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SCHEDULE Y
REGULATORY TOOL TO MANAGE RISK
5/23/2017
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SCENARIO FOR TODAY’S DISCUSSION:
Schedule Y
IEC
SCOPE
UTILITY
NEW DRUG
DEVELOPMENT
PROCESS IN
INDIA
RISKS
5/23/2017
RIGHTS SAFETY
WELL BEING OF
HUMAN SUBJECTS
FUTURE DIRECTION
BENEFITS
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SCHEDULE Y
DEFINE NEW DRUG
SCOPE:REGULATE THEIR
INTRODUCTION BASED ON SAFETY AND
EFFICACY CONSIDERATIONS
ENSURE QUALITY
IMPLEMENTATION
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SCHEDULE Y
(RULE 122 E)
NEW DRUG
DRUG SUBSTANCE(API)
DRUG PRODUCT(FORMULATION)
NOT USED IN COUNTRY *
•SR/FDC/VACCINES
• USE < 4 YEARS
EFFICACY=???
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SAFETY=???
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SCOPE OF SCHEDULE Y
Rule 122-A, 122-B, 122-D, 122-E under Drugs &
Cosmetics Rules 1945 in 1988/2000/2001/2002/2005
DRUG SUBSTANCE
DRUG PRODUCT
DEVELOPMENT STUDIES
/PRECLINICAL DATA
IMPORT FOR TESTING
ANALYSIS & EXAMINATION
CLINICAL STUDIES/BE STUDIES
DECISIONS BASED ON BEST AVAILABLE SCIENTIFIC EVIDENCE
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SCOPE OF SCHEDULE Y
HERBALS:INDIAN SYSTEM OF MEDICINE & HOMEOPATHY
:APPROVAL BY STATE DRUG CONTROLLER
BIOTECHNOLOGY PRODUCTS:RECOMBINANT PRODUCTS:
DCGI
DBT
RDAC
RCGM
IBSC
GEAC
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Ethical Guidelines for Biomedical Research on Human
Subjects ICMR 2000
STATEMENT
GENERAL
PRINCIPLES
SPECIFIC PRINCIPLES
•DRUGS
•DEVICES
•HERBALS
•VACCINES
PURPOSE
CLINICAL
EVALUATION
CONDUCT
EPIDEMIOLOGICAL STUDIES
GENETICS RESEARCH
EVALUATION
TRANSPLANTATION INCLUDING FOETAL
TISSUE TRANSPLANTATION
ASSISTED REPRODUCTIVE
TECHNOLOGIES
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SPECIFIC GUIDELINES
Guidelines by DBT under DST:
Biotechnology Products (Preclinical, clinical
data for r-DNA based vaccines; diagnostics
and other biological products
DCGI guidelines :BA/BE Studies
DCGI guidelines: Pharmacovigilance
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PROCESS OF NEW DRUG DEVELOPMENT IN INDIA
NDA vs. ANDA Review Process
Brand Name Drug NDA
Requirements
Generic Drug ANDA
Requirements
1
Chemistry
√
Chemistry
√
2.
Manufacturing
√
Manufacturing
√
3
Controls
√
Controls
√
4.
Labeling
√
Labeling
√
5.
Testing
√
Testing
√
6
Animal Studies
√ ?
Bioequivalence Studies
√
7
Clinical Studies
√ ?
8
Bioavailability Studies
√ ?
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IMPLEMENTATION:SCHEDULE Y
Application Form 44 Submission
Rule
Rule 122 A
Rule 122 B
Rule 122 DA
Purpose:
Marketing
Authorisation
Import
Manufacture
Clinical Study
Drug Substance
Form 45 A
Form 46 A
Drug Product
Form 45
Form 46
Form 46
Application Form 12 Submission
Purpose
Import For Examination, Test and Analysis
Drug Product
Form 11
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DOCUMENT SUBMISSION TO DCGI IN ADDITION TO FORM 44
 PROTOCOL
 CASE REPORT FORMS
 PRODUCT INFORMATION (Appendix I,II,III)
 INVESTIGATOR UNDERTAKING [Appendix IV)
 IEC APPROVAL [Appendix V] [Amendments/approvals]
 INFORMED CONSENT FORMS(TRANSLATIONS): [Appendix VI ]
 MARKETING /REGULATORY STATUS IN OTHER COUNTRIES
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Which studies ? When ?
Phase I
Phase II
√
Therapeutic
confirmatory
studies
Product Already
approved/
marketed in
another country
Product neither
approved/ nor
marketed in
another country
but phase III /II
studies are in
progress
Phase III
√ if phase II
Studies
Are over
√ if phase III
Studies
Are over
Trials are generally allowed to be initiated at one phase
earlier to the phase of trials in other countries
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Which studies ? When ?
Phase I
For new drug substances
discovered in other countries
Phase I trials are not usually
allowed to be initiated in India
unless Phase I data from other
countries are available. Exception
will be if product is of special
relevance to the health problem of
India.
For new drug substances
discovered in India
√ Allowed in stages
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Which studies ? When ?
Phase IV
Post Marketing Surveillance
Periodic Safety Update Reports Mandatory
Unexpected SAE
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14 days
Other investigators
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ENSURE QUALITY:STABILITY STUDIES
STORAGE CONDITIONS
LONG
ACCELERATED
TEMPERATURE
30±2°c
40 ±2°c
RH
65 ± 5%
75 ± 5%
MONTHS
12
06
5 ±3°c
25 ±2°c
GENERAL
REFRIGERATOR
TEMPERATURE
60 ± 5%
RH
MONTHS
12
06
FREEZER
TEMPERATURE
-20 ±5°c
MONTHS
12
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RESPONSIVE IEC COMPOSITION FUNCTION DOCUMENTATION APPROVAL
REVISED SCHEDULE Y(2005):PROTOCOL BASED ON
INDIAN GCP(2002) & ICMR ETHICAL GUIDELINES(2000)
SPONSOR
INDIAN GCP
IEC
SCIENTIFIC
GCP
INVESTIGATOR
ETHICAL
HUMAN SUBJECT
ICMR GUIDELINES
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THERAPEUTIC
EXPERIMENTAL
EXPERIMENTAL
BIOEQUIVALENCE
ELECTIVE
CLINICAL
PRACTICE
Operations on
donors for live donor
organ transplants,
aesthetic surgery,
and non-therapeutic
sterilization
RESEARCH
NONRESEARCH
NON ELECTIVE
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NON THERAPEUTIC
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Before CONSIDERING the study :IEC SHOULD OBTAIN
Investigator
Sponsor
Human
Subject
CV
IB
Advertisement
Protocol
ICF
Updates
Compensation
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WHILE CONSIDERING the study :
IEC :HOW IT SHOULD FUNCTION
LIST MEMBERS SOPS
SCHEDULE
PROCEDURE & NOTIFY
INVESTIGATOR REVIEW
QUORUM
NON MEMBER
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INITIAL
VOTING
CONTINUOUS
FINAL
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AFTER CONSIDERING the study :
IEC :HOW IT SHOULD COMMUNICATE
APPROVAL OR FAVOURABLE
OPINION
NOTIFY
MODIFICATIONS REQUIRED
PRIOR TO APPROVAL
PROVIDE
REASONS
PROCEDURES
FOR APPEAL
UNFAVORABLE OPINION
PROVIDE
REASONS
PROCEDURES
FOR APPEAL
TERMINATION OR SUSPENSION
OF PRIOR APPROVAL
PROVIDE
REASONS
PROCEDURES
FOR APPEAL
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Adverse Drug Reaction (ADR)
All noxious and unintended responses to a medicinal product
related to any dose should be considered adverse drug
reactions. The phrase responses to a medicinal product means
that a causal relationship between a medicinal product and an
adverse event is at least a reasonable possibility, i.e. the
relationship cannot be ruled out.
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Adverse Event (AE)
Any untoward medical occurrence in a patient or clinical
investigation subject administered a pharmaceutical product
and which does not necessarily have a causal relationship with
this treatment. An adverse event (AE) can therefore be any
unfavourable and unintended sign (including an abnormal
laboratory finding), symptom, or disease temporally associated
with the use of a medicinal (investigational) product, whether
or not related to the medicinal (investigational) product
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Serious adverse event (SAE)
Any adverse experience occurring that results in any of the
following outcomes
Death (irrespective of initial
impression of causality)
Life-threatening
REPORT
IMMEDIATELY
Hospitalization or prolongation of
existing hospitalization
A persistent or significant
disability/incapacity
A congenital anomaly or birth defect.
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SAE/AR Reporting
• Related to or associated with the use of the
investigational product
• There is a reasonable possibility that the event
was caused by the investigational product.
• Reasonable: Temporal Relationship
Known Pattern
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UNEXPECTED SAE
•Expected/unexpected/unanticipated
An expected event is one where the specificity
and severity of the event are consistent with
the information in the investigator brochure,
labeling for the product, or contained else
where in the investigational plan. Unexpected
events are all other occurrences.
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FUTURE DIRECTION:
PRDC (1999) Recommendations on CDSCO
PROTOCOL :ADVISORY BOARD
FULL TIME EXPERTS/EXPERT PANELS
TIME SCHEDULE FOR DRUG APPROVAL
* IND PHASE I :WITH IN 3 MONTHS
* IND PHASE II:WITHIN 6 MONTHS
* MARKETING APPROVAL:3 MONTHS
Pharmaceutical Research & Development Committee (PRDC)
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FUTURE DIRECTION:
INVESTIGATOR
SPONSOR
REGULATOR
RISK
MANAGEMENT
ACCESSIBILITY
IEC
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HUMAN SUBJECT
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