Pharma Business Management

GROUP 09

Current regulatory requirements for new drug approval and

clinical trial in India – NDCT 2019

Harshida Yeole 18
Rahul Patil 38
Tejal Sharma 48
Snehal Singh 55
Dhanashree Teli 57
Reena Yadav 60
Name: Harshida Yeole
Roll No: 18

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.
Chapter IV which includes provision for ‘Ethics committee for
biomedical and health research’ will be effective after 180 days i.e. 21
Sep 2019.
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. Actions taken according to the existing rules [Drugs &
Cosmetics Rules, 1945] shall continue to be in effect and valid. This
means existing licenses, orders, directions will continue to remain
valid.
Definitions of many previously undefined terms have been included.
New drug definition has been broadened, covers newer therapeutic
options like SR/MR, NDDS, Living modified organisms, monoclonal
antibodies, stem cells derived products, gene therapeutic products,
xenografts etc.
Defines orphan drug in the regulation as drug used to treat condition
which affects not more than 5 lac persons in India - Provision of
waiver of local phase III clinical trials if drug is approved and
marketed in certain countries [as notified from time to time] subject to
certain conditions and confirming conduct of Phase IV study.
The Phase IV study requirement could be reduced in case of drugs of
special relevance, in case of unmet need, for rare disease for which
drugs are not available or available at a high cost or orphan drugs.

Fees & Forms:

A hiked fee structure has been implemented. Key ones being :
3 lakh INR (approx. 3800 Euro/4500 USD) for Phase I
2 lakh INR (approx. 2500 Euro/2900 USD) for Phase II, III, IV &
BA/BE study.
5 lakh INR (approx. 6500 Euro/7200 USD) for pre submission
meeting.
50,000 INR (approx. 650 Euro/720 USD) for post submission
meeting.
5 lakh INR (approx. 6500 Euro/7200 USD) for registration of BA /
BE study centre.
5 lakh INR (approx. 6500 Euro/7200 USD) for new drug permission /
Finished formulation or API [import]

Name: Rahul Patil

Roll No: 38

Ministry of Health and Family Welfare (MoHFW), Government of

India has announced New Drugs and Clinical Trials Rules, 2019, on
March 19. New rules have made changes in the roles and
responsibilities, functioning of all the stake holders involved in the
conduct of the clinical trials.
Ethics Committee for Clinical Trial, Bioavailability And
Bioequivalence Study in Chapter III in the gazette mentions about
the changes in the EC constitution and training of ethical members
Ethics Committee for Biomedical and Health Research in Chapter IV
mentions about a separate EC for research involving basic, applied,
operational or clinical research (Biomedical and health research).

Differentiation of Phase IV and Post marketing studies is

described:

Phase IV (Post marketing trial) is expected to be conducted approved

protocol with definite scientific objectives, inclusion/ exclusion
criteria, safety/ efficacy assessment in approved indication in
approved patient population. All ethical guidelines including
Compensation rule needs to be followed and drug may be given free
of cost.

Post Marketing Surveillance or observational or non-interventional

study for active surveillance is expected to be conducted with
approved protocol with scientific objective, Inclusion/ exclusion as
per approved pack insert and regulatory provisions or guidelines of
clinical trial are not applicable.

Import or Manufacture of New Drug for Sale or for Distribution

in Chapter X mentions about waiver of local clinical trials if a person
or pharmaceutical company intends to sell the new drug approved and
marketed in the list of countries specified from time to time in rule
104.
We welcome this rule, though some are critical about it. 2,3 The rule
explicitly specifies the type of studies which do not require repetition
of clinical studies locally.

However, the applicant in such cases must give an undertaking to

CLA to conduct phase IV clinical trial to establish the safety and
efficacy of such new drug. This rule is certainly praiseworthy from
participants and sponsors perspective as it not only avoids
unnecessary exposure of participants into study risks but also evades
needless usage of resources.

Second schedule in the gazette provides provision for Accelerated

approval to a new drug if it is intended for the treatment of a serious
or life-threatening condition or disease, where treatment in such cases
is not addressed adequately by the available therapy.

The efficacy observed in phase II for the investigational new drug

may be considered for granting the marketing approval. This will
encourage the sponsors to take-up more of such studies and enables
early care of such needy patients in serious or life-threatening
conditions with promising drugs, without having to wait for long
regulatory process.

Name: Tejal Sharma

Roll No: 48
The New Drugs and Clinical Trials Rules 2019, released by the
Central Drugs Standard Control Organization (CDSCO), Ministry of
Health and Family Welfare (MOH & FW), Government of India,
became effective from March 25, 2019, except Chapter 4 (Ethics
Committee for Biomedical and Health Research), which became
effective after 180 days (i.e. Sep 21, 2019).

The new rules (Rule 97 (Rule 122DAA)) supersede existing Part XA

and Schedule Y of Drugs and Cosmetics Rules, 1945. However, all
existing licenses, orders and directions will remain valid.

These rules shall apply to clinical trials, bioavailability or

bioequivalence (BA/BE) studies of new drugs and regulation of
ethical committees approving them. The primary objectives of the
new rules are:

1. Promotion of research and development in India

2. Faster accessibility to new drugs
3. Predictability and transparency in approval process
4. Improvement data credibility and accuracy.

For the first time, orphan drug has been defined as one intended to

treat a condition affecting less than five lakh people in India. Clinical
trial fee has been waived off for such drugs along with the provision
of fast-track approval.

To promote indigenous drug development, the timelines of approval

process has been defined as 30 days. If no objection/query is raised by
the CDSCO, the application will be considered “approved”.

Provision of post-trial access has been made for patients if the new
drug is deemed effective without any alternative. This will be
provided free of cost by the sponsor.

It is now clarified that any type of study involving human subjects,

except drug trials (as defined in clause J), will be governed by the
National Ethical Guidelines for Biomedical and Health Research
Involving Human Participants, 2017 formulated by the Indian Council
of Medical Research (ICMR). Compensation for any study-related
serious adverse events will be decided by the Institutional Ethics
Committee (IEC)

CDSCO registration is now mandatory for all IECs to approve

regulatory clinical trials. However, accreditation by National
Accreditation Board for Hospitals and Healthcare Providers – Quality
Council of India (NABH–QCI) is not mandatory, although
recommended. For approving non-regulatory trials, all IECs, should
be registered with Department of Health Research (MOH & FW).

Provision of waiver of local phase III clinical trials if drug is

approved and marketed in certain countries [as notified from time to
time] subject to certain conditions and confirming conduct of Phase
IV study.

The Phase IV study requirement could be reduced in case of drugs of

special relevance, in case of unmet need, for rare disease for which
drugs are not available or available at a high cost or orphan drugs

Name: Snehal Singh

Roll No: 55
The Union Ministry for Health and Family Welfare has notified the
Drugs and Clinical Trials Rules, 2019 with an aim to promote
clinical research in the country.
These rules will be applicable to all new drugs, ethics committee and
investigational drugs applicable for human use, bioequivalence
studies and clinical trial in India.

Rule 2 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 under the NDCT Rules.

Defined timelines for review and approval of CT applications:

90 days for global clinical trials. 30 days for INDs being developed
in India - If no response from DCGI, “automatic approval” to
proceed, by notification to DCGI via Form CT-4A .
Application fee for Phase 1 to 4 clinical trials increased 6-8 folds.

Provisions for BA / BE studies are more clearly defined Provisions

like application process, inspection process, suspension or
cancellation of permission etc are defined clearly in the new
regulations.
Requirements of BA / BE centres registrations have been defined in
the new rules BE Permission will remain valid for a period of one
year from the date of its issue, unless suspended or cancelled by the
Central Licensing Authority
Requirements for Clinical Trial labels are defined under “Manner of
labelling” and in addition to routine contents, name of institute
where clinical trial is proposed to be conducted is required to be
added.

Ethics committee
Ethics Committee for Clinical Trial, Bioavailability And
Bioequivalence Study in Chapter III in the gazette mentions about
the changes in the EC constitution and training of ethical members
Ethics Committee for Biomedical and Health Research in Chapter IV
mentions about a separate EC for research involving basic, applied,
operational or clinical research (Biomedical and health research).

New provisions to be followed during trial:

 Enrolment status should be submitted on quarterly basis to
licensing authority.
 Six monthly status reports on the trial should be submitted in
SUGAM portal.
 Early termination of clinical trial should be reported to licencing
authority within 30 working days.
 In case of study related injury or death, compensation should be
provided within 30 calendar days of receipt of orders from
licencing authority [previously this was 30 days]
 If a drug is found to be useful in clinical development, firm
should submit application for import or manufacture of the drug
for sale in India, unless otherwise justified.

Name: Dhanashree Teli

Roll No: 57
New Drug and Clinical Trial Rules, 2019 are applicable from date of
release, 25th Mar 2019, except Chapter 4 [Ethics Committee for
Biomedical and Health Research], which came into force after 180
days (i.e. 21st Sep 2019)
Rule 97 (Rule 122DAA): New Rules supersede existing Part XA
and Schedule Y of D&C Rules, 1945
All existing licenses, orders, directions will continue to remain valid

Rule 2 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

under the NDCT Rules.

Two types of Ethics Committees (EC) defined:

1. Clinical Trials & BA/BE studies
2. Biomedical & Health Research
Validity of EC registration increased to 5 years (from 3 years)
Application for permission to import new drug for sale or
distribution
Local clinical trial (data) may not be required to be submitted along
with the application if:
 The new drug is approved and marketed in countries and if no
major SUSARs
  Already granted permission to conduct a global clinical trial
which is ongoing in India and in the meantime such new drug
has been approved for marketing in a country.
 There is no probability or evidence, of difference in Indian
population.
 Undertaking in writing to conduct Phase IV clinical trial.

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).

Compensation for injury or death No change in regulation:

Central licensing Authority at their discretion may or may not
constitute the Expert Committee to review reports of SAE submitted.
In case they don’t decided to formulate the committee, then the
Central Licensing Authority shall review the report and convey
the decision.

Name: Reena Yadav

Roll No: 60
Ministry of Health and Family Welfare [MoHFW] has notified the
“New Drugs and Clinical Trials Rules, 2019” on 25th March.
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.
Now, the Schedule Y along with Part XA of the D and C Rules have
been replaced by the New Drugs and Clinical Trial Rules 2019.
The arrangement of the New Drugs and Clinical Trial Rules 2019 is
very logical and easy to remember. The Rules are divided into
Chapters and each chapter refers to one aspect of research.
 Chapter I – Preliminary
 Chapter II – Authorities and Officers
 Chapter III – EC for Clinical Trials, BA and BE Studies
 Chapter IV – EC for Biomedical and Health Research
 Chapter V – Clinical Trials, BA and BE Studies on
Investigational/New Drugs
 Chapter VI - Compensation Chapter VII – BA/ BE Centre
 Chapter VIII – Manufacture of new drugs for CT, BA and BE
studies
 Chapter IX – Import of new drugs for CT, BA and BE studies
 Chapter X – Import of new drug for sale or distribution
 Chapter XI – Import or Manufacture of new drug for
treatment in Government hospitals
 Chapter XII – Amendment of Rules
 Chapter XIII – Miscellaneous All definitions have been
grouped together and arranged alphabetically in section 2 of
Chapter I. Similarly, there are seven schedules each dealing with a
particular heading, making searching of information very easy.

Ethics Committees
There were two types of ethics committees in the past, Institutional
and Independent. As per the registration letters, Institutional ECs had
wide powers to review and approve clinical trials, bioavailability and
bioequivalence studies.
The powers of Independent ECs were limited to the review and
approval of BA/BE studies only.

Conflict of Rule Numbers

The Drugs and Cosmetics Rules 1945 consisted of 169 Rules,
numbered 1 to 169. The NDCTR contains 107 rules numbered 1 to
107. Thus, there is a duplication of 107 rules.
To give an example Rule 96 of DCR is about Manner of Labelling,
while Rule 96 of the NDCTR is Licence to manufacture an
unapproved new drug but under clinical trial, for treatment of patient
of life threatening disease under the Drugs and Cosmetics Rules,
1945.
Thus, while mentioning or quoting any rules one would have to
specify whether the rule number referred to the D and C rules or the
NDCT Rules.