Akki Schedule y

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SCHEDULE Y

SUBMITTED

BY

Mr. AKSHAY A. JOSHI

ICBIO BANGALORE


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OBJECTIVES OF D & C ACT1940

The Drugs and Cosmetics Act 1940

provides the central legislation, which

regulates import, manufacture,

distribution & sale of drugs & cosmetics in thecountry.

The main objective of the Act is to ensure

that the drugs available to the people are

safe and efficacious and the cosmetics marketed

are safe for use.


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Drug and cosmetic act 1945

Rule Permission for

122

A - Import

B - Manufacture [except drugs underschedule C and C(1)]

D -Fixed dose combinations

DA - Clinical Trial

DAA - CT Definition

E - New Drug Definition


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Conti

122 DAA

Clinical Trial Definition

Systematic study of new drugs in human subjects; To

generate data for discovering/verifying clinical safety,pharmacological (PK & PD) or adverse effects; To

determine safety and efficacy of the new drug


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Conti..

122 ENew drug definition

Not used in the country

Approved drug : 1. New claims

(Indications,dosage,

dosage form, route)

2. FDCs

(New / Modified)

Note : Vaccines are new drugs unless

1. Certified

2. Till 4 year or

3. Included in IP


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SPONSORS RESPONSIBILITIES

Quality Assurance : Adopt GCP Guidelines Trial Status

Report to Licensing Authority : Annually Premature

Termination : Summary report within 3 month

( Study, Pt. no., Dose, Duration, ADR &reasons for discontinuation )

Serious Adverse Event : Report to RA & other

investigators within 14 days


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INVESTIGATORS RESPONSIBILITIES

Adhere to approved Protocol & GCP

Guidelines

Document SOPs

Management of all ADR / AE

Reporting unexpected AE to :

- Sponsor within 24 hours

- EC within 7 days


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EC RESPONSIBILITIES

Safeguard rights, safety & well being

Protect vulnerable subjects

Obtain and maintain record of SOPs Ongoing review based on Periodic progress

report

If EC revokes its approval

- Record reasons for it- Inform the Investigator & LA immediately


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ESSENTIAL STEPS OF CLINICAL

PHARMACOLOGY

Phase I (Human Pharmacology)

Safety & Tolerability ( PK, PD & MTD

Phase II (Th. Exploratory Trial)Therapeutic benefits in few patients

Phase III (Th. Confirmatory Trial)

Therapeutic benefit in more patientsPhase IV (Post Marketing Trials)

Related to Approved indication


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overview

Schedule Y what it covers and associated

rules

Application for permission underform 44,regulatory authorities and fees

Important consideration

Appendices of Schedule Y


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Schedule Y

Requirements & Guidelines for permission to IMPORT & / OR

MANUFACTURE of new drugs for SALE or to UNDERTAKECLINICAL TRIALS.

AMENDMENT OF SCHEDULE Y:The Ministry Of Health & Family Welfare In Jan2005 issued a

notification amending Schedule Y of Drugs & Cosmetic Rules

Now permits concurrent phase II & phase III trials in India

Why India ForClinical Trials ?

Ideal location for undertaking economical clinical trials

which cost less than in developed countriescan meet international standards

large & heterogeneous population of people with

infectious diseases


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Appendix X

Contents Of The Proposed Protocol

For Conducting Clinical Trials

Appendix IX

Stability Testing Of New Drugs

Appendix VIII

Ethics Committee

Appendix VII

Undertaking by the InvestigatorAppendix VI

Fixed Dose Combinations (Fdcs)

Appendix V

Informed ConsentAppendix IV

Animal pharmacology

Appendix III

Animal toxicology (non-clinical toxicity studies)

Appendix II

Structure, contents & format for clinical

study reports

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.

Appendix I

Data to be submitted along with the application

to conduct clinical trials / import / manufactureof new drugs for marketing in the country.

Appendix XI

Data Elements For Reporting Serious

Adverse Events Occurring In A Clinical Trial.

List of Appendices For Schedule Y


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Appendices I : Data to be submitted along with theapplication to conduct clinical trials/import/manufacture of new

drugs for marketing in the country

i. Introduction (About the drug and the therapeutic class )

ii. Chemical and pharmaceutical information

iii. Animal Pharmacology

iv. Animal Toxicology (Non-clinical Toxicity Studies)v. Human / Clinical pharmacology (Phase I)

vi. Therapeutic exploratory trials (Phase II)

vii. Therapeutic confirmatory trials (Phase III)

viii. Special studies(BA/BE, pregnant, children)

ix. Countries where the drug is approved

x. Prescribing information

xi. Samples and Testing Protocol


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AppendicesI-A: Data required to be submitted by anapplicant for grant of permission to import &/or manufacture a

new drug already approved in the country

i. Introduction (About the drug and the therapeutic class )

ii. Chemical and pharmaceutical information ()

iii. Marketing information

iv. Special studies(BA/BE, pregnant, children)


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Cont.

9.Study Objective(purpose)10.Investigational Plan: (Trial design, the Subject

selection, the treatment procedures, the data quality

assurance procedures and the statistical methods)

11.Trial Subjects12. Efficacy evaluation :Results

13. Safety Evaluation :Complete list

13.1 all serious adverse events, whether expected or

unexpected and13.2 unexpected adverse events whether serious or not

14. Discussion and overall Conclusion

15. List of References

16.Appendices for Clinical Study Reports


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APPENDIX IV ANIMAL PHARMACOLOGY

Cardiovascular System

Central Nervous System Respiratory System

o Follow up and Supplemental Safety Pharmacology


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APPENDIX VINFORMED CONSENTEssential Elements:

Voluntary participation

Study involves research and its purpose & Expected

duration of participation

Description of the procedures

Description of foreseeable risks or benefits to subject

Alternative procedures or therapies

Statement describing confidentiality of records

Trial treatment schedule(s)

Compensation and/or treatment

Whom to contact, rights of Subjects in the AE


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Cont

Additional elements, which may be required

Foreseeable circumstances under which the Subject's

Participation may be terminated without the Subject's

consent Additional costs to the Subject

Consequences to withdraw from the research and

procedures for orderly termination Notification in a timely manner if significant new findings

develop which may affect the Subject's willingness to

continue participation.


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APPEND VIFIXED DOSE COMBINATIONS

Fixed Dose Combinationreferto products containingone

ormore active ingredients used fora particularindication.

GROUP 1 : One or more of the active ingredients is a newdrug. Marketing data will be similar to data required for anynew drug (including clinical trials) (rule 122E)

GROUP 2 : Active ingredients already approved/marketedindividually. appropriate chemical and pharmaceutical datawill be submitted.

GROUP 3 : Already marketed, but in which it is proposedeither to change the ratio of active ingredients.

GROUP4 : Individual active ingredients have been widelyused in a particular indication(s) for years,

It will have to be demonstrated that the proposed dosageform is stable


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APPENDIX VIIUNDERTAKING BYINVESTIGATOR

Full name, address and title and MCR number of the

PI

Name/address of medical college, hospital or other

facility where the clinical trial will be conducted. Names of other members of the research team

Name and address of the Ethics Committee

Protocol Title and Study number

Signature of Investigator with Date on Commitments:


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APPENDIX VIIIETHICS COMMITTEE At least seven members

Should appoint Chairperson (who is from outside the

institution) and a Member Secretary.

Quorum at least 5 members with the following

representations:

1.basic medical scientists (preferably one

pharmacologist).

2.clinicians

3.legal expert

4.social scientist / representative of NGO voluntary

agency /philosopher / ethicist / theologian or a similar

person

5.lay person from the community


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APPENDIX IXSTABILITY TESTING OF NEW

DRUGS

.Evidence on how the quality of a drug substance or

formulation varies with time under the influence of

various environmental factors

To establish shelf life for the formulation /

recommended storage

Validated stability-indicating analytical procedures

Stress testing of the drug substance on single batch to

identify degradation products


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APPENDIX X PROPOSED PROTOCOL

1. Title Page - Full title, Protocol / Study number, and

Protocol version number with date, The INDname/number, Complete name and address of theSponsor and CRO, List of the Investigators,

2. Table of Contents

1. Background and Introduction-Preclinicalexperience, Clinical experience

2. Study Rationale

3. Study Objective(s)

3. Study Design

4. Study Population5. Subject Eligibility

1. Inclusion Criteria

2. Exclusion Criteria


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Cont.

6. Study Assessments

7. Study Conduct8. Discontinued Subjects(on which criteria)

9. Study Treatment (Dosing Schedule, route ofadministration, dose modification etc..

10. Unblinding procedures

11. Adverse Events

12. Ethical Considerations

13. Study Monitoring and Supervision

14. Investigational Product Management

15. Data Analysis

16. Undertaking by the Investigator

17. Appendices


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APPENDIX XIDATA FOR REPORTING SAE1. Patient Details

1. Initials & other relevant identifier (hospital/OPDrecord number etc.) Gender, Age and/or date

of birth

2. Weight & Hight

2. Suspected Drug(s)

1. Generic name of the drug & Indication

2. Dosage form and strength

3. Daily dose and regimen

4. Route of administration

5. Starting & Stopping date and time of day

3. Other Treatment(s)

4. Details of Suspected Adverse Drug Reaction

5. Outcome Information


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Revised Old

1. Applicationforpermission 1.1 Nature oftrials2. Clinical trial 1. Clinical trials

(1) Approval forclinical trial 1.2 Permissionfortrials

(2)ResponsibilitiesofSponsor1.3ResponsibilitiesofSponsor/Investigator

(3)Responsibilitiesofthe Investigator(s)

(4) Informed Consent New

(5)ResponsibilitiesofECs - New

(6) Human Pharmacology (Phase I) 5. Human clinical pharmacology (Phase I)

(7) Therapeutic exploratory trials(Phase II) 6. Exploratory trials(Phase II)

(8) Therapeutic confirmatory trials(Phase II) 7. Confirmatory trials(Phase II)

(9) Post Marketing Trials(Phase IV) New

3. Studiesinspecial populations 8. Special studies(1) Geriatrics

(2) Pediatrics

(3) Pregnantornursing women

4. Post Marketing Surveillance 12. Post-marketingsurveillance study

5. Special studies: BA/BE Studies New

Schedule Y 2005


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Revised Old

Data to be submitted along with the application

to conduct clinical trials/import/manufacture of

new drugs for marketing in the country

Data required to be submitted with application to

for permission to market a new drug

2.1 Information on active ingredients 2.3 Specifications of active and inactive

ingredients

2.2 Physicochemical Data 2.1 Physicochemical proportion

2.3 Analytical data New

2.4 Monograph specification 2.4 Tests for identification of the active

ingredient and method of its assay

2.5 Validations new

2.7 Data on Formulation 2.2 and 2.5

3.4 Safety Pharmacology New

4.3 Male Fertility Studies New

4.6 Allergenicity/Hypersensitivity New

11. Samples and Testing Protocols 10.3 Samplewith testing protocol


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Conclusion

When you start investigating a newmolecular entity, think it will be registeredaround the world and will provide a cure to

a specific disease, then the main concernis to ensure the finished product reachesthe population with approved criteria forQUALITY, EFFICACY and SAFETY

Every country has its own regulations andapproval process THAT MUST BE TAKENINTO CONSIDERATION


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Documents

Akki Schedule y