s), and the Drugs Controller General of India (DCGI), even before it is included in the IB.

IB Content Requirements
The IN-GCPs requires the IB to provide coverage of the following areas:

  • Physical, chemical, and pharmaceutical properties and formulation parameters
  • Non-clinical studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
  • Effects of IPs in humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; regulatory and post marketing experiences)
  • Summary of data and guidance for the investigator(s)
  • Bibliography

See Appendix IV of the IN-GCPs for detailed content guidelines. The NDA Cklist may also be referenced to ensure compliance with investigational new drug application requirements.

In addition, the sponsor is also accountable for supplying the IP, including the comparator(s) and placebo, if applicable. As defined in the IN-GCPs, he/she must ensure that the products are manufactured in accordance with Good Manufacturing Practices as laid down in Schedule M of the DCA, 1940/DCR, 1945.

As per the DCR-SecondAmdmt-2016, for new drugs already approved outside India, pre-clinical/toxicological animal studies do not have to be repeated in India in order to obtain DCGI approval to import/manufacture the new drug in India unless specific concerns are recorded in writing.

(See Investigational Products topic, Product Management subtopic for additional information on IP supply, storage and handling requirements).

ADDITIONAL RESOURCES

(A) (Checklist) Pre-screening Checklist for the Submission of New Drug Applications Submitted to CDSCO (NDA Cklist) (2013)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Section: Applications for Investigational New Drugs

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (December 21, 2004)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: Appendix IV

(2) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Schedule M

(3) (Regulation) Drugs and Cosmetics (Second Amendment) Rules, 2016 (DCR-SecondAmdmt-2016Hindi/Hindī and English) (March 16, 2016)
Department of Health and Family Welfare, Ministry of Health and Family Welfare, Government of India

Relevant Section: Schedule Y (Appendix I)

Investigational Products > Labeling & Packaging
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
Investigational product labeling in India must comply with the requirements set forth in the DCA, 1940/DCR, 1945, Schedule Y, and the IN-GCPs. Rules 96 and 97 of Part IX of the DCA, 1940/DCR, 1945 provide a detailed list of what must be included in a prominent manner on the label of the innermost container of any drug, and on every other covering in which the container is packaged. The label must also be either printed or written in indelible ink. The main items to be included on the label are as follows:

  • The drug name
  • A correct statement of the net content in terms of weight, measure, volume, number of units of contents, number of units of activity, and the weight (measure and volume shall be expressed in Metric system)
  • The content of active ingredients
  • The manufacturer name and address
  • A distinctive batch number

In addition, the IN-GCPs state that the label must also contain the following information:

  • The words - “For Clinical Studies only”
  • The study name or code number
  • The investigator(s) name and contact numbers
  • The institution name
  • The trial participant’s identification code

Clinical trial supplies (for phase I to III trials) must also be labeled in English and include the following:

  • Statement indicating “for clinical trial only”
  • Expiration dateRecommended storage conditions
  • Lot number
  • Protocol code or identification
  • Participant number
  • Treatment period (for example, week 1-4, week 5-8)

The products must also be suitably packaged in a manner that will protect them from deterioration and safeguard blinding procedures, if applicable. They must also include the appropriate investigational labeling. (See Investigational Products topic, Product Management subtopic for additional information on IP labeling requirements).

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Part IX, Rules 96 and 97

(2) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: Schedule Y, 1 (1)

(3) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (December 21, 2004)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 2.3.1.4, 2.3.1.6, and 3.1.9

Investigational Products > Product Management
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
In accordance with the IN-GCPs and Appendix X of Schedule Y, the sponsor is responsible for providing the investigator(s) with an Investigator’s Brochure (IB). The IB must contain all of the available chemical, pharmaceutical, toxicological, pharmacological and clinical data including any accessible data from previous and ongoing clinical studies with the investigational product (IP), and, where applicable, the comparator product. The information provided should be accurate and adequate enough to justify the nature, scale, and duration of the study,and to evaluate the potential safety and need for special precautions. Moreover, the sponsor must bring any new and relevant information arising during the study to the attention of the investigator(s) and the ethics committee(s). The sponsor should also include all of the information contained in the IB in the clinical trial protocol.

Investigational Product Supply, Storage and Handling Requirements
In addition to the sponsor’s responsibility for preparing the IB, he/she is also accountable for supplying the IP, including the comparator(s) and placebo, if applicable. As defined in the IN-GCPs, he/she must ensure that the products are manufactured in accordance with Good Manufacturing Practices as laid down in Schedule M of the DCA, 1940/DCR, 1945. The products must also be suitably packaged in a manner that will protect them from deterioration and safeguard blinding procedures, if applicable. They must also include the appropriate investigational labeling.

As per the IN-GCPs and Appendix X of Schedule Y, the sponsor must determine the IP’s storage conditions, reconstitution procedures, and devices for product infusions, if any. He/she must communicate this information on the product labeling, wherever possible, as well as in writing to all involved parties. If any significant formulation changes are made to the IP during the course of the clinical trial, the results of prior studies conducted using the new formulation (e.g., stability, bioavailability, dissolution rate, etc.) should be provided to the involved parties. This will enable the involved parties to determine the effects of the new formulation on the IP’s pharmacokinetic profile prior to using the product in the trial.

The sponsor must obtain all required documentation (i.e., the Drugs Controller General of India (DCGI) and the ethics committee(s) approval) prior to supplying the investigator(s)/institution(s) with any formulation of the product. Once approval is obtained, the sponsor must document all procedures and outline responsibilities for the following:

  • Adequate and safe product receipt, handling, storage, and dispensing,
  • Retrieval of unused product from the trial participants, and
  • Return of unused product to the sponsor (or its alternative disposal procedure)

As per the DCR-SecondAmdmt-2016, for new drugs already approved outside India, pre-clinical/toxicological animal studies do not have to be repeated in India in order to obtain DCGI approval to import/manufacture the new drug in India unless specific concerns are recorded in writing.

Record Requirements
The sponsor is required to maintain records for product retrieval (e.g., retrieval after study completion, expired product retrieval, etc.) per the IN-GCPs. He/she should maintain records of IP quantities with the proper batch numbers. In addition, the sponsor must ensure that the investigator is able to establish a system within his/her institution for the proper management of the products per delineated procedures. Finally, the sponsor should maintain sufficient samples from each batch and keep a record of their analyses and characteristics for reference so that, if necessary, an independent laboratory could reconfirm the same data.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 3.1.8 and 3.1.9

(2) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Section: Appendix X

(3) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Schedule M

(4) (Regulation) Drugs and Cosmetics (Second Amendment) Rules, 2016 (DCR-SecondAmdmt-2016Hindi/Hindī and English) (March 16, 2016)
Department of Health and Family Welfare, Ministry of Health and Family Welfare, Government of India

Relevant Section: Schedule Y (Appendix I)

Specimens > Definition of Specimen
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
The G-XBiolMat defines a specimen as human material with the potential for use in biomedical research. As per the ICMR Guidelines and the G-XBiolMat, this material specifically includes:

  • Organs and parts of organs
  • Cells and tissue
  • Sub-cellular structures and cell products
  • Blood
  • Gametes (sperm and ova)
  • Embryos and fetal tissue
  • Wastes (urine, feces, sweat, hair, epithelial scales, nail clippings, saliva, placenta, amniotic fluid, etc.)
  • Cell lines from human tissues

Material Sources
As per the ICMR Guidelines and the G-XBiolMat, these biological specimens or human material samples may be obtained from the following non-invasive 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
  • Stored in tissue banks
ADDITIONAL RESOURCES

No additional resources

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, Government of India

Relevant Section: I

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Section: Chapter III, Review Procedures, Section 3

Specimens > Import & Export
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
In India, which specimens import/export guidelines apply depends on whether they are for biomedical research or for commercial purposes. According to G-BioTransfer, for import/export of human biological material for biomedical research purposes, G-XBiolMat is to be followed. For import/export of human biological samples for commercial purposes, the BioCommercial is to be followed.

Import/Export for Biomedical Research
According to G-XBiolMat, the guidelines for considering requests for transfer of  biological material abroad for research/diagnostic purposes, and requests for transfer of biological material from abroad to Indian Iinstitutions for research purposes are as follows:

  • 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. No permission needs to be sought from any authority for this purpose.
  • Exchange of material from and to recognized laboratories such as WHO Collaborating Centres or WHO Centres may be allowed as part of their 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 envisaged as part of a collaborative research project, the project proposal as a whole must be routed through the appropriate authorities for evaluation and clearance. The exchange of human materials should be an integral part of a collaborative project, which should be approved by the institutional review and ethics committees, and not be a separate activity.
  • The availability of facilities within India for carrying out certain investigation need not prevent collaboration with scientists in other countries for the same investigations, including transfer of human material, if required.
  • On the issue of technology transfer/training of Indian scientists abroad/training of foreign scientists and students in India, and visits by the 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 field work to be undertaken in the community and other sensitive issues would have to be regulated according to the rules of the government.
  • In order to protect the rights of the Indian study subjects as well as Indian scientists/organisations, memoranda of understanding and/or agreements on material transfer should be entered into between the collaborating partners (Indian and foreign). These should, according to the requirements of the case under consideration, include items pertaining to identification of the collaborating or sending/receiving parties, background, the material to be transferred and its quantities, purpose of  the transfer, the research to be carried out using the material, confidentiality, intellectual property rights, filing of patents, arrangements for future commercial exploitation, reporting, publication rights, indemnification, termination of agreement, assignation or transfer of agreement/rights, safety norms to be observed, shipping arrangements, qualified user information, and any other matter that  may be relevant to the particular exchange of material.

Import/Export for Commercial Purposes
According to the BioCommercial, the import of human biological samples by the Indian diagnostic laboratories/Indian Clinical Research Centres for lab analysis/research and development testing or export of these materials to foreign laboratories should be permitted by customs authorities at the port of entry/exit without prior approvals (import licence/export permit) from any other government agency, provided the concerned Indian company/ agency submits an undertaking that they are following and will follow all the applicable rules, regulations and procedures for the safe transfer and disposal of the biological samples being imported/exported. For more information, see the BioCommercial.

ADDITIONAL RESOURCES

(A) (Application) Application Format for Transfer of Biological Material for Commercial Purposes and /or Research for Development of Commercial Products (Date Unavailable)
Indian Council of Medical Research, International Health Division, Ministry of Health and Family Welfare, Government of India

(B) (Application) Application Format for Import of Human Biological Material for Commercial Purposes and/or Research for Development of Commercial Products (Date Unavailable)
Indian Council of Medical Research, International Health Division, Ministry of Health and Family Welfare, Government of India

(C) (Document) Material Transfer Agreement (Date Unavailable)
Indian Council of Medical Research, International Health Division, Ministry of Health and Family Welfare, Government of India

(D) (Application) Application Format for the Obtaining of Export NOC of Biological Samples of Clinical Trial for Testing (Annexure) (July 20, 2012)
Directorate General of Health Services, Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

(E) (Application) Form 12 – Application for Licence to Import Drugs for Purpose of Examination, Test or Analysis (Date Unavailable)
Directorate General of Health Services, Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

(F) (Document) Checklist for Permission for Conducting Clinical Trial (Phase I, II, III) and Global Clinical Trial (Date Unavailable)
Biological Division, Office of Drugs Controller General (India), Directorate General of Health Services, Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

(G) (Checklist) Pre-screening Check List for the Export of Biological Samples (Biol Cklist) (Date Unavailable)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

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, Government of India

Relevant Sections: II, III, and IV

(2) (Guidance) Guidance on Transfer of Human Biological Material for Research Purposes/Commercial Purposes (G-BioTransfer) (Date unavailable)
Indian Council of Medical Research, International Health Division, Ministry of Health and Family Welfare, Government of India

(3) (Regulation) Notification: Import/Export Policy for Human Biological Samples for Commercial Purposes (BioCommercial – Hindi/Hindī and English) (August 4, 2016)
Directorate General of Foreign Trade, Department of Commerce, Ministry of Commerce and Industry

(4) (Legislation and Regulation) The Drugs and Cosmetics Act, 1940 and The Drugs and Cosmetics Rules, 1945 (DCA, 1940/DCR, 1945) (June 30, 2005)
Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Part IV (34), Part XA (Sections 122A, 122B, 122D, 122-DA, and 122-E), Part XIX (Forms 12 and 44)

(5) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (May 10, 2003)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 7.1 and Appendix III

(6) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Chapter IV (II)

(7) (Regulation) Drugs and Cosmetics (IInd Amendment) Rules, 2005–Notification: Schedule Y–Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials (Amended Version) (Schedule Y) (January 20, 2005)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

Relevant Sections: 1 (1 & 2) and Appendices I, I-A, III, IV, V, VI, VII, VIII, X, and XI

Specimens > Consent for Specimens
Back to Top
Email section Share    Print section Print
Last content review/update: December 12, 2016. Submit updates or comments.
SUMMARY

Overview
In accordance with the IN-GCPs and the ICMR Guidelines, prior to enrolling a research participant in a clinical trial, the investigator(s) is required to provide appropriate informed consent forms (ICFs) (including a patient information sheet) to communicate relevant information about the study.

The IN-GCPs and the ICMR Guidelines require the investigator(s) to communicate the following information to participants specifically regarding the use of their biological samples:

  • The participant has the right to prevent use of his/her biological sample (DNA, cell-line, etc.) at any time during the conduct of the research
  • The investigator(s) must inform the participant to the extent possible, of all current and future uses of his/her biological material, and if the material is likely to be used for secondary purposes or will be shared with others
  • The investigator(s) should convey to the participant any potential risks that may be associated with the discovery of biologically sensitive information
  • The participant should be informed about the storage period for his/her biological sample(s) and related data, be given a choice about the future use of the sample, be permitted to refuse storage, and be provided proof of the results
  • The participant must be given counseling per national guidelines if testing for genetics and human immunodeficiency virus (HIV) is to be conducted
  • For genetic research, the investigator must establish safeguards for confidentiality of participant data
  • For commercial research, researchers and participants must be protected from coercion by companies

See Chapter VI of the ICMR Guidelines for detailed consent requirements for genetic research.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Good Clinical Practices for Clinical Research in India (IN-GCPs) (December 21, 2004)
Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Government of India

(2) (Guidance) Ethical Guidelines for Biomedical Research on Human Participants (ICMR Guidelines) (October 2006)
Indian Council of Medical Research, Department of Health, Ministry of Health and Family Welfare, Government of India

Relevant Sections: Chapter III (I), Chapter IV (II), and Chapter VI (I)

Please help us understand our users better by providing your organizational affiliation.
Thank you for providing your affiliation information.
OMB #: 0925-0668
Expiration Date: 2/28/2019