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

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


The New Drugs and Clinical Trials Rules, 2019 was declared by the ministry of health and family welfare on 25th March 2019 (GSR Notification #227). The key focus of the new set of rules is to encourage advances in clinical research in India. The rules are meant to revolutionize the regulatory aspects for the conduct of clinical trials and the subsequent approval of new drugs. The New Drugs and Clinical Trials Rules, 2019 has been effective from 25th March 2019; however, the chapter four of the rules which pertains to “Ethics committee for biomedical and health research” came into action from 21st September 2019.

The new rules supersede Part XA and Schedule Y of Drugs and Cosmetics Rules and are applicable to all new drugs, investigational new drugs (INDs) for human use, clinical trial, bioequivalence/bioavailability study and ethics committee.



Application fees and modified approval formats

The application fees have been hiked for Phase 1 to 4 clinical trials. Additionally, application and approval formats have been modified. Some of the modified forms are mentioned below:

  • Form CT04 – Clinical Trial Application Form (Replaces Form 44)
  • Form CT 04 A- Automatic Approval Information to CDSCO
  • Form CT 06 - Permission to Conduct CTs by CDSCO
  • Form CT 16- Application to grant of License to Import of New Drug for Clinical Trials (Replaces Form 12)

Definitions have been revised

To bring in more clarity, many definitions have been newly incorporated, while some have been modified. As per the new definition, an orphan drug is defined as drug used to treat condition which affects not more than 5 lac persons in India.

Application review periods and automatic approvals

For the review and approval of clinical trial (CT) applications, fixed timelines have been put down.

  • Ninety working days for global clinical trials
  • Thirty working days for investigational new drugs (INDs) being developed in India. To encourage research and development in India, a new provision of “automatic approvals”

been introduced. If no response is received from the central licencing authority to the applicant within the said period (30 days), the permission to conduct clinical trial shall be deemed to have been granted by the central licencing authority. In such cases, before trial initiation the applicant is required to inform the central licencing authority in Form CT-4A; the central licencing authority on the basis of the said

Ethics committee

The new rules have incorporated significant changes in the constitution of ethics committee (EC). As per the new rules, the ethics committee should have a minimum of seven members from medical, non-medical, scientific and non-scientific areas with.

  • At least, one lay person
  • One woman member
  • One legal expert
  • One independent member from any other related field such as social scientist or representative of non-governmental voluntary agency or philosopher or ethicist or theologian

    At least 50% of members should not be affiliated with the institute or organization in which EC is constituted and every member of the EC shall be required to undergo such training and development programs.

    Two types of ethics committee have been defined:

    • Ethics committee for clinical trial,
    • Ethics committee for Biomedical and health research

Ethics committee registration certificate would be granted in Form CT-02 within a period of 45 working days. The validity of registration has been increased to a period of five years from the date of its issue. Application for the renewal of the registration can be submitted 90 days prior to the date of the expiry of the registration to ensure deemed continuity. As per the new rule, when a clinical trial site does not have its own EC, clinical trial at that site may be initiated after obtaining approval of the protocol from the EC of another trial site; however, in such cases the approving ethics committee should take responsibility for the study at another site or center and the approving ethics committee should be located within the same city or within the radius of 50 kilometres of the clinical trial site.

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.

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

“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;

Yes. As per clause (w) of rule 2 of the New Drugs and Clinical Trials Rules, 2019 modified/sustained/prolonged/controlled release and NDDS of an approved drug are always considered as new drug and hence, require prior permission from CLA before obtaining the manufacturing license from the SLA for such products.

Any new drugs or investigational new drugs imported for the purpose of clinical trial shall be kept in containers bearing labels, indicating the name of the drug or code number, batch or lot number, wherever applicable, date of manufacture, use before date, storage conditions, name of the institution or organisation or the centre where the clinical trial is proposed to be conducted, name and address of the manufacturer, and the purpose for which it has been imported. Where a new drug or an investigational new drug is imported by the licencee on behalf of another person, the licencee shall indicate on the label of the container of the such drug, the name and address of the importer and the person to whom it is being supplied along with the scientific name of such drug, if known, or the reference which shall enable such drug to be identified and the purpose for which it is manufactured. No person or importer shall alter, obliterate or deface any inscription or mark made on the container, label or wrapper of any new drug imported without permission of the Central Licencing Authority.

A subsequent new drug means 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. A subsequent new drug also includes a new drug already approved in the country.

Any person or institution or organisation having permanent establishment in India who intends to conduct clinical trial study of a new drug or an investigational new drug can submit application for clinical trial study

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

If a clinical trial site does not have its own ethics committee, clinical trial at that site may be initiated after obtaining approval of the protocol from the ethics committee of another trial site. Provided that the approving ethics committee for clinical trial shall be responsible for the study at the trial site and the same shall be located within the same city or within a radius of 50 kms of the actual clinical trial site.

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