2. Objective…
What actually schedule Y is?
Why changes in schedule Y?
Rules under schedule Y…
Appendices of schedule Y…
Conclusion
references
3. The main objectives of the drugs and
cosmetic acts 1940, is to regulate the import,
manufacture, distribution and sale of drugs &
cosmetics in the country
It also ensure that the drugs that are available
to the people are safe and efficacious and the
cosmetics marketed are safe for use
5. Schedule Y ,the current regulator (of CDSCO), enforced
law in India has been established under Drug and
Cosmetic Act,1945.
The regulations to be followed when conducting
Clinical Trial.
Schedule Y – requirements and guidelines for
permission to import and/or manufacture of new drugs
for sale or to undertake clinical trial
Date 20 January, 2005
6. To frame guidelines for the current scenario of Clinical
research.
CDSCO and DTAB formulated GCP under Schedule Y in 2005.
Schedule Y 1988 relevant to predominantly generic industry.
GCP trials since 1995, and arrival of IPR regime in 2005.
Integration of India in global clinical development and legal
support to GCP guidelines.
Improvements in quality of clinical trials.
It has outlined extensive study criteria in line with the
globally accepted formats such as ICH and US FDA guidelines
7. 122A - Application for permission to import new drug
122 B - Application for approval to manufacture new drug
122 D -Permission to import or manufacture FDC
122 DA- Permission to conduct clinical trials for New Drug /
Investigational New Drug
122 DAA –Definition Of “CLINICAL TRIAL”
“Clinical trial” - a systematic study of new drug(s) in human
subject(s) to generate data for discovering and / or verifying
the clinical, pharmacological effect (including
pharmacodynamic and pharmacokinetic) and /or adverse
effects with the objective of determining safety and / or
efficacy of the new drug.
8. 122-E
Definition of new drugs
Not been 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 is changed
10. It contains data to be submitted along with the application to
conduct clinical trials / import / manufacture of new drugs for
marketing in the country.
1. Introduction
• a. A brief description of the drug and
the therapeutic class to which it belongs.
2. Chemical and pharmaceutical information
• 2.1 Information on active ingredients
Drug information (Generic Name, Chemical Name etc.)
Physicochemical Data
A. Chemical name and Structure
Empirical formula
Molecular weight
B. Physical properties
Solubility
Rotation
Partition coefficient
Dissociation constant
11. 2.3 Analytical Data
Elemental analysis
Mass spectrum
NMR spectra
IR spectra
UV spectra
Polymorphic identification
2.4 Complete monograph specification including
Identification
Identity/quantification of impurities
Enantiomeric purity
Assay
2.5 validation
2.6 stability studies ( for details refer appendix IX)
12. 3.Animal pharmacology
(for details refer appendix IV)
Summary
Specific pharmacological actions
General pharmacological actions
Follow-up and Supplemental Safety Pharmacology Studies
Pharmacokinetics: absorption, distribution; metabolism;
excretion
2.7 data on formulation
• dosage form,
•composition,
•master manufacturing formula,
•In process quality control check,
•Excipients compatibility study
•Finished product specification
•Validation of the analytical method
13. 4. Animal toxicology (for detail refer appendix IV)
General Aspects
Systemic Toxicity Studies
Male Fertility Study
Female Reproduction and Developmental Toxicity
Studies
Local toxicity
Allergenicity/Hypersensitivity
Genotoxicity
Carcinogenicity
15. 6. Therapeutic exploratory trial (phase II)
•Summary
•Study report(s) as given in Appendix II
7. Therapeutic confirmatory trial (phase III)
•Summary
•Individual study reports with listing of sites
and Investigators.
8. Special studies
Summary
Bio-availability / Bio-equivalence.
Study on special group of population e.g. geriatrics, pediatrics ,
pregnant or nursing women
16. Geriatrics
•Geriatric patients should be included in Phase III clinical trials (and in
Phase II trials, at the Sponsor's option) in meaningful numbers,
•If the disease intended to be treated is characteristically a disease of
aging; or
the population to be treated is known to include substantial
numbers of geriatric patients;
17. The pediatric studies should include -
clinical trials,
relative bioequivalence comparisons of the pediatric formulation
with the adult formulation performed in adults
definitive pharmacokinetic studies for dose selection across the age
ranges of pediatric patients in whom the drug is likely to be used.
These studies should be conducted in the pediatric patient population
with the disease under study
The timing of pediatric 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.
Pediatrics
18. Pregnant or Nursing Women
•Pregnant or nursing women should be included
in clinical trials only when the drug is intended for use by
pregnant/nursing women or fetuses/nursing infants and
where the data generated from women who are not pregnant or
nursing, is not suitable.
•For new drugs intended for use during pregnancy, follow-up data
(pertaining to a period appropriate for that drug) on the pregnancy,
fetus and child will be required.
19. 9. Regulatory status in other countries
9.1 countries where the drug is
a. marketed
b. Approved
c. approved as IND
d. withdrawn, if any , with reason
9.2 restriction use, if any , in countries where marketed/ approved
9.3 free sale certificate or certificate of analysis , as appropriate.
10. Prescribing information
10.1 proposed full prescribing information
11. Samples and testing protocol
NOTE : All items may not be applicable to all drugs. For
explanation, refer text of Schedule Y.
•For requirements of data to be submitted with application for
clinical trials we should refer text of this Schedule
20. Data required to be submitted by an applicant for grant of
permission to import and/or manufacture a new drug already
approved in the country
Introduction ( About the drug and its therapeutic class)
Chemical and pharmaceutical information (Chemical name, Generic
name, Structure , Physico chemical properties)
Marketing information (Promotional literature)
Special studies conducted with approval of licensing authority
◦ Bioavailability/ Bioequivalance and comparative dissolution
studies for oral dosage forms
◦ Sub acute animal toxicity studies for intravenous infusions and
injectables.
21. 1. Title page :- title of the study, the protocol code,
name of the investigational product tested,
development phase, indication studied, a brief
description page, the start and end date of patient
accrual and the names of the sponsor and the
participating institute
2. Study synopsis(1 to 2 pages) :- a brief review of
study from the protocol development to the trial closure
should be given here. This section will only summarize
the important conclusions derived from the study
3. statement of compliance
4.list of abbreviation and definitions
Table of contents
22. 6. ethics committee:
7.study team
8.study objective
9.investigational plan
Trial subjects
Efficacy evaluation
Safety evaluation
Discussion and overall conclusion
List of references
appendices
23. ANIMAL TOXICOLOGY (NON-CLINICAL TOXICITY STUDIES)
• Acute toxicity
• Long-term toxicity
Reproduction studies
• Fertility studies
• Teratogenicity studies:
Local toxicity:
Mutagenicity and Carcinogenicity
Application Of Good Laboratory Practices (GLP)
24. Animal pharmacology
General Principles
◦ Specific and general pharmacological studies should be
conducted to support the use of therapeutics in human
◦ Safety pharmacological studies investigates potential undesirable
pharmacodynamic effect of as substance on physiological
function in relation to exposer within the therapeutic range or
above.
Specific Pharmacological Actions
Are those which demonstrate the therapeutic potential for humans.
General pharmacological Actions
Essential Safety Pharmacology
To study the effect of the test drug on vital functions such as
cardiovascular, respiratory and central nervous system are
studied
25. Supplemental Safety Pharmacology Studies
Investigation of the adverse pharmacological effect that are not
assessed in the in the essential safety pharmacological studies
and are a cause for concern
Urinary System
Includes urine volume, specific gravity , osmolality, pH ,
proteins, cytology, and blood urea nitrogen , creatinine ,
plasma protein estimation .
Autonomic Nervous System
Binding to receptor relevant to ANS and functional response
to agonist or antagonist responses in in vitro or in vivo.
Gastrointestinal System
Studies of gastric secretion, gastric pH, bile secretion,
gastric emptying time etc
Other Organ Systems
26. Trial involves research
Purpose
Trial treatment and randomization
Trial procedures
Risk
Benefit
Alternative treatments
Compensation /treatment for injury
Subject responsibilities
Experiment aspects
Any payment
27. Confidentiality
New information
Voluntary participation
Persons to contact for study information
Rights of subjects, if study related injury
Reasons for termination
Duration of study
Number of subjects
Any other pertinent information
28. Study title
Subject initials e.g. subjects name/date of
birth/age
Consent statement with initials in
A) signature of the subject
B) Legally acceptable representative
Signature of the investigator
Study investigators name
Signature of the witness
Name of the witness
29. Combination therapy with two or more agents having complementary
mechanism of action is an example of incremental innovation
that may extend the range of therapeutic options in the
treatment of almost every human disease
Fixed dose combination(FDC) fall into four categories
A. one or more of the active ingredients is a new drugs
B. First time combination of individually approved/marketed drugs,
where the ingredients are likely to have significant interaction of
a pharmacodynamic or pharmacokinetic nature
C. Combination already marketed, but in which it is proposed either
to change the ratio of active ingredients or to make new
therapeutic claim
D. Combined only for the purpose of convenience
30. 1. - Full name
- Address
- Title of Principal Investigator (or Investigator if no PI)
2. -Name & Address of the medical college, hospital or facility.
- Education training & experience of the Investigator
3. Name & address of all clinical laboratory facilities
4. Name and address of EC
5. Name of other members of the research team
6. Protocol title & Study number (if any)
7. Commitments
8. Signature of the Investigator with Date.
31. Appendix VIII - ETHICS COMMITTEE
•It should have at least seven members .
• a chair person (who is from outside the institution) and a
member secretary
•Other member should be mix of medical/ non-medical
scientific/ non-scientific persons including lay public , to
reflect their different view point
•The quorum of ethics committee should have at least 5
members
•Basic medical scientist( pharmacologist)
•Clinician
•Legal expert
•Social scientist/ethicist/philosopher etc.
•Lay person from the community
NOTE : ONLY THOSE ETHICS COMMITTEE MEMBER WHO ARE INDEPENDENT OF THE
CLINICAL TRIAL AND THE SPONSOR OF THE TRIAL SHOULD VOTE / PROVIDE OPINION IN
MATTERS RELATED TO STUDY .
32. Stability testing is to be performed to provide evidence on how the
quality of the drug substance or formulation varies with time under
influence of environmental factors such as temperature , humidity ,
and light , and to establish shelf life for the formulation and
recommended storage condition
It includes testing of those attributes of the drug that are susceptible to
change during storage and are likely to influence quality , safety and /
or efficacy .
33. Title page
◦ Full title of the clinical study
◦ Protocol/study number and protocol version number with date
◦ The Investigational New Drug (IND) name/number of the
investigational drugs
◦ Complete name and address of the sponsor and contract research
organization if any
◦ List of the investigators who are conducting the study
◦ Names of clinical laboratories and other departments and/ or facilities
participating in the studies
Table of content
◦ A complete table of content including a list of all appendices
1. Background and Introduction
a. Preclinical experiences
b. Clinical experiences
34. 2 . Study rationale
This section should describe a brief summary of the background
information relevant to the study design and protocol
methodology
3. Study design
a. Overview of the study design
b. Flowchart of the study
c. A brief description of the methods and procedure used during
the study
4. Study population
the number of subject required to be enrolled in the study at the
investigative site and by all site along with a brief description of
the nature of the subject population required is also mentioned
5.Subject eligibility
a. Inclusion criteria
b. Exclusion criteria
35. 6. Study treatment:
Dosing schedule , details of product stability, storage
requirements , dispensing requirements, possible drug
interactions
7. Adverse events: Description of expected adverse events should be
given
8. Data analysis
9. Undertaking by the investigator (appendix VII)
NOTE- protocol is assigned by sponsor after getting CDA from
investigator
36. 1. Patient details
Initials & other relevant identifier (hospital/ OPD record number etc)
Gender
Age &/or date of birth
Weight
Height
2. Suspected drug(s)
- Generic name of the drug
- Indication(s) for which suspect drug was prescribed or tested
- Dosage form and strength
- Daily dose & regimen (specify units-e.g. mg, ml, mg/kg)
- Route of administration
- Starting date & time of the day
- Stopping date and time, or duration of treatment
37. 3. Details of suspected Adverse Drug Reaction(s)
Full Description of reaction(s) including:
- body site
- severity
- criterion for considering the
report as serious.
In addition to the description of signs & symptoms whenever possible
describe a specific diagnosis for the reaction.
- Start date (& time) of onset of reaction
- Stop date (& time) of duration of reaction
4. Details about Investigator
- Name
- Address
- Telephone number
- Profession (Specialty)
- Date of reporting the event to the Licensing Authority
- Date of reporting the event to Ethics Committee over seeing the site
- Signature of the Investigator
38. “With The Schedule Y The 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
World Wide”
39. 1. GUPTA S. K. BASIC PRINCIPLE OF CLINICAL RESEARCH AND
METHODOLOGY
2. http://www.slideshare.net/slideshare006/schedule-y-mk-
sharma.(date-08.12.2016)
3. http://www.cdsco.nic.in/html/D&C_Rules_Schedule_Y.pdf(11.1
2.2016)