Case study with reference to drug regulatory affairs and brief introduction about schedule M and Y

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1
Guided by
Dr. K.G. Bothara
SINHGAD INSTITUTE OF PHARMACY,
NARHE
25/2/2016
Prepared by
Wani Rakesh. M
(M. pharm 2nd Semester)
Dept. of QAT

2. 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

3. 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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4. 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)
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8. • 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.
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9. Goa
New Delhi
Chennai
CDSCO North Zone (Ghaziabad)
Kolkata
.
CDSCO West Zone (Mumbai)
CDSCO South Zone (Chennai)
CDSCO East Zone (Kolkata)
CDSCO, HQ
• Hyderabad
Ahmedabad
*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&K
HQ
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“Assure that safe and effective
drugs are marketed in the country
and are available to the people”
Regulatory Authority Mission

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12. Novartis Loses Indian Patent Case On Cancer Drug ‘Glivec’
4/17/2017 12

13. Novartis
Glivec
1993 (Imatinib)
2006 Sec. 3(d)
2007, 2009
1997 (Imatinib
Mesylate)
Final decision 2013
Novartis
Chronic myeloid leukemia
13

14. 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
4/17/2017 14

15. Basmati Rice
4/17/2017 15
Golden
Basmati
Raw
Basmati
Silky Raw Basmati

16. Basmati Rice
4/17/2017
16
Patenting Authority
US Patent
International market
Kasmati Texmati
RiceTec Inc, (Basmati 867)
Patent application1995 Patent in 1997

17. 4/17/2017 17
Opposed by Government of India
In 2000 re-examination application
by APFDA
Patent cancelled in 2000 and India
won the case

18. Turmeric ( Curcuma longa)
4/17/2017 18

19. 4/17/2017 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

20. 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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21. 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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22. 4/17/2017 22
Vs
Natco vs Bayer case of compulsary
license

23. 4/17/2017
23
• Patent grant by
India
• Natco and
voluntary license
• Patent application• Bayer invented
Sorafenib
1990 1999
20082011

24. 4/17/2017 24
Natco filed application for compulsory license
2012 Natco grant compulsory license(6% royalty)
2013 modification in royalty 7%
Sec -84

25. SCHEDULE M
INDIAN 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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26. SCHEDULE M
GMP for premises and materials:
1.General requirements
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LOCATI
ON AND
SURROU
NDINGS
BUILDINGS
WATER
SYSTEM
DISPOSAL
OF
WASTE

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2. Warehousing area
3. Production area
4. Ancillary areas
5. Quality control area
6. Personnel

28. 28
7. Health, clothing and sanitation of workers
8. Manufacturing operations and controls
9. Sanitation in manufacturing area
10.Raw materials
11.Equipment

29. 29
12. Documentation and records
13. Labels and printed materials
14. Quality assurance
15. Self inspection and quality audits
16.Quality control systems

30. 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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34. D & C Rules, 1945
 122-AApplication 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.
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35. 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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36. 4/17/2017 36

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38. Application Form 44
FORM 44
(See Rules 122A, 122B, 122D and 122DA)
Application for grant of permission to import or manufacture a New Drug or to undertake clinical trial
I/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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39. FORM 44 Contd
Data 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

40. FORM 44 Contd
B. 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
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41. 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.
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42. IMPORTANT CONSIDERATIONS - 2
BA/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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43.  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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44. 44
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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