Requirements And Guidelines For Permission To Import / or Manufacture of New Drugs For Sale or To Undertake Clinical Trials Schedule Y was introduced under the Drugs and Cosmetics Act 1940, to introduce requirements for countries to get permission for: Importing Manufacturing new drugs Conducting Clinical Trials. Application for permission Clinical Trial Studies in specific population Post marketing surveillance Special studies: BA/BE studies

1. Clinical Research Regulation
in India: Schedule Y
Presented by:
Vanshika Gupta
1st sem M.Pharm (RA)
CRR (MRA103T)
1
PARUL INSTITUTE OF PHARMACY
PARUL UNIVERSITY

2. Content
 Schedules under D&C Act 1940
 Rules under Schedule-Y
 Amendments in 2013 & 2014
 Introduction to Schedule Y
 Schedule Y
1. Application for permission
2. Clinical Trial
3. Studies in special populations
4. Post Marketing Surveillance
5. Special studies: Bioavailability / Bioequivalence Studies
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3. Schedules under Drugs and
Cosmetics Act 1940
 Schedule A: Describes application forms and licenses types.
 Schedule-B: Fees for test or analysis by the Central Drugs
Laboratories or State Drugs Laboratories.
 Schedule-C: Contains various biological products and their
regulation. Examples: Serums, Adrenaline, Vitamins etc.
 Schedule-D: List of drugs exempted from the provision of
import of drugs.
 Schedule-E: List of poisonous substances under the Ayurvedic,
Siddha and Unani systems.
 Schedule-F: This contains regulations and standards for
running a blood bank.
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4. Cont...
 Schedule-F I: Provisions applicable to the production of
bacterial vaccines
 Schedule-F II: Standards for surgical dressings
 Schedule-F III: Standards for umbilical tapes
 Schedule-FF: Standards for ophthalmic preparations
 Schedule-G: List of drugs falls under Schedule-G (taken only
under the supervision of a Registered Medical Practitioner)
Most of these drugs are hormonal preparations.
 Schedule-H: List of drugs falls under Schedule-H (sold by
retail only on the prescription of Registered Medical
Practitioner)
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5. Cont...
 Schedule-J: Contains a list of various diseases and conditions
that cannot be treated under any drug currently in market and
No drug may legally claim to treat these diseases
 Schedule-K: Contains various substances and drugs and their
corresponding regulation.
 Schedule-L I: It prescribes list of drugs to be sold on
prescription only- omitted.
 Schedule-M: (GMP) Good manufacturing practices
requirements of factory premises, plant, equipments, etc for
manufacturing of drugs.
 Schedule-N: List of minimum equipment for the efficient
running of a pharmacy
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6. Cont...
 Schedule-O: Contains various regulations and requirements
for disinfectant fluids.
 Schedule-O I: Provisions applicable to Black Fluids and White
Fluid (disinfectants)
 Schedule-P: Storage conditions of drugs
 Schedule-P I: Pack size of drugs
 Schedule-Q: List of dyes, colours and pigments permitted to
be used in cosmetics and soaps.
 Schedule-R: Standards for condoms made of rubber latex
intended for single use and other mechanical contraceptives
 Schedule-S: Standards for cosmetics
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7. Cont...
 Schedule-T: The requirements of factory premises, plant,
equipments and hygienic conditions for manufacture of
Ayurvedic, Siddha, and Unani
 Schedule-U: Particulars to be shown in manufacturing records
 Schedule-V: Standards for patent or proprietary medicines
 Schedule-X: List of drugs falls under Schedule-X (Narcotic
drugs and Psychotropic)
 Schedule-Y: Requirements and guidelines for permission to
import and / or manufacture of new drugs for sale or to
undertake clinical trials.
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8. Rules under Schedule-Y
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Section 122A: Application for Permission to import new drug
Section 122B: Application for approval to manufacture new drug
Section 122D: Permission to import or manufacture fixed dose
combination
Section 122DA: Application for permission to conduct clinical trials
for New Drug/ Investigational New Drug.
Section 122DAA: Definition of Clinical trial.
Section 122DB: Suspension or cancellation of permission/approval
Section 122-E: Definition of new drug

9. Amendments in 2013 & 2014
 Rule 122DAB – Compensation in case of injury or death
during clinical trial
 Rule 122DAC – Condition of clinical trial permission and
inspection.
 Rule 122DD – Registration of ethic Committee - Requirement
and guidelines for registration of ethic committee
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10. Introduction
Requirements And Guidelines For Permission To
Import / or Manufacture of New Drugs For Sale or
To Undertake Clinical Trials
 Schedule Y was introduced under the Drugs and Cosmetics Act
1940, to introduce requirements for countries to get permission
for:
1. Importing
2. Manufacturing new drugs
3. Conducting Clinical Trials.
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11. Requirements And Guidelines
11
Application for permission
Clinical Trial
Studies in specific population
Post marketing surveillance
Special studies: BA/BE studies

12. SCHEDULE Y
(1) Application for permission:
- Application for permission to import or manufacture new
drugs for sale or to undertake clinical trials shall be made in
Form 44 accompanied with following data in accordance
with the appendices
It includes:
(i) Chemical and pharmaceutical information
(ii) Animal pharmacology data
(iii) Animal toxicology data
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13. Cont...
(iv) Human Clinical Pharmacology Data
(v) Regulatory Status in other country
(vi) Prescribing Information
- Form 12 – To import study drug for examination, test or
analysis.
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14. Cont...
2. Clinical Trial:
(i) Approval for clinical trial:
- Clinical trial on a new drug shall be initiated only after the
permission has been granted by the Licensing Authority
under rule 21 (b)
- All trial Investigator(s) should possess appropriate
qualifications, training and experience.
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15. Cont...
- Protocol amendments if become necessary before initiation or
during the course of a clinical trial, all such amendments
should be notified to the Licensing Authority in writing along
with the approval by the ethics committee which has granted
the approval for the study.
(ii)Responsibilities of Sponsor: The clinical trial Sponsor is
responsible for implementing and maintaining quality
assurance systems to ensure that the clinical trial is conducted
and data generated, documented and reported in compliance
with the protocol
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16. Cont...
- Standard operating procedures (SOPs) should be documented
to ensure compliance with GCP and applicable regulations.
- Sponsors are required to submit a status report on the clinical
trial to the Licensing Authority
- Any unexpected serious adverse event (SAE) occurring during
a clinical trial should be communicated promptly (within 14
calendar days) by the Sponsor to the Licensing Authority and
to the other Investigator(s) participating in the study.
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17. Cont...
(iii) Responsibilities of the Investigator(s):
- Responsible for the conduct of the trial according to the
protocol and the GCP Guidelines
- SOP are required to be documented by the investigators for the
tasks performed by them.
- To ensure adequate medical care is provided to the subject.
- Investigator(s) shall report all serious and unexpected adverse
events to the Sponsor within 24 hours and to the Ethics
Committee that accorded approval to the study protocol within
7 working days of their occurrence
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18. Cont...
(iv) Informed Consent:
- Informed consent should be Non-technical and in
understandable language.
- Investigator must provide information about the study verbally
and in written.
- The Subject’s consent must be obtained in writing using an
‘Informed Consent Form.
- Legally acceptable representative.
- The patient information sheet as well as the Informed Consent
Form should have been approved by the ethics committee and
furnished to the Licensing Authority.
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19. Cont...
(v) Responsibilities of the Ethics Committee:
- The responsibility of the ethics committee that to reviews and
grant its approval to a trial protocol to safeguard the rights,
safety and well being of all trial subjects.
- Conduct ongoing review of the trial.
- Ethics committee(s) should get document ‘standard operating
procedures’ and should maintain a record of its proceedings.
(vi) Human Pharmacology (Phase I) :
- The objective of studies in this Phase is the estimation of safety
and tolerability with the initial administration of an
investigational new drug into human(s).
- Phase I trials should preferably be carried out by Investigators
trained in clinical pharmacology with access to the necessary
facilities to closely observe and monitor the Subjects.
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20. Cont...
(vii) Therapeutic exploratory trials (Phase II) :
- The primary objective of Phase II trials is to evaluate the
effectiveness of a drug for a particular indication or indications
in patients with the condition under study and to determine the
common short-term side-effects and risks associated with the
drug.
- An important goal for this Phase is to determine the dose(s)
and regimen for Phase III trials.
(viii) Therapeutic confirmatory trials (Phase III) :
- Phase III are designed to confirm the preliminary evidence
accumulated in Phase II that a drug is safe and effective for use
in the intended indication and recipient population.
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21. Cont...
- These studies should be intended to provide an adequate basis
for marketing approval.
- Studies in Phase III may also further explore the dose response
relationships (relationships among dose, drug concentration in
blood and clinical response)
- Use of the drug in wider populations, in different stages of
disease, or the safety and efficacy of the drug in combination
with other drug(s).
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22. Cont...
(ix) Post Marketing Trials (Phase IV):
- Post Marketing trials are studies
- These trials go beyond the prior demonstration of the drug’s
safety, efficacy and dose definition
- Phase IV trials include additional drug-drug interaction(s),
dose-response or safety studies and trials designed to support
use under the approved indication(s), e.g. mortality/morbidity
studies, epidemiological studies etc.
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23. Cont...
(3) Studies in Special Populations:
- The use of the drug in children, pregnant women, nursing
women, elderly patients, patients with renal or other organ
systems failure, and those on specific concomitant medication
is required to be submitted.
- Geriatrics- Geriatric patients should be included in Phase III
clinical trials in meaningful numbers, if-
- The disease intended to be treated is characteristically a disease
of aging.
- When there is specific reason to expect that conditions
common in the elderly are likely to be encountered.
- When the new drug is likely to alter the geriatric patient's
response compared with that of the non-geriatric patient.
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24. Cont...
- Pediatrics: Studies in the new drug development program will
depend on the medicinal product
- The type of disease being treated
- Safety considerations, and
- The efficacy and safety of available treatments.
- Pregnant or nursing women
- Should be included in clinical trials only when the drug is
intended for use by pregnant/nursing women or
foetuses/nursing infants.
- Follow-up data (pertaining to a period appropriate for that
drug) on the pregnancy, foetus and child will be required.
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25. Cont...
(4) Post Marketing Surveillance:
- Subsequent to approval of the product, new drugs should be
closely monitored for their clinical safety once they are
marketed.
- The applicants shall furnish Periodic Safety Update Reports
(PSURs). Submitted every 6 months for first 2 years.
(5) Special studies: Bioavailability / Bioequivalence Studies:
- For drugs approved elsewhere in the world and absorbed
systemically, bioequivalence with the reference formulation
should be carried out wherever applicable.
- All bioavailability and bioequivalence studies should be
conducted according to the Guidelines for Bioavailability and
Bioequivalence studies as prescribed.
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26. Appendix
 Some highlights of Schedule Y in terms of its appendices;
which provide the guidelines to conduct clinical trials are:
 APPENDIX 1- Conduct clinical trials/import/manufacture of
new drugs
 APPENDIX IA- For grant of permission to import and / or
manufacture a new drug
 APPENDIX II- Structure, contents and format for clinical
study reports
 APPENDIX III- Animal toxicology (non-clinical toxicity
studies)
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27. Cont...
 APPENDIX IV- Animal pharmacology
 APPENDIX V- Informed consent
 APPENDIX VII - Undertaking by the Investigator
 APPENDIX VIII- Ethics Committee
 APPENDIX X- Contents of Protocol
 APPENDIX XI- Data elements for reporting SAE
 APPENDIX XII- Compensation in case of injury or death
during clinical trial
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28. Data To Be Submitted Along With The Application To Conduct
Clinical Trials / Import / Manufacture Of New Drugs For
Marketing In The Country.
1. Introduction
2. Chemical and pharmaceutical information
3. Animal Pharmacology (for details refer Appendix
4. Animal Toxicology (for details refer Appendix
5. Human / Clinical pharmacology (Phase I)
6. Therapeutic exploratory trials (Phase II)
7. Therapeutic confirmatory trials (Phase III)
8. Special studies
9. Regulatory status in other countries
10. Prescribing information
11. Samples and Testing Protocol/s 28

29. Reference
 https://rgcb.res.in/documents/Schedule-Y.pdf
 Schedule Y. Requirements and guidelines for permission to
import and/or manufacture of new drugs for sale or to
undertake clinical trials. New Delhi, India: Central Drug s
Standard Control Organization. 2013.
 https://ccrps.org/clinical-research-blog/difference-between-ich-
gcp-and-schedule-y
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