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01/16/15 1
Drug Regulatory
Affairs
By, Mahesh Shinde
The Bridge Between
Pharma Companies & Govt.
Agency
2
Regulatory affairs
• It is by no means boring! It’s interesting.
3
Role of Regulatory Affairs
What is
this?
4
Regulatory System
YES YES YES
YES
YES
YES
Govt. Prescriber Distributor Patient
Govt.
Prescriber
Distributor
Patient
5
• Drug = medicinal product
= pharmaceutical product
6
Drug regulatory affairs
Any activity with drugs
By whom? (the authority)
no (=does not belong to
drug regulatory affairs...
7
Activities with drugs…
• research (chemical, biological)
• clinical trials on human beings
• manufacture
• registration
...
8
Activities with drugs (cont’d)
• pricing
• prescribing
• reimbursement/subsidy
• advertising (if any)
• special control ...
Quality = Quality of Personnel (Qualification, Training…)
+ Quality of Materials (Specifications, Approved Suppliers...)
+...
Functions of a Quality UnitFunctions of a Quality Unit
10
Quality Control
– Sampling and testing of components Raw materia...
Functions of a Quality UnitFunctions of a Quality Unit
11
Quality Assurance
– Designing robust quality systems
– Ensure co...
Value addition in QA functionValue addition in QA function
12
Quality Assurance:
– Perform structured self-inspection
audi...
Value addition in QA function
13
Quality Assurance:
– Perform documentation audit to
ensure realistic recording of all the...
Value addition in QA function
14
Quality Assurance:
– Training & Knowledge Management
– Perform literature survey of FDA /...
What is Dossier?
15
• Dossier is collection or file of documents that contains all the
technical data of pharmaceutical pr...
What is DMF?
Drug Master File (DMF)
• US : United State Drug Master File (US-DMF)
• EU : European Drug Master File (EDMF) ...
What is CTD/eCTD?
Common Technical Documents (CTD)
• The Common Technical Document (CTD) is a set
of specification for app...
The CTD Triangle
18
Module 1 Administrative & Prescribing
Information (Region Specific):
Should Contain Documents specific to each region:
19
Module 1 Administrative & Prescribing
Information (Region Specific):
(1) SITE MASTER PLAN OF PLANT
(2) COMPANY PROFILE IN ...
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 ...
Module 3 Quality: Chemistry, Manufacturing & Controls (CMC)
22
3.1 Table of content (Module 3)3.1 Table of content (Module...
Module 3 Quality: Chemistry, Manufacturing & Controls (CMC)
23
3.2 P Drug Product3.2 P Drug Product
3.2 P1 Description and...
Module 3 Quality: Chemistry, Manufacturing & Controls (CMC)
24
3.2 A Appendices3.2 A Appendices
3.2 A1 Facility & Equipmen...
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....
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. Si...
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 ...
Sample
• Dossier • DMF
Regulatory
Compliance
National Regional Global
Regulatory Compliance
29
National (India)
License Application Receipt
Manufacturing license Form No. 24 Form No. 25
Test license Form No. 30 Form N...
National (India)
Drug Regulatory
approval
Schedule Y Compliance
Form 44
Manufacturing Schedule M Compliance
Documentation ...
Regulatory Dossier
 Regulatory approach:
Parameters US Europe Other markets India
API USP Ph.Eur. USP / Ph.Eur. IP
USDMF ...
Regulatory Dossier
 Regulatory approach:
Parameters US Europe Other markets India
Stability data 1 batch 2 batches 2 or 3...
Regulatory Authorities
 India: DCGI & State Drug Administration
 European Union: MHRA
 USA : Food and Drug Administrati...
Important sites
Regulatory sites:
www.fda.gov
www.tga.gov.au
http://www.emea.europa.eu/
 www.ministeriodesalud.go.cr
...
Important sites
Useful links:
•www.usp.org
•www.pheur.org
•www.jpdb.nihs.go.jp
•www.picscheme.org
•www.pda.org
•www.phrma....
E-mail: shinde.mahesh51@gmail.com
37
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Regulatory affairs-Introduction to CTD

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Introduction to Drug regulatory affairs

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Regulatory affairs-Introduction to CTD

  1. 1. 01/16/15 1 Drug Regulatory Affairs By, Mahesh Shinde The Bridge Between Pharma Companies & Govt. Agency
  2. 2. 2 Regulatory affairs • It is by no means boring! It’s interesting.
  3. 3. 3 Role of Regulatory Affairs What is this?
  4. 4. 4 Regulatory System YES YES YES YES YES YES Govt. Prescriber Distributor Patient Govt. Prescriber Distributor Patient
  5. 5. 5 • Drug = medicinal product = pharmaceutical product
  6. 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. 7 Activities with drugs… • research (chemical, biological) • clinical trials on human beings • manufacture • registration – evaluation – authorisation • (wholesale) distribution continued
  8. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 18. The CTD Triangle 18
  19. 19. Module 1 Administrative & Prescribing Information (Region Specific): Should Contain Documents specific to each region: 19
  20. 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. 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. 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. 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. 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. 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. 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. 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. 28. Sample • Dossier • DMF
  29. 29. Regulatory Compliance National Regional Global Regulatory Compliance 29
  30. 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. 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. 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. 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. 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 34
  35. 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 35
  36. 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 36
  37. 37. E-mail: shinde.mahesh51@gmail.com 37

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