Regulatory affairs is the bridge between pharmaceutical companies and government regulatory agencies. It involves all activities related to drugs, including research, clinical trials, manufacturing, registration, distribution, pricing, advertising, and post-marketing surveillance. Regulatory dossiers contain all required technical data and documentation needed to obtain approval to market a drug in a given country or region. Common formats include the Common Technical Document for Europe, US, and other markets and Form 44 for India. Compliance with good practices and local regulations is essential for regulatory approval.

1. 01/16/15 1
Drug Regulatory
Affairs
By, Mahesh Shinde
The Bridge Between
Pharma Companies & Govt.
Agency

2. 2
Regulatory affairs
• It is by no means boring! It’s interesting.

3. 3
Role of Regulatory Affairs
What is
this?

4. 4
Regulatory System
YES YES YES
YES
YES
YES
Govt. Prescriber Distributor Patient
Govt.
Prescriber
Distributor
Patient

5. 5
• Drug = medicinal product
= pharmaceutical product

6. 6
Drug regulatory affairs
Any activity with drugs
By whom? (the authority)
no (=does not belong to
drug regulatory affairs)
yes
Prior authorisation needed?
Based on which (objective
and subjective) criteria?
Subject to regular control
(quality, inspection)?
By whom? (the authority)
Based on which (objective
and subjective) criteria?

7. 7
Activities with drugs…
• research (chemical, biological)
• clinical trials on human beings
• manufacture
• registration
– evaluation
– authorisation
• (wholesale) distribution
continued

8. 8
Activities with drugs (cont’d)
• pricing
• prescribing
• reimbursement/subsidy
• advertising (if any)
• special control (e.g. narcotics)
• post-marketing surveillance
– national drug quality control lab
– adverse effect reporting system
• (retail) distribution
• etc.
poppy

9. Quality = Quality of Personnel (Qualification, Training…)
+ Quality of Materials (Specifications, Approved Suppliers...)
+ Quality of Means (Qualified equipment's, maintenance…)
+ Quality of Media (GMP premises, Controlled environment…)
+ Quality of Methods (Calibration, Validation…)
Composition of Quality
9
QUALITYQUALITY
Raw Materials
Personnel
Procedures
Validated processes
Equipment
Premises
Environment
Packing Materials

10. Functions of a Quality UnitFunctions of a Quality Unit
10
Quality Control
– Sampling and testing of components Raw materials,
Packing materials, intermediates and finished
products
– Compliance to Good Laboratory Practices (GLPs)

11. Functions of a Quality UnitFunctions of a Quality Unit
11
Quality Assurance
– Designing robust quality systems
– Ensure compliance to relevant
regulatory requirements
– Ensure compliance to
requirements of Good
Manufacturing Practices (GMP)

12. Value addition in QA functionValue addition in QA function
12
Quality Assurance:
– Perform structured self-inspection
audits at regular intervals to prevent
any failure or non-conformance
– Critically analyze the quality non-
conformance issues and suggest
corrective and preventive actions

13. Value addition in QA function
13
Quality Assurance:
– Perform documentation audit to
ensure realistic recording of all the
relevant process parameters
– Review the adequacy of in-process
control checks to prevent any
potential failures

14. Value addition in QA function
14
Quality Assurance:
– Training & Knowledge Management
– Perform literature survey of FDA /
ICH / ISO guidelines, revisions in the
Pharmacopoeial specifications and the
current regulatory requirements and
provide training to the production
personnel.

15. What is Dossier?
15
• Dossier is collection or file of documents that contains all the
technical data of pharmaceutical product to be approved/
registered /marketed in country.
• It is commonly called as registration dossier.
In US : New Drug Application
In EU : Marketing Authorization Application

16. What is DMF?
Drug Master File (DMF)
• US : United State Drug Master File (US-DMF)
• EU : European Drug Master File (EDMF) or
Active Substance Master File (ASMF)
• TYPES OF DMFs
• The types of DMFs are:
• Type I - Manufacturing Site, Facilities, Operating Procedures, and Personnel (no
longer applicable)
• Type II - Drug Substance, Drug Substance Intermediate, and Material Used in
Their Preparation, or Drug Product
• Type III - Packaging Material
• Type IV - Excipient, Colorant, Flavor, Essence, or Material Used in Their
Preparation
• Type V - FDA Accepted Reference Information
16

17. What is CTD/eCTD?
Common Technical Documents (CTD)
• The Common Technical Document (CTD) is a set
of specification for application dossier for the registration
of Medicines and designed to be used across Europe,
United States & ROW.
• Its electronic version called as Electronic Common
Technical Document (eCTD)
17

18. The CTD Triangle
18

19. Module 1 Administrative & Prescribing
Information (Region Specific):
Should Contain Documents specific to each region:
19

20. Module 1 Administrative & Prescribing
Information (Region Specific):
(1) SITE MASTER PLAN OF PLANT
(2) COMPANY PROFILE IN SHORT
(3) ATTESTED COPY OF MANUFACTURING LICENCE
(4) ATTESTED COPY OF PRODUCT PERMISSION FROM FDA
(5) ATTESTED COPY OF COPP
(6) ATTESTED COPY OF WHO/GMP CERTIFICATE
(7) COA OF SAMPLE
(8) ATTESTED COPY OF WHOLE SELL LICENCE.
(9) LETTER OF AUTHORISATION
20

21. Module 2 CTD Summaries (QOS):
21
It contain 7 sections in the following order:
2.1 CTD Table of content (Module 2-
5)
2.1 CTD Table of content (Module 2-
5)
2.2 CTD Introduction2.2 CTD Introduction
2.3 Quality Overall Summary2.3 Quality Overall Summary
2.4 Non-Clinical Overview2.4 Non-Clinical Overview
2.5 Clinical Overview2.5 Clinical Overview
2.6 Non-Clinical Summary2.6 Non-Clinical Summary
2.7 Clinical Summary2.7 Clinical Summary

22. Module 3 Quality: Chemistry, Manufacturing & Controls (CMC)
22
3.1 Table of content (Module 3)3.1 Table of content (Module 3)
3.2 Body of Data3.2 Body of Data
3.2 S Drug Substance3.2 S Drug Substance
3.2 S1 General Information (Name, Mfg.)3.2 S1 General Information (Name, Mfg.)
3.2 S2 Manufacture3.2 S2 Manufacture
3.2 S3 Characterization3.2 S3 Characterization
3.2 S4 Control of Drug Substance
(Specification, Analytical procedures, Validation of
Analytical procedures, etc. )
3.2 S4 Control of Drug Substance
(Specification, Analytical procedures, Validation of
Analytical procedures, etc. )
3.2 S5 Reference Standards3.2 S5 Reference Standards
3.2 S6 Stability3.2 S6 Stability

23. Module 3 Quality: Chemistry, Manufacturing & Controls (CMC)
23
3.2 P Drug Product3.2 P Drug Product
3.2 P1 Description and Composition of the Drug Product3.2 P1 Description and Composition of the Drug Product
3.2 P2 Pharmaceutical Development (name, dosage form)3.2 P2 Pharmaceutical Development (name, dosage form)
3.2 P3 Manufacturer3.2 P3 Manufacturer
3.2 P4 Control of Excipients3.2 P4 Control of Excipients
3.2 P5 Control of Drug Product (Specification, Analytical
procedures, Validation of Analytical
procedures, etc. )
3.2 P5 Control of Drug Product (Specification, Analytical
procedures, Validation of Analytical
procedures, etc. )
3.2 P6 Reference Standards3.2 P6 Reference Standards
3.2 P7 Stability3.2 P7 Stability

24. Module 3 Quality: Chemistry, Manufacturing & Controls (CMC)
24
3.2 A Appendices3.2 A Appendices
3.2 A1 Facility & Equipment's3.2 A1 Facility & Equipment's
3.2 A2 Advertising agents safety evaluation3.2 A2 Advertising agents safety evaluation
3.2 A3 Excipients3.2 A3 Excipients
3.2 R Regional Information3.2 R Regional Information
3.3 Literature References3.3 Literature References

25. Module 4 Non-Clinical Study Reports:
25
4.1 Table of content (Module 4)4.1 Table of content (Module 4)
4.2 Study Reports4.2 Study Reports
4.2.1 Pharmacology4.2.1 Pharmacology
4.2.1. 1. Pharmacodynamics4.2.1. 1. Pharmacodynamics
4.2.1. 2. Safety Pharmacology4.2.1. 2. Safety Pharmacology
4.2.1. 3. Pharmacodynamics Drug Interaction4.2.1. 3. Pharmacodynamics Drug Interaction
4.2.2 Pharmacokinetics4.2.2 Pharmacokinetics
4.2.2. 1. ADME4.2.2. 1. ADME
4.2.2. 2. Pharmacokinetic Drug Interaction4.2.2. 2. Pharmacokinetic Drug Interaction
4.2.2. 3. Other Pharmacokinetic Study4.2.2. 3. Other Pharmacokinetic Study

26. Module 4 Non-Clinical Study Reports:
26
4.2.3 Toxicology4.2.3 Toxicology
4.2.3. 1. Single/Repeat Dose Toxicity4.2.3. 1. Single/Repeat Dose Toxicity
4.2.3. 2. Genotoxicity4.2.3. 2. Genotoxicity
4.2.3. 3. In-Vivo/Vitro Toxicity4.2.3. 3. In-Vivo/Vitro Toxicity
4.2.3. 4. Carcinogenicity4.2.3. 4. Carcinogenicity
4.2.3. 5. Local Tolerance/Dependence4.2.3. 5. Local Tolerance/Dependence
4.2.3. 6. Other Studies4.2.3. 6. Other Studies
4.3 Literature References4.3 Literature References

27. Module 5 Clinical Study Reports:
27
5.1 Table of content (Module 5)5.1 Table of content (Module 5)
5.2 Tabular listing of Clinical Studies5.2 Tabular listing of Clinical Studies
5.3 Clinical study reports5.3 Clinical study reports
5.3.1 Reports of Biopharmaceutical (BA-BE) Study5.3.1 Reports of Biopharmaceutical (BA-BE) Study
5.3.2 Reports of Pharmacokinetic (biomaterial) study5.3.2 Reports of Pharmacokinetic (biomaterial) study
5.3.3 Reports of Pharmacokinetic (PK) studies5.3.3 Reports of Pharmacokinetic (PK) studies
5.3.4 Reports of Pharmacodynamics (PD) studies5.3.4 Reports of Pharmacodynamics (PD) studies
5.3.4 Reports of Efficacy and Safety studies5.3.4 Reports of Efficacy and Safety studies
5.3.4 Reports of Post-Marketing experience5.3.4 Reports of Post-Marketing experience
5.3.4 Case Report Forms & Individual patient listings5.3.4 Case Report Forms & Individual patient listings
5.4 Literature References5.4 Literature References

28. Sample
• Dossier • DMF

29. Regulatory
Compliance
National Regional Global
Regulatory Compliance
29

30. National (India)
License Application Receipt
Manufacturing license Form No. 24 Form No. 25
Test license Form No. 30 Form No. 29
Import license Form No. 12 Form No.11
30
Compliance to (Drugs & Cosmetics Act 1940 & Rules under)

31. National (India)
Drug Regulatory
approval
Schedule Y Compliance
Form 44
Manufacturing Schedule M Compliance
Documentation Schedule U Compliance
Packaging Schedule P Compliance
API/Excipients/FP/PM IP Inputs if not BP/USP/ or IH
31

32. Regulatory Dossier
 Regulatory approach:
Parameters US Europe Other markets India
API USP Ph.Eur. USP / Ph.Eur. IP
USDMF COS (CEP) / EDMF DMF requirement
depends on the
target market
Excipients USP Ph.Eur. USP / Ph.Eur. IP
Reference product US Europe Depends on the
target market
Indian (if not
available, then
US or Europe)
Packaging
materials
Complying to USP Ph.Eur. USP / Ph.Eur. IP
Finished product USP As per Ph.Eur.
General requirement
USP / Ph.Eur. IP
Submission batch 1 2 2 or 3 -
Submission batch
size
100,000 units or
1/10th of commercial
batch
100,000 units or
1/10th of
commercial batch
Depends on the
target market
No such
requirement
32

33. Regulatory Dossier
 Regulatory approach:
Parameters US Europe Other markets India
Stability data 1 batch 2 batches 2 or 3 batches 3 batches
Stability condition Zone I & II condition Zone I & II condition Depends on the
target market
Zone IV condition
Comparative
dissolution study
3 media 3 media Depends on the
target market
1 to 3 media
Input materials TSE/BSE, OVI
statements
TSE/BSE Depends on the
target market
No such requirement
Packaging materials Food grade certificate Food grade certificate Depends on the
target market
No such requirement
Method validation data As per ICH ICH ICH No such guideline
Process validation
data
Not required Not required Depends on the
target market
Not required for
submission
Bioequivalence study US reference product
under fast and fed
condition
European reference
product (generally
under fasting condition)
Generally fasting
bio study
Fasting bio study
Bioequivalence study In USFDA approved
CRO anywhere in the
world
MHRA/EU approved
CRO anywhere
Depends on the
target market
Indian study required
33

34. Regulatory Authorities
 India: DCGI & State Drug Administration
 European Union: MHRA
 USA : Food and Drug Administration (FDA)
 Australia : Therapeutic Goods Administration
 Newzeland : Medsafe
 South Africa: Medicines council control
 Japan : Ministry of Health & Labour Welfare
 Switzerland : Swissmedic
 Brazil : ANVISA (The National Health Surveillance Agency)
 Mexico: COFEPRIS (The Federal Commission for the Protection against Sanitary Risk)
 Chile : ISP - Instituto de Salud Pública de Chile
 Columbia: INVIMA – Instituto Nacional de Vigilancia de Medicamentos
Alimentos Carrera 68 D No. 17 - 11 / 21
 Argentina: ANMAT - set in 1992 Argentine National Administration of
Drugs, Food & Medical Technology
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Germany: Federal Institute for Drugs and Medical Devices
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35. Important sites
Regulatory sites:
www.fda.gov
www.tga.gov.au
http://www.emea.europa.eu/
 www.ministeriodesalud.go.cr
 www.mspas.gob.gt
http://www.minsa.gob.pa/minsa2006/inicio.php
http://www.minsa.gob.ni
http://www.salud.gob.hn/
www.cssp.gob.sv
http://www.sns.gov.bo/
http://www.inh.gov.ec/
http://www.mspbs.gov.py/
http://www.msp.gub.uy/index_1.html
http://digemid.minsa.gob.pe
http://www.inhrr.gov.ve
http://pharmacos.eudra.org
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36. Important sites
Useful links:
•www.usp.org
•www.pheur.org
•www.jpdb.nihs.go.jp
•www.picscheme.org
•www.pda.org
•www.phrma.org
•www.pharmacy.org
•www.elsevier.com
•www.ich.org
•www.ijpsonline.com
•www.pharmj.com
•www.scripnews.com
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37. E-mail: shinde.mahesh51@gmail.com
37