NDCT STANDS FOR NEW DRUG CLINICAL TRIAL RULE. HERE YOU WILL GET TO KNOW ABOUT THE NDCT RULE HISTORY, FORMATION, CHANGES AND FEATURES

1. NDCT RULES 2019
By-Manisha Chauhan
(Apeejay Stya University)

2. INTRODUCTION
Ministry of Health and Family Welfare [MoHFW] has notified the “New
Drugs and Clinical Trials Rules, 2019” on 25th March 2019. The new
rules aim to promote clinical research in the country and will change
the regulatory landscape for the approval of new drugs and conduct of
clinical trials in the country.
The rules will apply to all new drugs, investigational new drugs for
human use, clinical trial, bioequivalence study, bioavailability study and
Ethics Committee. The new rules will supersede Part XA and Schedule Y
of Drugs and Cosmetics Rules, with immediate effect. If there is any
inconsistency between these rules and any other rule made under the
Drugs & Cosmetics Act, the provisions of these rules shall prevail over
such other rules.

3. LEGISLATIVE HISTORY OF NDCT
RULES
• Clinical trials were earlier conducted in accordance with the requirements set out
in Schedule Y of the Drugs and Cosmetics Rules, 1945 (D&C Rules) which
concerns regarding patient safety and compensation provided to patients in cases
of adverse effects.
• In an order dated October 21, 2013, the Hon’ble Supreme Court opined that
approvals for clinical trials should be based on all relevant aspects of safety and
efficacy, particularly in terms of assessment of risk versus benefit to the patients,
innovation vis-a-vis existing therapeutic options and unmet medical need in the
country.
• In 2013, certain amendments were made to the D&C Rules, to regulate the
clinical trials conducted in India. Rule-122DAB was inserted into the D&C
Rules, vide the Drugs and Cosmetics (First Amendment) Rules, 2013[3].

4. • Rule-122DAC was inserted into the D&C Rules, vide the Drugs and
Cosmetics (Second Amendment) Rules, 2013, which lists out the conditions
for the conduct of clinical trials.
• Further, the guidelines in relation to composition and registration of ethics
committees were notified vide the Drugs and Cosmetics (Third
Amendment) Rules, 2013.
• Deficiencies in regulation of clinical trials had been observed in the 59th
Report of the Parliamentary Standing Committee on Health and Family
Welfare on the functioning of the Central Drugs Standard Control
Organisation (CDSCO).
• It took the MoHFW a long time to consider the Rules and finalise them. The
Supreme Court took notice of this delay, and in an order dated December
4, 2018, noted the Government’s submission that the rules will be finalised
within two months.
• The Government assured the Court that, if possible, the NDCT Rules could
be finalised even before that[8]. They were finally notified on March 19,
2019.

5. FEATURES OF NDCT RULES
The NDCT Rules have come into force from March 19, 2019 onwards, except for Chapter
IV, which shall come into effect 180 days after publication in the Gazette, i.e. 180 days after
March 19, 2019.
Rule 2(w) defines a “new drug” to include, inter alia, ‘a drug, including active pharmaceutical
ingredient or phytopharmaceutical drug, which has not been used in the country to any significant
extent’, ‘a drug approved by the Central Licensing Authority for certain claims and proposed to be
marketed with modified or new claims’, ‘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’, ‘a
modified or sustained release form of a drug or novel drug delivery system of any drug approved by
the Central Licensing Authority’, or ‘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’. Stem cell based products are, therefore, also
deemed to be “new drugs” under the NDCT Rules.
The NDCT Rules are applicable to, and regulate, all new drugs, investigational new drugs for human
use, clinical trials, bioequivalence studies, bioavailability studies and Ethics Committees.

6. “Adverse event” has been defined under Rule 2(d) to mean any untoward medical occurrence (including a
symptom or disease or an abnormal laboratory finding) during treatment with an investigational drug or a
pharmaceutical product in a patient or a trial subject. In cases of adverse events, compensation is payable to
the trial subject/ patient.
1.The Drugs Controller, India, appointed by the Central Government in the MoHFW has been designated as the
Central Licensing Authority under the NDCT Rules, to act as the nodal entity for licensing and approvals under
these rules (Section 3).
1.Ethics Committee: Under the NDCT Rules, an Ethics Committee is required to be set up and registered by
whoever intends to conduct clinical trials or bioavailability studies or bioequivalence studies. The study/ trial
can be conducted only with the approval of this Committee, whose registration with the Central Licensing
Authority will be valid for a period of five years. In case of any serious adverse event during a clinical trial or
bioavailability or bioequivalence study, the Ethics Committee is required to analyse the relevant documents
pertaining to such event and forward its report to the Central Licensing Authority (Chapter III).
1.The Application for permission to conduct clinical trials is required to be submitted to the Central Licensing
Authority in Form CT-04. Further, the application has to be accompanied with information and documents as
specified in the Second Schedule and Fee as specified in the Sixth Schedule (Rule 21).
Deemed Approval: Under Rule 23, when a drug is discovered in India, or research and development of the
drug are being done in India and also the drug is proposed to be manufactured and marketed in India, the
application for permission to conduct clinical trials.

7. Compensation: The most important changes brought in by the NDCT Rules, are the provisions
related to compensation. Chapter VI of the NDCT Rules, deals with compensation in case of
injury or death in clinical trial or bioavailability or bioequivalence studies of new drugs or
investigational new drugs.
1.Manufacture of New Drugs for Clinical Trial: Permission of the Central Licensing Authority
must be obtained to manufacture a new drug for conducting a clinical trial or bioavailability or
bioequivalence study or for examination, test and analysis. The permission, if granted, is valid
for a period of three years. The labelling requirements and other conditions for grant of
permission have also been laid down in the NDCT Rules (Chapter VIII).
Import of New Drugs for Clinical Trial: A licence from the Central Licensing Authority must be
obtained to import a new drug for conducting a clinical trial or bioavailability or
bioequivalence study or for examination, test and analysis. The licence, if granted, is valid for
a period of three years. The labelling requirements and other conditions for grant of the
licence have also been laid down in the NDCT Rules (Chapter IX).

8. GENERAL PROCEDURE OF GRANT OF APPROVAL TO
CONDUCT CLINICAL TRIALS IN INDIA
Application must make registration in form CT-04
accompanied by relevant documents to Central Licensing
Authority (CLA).
Permission is granted in form CT-06 Application is rejected
Complies with rules Does not complies with rules
Within 90 days
Applicant must submit required information within specific period of time as
suggested by CLA
In case of deficiency of info in application
Permission is granted in form CT-06 Application is rejected
Complies with rules Does not comply with rules

9. Within 60 days
Request for reconsideration by applicant
After review
Approve Appeal to central government
within 45 days
Rejected

10. COMPENSATION PROCEDURES IN CASE SERIOUS ADVERSE
EVENTS AND DEATH DURING THE CLINICAL TRIALS
1. In case of serious adverse events Investigator
Within 24 hours
CLA, sponsor or its representative and Ethics
Committee
2. In case of serious adverse event of death
Reports shall be forwarded by
sponsor or investigator
Ethics Committee with its opinion
Within 14 days Within 30 days
Central Licensing Authority
Chairperson of Expert Committee
Central Licensing Authority
Within 60 days

11. Decide the compensation and pass the orders to the sponsor and its
representatives
Within 90 days
sponsor
Shall pay the compensation within 30 days of the receipt of the order

12. THREE TIERED REGULATORY PROCESS TO REVIEW
CLINICAL TRIAL APPLICATIONS
Applicant must submit the application accompanied by executive summary to DCGI.
Commencement of review process
Application is initially reviewed by Subject Expert Committee (SEC). This committee
emphasizes on the scientific rationale of the proposed study and also highlights on the
risk benefit ratio.
Consequent review is carried out by Technical Committee which is headed by Director
General for health sciences who has the authority to overrule the decision made by
the SEC and can appeal them to reconsider the decision.
The final review is done by Apex committee. If the application is accepted the final
approval will be given by DCGI.

13. CONCLUSION
The notification of a dedicated, comprehensive set of rules to regulate “new
drugs” and clinical trials will lead to greater clarity and synchronisation in the
regulatory requirements to conduct clinical trials in India.
The attempt to prescribe a system for compensation to trial subjects in cases of
death and injury may be seen as an attempt by the executive to surpass its
mandate and cross over into the domain of the judiciary. This is especially so
because provisions of the D&C Act do not provide for payment of compensation
in such cases.
The D&C Act is silent on the issue of compensation, and the compensation
formula contained in the NDCT Rules can be seen as the rules going beyond the
scope of the D&C Act.

14. THANK YOU