CTD file submission for marketing authorization in Pakistan

1. CTD Implementation by DRAP
Presented By:
Rashid Mureed
Head OF Regulatory Affairs-OBS Group

2. DRUG REGULATORY AUTHORITY OF PAKISTAN
► SRO. 932(I)/2017
► Enforcement of CTD (Common
Technical Document) as Standard
Dossier Document for Applying Drug
product Registration in DRAP
► Implementation Date: 01-01-2018

3. What is CTD
► CTD stand of Common Technical Document
► A CTD is a set of Technical Document required by International Regulatory
Agencies /HA’s for the purpose of Granting Marketing Authorization of a
Pharmaceutical Product in their respective countries.
► In Now days these CTD based Technical documents are included in the
Application Dossier for Registration/Renewal of Pharmaceutical Products for
Human use.

4. History of CTD
► Before CTD Regulators from Different countries HA receives a Dossier
application and spends about 2 to 3 Years in its review before giving any
decision for its approval of Marketing Authorization for use in Human Beings.
► Reason for such delay was more on ambiguity based on different types of
technical documents in which a Application Dossier were submitted by different
Pharmaceutical Companies.
► To harmonize these ambiguity Industries came up with CTD-Documents in
order to speed up Regulatory Approvals.

5. History of CTD

6. Purpose of CTD

7. Nations/Region who first adopted CTD
CTD IS A JOINT EFFORT OF 3 REGULATORY AGENCIES:
1.European Medicines Agency (EMEA, Europe),
2. Food and Drug Administration (FDA, USA) and
3. Ministry of Health, Labour and Welfare (MHLW,Japan)
And there Pharmaceutical associations

8. Current CTD Accepting Regions
► USA
► CANADA
► EUROPE
► AUSTRALIA
► JAPAN
► AFRICA
► ASEAN
► CHINA

9. CTD-TRIANGLE
Module 1
Regional
Admin
Information
Module 3
Quality
Module 4
Nonclinical
Study Reports
Module 5
Clinical
Study Reports
Quality
Overall
Summary
Nonclinical
Summary
Nonclinical
Overview
Clinical
Summary
Clinical
Overview
Module 2
NOT Part of
the CTD
The CTD

10. October 14, 2017 10
Documentation for Marketing
Authorization

11. MODULE 1-Administrative Part
Regional Requirements of DRAP for
Marketing Authorization

13. MODULE 1-Administrative Part

14. MODULE 1-Administrative Part

15. MODULE 1-Administrative Part

16. MODULE 2- Overviews and Summaries
*QOS has been explained by a WHO QOS - PD template MODULE 2.3

17. 17
MODULE-2 SUMMARY
Module
Sections
Documents required as per ICH Data from Module 3 DRAP Req.
2.3.S Drug Substance YES
2.3.S.1 General Information 3.2.S.1 YES
2.3.S.2 Manufacture 3.2.S.2, 3.2.2.2-3.2.2.6 YES
2.3.S.3 Characterization 3.2.S.3.1, 3.2.S.3.2 YES
2.3.S.4 Control of Drug Substance 3.2.S.4.1, 3.2.S.4.4 YES
2.3.S.5 Reference standards or Materials 3.2.S.5 YES
2.3.S.6 Container Closure System 3.2.S.6 YES
2.3.S.7 Stability 3.2.S.7.1, 3.2.S.7.2, 3.2.S.7.3 YES
2.3.P Drug Product YES
2.3.P.1 Description and Composition of the Product 3.2.P.1 YES
2.3.P.2 Pharmaceutical Development 3.2.P.2 YES
2.3.P.3 Manufacture 3.2.P.3, 3.2.P.3.3, 3.2.P.3.5 YES
2.3.P.4 Control of Excipients 3.2.P.4 YES
2.3.P.5 Control of Drug Product 3.2.P.5.1, 3.2.P.5.4 YES
2.3.P.6 Reference Standards or Materials 3.2.P.6 YES
2.3.P.7 Container Closure System 3.2.P.7 YES
2.3.P.8 Stability 3.2.P 8.3, 3.2.P.8.2 YES

18. MODULE 3-QUALITY PART

19. MODULE-3 (S PART DETAIL)
Module
Section
Document required as per ICH (DMF Part) Reference ICH Availability of Docs
3.2.S Drug Substance DMF documents on CTD
format req.
3.2.S.1 General Information Q6Q Do
3.2.S.2 Manufacturing Details Closed Part
(Q6A/Q3A)
Do
3.2.S.3 Characterization of Structure & Impurities Q3A(R),Q3C,Q6A Do
3.2.S.4 Control of Drug Substance Q3A(R),Q3C,Q6A
Q2A,Q2B,Q6B
Do
3.2.S.5 Reference Standards of Materials Q6A Do
3.2.S.6 Container Closure System Q6A Do
3.2.S.7 Stability studies Q1A(R2)/Q1B Do

20. MODULE-3 (P PART DETAIL):
Module
Section
Documents required as per ICH Reference ICH Availability of Docs
3.2.P.1 Description and Composition of the Drug Product Q6A Present
3.2.P.2 Pharmaceutical Development Q8 Document required
From NPD Dept.
3.2.P.2.1 Components of the Drug Product do
3.2.P.2.1.1 Drug Substance do
3.2.P.2.1.2 Excipients do
3.2.2.2 Drug Product do
3.2.P.2.2.1 Formulation Development do
3.2.P.2.2.2 Overages do
3.2.P.2.2.3 Physicochemical and Biological Properties do
3.2.P.2.3 Manufacturing Process Development do
3.2.P.2.4 Container Closure System do
3.2.P.2.5 Microbiological Attributes do
3.2.P.2.6 Compatibility do

21. MODULE-3(P PART-DRUG PRODUCT):
Module
Section
Document Required as Per ICH Reference ICH Availability of Docs
3.2.P.3 Manufacture
3.2.P.3.1 Manufacturer(s) Mfg. Address
3.2.P.3.2 Batch Formula Present
3.2.P.3.3 Manufacturing Process and Process Controls Present
3.2.P.3.4 Controls of Critical Steps and Intermediates Q2A, Q2B, Q6A Not available
3.2.P.3.5 Process Validation and/or Evaluation Not available for under
registered generics
3.2.P.4 Control of Excipients
3.2.P.4.1 Specifications Q6A Excipient control document
3.2.P.4.2 Analytical Procedures Q2A,Q6A do
3.2.P.4.3 Validation of Analytical Procedures Q2A, Q2B Not available for under
registered generics
3.2.P.4.4 Justification of Specifications Q3C No control document available
3.2.P. 4.5 Excipients of Human or Animal Origin Q6B TSE/BSE Certificate required if
any
3.2.P.4.6 Novel Excipients Undertaking req.

22. MODULE-3: (DRUG PRODUCT)
Module
Section
Documents required as per ICH Reference ICH Availability of Docs
3.2.P.5 Control of Drug Product -
3.2.P.5.1 Specification(s) Q3B(B),Q6A Present
3.2.P.5.2 Analytical Procedures Q2A,Q6A do
3.2.P.5.3 Validation of Analytical Procedures Q2A,Q2B Not Available for under
registered generics
3.2.P.5.4 Batch Analyses Q3C,Q6A do
3.2.P.5.5 Characterization of Impurities Q6A do
3.2.P.5.6 Justification of Specification(s) Q6A do
3.2.P.6 Reference Standards or Materials Q6A do
3.2.P.7 Container Closure System do
3.2.P.8 Stability
3.2.P.8.1 Stability Summary and Conclusion Q1A(R2),Q1B, Q1E do
3.2.P.8.2 Post-approval Stability Protocol & Stability
Commitment
Q1A(R2) do
3.2.P.8.3 Stability Data Q1A(R2),Q1B, Q1E do

23. GAP ANALYSIS:
Current Documents Required By DRAP
as per Form- 5F CTD:
Current Documents Providing Practice in
DRAP for dossier submission:
 DMF (on CTD format)  Product Formula
 Product Development documents (Undertaking)  Manufacturing Method
 BMR of trial batches  Finished Product Specification
 Control of Critical Steps in Mfg.  Finished Product Testing Methods
 Mfg. Process Validation (Under Taking)  API specification
 Excipient Control Documents  API testing methods
 API & Excipient Supplier & Company COA (all documents are not on control format)
 Analytical Validation of Finished Product
 Finished Product COA
 Stability Protocol, Summary, Conclusion, Post-
approval Stability Protocol, Stability Commitment
and 3 Batches stability data (on Long term 30/65
and Accelerated conditions 40/75)

24. GAP ANALYSIS:
Current Documents Required By DRAP as per
Form- 5F CTD:
Current Documents Providing Practice in
DRAP for dossier submission:
 API working Std Certificates
 Container closure system (Packaging
material specs., COA’s and analytical
procedures
 BA/BE Studies
 Comparative Study if bio waiver is applicable

25. Thanks