Safety Reporting Requirements in India

As per the Notification of Ministry of Health and Family Welfare dated 30th January 2013, there is a change in safety reporting requirements in clinical trials.

A draft rules for the same to amend the Drugs and Cosmetic Rules 1945 (which is a requirement as per Drugs and Cosmetic Act of 1940) was published were in the gazette on 18th Nov 2011 inviting objections and suggestions from all persons likely to be affected thereby before the expiry of a period of 45 days from the date on which the copies of the official gazette of the said notification were made available to the public. The ops were made available to the public on 24th November, 2011.

Definitions:

Gazette of India -

The Gazette of India is a public journal and an authorised legal document of the Government of India, published weekly by the Department of Publication, Ministry of Urban  Development. As a public journal, the Gazette prints official notices from the government. It is authentic in content, accurate and strictly in accordance with the Government policies and decisions. The gazette is printed by the Government of India Press.




After the suggestions and objections received from public were received and considered by Government of India, the following amendment to the Drugs and Cosmetics Rules, 1945 took place. THIS IS KNOWN AS THE FIRST AMENDMENT OF THE DRUGS AND COSMETIC RULES, 2013. They came into force on the date of their publication in the official gazette I.e., 30th January 2013.





COMPENSATION IN THE CASE Of DEATH OR INJURY

1. In case of injury occurring to the clinical trial subject, he or she shall be given free medical management as long as required.
2. In case the injury occurring to the trial subject is related to the clinical trial, such subject shall also be entitled for financial compensation as per order of the licensing authority defined under clause (b) of rule 21, and the financial compensation will be over and above any medical expenses incurred on the medical management of the subject.
3. In case of clinical trial related death of the subject, his/her nominee(s) would be entitled for financial compensation, as per the order of the Licensing Authority defined under clause (b) of rule 21, and the financial compensation will be over and above any expenses incurred on the medical management of such subject.
4. The expenses on medical management and financial compensation in case of clinical trial injury or death of the trial subject will be borne by the sponsor of the clinical trial.
5. Any injury or death of the subject occuring in clinical trial due to the following reasons shall be considered as clinical trial related injury or death and the subject or his/her nominee(s), as the case may be, are entitled for financial compensation for such injury or death:

• Adverse effect of investigational products
• Violation of the approved protocol , scientific misconduct or negligence by the sponsor or his representative or the Investigator
• Failure of investigational product to provide intended therapeutic effect
• Use of placebo in a placebo-controlled trial
• Adverse effects due to concomitant medication excluding standard care, necessitated as a part of approved protocol.
• For injury to a child in -utero because of participation of parent in clinical trial
• Any clinical trial procedures involved in the study.

6. The Sponsor, whether a pharmaceutical company or an institution shall give an undertaking along with the application for clinical trial permission to the Licensing Authority defined in clause (b) of Rule 21, to provide compensation in the case of clinical trial related death for which subjects are entitled to compensation.

7. In case the sponsor fails to provide medical management for the injury to the subject and/or financial compensation to the trial subject for clinical trial related injury or financial compensation to the subjects nominee(s) in case of clinical trial related death of the subject, the Licensing Authority may after giving an opportunity to show cause why such an order should not be passed, by an order in writing , stating the reason thereof, suspend or cancel the clinical trial and/or restrict Sponsor including his representatives to conduct any further clinical trials in the country or take any other action deemed fit under the rules.


In the said rules, in Schedule Y, in paragraph 2 relating to Clinical Trial ,
(A) in subparagraph (2) relating to Responsibilities of the Sponsor (i) clause (iv) shall be substituted by the following, namely:


SPONSOR RESPONSIBILITY

SAE OF DEATH
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(Iv) any report of serious adverse event of death occuring in clinical trial,  after due analysis shall be forwarded by the sponsor to

• Chairman of ethics committee
• Chairman of k committee constituted by Licensing Authority
• copy of the report to licensing authority
• Copy of report to head of the institution where trial has been conducted

These reports have to be sent within 10 calender days of occurrence of the SAE of DEATH

SAE OTHER THAN DEATH
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The report of SA other than death after due analysis shall be forwarded by the sponsor to :

• Licensing Authority
• Chairman of Ethics committee
• Head of institution where trial has been conducted.

Within 10 calendar days of occurrence of the  SA

(B ) after clause iv,  the following shall be inserted, namely:

(V) in case of injury or death occuring to the clinical trial subject, the sponsor (whether a pharmaceutical company or an institution) or his representative, whosoever had obtained permission from the Licensing Authority for conduct of the clinical trial, shall make payment for medical management of the subject and also provide financial compensation for the clinical trial related injury or death in the manner as prescribed in Appendix XII

(vi) the sponsor (whether a pharmaceutical company or an institution) or his representative, whosoever had obtained permission from the Licensing Authority for conduct of the clinical trial, shall submit details of compensation provided or paid for clinical trial related injury or death, to the Licensing Authority within thirty days of the receipt of the order from licencing authority.

(C) RESPONSIBILITIES OF THE INVESTIGATOR

Investigator shall report all serious and unexpected adverse events to the

• Licensing Authority as defined under clause (b) of Rule 21, 
• the Sponsor or his representative, whosoever had obtained permission from the Licensing Authority for conduct of the clinical trial and
• the ethics committee that accorded approval to the study protocol within 24 hours of their occurrence as per Appendix XI, and the said Licensing Authority  shall determine the cause of injury or death as per the procedure prescribed under Appendix XII and pass orders as deemed necessary.

In sub paragraph (3) relating to Responsibilities of the Investigator(s)-

(i) the sub paragraph (3) shall be numbered as (3) (i);
( ii) in the so numbered clause (i) the words and figures "sponsor within 24 hours and to Ethics committee that accorded approval to the study protocol within 7 working days of their occurrence shall be substituted by "

• licensing authority defined under clause (b) of rule 21, 
• the sponsor or his representative, whosoever had obtained permission from the Licensing authority for conduct of the clinical trial,and 
• Ethics Committee which accorded approval to the study protocol , within 24 hours of their occurrence.

The report of the SAE of death, after due analysis,  shall be forwarded by the Investigator to the

•  chairman of the Ethics committee
• Chairman of the expert committee constituted by the licensing authority.
• Head of institution where the trial has been conducted

Within 10 calendar days of occurrence of the SAE.

(iii) after so numbered clause (i) the following shall be inserted, namely:
(ii) the investigator shall provide information to the clinical trial subject through informed consent process as provided in Appendix V about the essential elements of the clinical trial and subject's right to claim compensation in case of trial related injury or death. He shall also inform the subject or his/ her representative whosoever had obtained permission from the Licensing Authority for conduct of the clinical trial for the purpose of making claims in the case of trial related injury or death.

(d) in clause (5) relating to RESPONSIBILITIES OF ETHICS COMMITTEES after sub clause (iii) the following sub clause shall be inserted, namely:

(iv) IN CASE OF SAE of DEATH occuring to the clinical trial subject , the ETHICS COMMITTEE shall forward it's report  on SAE of death , after due analysis, along with its opinion on the financial compensation, if any, to be paid by the Sponsor or his representative, whosoever had obtained permission from the Licensing Authority as defined under rule 21(b) for conducting the clinical trial to the

• Chairman of expert committee constituted by Licensing Authority
• Copy of report to licensing authority

Within 21 days of occurrence of the SAE of death.

IN CASE OF SAE other than that of death occuring to the clinical trial subject , the ETHICS COMMITTEE shall forward it's report  on SAE , after due analysis, along with its opinion on the financial compensation, if any, to be paid by the Sponsor or his representative, whosoever had obtained permission from the Licensing Authority as defined under rule 21(b) for conducting the clinical trial to the

•  Licensing Authority

Within 21 days of occurrence of the SAE of death.