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 drugsâŚ
⢠research (chemical, biological)
⢠clinical trials on human beings
⢠manufacture
⢠registration
â evaluation
â authorisation
⢠(wholesale) distribution
continued
8. 8
Activities with drugs (contâd)
⢠pricing
⢠prescribing
⢠reimbursement/subsidy
⢠advertising (if any)
⢠special control (e.g. narcotics)
⢠post-marketing surveillance
â national drug quality control lab
â adverse effect reporting system
⢠(retail) distribution
⢠etc.
poppy
9. Quality = Quality of Personnel (Qualification, TrainingâŚ)
+ Quality of Materials (Specifications, Approved Suppliers...)
+ Quality of Means (Qualified equipment's, maintenanceâŚ)
+ Quality of Media (GMP premises, Controlled environmentâŚ)
+ Quality of Methods (Calibration, ValidationâŚ)
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
â Sampling and testing of components Raw materials,
Packing materials, intermediates and finished
products
â Compliance to Good Laboratory Practices (GLPs)
11. Functions of a Quality UnitFunctions of a Quality Unit
11
Quality Assurance
â Designing robust quality systems
â Ensure compliance to relevant
regulatory requirements
â Ensure compliance to
requirements of Good
Manufacturing Practices (GMP)
12. Value addition in QA functionValue addition in QA function
12
Quality Assurance:
â Perform structured self-inspection
audits at regular intervals to prevent
any failure or non-conformance
â Critically analyze the quality non-
conformance issues and suggest
corrective and preventive actions
13. Value addition in QA function
13
Quality Assurance:
â Perform documentation audit to
ensure realistic recording of all the
relevant process parameters
â Review the adequacy of in-process
control checks to prevent any
potential failures
14. Value addition in QA function
14
Quality Assurance:
â Training & Knowledge Management
â 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
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
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
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
ďś 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
ďś 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
ďś India: DCGI & State Drug Administration
ďś European Union: MHRA
ďś USA : Food and Drug Administration (FDA)
ďś Australia : Therapeutic Goods Administration
ďś Newzeland : Medsafe
ďś South Africa: Medicines council control
ďś Japan : Ministry of Health & Labour Welfare
ďś Switzerland : Swissmedic
ďś Brazil : ANVISA (The National Health Surveillance Agency)
ďś Mexico: COFEPRIS (The Federal Commission for the Protection against Sanitary Risk)
ďś Chile : ISP - Instituto de Salud PĂşblica de Chile
ďś Columbia: INVIMA â Instituto Nacional de Vigilancia de Medicamentos
Alimentos Carrera 68 D No. 17 - 11 / 21
ďś Argentina: ANMAT - set in 1992 Argentine National Administration of
Drugs, Food & Medical Technology
ďśFrance: Agence Française de SĂŠcuritĂŠ Sanitaire des Produits de SantĂŠ
ďśGermany: Federal Institute for Drugs and Medical Devices
34