CTD Guidelines Overview

Phr_ali91@hotmail.com
Overview of Dossier Requirements and
Guidelines for Generic Product
Muhammad Ali
email: phr_ali91@hotmail.com
CTD
Common Technical Document

Phr_ali91@hotmail.comPhr_ali91@hotmail.com
COMMON TECHNICAL DOSSIER
CTD is an internationally agreed “well structured common format” for
the organization of the technical requirements that is to be submitted
to the regulatory authority as an application for the registration of
pharmaceuticals for human use.
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CTD Table of Content
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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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CTD format: Overall Table of Contents

Module 2
2.1 OVERALL CTD TABLE OF CONTENTS OF MODULES 2, 3, 4, AND 5
2.2 INTRODUCTION
2.3 QUALITY OVERALL SUMMARY
2.3.S DRUG SUBSTANCE
2.3.S.1 General Information
2.3.S.2 Manufacture
2.3.S.3 Characterization
2.3.S.4 Control of Drug Substance
2.3.S.5 Reference Standards or Materials
2.3.S.6 Container Closure System
2.3.S.7 Stability
2.3.P DRUG PRODUCT
2.3.P.1 Description and Composition of the Drug Product
2.3.P.2 Pharmaceutical Development
2.3.P.3 Manufacture
2.3.P.4 Control of Excipients
2.3.P.5 Control of Drug Product
2.3.P.6 Reference Standards or Materials
2.3.P.7 Container Closure System
2.3.P.8 Stability
Module 2
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Module 2 (Cont.)
2.3.A APPENDICES
2.3.A.1 Facilities and Equipment
2.3.A.2 Adventitious Agents Safety Evaluation
2.3.A.3 Novel Excipients
2.3.R REGIONAL INFORMATION
2.4 NONCLINICAL OVERVIEW
2.4.1 Overview of the Nonclinical Testing Strategy
2.4.2 Pharmacology
2.4.3 Pharmacokinetics
2.4.4 Toxicology
2.4.5 Integrated Overview and Conclusions
2.4.6 List of Literature Citations
2.5 CLINICAL OVERVIEW
2.5.1 Product Development Rationale
2.5.2 Overview of Biopharmaceutics
2.5.3 Overview of Clinical Pharmacology
2.5.4 Overview of Efficacy
2.5.5 Overview of Safety
2.5.6 Benefits and Risks Conclusions
2.5.7 References
Module 2 (Cont.)
2.6 CONTENT OF NONCLINICAL WRITTEN
AND TABULATED SUMMARIES
2.6.1 Introduction
2.6.2 Pharmacology Written Summary
2.6.3 Pharmacology Tabulated Summary
(Appendix B)
2.6.4 Pharmacokinetics Written Summary
2.6.5 Pharmacokinetics Tabulated Summary
(Appendix B)
2.6.6 Toxicology Written Summary
2.6.7 Toxicology Tabulated Summary (Appendix
B)
2.7 CLINICAL SUMMARY
2.7.1 Summary of Biopharmaceutics and
Associated Analytical Methods
2.7.2 Summary of Clinical Pharmacology Studies
2.7.3 Summary of Clinical Efficacy
2.7.4 Summary of Clinical Safety
2.7.5 References
2.7.6 Synopses of Individual Studies
Module 2
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Module 3
3.1 MODULE 3 TABLE OF CONTENTS
3.2 BODY OF DATA
3.2.S DRUG SUBSTANCE
3.2.S.1 General Information
3.2.S.2 Manufacture
3.2.S.3 Characterisation
3.2.S.4 Control of Drug Substance
3.2.S.5 Reference Standards or Materials
3.2.S.6 Container Closure System
3.2.S.7 Stability
3.2.P DRUG PRODUCT
3.2.P.1 Description and Composition of the Drug
Product
3.2.P.2 Pharmaceutical Development
3.2.P.3 Manufacture
3.2.P.4 Control of Excipients
3.2.P.5 Control of Drug Product
3.2.P.6 Reference Standards or Materials
3.2.P.7 Container Closure System
3.2.P.8 Stability
Module 3 (Cont.)
3.2.A APPENDICES
3.2.A.1 Facilities and Equipment
3.2.A.2 Adventitious Agents Safety Evaluation
3.2.A.3 Novel Excipients
3.2.R REGIONAL INFORMATION
3.3 LITERATURE REFERENCES
Module 3
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Module 4
4.2 STUDY REPORTS
4.2.1 Pharmacology
4.2.2 Pharmacokinetics
4.2.3 Toxicology
Module 4
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Module 5
5.2 TABULAR LISTINGS OF ALL CLINICAL STUDIES
5.3 CLINICAL STUDY REPORTS
5.3.1 Reports of Biopharmaceutic Studies
5.3.2 Reports of Studies Pertinent to Pharmacokinetics
using Human Biomaterials
5.3.3 Reports of Human Pharmacokinetic (PK) Studies
5.3.4 Reports of Human Pharmacodynamic (PD) Studies
5.3.5 Reports of Efficacy and Safety Studies
5.3.6 Reports of Post-Marketing Experience
5.3.7 Case Report Forms and Individual Patient Listings
Module 5
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Overview of Dossier Requirements and Guidelines
Generic Products
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Generic Guide: Definitions
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Active Pharmaceutical Ingredient (API)
A substance or compound that is intended to be used in the manufacture of a
pharmaceutical product as a therapeutically active compound (ingredient)
Pharmaceutical Product
Any preparation for human or veterinary use that is intended to modify or explore
physiological systems or pathological states for the benefit of the recipient.
Finished Pharmaceutical Product (FPP)
A product that has undergone all stages of production, including packaging in its final
container and labelling.

Multisource (Generic) product
Multisources are Pharmaceutically equivalent (WHO definition)
• same amount of the same API
• same dosage form
• meet the same or comparable standards
• intended to be administered by the same route
Multisources which are therapeutically equivalent are interchangeable
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Quality of a Generic product
Multisource products must be of good quality and at least as safe and efficacious as
existing products (WHO Manual, Blue Book, P. 29, chapter H., Interchangeability)
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Demonstration of pharmaceutical equivalence of the FPP including that of the API
Same Safety –
Same efficacy
Equal quality with the
comparator or a quality shown and
assessed to be as acceptable

PREPARING & ORGANIZATION OF CTD
It is organized into:-
• Module 1: General Information
• Module 2: Summary (Quality, Non clinical , Clinical)
• Module 3: Quality
• Module 4: Nonclinical study reports (Not Applicable for Generic product)
• Module 5: Clinical study reports (Not Applicable for Generic product some
exception may allow)
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MODULE 1
Administrative information and prescribing information.
• Covering letter
• Company Intro / Company Profile
• Application Form
• Agency Agreement
• GMP
• COPP
• Product info
• SPC
• Labeling (immediate and outer label)
• PIL
• Evidence for an application fee
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MODULE 2
Dossier Overall Summary (DOS)
• Outline of body of data of module 3 ,4 and 5
• Module 3 Quality Overall Summary(Applicable)
• Module 4 (Not applicable for generic product)
• Module 5 Summary (Not Applicable for Generic product some exception may
allow)
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Module 2 ……Cont’
Quality Overall Summary templates
• apps.who.int/prequal/info_general/documents/generic_guide/QOS-PD.doc
• http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsa
reDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplication
ANDAGenerics/ucm120979.pdf
• http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsa
reDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplication
ANDAGenerics/ucm120977.pdf
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Module 3
Two parts i.e.
• “S” portion related to DMF of API (Active Pharmaceutical Ingredient)
• “P” portion related to FPP(Finished Pharmaceutical Product)
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Module 3….. Cont’
Documents required
1. Manufacturing flow chart
2. Manufacturing formula, unit formula and detailed mfg procedure
3. Analytical Method Validation (AMV) report and protocol
4. Process validation protocol and report (PVR)
5. Stability studies of Finish Product 3 batches, accelerated and real time, ongoing
stability if any
6. Working standard/Reference standard COA
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7. Raw material specifications and test procedures
8. Finish product specifications and test procedures
9. Finish product COA (of three batches of each product)
10. Packing materials Specification
11. Artworks of printed packing material (primary, secondary)
12. API DMF
13. Bioavailability/ Bioequivalence report if available
14. Preclinical/Clinical studies if available
12. Official documents as per country requirement
(Manufacturing license, COPP, Free Sale certificate, plant approvals if any)
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MODULE 5
The majority of PDs for multisource products are supported by one or more pivotal
comparative bioavailability studies. When filing a PD in the CTD format, it is
anticipated that only the following relevant sections of Module 5 will normally be
required.
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MODULE 5… Cont’
Module 5: Clinical study reports
• 5.1 Table of contents for Module 5
• 5.2 Tabular listing of all clinical studies
• 5.3 Clinical study reports
• 5.3.1 Reports of biopharmaceutic studies
5.3.1.2 Comparative bioavailability and bioequivalence study reports
5.3.1.3 In vitro-in vivo correlation study reports if available
*5.3.1.4 Reports of bioanalytical and analytical method for human studies
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MODULE 5… Cont’
• 5.3.7 Case report forms and individual patient listings: Only CRFs for subjects that
experienced serious adverse events should be included. All CRFs should be
available upon request.
• 5.4 Literature references
* Bioanalytical or analytical methods for BA/BE or in vitro dissolution studies should
ordinarily be provided in the individual clinical study reports. However, where a method is used in
multiple studies, the method and its validation should only be included once in section 5.3.1.4 and
referenced in the appropriate individual clinical study reports.
For guidance regarding biowaivers, refer to the biowaiver implementation documents
available on the Prequalification website. For guidance regarding comparator
products, refer to the information available under
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Thank you
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CTD Guidelines Overview

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