common technical dossier

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Overview of Dossier Requirements and Guidelines for Generic Product

Muhammad Ali email: [email protected]

CTD

Common Technical Document

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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

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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/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/ucm120979.pdf

• http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/ucm120977.pdf

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http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/ucm120979.pdf








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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common technical dossier

Health & Medicine