Comparison of Clinical Trial Application requirement of India, USA and Europe.

1. Drug Regulation & Regulatory Authorities
Dept. Of Quality Assurance & Regulatory Affairs
L. J. Institute of Pharmacy, Ahmedabad.
EXPERIMENT NO.: DATE:
AIM: Comparison of Clinical Trial Application requirement of India, USA and
Europe.
REFERENCES:
1) http://cdsco.nic.in/CDSCO-GuidanceForIndustry.pdf
2) http://www.slideshare.net/RETIRE/clinical-trial-requirements-us-vs-eusimilarities-
and-differences
3) http://blog.worksure.org/clinical-trial-application-cta-submission-in-india/
4) http://www.amarexcro.com/articles/docs/RAPS_Focus_Practical_Feb2009.pdf
COMPARISION:
PARAMETERS EUROPE USA INDIA
1. LEGAL FRAME
WORK
 European Union EU
Directives
applicable to all
members
 National laws apply
 Legal representative
required
 Federal statutes
and regulations
applicable to all 50
states
 Individual state
laws apply
 Authorized
representative
 CDSCO under the
aegis of Ministry
of Health &
Family Welfare
have the duty of
regulating and
ensuring the
quality of
medicines and
pharmaceuticals
under the Drugs &
Cosmetic Act.
2. CLINICAL
TRIAL
APPLICATION
 CTA written
approval required
 Approval timeframe
varies
 IND written
approval not
required to
proceed
 Form 44 is an
application made
for grant of
permission to

2. Drug Regulation & Regulatory Authorities
Dept. Of Quality Assurance & Regulatory Affairs
L. J. Institute of Pharmacy, Ahmedabad.
 Annual safety report
only required
 Format CTD paper
or electronic
 National CTA fees
may apply
commence CT
 May proceed 30-
days after FDA
receives IND
unless notified
otherwise
 IND annual report
required
 Format paper or
electronic, US
format or CTD
 No fees Required
import or
manufacture a new
drug or to
undertake Clinical
Trial.
 documents
pertaining to
chemical and
pharmaceutical
information,
animal
pharmacology,
toxicology data
and clinical
pharmacology
data.
 Investigator’s
Brochure, trial
protocol, case
report form,
informed consent
form, patient
information sheet,
investigator’s
undertaking and
IEC approvals (if
obtained during
review process).
 Regulatory status
of the trial in other
participating
countries also
needs to be

3. Drug Regulation & Regulatory Authorities
Dept. Of Quality Assurance & Regulatory Affairs
L. J. Institute of Pharmacy, Ahmedabad.
reported.
 Fees for phase I
application is Rs
50000
 Fees for phase II
and III application
is 25000
3. INSTITUTIONAL
REVIEW BOARD
 EC approval
required
 ECs appointed or
authorized by States
 IRB approval
required
 IRB registration
required
 DCGI approval
 IRB / EC approval
required
4. FORM/S
REQUIRED
 Statement of
Investigator not
required by member
states
 Form FDA 1572 is
required to be
signed by the PI, if
study is conducted
in US and
submitted to IND
 Form no: 44 is
required for
application of
clinical trial.
5. RECORD
RETENTION
 Essential Document
Record includes
CRF, excluding
medical records: ≥ 5
years
 ≥ 15 years or CT
discontinuation if
data used to support
a marketing
application
 Record retention 2
years after
marketing
application is
approved
 Record retention 2
years after last
shipment and
delivery of IMP if
marketing
application is not
approved.
 Retention of
records 3 years
after marketing
application is
approved

4. Drug Regulation & Regulatory Authorities
Dept. Of Quality Assurance & Regulatory Affairs
L. J. Institute of Pharmacy, Ahmedabad.
6. INVESTIGATION
AL MEDICINAL
PRODUCT
REQUIREMENTS
 Label must comply
with Annex 13 of
EU Directive
2001/83/EC
 Language
requirements varies
between member
states
 Sponsor is
responsible for
destruction of
unused and/or
returned IMP
 Label must be in
English, except for
Puerto Rico
 The following
statement is
required:
“Caution: New
Drug Limited by
Federal (or United
States) law to
investigational
use”
 Study code
 API and
formulation
 Batch no. , expiry
date and retest
date
 Dosage
 Direction of use
 Manufactured by
 “FOR CLINICAL
TRIAL USE
ONlLY”
7. ADVERSE
EVENT
REPORTING
 Review and
monitors the safety
information of IMPs
used in clinical
trials conducted in
their respective
territories through
the use of the
EudraVigilance
Clinical Trial
module (EVCTM)
 Report to the
sponsor all serious
adverse events
immediately
 Required to report
to the Sponsor any
adverse events
caused by or
probably caused
by IMP
 Notify FDA and
all participating
investigators in a
written IND safety
report of: Any
adverse experience
associated with the
use of the drug
that is both serious
and unexpected.
 Required to report
unexpected fatal
or life threatening
 Upon the
discovery of any
injury or death
related to a clinical
trial, sponsors will
now be required to
inform the DCGI
within 24 hours.
 Following this
reporting line,
relevant clinical
trial stakeholders
will be required to
submit individual
reports for
scrutiny by an
independent
review committee,
due to be created

5. Drug Regulation & Regulatory Authorities
Dept. Of Quality Assurance & Regulatory Affairs
L. J. Institute of Pharmacy, Ahmedabad.
experiences
ASAP, but not
later than 7 days;
Follow-up reports
ASAP but no later
than 15 days of
receipt of new
information
by the DCGI.
8. REGULATORY
COMPLIANCE
 covered under
Article 15 of
Directive
2001/20/EC CA
responsible for
implementing
provisions for the
suspension of a CT
 conducting
inspections and
verifying
compliance
Inspection reports
may also be made
available to
Sponsor, EC,
EMEA and other
member states Must
comply with Good
Distribution
Practices (GDPs)
and Good
Laboratory
 All clinical trials
must comply with
21 CFR Parts 50,
54, 56, 58 and 312
 Phase 1 IMPs are
exempt from
certain parts of 21
CFR Part 211,
unless the clinical
trial involves a
marketed drug
product or one that
was manufactured
in a Phase 2 and/or
3 study
 Indian GCP states
that if the sponsor
is a foreign
company,
organization or
person(s) – it shall
appoint a local
representative
or CRO to
fulfill the
appropriate
local
responsibilities
as governed
by the Indian
regulations.

6. Drug Regulation & Regulatory Authorities
Dept. Of Quality Assurance & Regulatory Affairs
L. J. Institute of Pharmacy, Ahmedabad.
Practices (GLPs)
 no comparable EU
regulation specific
to Phase 1 CGMPs
(Annex 13 guideline
provides flexibility
dependent upon the
stage of
development of the
product)