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CASE STUDY WITH REFERENCE TO INDIAN DRUG REGULATORY AFFAIRS

IN INDIA & BRIEF INTRODUCTION ABOUT SCHEDULE M &Y DRUGS

Guided by Dr. K.G. Bothara

SINHGAD INSTITUTE OF PHARMACY, NARHE

25/2/2016

Prepared byWani Rakesh. M

(M. pharm 2nd Semester) Dept. of

QAT

Content

Indian drug regulatory authorities

Central and State regulatory bodies (CDSCO)

Case studies

Drugs and Cosmetics Act and Rules with latest

Amendments (Special emphasis Schedule M and Y)

References 2

Drug regulatory system in India

Drugs and Health is in concurrent list of Indian Constitution It is governed by both Centre and State Governments under the Drugs & Cosmetics Act, 1940, Rule 1945.

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Central Drug Standard Control Organization (CDSCO)

Drugs Control General of India (DCGI )

Genetic Engineering Approval Committee (GEAC)Indian Council Of Medical Research (ICMR)

Central License Approving Authority (CLAA)

Drug Technical Advisory Board (DTAB)

Drugs Consultative Committee (DCC)

Central Drugs Laboratory (CDL)

National Pharmaceutical Pricing Authority (NPPA)

MAIN BODIES

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Central Drugs Standard Control Organization

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• Approval of new drugs and clinical trials.

• Import Registration and Licensing .

• Licensing of Blood Banks,Vaccines, r-DNA products & some Medical Devices.

• Banning of drugs and cosmetics .

• Drug Alert month wise.

• NOCs for Export of Drugs.

FUNCTION OF CDSCO

Goal of regulatory

To guarantee the safety, efficacy and quality of drugs.8

Goa

New Delhi

Chennai

CDSCO North Zone (Ghaziabad)

Kolkata.

CDSCO West Zone (Mumbai)

CDSCO South Zone (Chennai)

CDSCO East Zone (Kolkata)

CDSCO, HQ

• HyderabadAhmedabad

*New Zonal Offices : 2 (Ahmedabad & Hyderabad)*Sub- Zonal Office : 3*Port Offices/Airports : 13*Central Laboratories : 8

35 SLAs= 29 States+ 6 UTs

Bengaluru

Geographical Location of CDSCO

Chandigarh

J&KHQ

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“Assure that safe and effectivedrugs are marketed in the countryand are available to the people”

Regulatory Authority Mission

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05/02/2023

Novartis Loses Indian Patent Case On Cancer Drug ‘Glivec’ 12

Novartis

Glivec

1993 (Imatinib)

2006 Sec. 3(d)

2007, 2009

1997 (Imatinib Mesylate) Final decision 2013

Novartis

Chronic myeloid leukemia13

Parameter Glivec Generic version of Glivec

Company Novartis Natco (local company)

Nature Expensive Least expensive

Cost 1 tablet -2200 Rs

1 tablet -500 Rs

Preference 16000 people 300000 people

05/02/2023 14

05/02/2023

Basmati Rice

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Golden Basmati

Raw Basmati

Silky Raw Basmati

05/02/2023

Basmati Rice

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Patenting Authority

US Patent

International marketKasmati Texmati

RiceTec Inc, (Basmati 867) Patent application1995 Patent in 1997

05/02/2023 17

Opposed by Government of India

In 2000 re-examination application by APFDA

Patent cancelled in 2000 and India won the case

05/02/2023

Turmeric ( Curcuma longa)

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05/02/2023 19

(1993) Patent application by University of Mississippi Medical Center

(1995) USPTO granted patent for use of turmeric in wound healing

Opposed by India's Council of Scientific and Industrial Research(CSIR)

1997 Patent cancelled

Key words: Sun pharmaceutical’s U.S subsidiary ,caraco pharmaceutical

Laboratories recall 128,363 bottles decongestant.

Caraco also recall 251,882 bottle antidepressant venlafaxine company failed

to dissolve the human body.

Type of recall: Statutory recall.

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Customer report of an incorrent barcode on primary bag labeling .

Barcode on the overwrap is correct.

Primary container barcode to be mislabeled with barcode .

Heparin Sodium 2000USP in 0.9% Sodium Chloride Injection.

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05/02/2023 22

VsNatco vs Bayer case of compulsary

license

05/02/2023 23

• Patent grant by India

• Natco and voluntary license

• Patent application• Bayer invented Sorafenib

1990 1999

20082011

05/02/2023 24

Natco filed application for compulsory license

2012 Natco grant compulsory license(6% royalty)

2013 modification in royalty 7%

Sec -84

SCHEDULE MINDIAN DRUGS & COSMETICS ACT

Type Content

“M” Requirements of Manufacturing Premises, GMP Requirements of Factory Premises, Plants And Equipments

“M1” Requirements of Factory Premises For Manufacture of Homeopathic Medicines

“M2” Requirements of Factory Premises For Manufacture of Cosmetics

“M3” Requirements of Factory Premises For Manufacture of Medical Devices

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SCHEDULE MGMP for premises and materials:

1.General requirements

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LOCATION AND

SURROUNDIN

GS

BUILDINGS

WATERSYSTEM

DISPOSAL

OFWASTE

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2. Warehousing area

3. Production area

4. Ancillary areas

5. Quality control area

6. Personnel

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7. Health, clothing and sanitation of workers

8. Manufacturing operations and controls

9. Sanitation in manufacturing area

10.Raw materials

11.Equipment

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12. Documentation and records

13. Labels and printed materials

14. Quality assurance

15. Self inspection and quality audits

16.Quality control systems

17. Specifications

18. Master formula record

19. Packaging records

20. Batch packaging records

21. Batch processing records

22. Standard operating procedures SOP and

records 30

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23. Reference samples

24. Reprocessing and recoveries

25. Distribution records

26. Validation and process validation

27. Product recalls

28. Complaints and adverse reactions etc

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Schedule Y

• Requirements and Guide- lines for permission to import and/or manufacture of

New Drugs for sale or undertake Clinical Trials.

• RULES 122A, 122B, 122D, 122DA, 122DAA.

• Application for permission under form 44, regulatory authorities, and there fees.

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D & C Rules, 1945

122-A 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.34

FEES• Import ff/ Mfg ff/ Import bulk + Mfg ff = Rs 2,50,000/- of new drug

• Application by same applicant, = Rs 15,000/- for modified dosage form or with new claim

• Secondary applicants after 1 = Rs 15,000/- year of approval

• Import / Mfg FDC = Rs 15,000/-

• Conduct Clinical trial with ND/IND – Phase I = Rs 2,50,000/-– Phase II = Rs 2,50,000/- – Phase III = Rs 2,50,000/-– No separate fee to be paid along with application for import / mfg based on successful completion

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05/02/2023 36

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Application Form 44FORM 44

(See Rules 122A, 122B, 122D and 122DA)Application for grant of permission to import or manufacture a New Drug or to undertake clinical trialI/We..……….. of ……….., hereby apply for grant of permission for import and / or clinical trial or for approval

to manufacture of a new drug or fixed dose combination or subsequent permission of already approved new drug. The necessary information / data is given below :

1. Particulars of New Drug : Name of the drug : Dosage Form : Composition of the formulation : Test specifications :

Active ingredients : Inactive ingredients :

Pharmacological classification of the drug : Indications for which proposed to be used : Manufacturer of the raw material : Patent status :

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FORM 44 ContdData submitted along with the application

A. Permission to market new drug

1. Chemical and Pharmaceutical information

2. Animal Pharmacology

3. Animal Toxicology

4. Human / Clinical Pharmacology

5. Bioavailability / dissolution and stability data

6. Regulatory status in other countries

7. Marketing information :

(a) Drafts of labels and cartons 39

FORM 44 ContdB. Subsequent approval / permission for manufacture of already approved new

drug

a) Formulation :

Bioavailability / bioequivalence

Name of the investigator / centre

b) Raw Material

Manufacturing Method

QC parameters 40

Important Considerations - 1 HUMAN CLINICAL PHARMACOLOGY :-

a) Phase I (Human Pharmacology) – Safety and Tolerability with the initial

administration of IND – MTD, Kinetics and Dynamics.

b) Phase II (Therapeutic Exploratory Trials) – Effectiveness for a particular indication,

small group.

c) Phase III (Therapeutic Confirmatory Trials) – Therapeutic benefit in large number of

patients.

d) Phase IV (Post Marketing Trials) – Related to approved indication.41

IMPORTANT CONSIDERATIONS - 2BA/BE

i. For drugs approved elsewhere in the world and absorbed systemically,

bioequivalence with the reference formulation should be carried out.

ii. Evaluation of the effect of food.

iii. Dissolution and bioavailability data to be submitted.

iv. All bioavailability and bioequivalence studies should be conducted according to

the Guidelines for Bioavailability and Bioequivalence studies.

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REFERENCES

Itkar S.C., Vyawahare N.S., Drug regulatory affairs, 2th edition 2011, Nirali prakashan,

page no.1.1-1.10. Kuchekar B.S, Khadatare A.M, Forensic pharmacy, 8thedition, Nirali prakashan, page no,

5.1-5.60.

Divakar G.S, 2012, pharmaceutical marketing management, 5th edition, Nirali prakashan,

page no,3.1-8.22.

Itkar.S.C,, Pharmaceutical Management, 5th edition 2012, Nirali prakashan, page

no,10.6-19.32.

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Alice Kuruvilla, Paul A.D., Clinical trials 1st edition 2013, Paras medical publisher, page no

15-33.

www.cdsco.gov.in access on 05.02.2016

http://timesofindia.indiatimes.com/business/india-business/Bayer-loses-cancer-drug-patent-

appeal/article show/18805475.cms, access on 11.02.2016

http://www1.american.edu/ted/basmati.htm, access on 11.02.2016

http://www.novartis.com/newsroom/product-related-info center/glivec.shtml, access on

11.02.2016

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