ACTD DOSSIERS

1. AUDITABLE DATA AND DOSSIERS
REGULATORY AFFAIRS
Presented By: Dr. Jibran Khan

2. AGENDA
Standard criteria for International Dossier preparation.
Departmental requirements and conditions to prepare
Auditable Dossiers.
Auditable Dossiers (ACTD / CTD/All Dossiers)

3. CTD DOSSIER
The CTD is organized into five modules:
Module 1 is region specific.
Modules 2, 3, 4, and 5 are intended to be common
for all regions.
Module 1. Administrative Information and
Prescribing Information
Should contain documents specific to each region;
e.g. application forms or the proposed label for
use in the region. The content and format of this
module can be specified by the relevant
regulatory authorities.
Module 1: Administrative Information and
Prescribing Information
1.1 Table of Contents of the Submission Including
Module 1
1.2 Documents Specific to Each Region (for example,
application forms, prescribing information)

4. CTD DOSSIER
Module 2. Common Technical Document Summaries
2.1 Common Technical Document Table of
Contents (Modules 2-5)
2.2 CTD Introduction
2.3 Quality Overall Summary
2.4 Non-clinical Overview
2.5 Clinical Overview
2.6 Non-clinical Written and Tabulated
Summaries
Pharmacology
Pharmacokinetics
Toxicology
2.7 Clinical Summary
Biopharmaceutical Studies and Associated
Analytical Methods
Clinical Pharmacology Studies
Clinical Efficacy
Clinical Safety
Literature References
Synopses of Individual Studies

5. CTD DOSSIER
Module 3. Quality
Information on Quality should be presented in
the structured format described in Guideline
M4Q.
Module 3: Quality
3.1 Table of Contents of Module 3
3.2 Body of Data
3.3 Literature References

6. CTD DOSSIER
Module 4. Non-clinical Study Reports
The non-clinical study reports should be
presented in the order described in Guideline
M4S.
Module 4: Non-clinical Study Reports
4.1 Table of Contents of Module 4
4.2 Study Reports
4.3 Literature References

7. CTD DOSSIER
Module 5. Clinical Study Reports
The human study reports and related
information should be presented in the order
described in Guideline M4E.
Module 5: Clinical Study Reports
5.1 Table of Contents of Module 5
5.2 Tabular Listing of All Clinical Studies
5.3 Clinical Study Reports
5.4 Literature References

8. ACTD DOSSIER

9. P- PART (ACTD GUIDELINE)
Drug Product :
P1 Description and Composition
P 1.1 Components of the Drug Product
Description, Dosage form, Diluents (If any),
Type of container closure.
P 1.1.1 Active Ingredient
Name, Quantity, Function, Reference Specs.
P 1.1.2 Excipients
Name, Quantity, Function, Reference Specs.

10. P- PART (ACTD GUIDELINE)
Drug Product :
P2 : Pharmaceutical Development
P2.1 Information on Development Studies.
Innovator specs with Invoice.
Innovator Bench mark Sample.
Data on development. General Protocol along with
Product development Protocol.

11. P- PART (ACTD GUIDELINE)
Drug Product :
P2 : Pharmaceutical Development
P2.1 Information on Development Studies.
Trial management
(success full Batches Analytical Reports along with complete
data).
Trial management
(Failed Batches Analytical Reports along with complete data).
Dose Proportionality in Batches .
Calibration of Equipment's/ Instruments.
Qualification/ Requalification of Equipment's / Instruments.

12. P- PART (ACTD GUIDELINE)
Drug Product :
P2 : Pharmaceutical Development
P2.1 Information on Development Studies.
Reproducible batches management
( Analytical Reports along with complete data).
Microbiological Testing of Reproducible Batches
( Analytical Reports along with complete data).
Reproducible Batches Stability.
( Analytical Reports along with complete data)

13. P- PART (ACTD GUIDELINE)
Drug Product :
P2 : Pharmaceutical Development
P2.1 Information on Development Studies.
Pilot batch (1 Lac tabs or 10% of Commercial
Batch)
Analytical Testing reports of Pilot Batch
Pilot Batches Stability.
( Analytical Reports along with complete data)
Dosage Form, Formulation, manufacturing process,
Container closure system.
Microbiological attributes

14. P- PART (ACTD GUIDELINE)
Drug Product :
P2 : Pharmaceutical Development
P2.2 Components of the Drug Product.
P2.2.1 Active Ingredients
Approved Source of API
DMF from approved sources and according to Ref Specs.
GMP Certificate of Manufacturer .
MSDS with invoices.
Justification of Compatibility with Excipients and with
Diluents

15. P- PART (ACTD GUIDELINE)
P2 : Pharmaceutical Development
P2.2 Components of the Drug Product.
P2.2.2 Excipients
Justification of the choice of excipients
Details of excipients Manufacturer
P2.3 Finished Product
P2.3.1 Formulation Development
P2.3.2 Overages.
P2.3.3 Physiochemical and Biological Properties.
P2.4 Manufacturing Process development

16. P- PART (ACTD GUIDELINE)
Drug Product :
P2 : Pharmaceutical Development
P2.5 Container Closure System.
P2.6 Microbial Attributes
P2.7 Compatibility
Compatibility of the finished Product with
reconstitution diluents.

17. P- PART (ACTD GUIDELINE)
Drug Product :
P2 : Pharmaceutical Development
Mandatory Requirements:
1- Head Count.
2- Qualification / Requalification of Equipment's /
Instruments from Engineering.
3- Sufficient quantity of API is required to manufacture
Trial/ Reproducible/Pilot batches as per guideline.
4- Requisition from marketing.
5- Approved source of API along with reference standard
testing method / Excipients. (DMF and COAs of raw
material (Current Pharmacopeia, GMP Certificate of
Manufacturer, MSDS with invoices).
6- Innovator specs with invoice.

18. P- PART (ACTD GUIDELINE)
Drug Product :
P2 : Pharmaceutical Development
Mandatory Requirements:
7- Innovator bench mark samples.
8- Proper trial management record with successful and
failed trails along with analytical testing reports and data
(Record, hardcopy and soft copy both).
9- Proper record management of 3 reproducible batches,
along with complete analytical testing record including
stability reports and data.
10- Proper record management of Pilot batch, batch size
should be of 100000 tablets or 10% of Batch size (If batch
size is greater than 1Lac) along with complete analytical
testing record including stability reports and data.

19. P- PART (ACTD GUIDELINE)
Drug Product :
P2 : Pharmaceutical Development
Mandatory Requirements:
11- Complete testing record of reproducible batches
along with microbiological testing data from QC.
12- For commercial scale manufacturing, development of
proper updated BMR required.
13- FPS and Stability specs would be produced on the
basis of Trial #03 and Reproducible 01, 02, 03 applicable
on complete dossier.
14- Container closure system and Compatibility will be
finalized on the basis of stability testing and chemical
testing of Reproducible 01, 02, and 03. Required complete
testing data, reports with graphs.

20. P- PART (ACTD GUIDELINE)
Drug Product :
P2 : Pharmaceutical Development
Mandatory Requirements:
15- In case of source change of Active material and
packaging ; above mentioned procedure will be re
applicable .
16- Back Up data collection is mandatory for complete
procedure; all documents should be available in hard
and soft copy with accessible traceability.

21. P- PART (ACTD GUIDELINE)
Drug Product :
P3 : Manufacture
P3.1 Batch Formula
(Batch size is not standard)
P3.2 Manufacturing Process and Process Control
P3.3 Control of Critical Steps
P3.4 Process Validation and Evaluation
Documentation (Protocol and Report)
Results of Validation(Complete data, Evaluation Studies)
Critical Steps and Assays used in Manufacturing

22. P- PART (ACTD GUIDELINE)
P4 : Control of Excipients
P4.1 Specs of Excipients with Compendial
requirements
Manufacturer COAs with details P4.2
Analytical Procedures
P4.3 Excipients of Animal and Human Origin
Information regarding source and adventurous
material Compendial requirements and Information

23. P- PART (ACTD GUIDELINE)
P4 : Control of Excipients
P4.4 Novel Excipients
Full details of manufacturer
Characterization and Control
Supporting Safety Data

24. P- PART (ACTD GUIDELINE)
P5 Control of finished Product
P 5.1 Specifications
Specifications
P 5.2 Analytical Procedure

25. P- PART (ACTD GUIDELINE)
Drug Product :
P5 Control of Finished Product
P 5.3 Validation of Analytical Procedures
Complete information regarding data including
experimental data.
Verification of Method.
Calibration and qualifications of equipment's
P5.3.1 Assay method validation
P5.3.2 Dissolution method validation
P5.3.3 Related Substance method validation

26. P- PART (ACTD GUIDELINE)
Drug Product :
P5 Control of Finished Product
P 5.4 Batch Analysis
COA
Testing data and report.
P5.5 Characterization of Impurities
Information on Characterization of Impurity

27. P- PART (ACTD GUIDELINE)
Drug Product :
P5 Control of Finished Product
P 5.6 Justification of Specifications
Justification of purposed Specifications
Complete Compendial Requirements
Information from manufacturer
P6 Reference Standard or material
Complete information
Compendial requirements along with primary
standard.

28. P- PART (ACTD GUIDELINE)
Drug Product :
P7 Container Closure System
Specifications
Approved Art work
Control of Primary and secondary Packaging
Type of Packaging along with Packaging material
Packaging Size and details of Packaging inclusion
(e.g. Desiccant) Testing reports of Packaging material

29. P- PART (ACTD GUIDELINE)
Drug Product :
P8 Stability
Specifications
Stability protocol as per marketing requirement
Stability Raw Data Testing Report along with Graphs
(Un auditable) Commitment on Post approval stability
P9 Product interchangeability Equivalence evidence
In vitro Comparative dissolution study (as required
In Vivo Bioequivalence (study as required)