The dossier is a collection of documents that contain all the technical data of pharmaceutical products to be approved\ registered\ marketed in a country.

1. ROLE OF REGULATORY AFFAIRS DEPARTMENT
IN
PHARMACEUTICAL INDUSTRY
1
Induction Seminar
by
Tarun Kumar

2. Significance of the Regulatory affairs department
Regulatory affairs provides insight into the development by providing guidance,
previous experience, market precedence of a particular substance and hence helps
to reduce the number of development failures.
They are responsible for the presentation of registration documents to regulatory
agencies and carry out the negotiations necessary to obtain and maintain
marketing authorization for the products.
Functions of Regulatory Affairs
❏ To keep a track on the guidelines given by the legislation.
❏ Registration of dossiers to regulatory agencies.
❏ To give strategic and technical advice to R&D, Production, Quality Control
and the other various departments.
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3. What is dossier
Dossier is a collection of documents that contain all the technical data of
pharmaceutical product to be approved registered marketed in a country.
Difference between the ACTD, CTD and e-CTD*
This ASEAN Common Technical Document (ACTD) is a guideline of the agreed
upon common format for the preparation of a well-structured Common
Technical Document applications that will be submitted to ASEAN regulatory
authorities for the registration of pharmaceuticals for human use.
Common Technical Document (CTD) is a format set by Regulatory Agencies of U.S,
Europe and Japan.
Electronic Common Technical Document (eCTD), it is a digital version of CTD.
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*Not included in this presentation.

4. • Objective of the presentation:
– To give an overview of the dossier requirements and
Guidelines used or referenced during the evaluation of
dossiers.
– To demonstrate how the requirements and guidelines
can be applied or used as reference during dossier
evaluation
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5. ❑ What is the product?
❑ Is the quality presented acceptable on grounds of safety
and efficacy?
❑ Is the quality presented reproducible?
❑ How long can the quality be maintained?
❖ Quality must ensure consistency of safety and efficacy
during the shelf life of all batches produced.
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Main purpose of documentation (Dossier)

6. PART I
Administrative
Data
Nonclinical
Study Reports
Clinical
Study Reports
PART II
Quality
PART III PART IV
THE ASEAN COMMON
TECHNICAL DOSSIER (ACTD)

7. Part I: Table of Content Administrative Information and Prescribing Information
Section A: Introduction
Section B: Overall ASEAN Common Technical Dossier Table of
Contents
Section C: Documents required for registration (for example,
application forms,
labelling, Product Data Sheet, prescribing information)
Part II: Quality Document
Section A: Table of Contents
Section B: Quality Overall Summary
Section C: Body of Data
Part III: Nonclinical Document
Section A: Table of Contents
Section B: Nonclinical Overview
Section C: Nonclinical Written and Tabulated Summaries
1. Table of Contents
2. Pharmacology
3. Pharmacokinetics
4. Toxicology
Section D: Nonclinical Study Reports
1. Table of Contents
2. Pharmacology
3. Pharmacokinetics
4. Toxicology
Part IV: Clinical Document
Section A: Table of Contents
Section B: Clinical Overview
Section C: Clinical Summary
1. Summary of Biopharmaceutics and
Associated Analytical Methods
2. Summary of Clinical Pharmacology
Studies
3. Summary of Clinical Efficacy
4. Summary of Clinical Safety
5. Synopses of Individual Studies
Section D: Tabular Listing of All Clinical Studies
Section E: Clinical Study Reports
Section F: List of Key Literature References
ACTD Format
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8. Common Technical Document
(CTD)
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9. Quick points on CTD format
• A common format for the technical documentation:
– significantly reduces the time and resources needed to compile
applications for registration of human pharmaceuticals
– Eases the preparation of electronic submissions
– Facilitates regulatory reviews and communication with the
applicant by a standard document of common elements
– Simplifies exchange of regulatory information between
Regulatory Authorities
• This guideline is not intended to indicate what studies are required. It
merely indicates an appropriate format for the data that have been
acquired.
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10. • GENERAL PRINCIPLES
– Text and tables should be prepared using margins that allow the
document to be printed on A4 paper.
– The left-hand margin should be sufficiently large that information is
not obscured by the method of binding.
– Font sizes for text and tables should be easily legible, even after
photocopying. Times New Roman, 12-point font, is recommended
for narrative text.
– Every page should be numbered.
– Acronyms and abbreviations should be defined the first time they
are used in each module.
– References should be cited in accordance with the current edition of
the Uniform Requirements for Manuscripts Submitted to Biomedical
Journals, International Committee of Medical Journal Editors
(ICMJE)1.
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11. • 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)
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12. • Module 2 :- Common Technical Document Summaries
– Should begin with a general introduction to the pharmaceutical, including its pharmacological class,
mode of action, and proposed clinical use. In general, the Introduction should not exceed one
page.
– Should contain 7 sections in the following order :
• 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
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13. Module 3 :- Quality
– Information on Quality should be presented in the structured format
described in Guideline M4Q.
• Main sections
– 3.1 Table of Contents of Module 3
– 3.2 Body of Data
– 3.3 Literature References
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Module 4 :- Non-clinical Study Reports
– The non-clinical study reports should be presented in the order
described in Guideline M4S.
• Main sections
– 4.1 Table of Contents of Module 4
– 4.2 Study Reports
– 4.3 Literature References

15. Module 5 :- Clinical Study Reports
– The human study reports and related information should be presented in
the order described in Guideline M4E.
• Main sections
– 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
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16. Overall Table of Contents (ToC)
1.1
ToC of Module 1
or overall ToC,
including Module 1
2.1
ToC of the
CTD
(Mod 2,3,4,5)
Module 1
Module 3 Module 4 Module 5
2.1
2.2
2.3
2.4 2.5
2.6 2.7
Module 2
3.1
ToC for Module
3
4.1
ToC for Module
4
5.1
ToC for Module
5 16

17. CTD format: Numbering System
1.0 Regional Administrative Information
1.1 ToC of Module 1 or overall ToC, including Module 1
2.1 ToC of the CTD (Mod 2,3,4,5)
2.2 Introduction
2.3 Quality Overall Summary
2.4 Non-clinical Overview
2.5 Clinical Overview
2.7 Clinical Summary
2.6 Non-clinical Written and
Tabulated Summaries
Module 1
Module 3 Module 4 Module 5
2.1
2.2
2.3
2.4 2.5
2.6 2.7
1.0
Quality
Nonclinical
Study Reports
Clinical
Study Reports
Module 2
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18. Brief outlook of Documents required
in each
Section/Module
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19. Administrative Documents (Module 1)
- Covering letter
- Certificate of Pharmaceutical Products
- Free Sale Certificate
- Letter of Authorization
- Registration certificate
- G.M.P certificate
- Product licensing certificate
- Manufacturing licensing certificate
- Company registration certificate
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20. • A valid Certificate of Suitability (CoS) or CEP, latest version, with all its
annexes issued by EDQM
• An APIMF (Active Pharmaceutical Ingredient Master File) submitted by
the API manufacturer, containing the whole information requested in
section 2
• Complete submission of data requested in Section 2
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Information on the Active Pharmaceutical
Ingredient (API)
(QOS)

21. Active Pharmaceutical Ingredients (QOS)
2.1. Nomenclature (INN, chemical name, CAS No.)
2.2. Properties of the API**
2.3. Site(s) of manufacture
2.4. Route(s) of synthesis**
2.5. Specifications**
2.6. Container- closure system
2.7. Stability testing
** The requirements may differ depending on if the API is pharmacopoeial or non-
pharmacopoeial
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22. 1.1. Details of the Product
- Name, dosage form and strength of the product
- Approved generic name (INN)
- Visual description of the FPP
- Visual description of the packaging
1.2. Samples (visual examination and comparison with the SPC and PIL
1.3. Regulatory situation in Member States / list countries
- Countries where a MA has been issued
- Countries where a MA has been withdrawn
- Countries where a Marketing Application has been rejected, deferred
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Information on the Finished Pharmaceutical
Product (FPP)
(QOS)

23. Bioequivalence (BE)
requirements
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24. Module 5 Clinical Studies
5.1 Bioequivalence study
5.2 Summary of pharmacology, toxicology* and
efficacy of the product (expert reports)
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In accordance with the guidelines on clinical trials :
• Good Clinical Practice
• Good Manufacturing Practice
• Good Laboratory Practice

25. BE Dossier requirements (contd.,)
Additional guidance
• WHO TRS No. 937, 2006, Annex 9
Guidelines for organizations performing in vivo
bioequivalence studies. In: WHO Expert
Committee on Specifications for
Pharmaceutical Preparations. Fortieth report.
Geneva, World Health Organization
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26. BE Dossier requirements (contd.,)
The Bioequivalence study report should
include information on:
• Ethics, Investigators and administrative
structure
• Clinical phase of a study
• Bioanalytical method of study
• Pharmacokinetic and statistical analysis
• Study protocol
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27. BE Dossier requirements (contd.,)
Complete structure is presented:
• Table of Contents
• Bioequivalence Trial Information Form (BTIF)
• Summary of Product Characteristics (SPC)
• Patient Information Leaflet (PIL)
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28. Closing remarks
❏ The dossier submitted must conform to the
requirements set out in the current guidelines, as
posted on official site.
❏ The assessment of quality and safety/efficacy
data presented is based on the current guidelines.
❏ The quality assessment includes variations or
changes to already prequalified products
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29. Post Approval Life Cycle Management (LCM)
Pharmacovigilance
Licensing
GMP
GLP
GCP
PATENT
COPYRIGHT
TRADEMARK
Registration
Development
Manufacturing
Quality guidance
Pricing
Marketing
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