GSR Notification #227: Paving the Way to Clinical Research in India (Part II)

GSR Notification #227: Paving the Way to Clinical Research in India (Part II)


The application for permission to conduct clinical trial of a new drug or investigational new drug has to be made in Form CT-04 in place of Form 44. The following are the new provisions to be followed during trial conduction.

Enrolment status

The enrolment status of the trial subjects should be submitted on quarterly basis to the central licensing authority. Six monthly status report, pertaining to whether the trial is on-going, completed or terminated, should be submitted in SUGAM portal.

Serious adverse event reporting timeline

Serious adverse event (SAE) reporting timeline for sponsor has been changed to 14 calendar days of the “knowledge of occurrence” of SAE and not “occurrence/onset of SAE”.

Termination of clinical trial

In cases where the clinical trial is terminated early, the same should be reported to central licencing authority within a period of 30 working days. If there is occurrence of study related injury or death, compensation should be provided within 30 calendar days of receipt of orders from licencing authority.

Provision of Post-Trial Access

If the drug is beneficial, and there is no alternative therapy, investigator can recommend post trial access for the patient. In such cases ethic committee (EC) approval and patient/legal heir’s consent is required. The rule also states that there is no liability on sponsor for post-trial use of the drug by patient.

Provisions for bioavailability and bioequivalence (BA/BE) studies

Provisions like application process, inspection process, suspension or cancellation of permission have been defined in the new regulations. The permission to conduct bioequivalence studies is valid for a period of one year from the date of its issue, unless suspended or cancelled by the central licensing authority. The new rules have also laid down requirements of bioavailability and bioequivalence study centres registrations.

Compensation

There are no significant changes in payment of compensation and the process of determination of causality assessment. Requirement of medical management (in clinical trial or BA/BE study of new drug or investigational new drug) to be provided by the sponsor has been clearly defined. The sponsor has to provide free medical management to the subject as long as required “as per the opinion of investigator”, or till such time it is established that the injury is not related to the clinical trial, whichever is earlier.

A provision for pre and post submission meetings

With the provision of pre-submission meetings, the applicant can seek guidance about the requirements of law and procedure applicable for their projects before making actual submission to the regulator. The applicants can discuss their projects with the regulators and subject experts by paying a certain amount of fee. In the provision of post-submission meetings, the applicant can seek clarification in person with regards to pending application and can discuss related queries. For this the applicant has to apply for a post-submission meeting with the officer designated by the central licencing authority within a period of fifteen days (from the date the query was received) for seeking guidance with regards to the queries concerning pending application.

Phase IV and Post Marketing Surveillance

The new rules make certain clear requirements for phase IV and post marketing studies. Phase IV (Post marketing) trial include additional drug-drug interactions/dose-response/safety studies & trials designed to support use under the approved indications. Such trials have to be conducted under an approved protocol comprising definite scientific objectives, inclusion/ exclusion criteria, safety/ efficacy assessment etc. in approved indication in approved patient population. While conducting such studies, all ethical guidelines (including compensation rule) have to be followed and drug may be given free of cost. For post marketing surveillance (or observational or non-interventional study) regulatory provisions and guidelines of clinical trial are not applicable as drugs are already approved for marketing. However, they need to be conducted as per an approved protocol with scientific objective and should follow inclusion/ exclusion of subjects as per approved package insert.

Reference

New Drugs and Clinical Trials Rules, 2019, Ministry of Health & Fam. Welfare, Notification, G.S.R. 227(E), (March 19, 2019).



Frequently Asked Questions

What is an “orphan drug” as per the New Drugs and Clinical Trial Rules, 2019?

“Orphan drug” means a drug intended to treat a condition which affects not more than five lakh persons in India.

The extrapolation of the safety and efficacy data of a particular clinical indication (for which clinical studies has been done) of a similar biologic to other clinical indications may be possible if following conditions are met: Similarity with respect to quality has been proven to reference biologic Similarity with respect to preclinical assessment has been proven to reference biologic Clinical safety and efficacy is proven in one indication Mechanism of action is same for other clinical indications Involved receptor(s) are same for other clinical indications New indication not mentioned by innovator will be covered by a separate application.

The permission to initiate clinical trial granted in Form CT-06 or automatic approval in Form CT 4A shall remain valid for a period of 2 years from the date of its issue, unless extended by the CLA.

Yes. Clinical trial at each site shall be initiated after the approval of the clinical trial protocol and other related documents by the Ethics Committee for that site, registered with the CLA.

Yes. Before enrolment of first participant in any clinical trial, registration in CTRI is mandatory

The three tier mechanism comprises the following authorities: 1. Institutional Biosafety Committee (IBSC) at the Institute/ company – To ensure biosafety on-site 2. Review Committee on Genetic Manipulation (RCGM) in the Department of Biotechnology - Managed genetically engineered cell banks 3. Genetic Engineering Appraisal Committee (GEAC) in the Ministry of Environment & Forests (MoE&F)- for genetically modified organisms/ living modified organisms

Any person or institution or organisation having permanent establishment in India who intends to conduct clinical trial of a biological product can submit application for clinical trial.

After obtaining permission in CT-11 or CT-14 or CT-15 as the case may be, the person, who intends to manufacture the biological product for CT, shall make an application for grant of license to manufacture the biological product by the respective State Licensing Authority (SLA) in accordance with the provisions of the Act and the Drugs and Cosmetics Rules, 1945.

“New drug” means, (i) a drug, including active pharmaceutical ingredient or phytopharmaceutical drug, which has not been used in the country to any significant extent, except in accordance with the provisions of the Act and the rules made thereunder, as per conditions specified in the labelling thereof and has not been approved as safe and efficacious by the Central Licencing Authority with respect to its claims; or (ii) a drug approved by the Central Licencing Authority for certain claims and proposed to be marketed with modified or new claims including indication, route of administration, dosage and dosage form; or (iii) a fixed dose combination of two or more drugs, approved separately for certain claims and proposed to be combined for the first time in a fixed ratio, or where the ratio of ingredients in an approved combination is proposed to be changed with certain claims including indication, route of administration, dosage and dosage form; or (iv) a modified or sustained release form of a drug or novel drug delivery system of any drug approved by the Central Licencing Authority; or (v) a vaccine, recombinant Deoxyribonucleic Acid (r-DNA) derived product, living modified organism, monoclonal anti-body, stem cell derived product, gene therapeutic product or xenografts, intended to be used as drug; Explanation: The drugs, other than drugs referred to in sub-clauses (iv) and (v), shall continue to be new drugs for a period of four years from the date of their permission granted by the Central Licencing Authority and the drugs referred to in sub-clauses (iv) and (v) shall always be deemed to be new drugs;

In India, genetically modified organisms (GMOs) and the products thereof are regulated under the “Rules for the manufacture, use, import, export & storage of hazardous microorganisms, genetically engineered organisms or cells, 1989” (referred to as Rules, 1989) notified under the Environment (Protection) Act, 1986.

Related Articles

Drug |
Are Investigational New Drug Trials in India A Positive Sign For Healthcare

Are Investigational New Drug Trials in India A Positive Sign For Healthcare: The Researchers Perspective

Drug |
Medical Devices |
Diagnostic Kits |
Biologicals |
Consumer Claims |
Conducting Clinical Trial During COVID-19

COVID-19 has caused a massive shift in how we manage clinical trials. Due to inadequate resources and restrictions placed due to the pandemic, companies are struggling to maintain the safety of study participants and staff while ensuring the continuity of ongoing trials.

Drug |
Medical Devices |
Diagnostic Kits |
Biologicals |
The Drug Development Process – From Conception to Market

Drug development encompasses the entire process of bringing a new drug to market. The drug discovery journey starts with the identification of a disease or disease area with an unmet medical need and ends with regulatory submissions and market launch.


*All the above fields are mandatory