SCHEDULE Y

Presented by-DEBASHIS DASM.Pharm 1st SemRIPANS

Objective…

What actually schedule Y is?

Why changes in schedule Y?

Rules under schedule Y…

Appendices of schedule Y…

Conclusion

references

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

Schedule Y

It’s a law

Not merely a

Guideline

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

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

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.

122-E

Definition of new drugs

Not been used in the country under labeling conditionsApproved 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

APPENDICES of schedule y

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 DataA. Chemical name and Structure

Empirical formulaMolecular weight

B. Physical propertiesSolubilityRotationPartition coefficientDissociation constant

2.3 Analytical DataElemental analysisMass spectrumNMR spectraIR spectraUV spectraPolymorphic identification

2.4 Complete monograph specification includingIdentificationIdentity/quantification of impuritiesEnantiomeric purityAssay

2.5 validation2.6 stability studies ( for details refer appendix IX)

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

4. Animal toxicology (for detail refer appendix IV)

General AspectsSystemic Toxicity StudiesMale Fertility StudyFemale Reproduction and Developmental Toxicity StudiesLocal toxicityAllergenicity/HypersensitivityGenotoxicityCarcinogenicity

5. Human/clinical pharmacology (phase I)

•Summary•Specific Pharmacological effects•General Pharmacological effects•Pharmacokinetics, absorption, distribution, metabolism, excretion•Pharmacodynamics /early measurement of drug activity

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 studiesSummaryBio-availability / Bio-equivalence.Study on special group of population e.g. geriatrics, pediatrics , pregnant or nursing women

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;

The pediatric studies should include -clinical trials, relative bioequivalence comparisons of the pediatric formulation with the adult formulation performed in adultsdefinitive 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

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.

9. Regulatory status in other countries9.1 countries where the drug is

a. marketedb. Approvedc. approved as INDd. withdrawn, if any , with reason

9.2 restriction use, if any , in countries where marketed/ approved9.3 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

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.

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

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

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)

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

Supplemental Safety Pharmacology StudiesInvestigation of the adverse pharmacological effect that are not assessed in the in the essential safety pharmacological studies and are a cause for concern

Urinary SystemIncludes 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 SystemStudies of gastric secretion, gastric pH, bile secretion, gastric emptying time etc

Other Organ Systems

Trial involves research

Purpose

Trial treatment and randomization

Trial procedures

Risk

Benefit

Alternative treatments

Compensation /treatment for injury

Subject responsibilities

Experiment aspects

Any payment

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

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

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

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.

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 .

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 .

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 Introductiona. Preclinical experiencesb. Clinical experiences

2 . Study rationaleThis section should describe a brief summary of the background

information relevant to the study design and protocol methodology

3. Study designa. Overview of the study designb. Flowchart of the studyc. A brief description of the methods and procedure used during

the study4. 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 eligibilitya. Inclusion criteriab. Exclusion criteria

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

1. Patient details

Initials & other relevant identifier (hospital/ OPD record number etc) Gender Age &/or date of birth Weight Height2. 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

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

“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”

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(11.12.2016)