2. OUTLINE
History
Drug and cosmetic Act,1940 and Schedules
What actually Schedule Y is ?
Rules under it
Divisions of Schedule Y
New Amendments
Conclusion
2
3. RULES….
Drug and Cosmetic Act, 1940 was enacted(D/C Act)
Pharmacy Act , 1948
Drug and Magic Remedies Act,1954
The Narcotic and Psychotropic Substance Actand Rules, 1985
Ethical guidelines for Biomedical Research on Human
Participants,2000, 2018 by ICMR
Indian GCP Guidelines,2001
Amendments to Drug andCosmetic Act,2002
Revised Schedule Y,2005
Guidelines for Pre Clinical Data forr-DNA Vaccines,2007
3
4. In 1940 D/C Act Was enacted
in 1945 Drug Rules were Promulgated in
December and enforcement Start in 1947
Now have been called as D/C
Act
Objective- drug is available to the people are safe and
cosmetics marketed for safer use.
4
7. Schedule A- Forms for marketing application for licenses, issue renewal
B- Fee for test/analysis by CDL or SDL
C/C1- talk about I/M/S/D of sera, vaccines
D-List of drugs exempted from the provisions that are applicable to import of other
drug
E- Omitted , E1- list of poisonous substance under Ayurveda,Unani,Sidha system
F- Production/testing/storage/packaging/labeling
F1-biological preparations F2- SD F3- umbilical tapes
G- List of drug used under medical supervision
H- List of drug sold under Prescription
I-Omitted
J-Diseases may not cure/prevent by drugs
K-List of drugs exempted from the provisions that are applicable to Manufacture of
other drug
7
8. M-GMP
N-List of minimum equipment in Pharmacy
O-Standards for disinfections
P- Life period of drug
Q-List of dyes/coloring agents in soap/cosmetics
R-Standards for Mechanical contraceptives
S-Standards for cosmetics
T-GMP for A/U/S system of medicines
U- Records for manufacturing/raw materials in drugs
V- Standards for potent medicines
W- Omitted
X- List of drugs whose I/M/S are governed by special provision
Y- About CT
8
14. Drug Regulatory body
Schedule Y ,the current regulator (of Central
Drugs Standard Control Organisation CDSCO),
enforced law in India has been established under
Drug and Cosmetic Act,1945.
The regulations to be followed when conducting
Clinical Trial in India.
14
15. Indian Regulatory authorities
Ministry of Chem &
Fertilizers
NPPA
National
Pharmaceutical
Pricing Authority
Pricing
Regulations
Ministry of Sci &
Tech
DBT
Departmentof
Biotechnology
Ministryof
Environment
Additional
Secretary
State Drug Regulatory Authority:FDA
GEAC
Genetic
Engineering
Approval
Committee
DGHS
Director Generalof
Health Services
Health Secretary
Ministry of Health
and family welfare
DCGI
Drug Controller
General of India
CDRL/CDTL
Gov. Drug Testing
Laboratories
15
16. Basis of Schedule Y
Schedule Y is in line with ICH-GCP
(International Council of Harmonization and
Good Clinical Practice) standard was put forth
in 1995.
16
17. Schedule Y advantages
legal requirement and it is a global requirement.
Improvements in quality of clinical trials.
It has outlined extensive study criteria in line with the
globally accepted formats such as US FDA guidelines.
17
18. CONTENTS APPENDIXES
Application 1 APPLICATION FORMAT
Approval for CT 2 CLINICAL STUDY REPORTS
Responsibilities of sponsor 3 ANIMAL TOXICOLOGY STUDIES
Responsibilities of investigator 4-ANIMAL PHARMACOLOGY
Informed consent 5-ICF
Responsibilities of ethics committee 6-FDC
Phase 1 7-UNDERTAKING BY THE INVESTIGATOR
Phase 2 8-ETHICS COMMITTEE
Phase 3 9-STABILITY TESTING OF NEW DRUGS
Phase 4 10-PROTOCOL STANDARD CONTENTS
Studies in special populations 11-SERIOUS ADVERSE EVENTS
• Geriatrics/Paediatrics/Pregnancy
Post marketing surveillance
Special studies bioavailbility and
bioequivalence
18
19. RULES PERMISSION
122 A To import new drugs
122 B To manufacture new drugs
122 D To import or manufacture fixed drug
combinations
122 DA To conduct clinical trials for new drugs/
investigational new drugs
122 DAA Definition of clinical trial
122 E Definition of new drug
19
20. New Drug/Investigational New Drug
New chemical entity or a product having
therapeutic indication but which has
never been earlier tested on human
beings.
20
21. 122-E.
122-E. -Never used in the country under labeling conditions
Approved but now proposed to be marketed with modified
or new claims –indications, dosage, dosage form , route of
administration-FDC, individually approved, to be combined
for the first time in a fixed ratio or if ratio ischanged
21
23. Old schedule Y
in the older version there are only 5 appendices
Appendix I: Declaration of Helsinki
Appendix II: ScheduleY
Appendix III: Format for submission of Pre-clinical and
clinical data for r-DNA based vaccines, diagnostics and
other biologicals.
Appendix IV: Investigator’s Brochure
Appendix V: Essential Documents
23
24. CONTENTS APPENDIXES
Application 1 APPLICATION FORMAT
Approval for CT 2 CLINICAL STUDY REPORTS
Responsibilities of sponsor 3 ANIMAL TOXICOLOGY STUDIES
Responsibilities of investigator 4-ANIMAL PHARMACOLOGY
Informed consent 5-ICF
Responsibilities of ethics committee 6-FDC
Phase 1 7-UNDERTAKING BY THE INVESTIGATOR
Phase 2 8-ETHICS COMMITTEE
Phase 3 9-STABILITY TESTING OF NEW DRUGS
Phase 4 10-PROTOCOL STANDARD CONTENTS
Studies in special populations 11-SERIOUS ADVERSE EVENTS
• Geriatrics/Paediatrics/Pregnancy
Post marketing surveillance
Special studies bioavailbility and
bioequivalence
24
25. Appendix I
Data to be submitted along with the application to conduct
clinical trials / import / manufacture of new drugs for
marketing in the country.
a. Introduction about the drug
b. Chemical and pharmaceutical information (e.g.
Enatiometry)
c. Animal pharmacology
d. Animal toxicology
e. Human /clinical pharmacology(Phase-I)
f. Therapeutics exploratory(Phase-II)
g. Therapeutics confirmatory(Phase-III)
h. Special studies( paediatrics, pregnant)
i. Regulatory status in other countries if available
j. Prescribing information(drug labeling and prescribing inf.)
25
27. Fee according to Schedule Y
Import ff/ Mfg ff/ Import bulk + Mfg ff = Rs 50,000/- of new
drug
Application by same applicant, = Rs 5,00,000/-
for modified dosage form or with new claim
Secondary applicants after 1 = Rs 50,000/- year of
approval
Import / Mfg FDC = Rs 5,000/-
Conduct Clinical trial with
ND/IND
Phase I
Phase II
Phase III, IV
= Rs 3,00,000/-
= Rs 2,00,000/-
= Rs 2,00,000/-
27
28. Appendix I-A
Data required to be submitted by an applicant for grant of permission to
import
&/or manufacture a new drug already approved in the
country.
a) Introduction
b) Chemical and pharmaceutical information
c) Marketing information
d) Special studies
28
29. Appendix III
Animal toxicology (Non-clinical toxicity studies)
1)SDTS- Minimum 5 animal, 24hr observation
2)DRS- On one Rodent Species
3)RDTS- a) 14 to 28 days- on 1 Rodent and 1 Non Rodent
b)90 days- same as above but introduction of HIGH
DOSE REVERSAL .
4)MFS- Rodent Species, Dose selection should be done on
basis of 14 to 28 days studies.
5)FFS- should be carried out for all drugs( Appendix I- 4.4)
29
31. Appendix IV- Animal Pharmacology
Animal pharmacology studies are done to see the
effect if Investigational Product on different
systems like
CVS/CNS/ANS/RS/GIT/GUT
31
32. Appendix V- INFORMED CONSENT
Trial involves research
Purpose
Trial treatments and randomization
Trial procedures
Risk/Benefit
Alternative treatments
Compensation / treatment for injury
Subject’s responsibilities
Any payment
32
33. Essential Elements of Informed Consent
Confidentiality
New information
Voluntary participation
Person/s to contact for study information
Rights of subject, if study related injury
Reasons for termination
Duration of study
Number of subjects
Any other pertinent information
33
34. Format of Informed Consent Form
Study Title
Subject’s Initials e.g. Subject’s Name/ Date of Birth / Age
Consent Statements with initials in
a) Signature (or Thumb impression) of the Subject
b) Legally Acceptable Representative
Signature of the Investigator
Study Investigator’s Name
Signature of the Witness
Name of the Witness
34
35. Appendix VI- FDC’s
Data requirements of Fixed Dose Combinations
Fixed Dose combinations (FDC) fall into four groups
and their data requirements accordingly.
The first group -new drug.
The second group -combined for the first time
The third group -change in ratio or now tried for
the new indications
The fourth group -used for years.
35
36. Appendix VII
Undertaking By TheInvestigator
1) Full name, address and title of the Principal Investigator
2) Name and address of the medical college, hospital or other facility where
the clinical trial will be conducted: Education, training &experience that
qualify the Investigator for the clinical trial (Attach details including Medical
Council registration number, and / any other statement of qualification
3) Name and address of all clinical laboratory facilities to be used in the
study.
4) Name and address of the Ethics Committee ,responsible for approval
and continuing review of the study.
5) Names of the other members of the research team (Co- or sub-
Investigators) who will be assisting the Investigator in the conduct of the
investigation.
36
37. VII.2 Commitments by The Investigator
a. Study not to begin until EC / DCGI approval
b. Adherence to protocol
c. Personal supervision
d. Ensure requirements of IC and EC review
e. Report of AE to sponsor
f. Understanding of investigator’s brochure
g. Ensure that all associates, colleagues and employees suitably qualified and
experienced and aware of their obligations
h. Report all unexpected serious adverse events to the Sponsor in 24 hrs and
EC within 7 days.
i. Maintenance of records and availability for audits/sponsor inspection/EC and
DCGI. Cooperation in audits
37
39. Appendix IX- Stability testing of New Drugs
Stability testing is to be performed to provide evidence on
how the quality of a drug substance or formulation varies
with time under the influence of various environmental
factors such as-
a. Temperature
b. Humidity and
c. Light
Objective. - To establish shelf life for the formulation and recommended
storage conditions.
39
40. Appendix X – Contents of the Proposed Protocol
Titlepage
Table of content
a) Introduction
b) Study rationale
c) Study design
d) Study population
e) Subject eligibility
f) Study treatment
g) AE
h) Data analysis
i) Undertaking by investigator
NOTE- Protocol is assigned by sponsor after getting CDA from investigator
40
41. Appendix XI- Data Elements For Reporting a
SAE in Clinical Trial
a) Patient details(Age, sex, weight,height)
b) Suspected drug( Generic name, DFD,ROA)
c) Detail of SUSPECTED ADR( severity, start date,stop date,
hospitalization ornot)
d) Details about investigator
41
42. New Amendments on 30.06.2009
CLINICAL RESEARCH ORGANISATION –
REGISTRATION
These guidelines have been approved by DTAB
1)Rule 122 DAB. – Registration of clinical research
organization for conducting clinical trials.
42
43. New Amendments on 18th Nov.2011
1)Rule 122-DAB- compensation during injury or death during clinical trial
43
45. 45
• After approval of CT -3 years
• 2 types of EC-CT/BABE and biomedical and health research
• 5 years of EC registration
• EC approval, DCGI should be notified within 15 days
• Quarterly patient enrollment report to DCGI
• Six monthly status report
• Termination of study to be notified within 30 daysProvision of Pre-
and Post-submission meeting with DCGI
• Provision of waiver of local clinical trials, if drug is approved and
marketed in certain countries
• Conditions for post-trial access of study drug to trial participants
outlined
• EC Accreditation is not mandatory
• Academic clinical trial
46. 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 not affiliated with the institute or organization in
which EC is constitute
Every member of the EC shall be required to undergo such training and
development programs
Any change in the membership or the constitution to be intimated to DCGI
within 30 days days
Show cause notice / warning letter / rejection of results / suspension /
debarment
46
47. Conclusion
With the Schedule Y, efforts are aligned in a single
direction to ensure that irrespective of the country,
the data generated is of good quality and
standard which can be accepted worldwide
47
