Hints about Drug Regulatory Affairs Department.

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Drug Regulatory
Affairs
By
Eknath Babu T B
The Bridge Between
Pharma Companies & Govt.
Agency

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

3. Role of Regulatory Affairs
3
What is
this?

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

5. ∗ Drug = medicinal product
= pharmaceutical product
5

6. Any activity with drugs
6
Drug regulatory affairs
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
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QUALITYQUALITY
Raw Materials
Personnel
Procedures
Validated processes
Equipment
Premises
Environment
Packing Materials

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

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

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Value addition in QA functionValue addition in QA function
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.

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What is Dossier?
• 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. ∗ 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
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What is DMF?
Drug Master File (DMF)

17. ∗ 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)
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What is CTD/eCTD?
Common Technical Documents (CTD)

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The CTD Triangle

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

20. (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
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Module 1 Administrative & Prescribing Information
(Region Specific):

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

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

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

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Module 3 Quality: Chemistry, Manufacturing & Controls (CMC)
3.2 A Appendices
3.2 A1 Facility & Equipment's
3.2 A2 Advertising agents safety evaluation
3.2 A3 Excipients
3.2 R Regional Information
3.3 Literature References

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Module 4 Non-Clinical Study Reports:
4.1 Table of content (Module 4)
4.2 Study Reports
4.2.1 Pharmacology
4.2.1. 1. Pharmacodynamics
4.2.1. 2. Safety Pharmacology
4.2.1. 3. Pharmacodynamics Drug Interaction
4.2.2 Pharmacokinetics
4.2.2. 1. ADME
4.2.2. 2. Pharmacokinetic Drug Interaction
4.2.2. 3. Other Pharmacokinetic Study

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Module 4 Non-Clinical Study Reports:
4.2.3 Toxicology
4.2.3. 1. Single/Repeat Dose Toxicity
4.2.3. 2. Genotoxicity
4.2.3. 3. In-Vivo/Vitro Toxicity
4.2.3. 4. Carcinogenicity
4.2.3. 5. Local Tolerance/Dependence
4.2.3. 6. Other Studies
4.3 Literature References

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Module 5 Clinical Study Reports:
5.1 Table of content (Module 5)
5.2 Tabular listing of Clinical Studies
5.3 Clinical study reports
5.3.1 Reports of Biopharmaceutical (BA-BE) Study
5.3.2 Reports of Pharmacokinetic (biomaterial) study
5.3.3 Reports of Pharmacokinetic (PK) studies
5.3.4 Reports of Pharmacodynamics (PD) studies
5.3.4 Reports of Efficacy and Safety studies
5.3.4 Reports of Post-Marketing experience
5.3.4 Case Report Forms & Individual patient listings
5.4 Literature References

28. Sample
∗ Dossier ∗ DMF

29. Regulatory
Compliance
National Regional Global
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Regulatory Compliance

30. 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
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National (India)
Compliance to (Drugs & Cosmetics Act 1940 & Rules under)

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

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
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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
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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. 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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Important sites

36. 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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Important sites

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E-mail:tbeknath@gmail.com