Common technical document (CTD – ICH)

Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 20071 |

Regulatory Requirement on Dossier of Medicinal Products

WHO Workshop, October 2007

Sultan Ghani, DirectorBureau of Pharmaceutical Sciences

Therapeutic Products Directorate, Health Canada


Outline

Common Technical Document (CTD – ICH)

Quality Overall Summary (QOS)


An Overview of the CTD

The CTD is not a “Global Dossier” !It is an agreed-upon common format for the “modular”

presentation of summaries, reports and dataIncorporates relevant ICH guidelinesIt is organized into five sections:

All “modules” harmonized except Module 1 – regional specific Raw data per regional requirements


Module 1

Regional Administrative

Information

NonclinicalOverviewQuality

OverallSummary Clinical

Summary

Module 3

Quality

Module 4

NonclinicalStudy Reports

Module 5

ClinicalStudy Reports

ClinicalOverview

NonclinicalSummaries

Not Part of CTD

CTD

Module 2NDS

Result was the CTD Triangle


CTD Structure

Full dossier contains 5 “Modules” - - - Only Modules 2-5 are “CTD”

Module 1 – region-specific but always included in complete CTD structure

Module 2- All summaries / overviews Module 3 – CMC (“Quality”) Module 4 – Preclinical Module 5 - Clinical


Module 2 - CTD Summaries

2.1 Overall CTD ToC2.2 CTD Introduction2.3 Quality Overall Summary2.4 Non-Clinical Overview2.5 Clinical Overview2.6 Non-Clinical Written and Tabulated Summaries2.7 Clinical Summary


2.2 CTD Introduction

General introduction to the pharmaceutical, including Pharmacologic class Mode of action Proposed clinical use

Typically 1 page


2.3 Quality Overall Summary - Content

A Summary that follows the scope and outline of the Body of Data in Module 3

Emphasize and discuss critical key parameters of the product

Discuss key issues to integrate information from Module 3 and other modules

Typically 40 pages, excluding tables, figures


2.3 Quality Overall Summary - Format

2.3 Introduction2.3.S Drug Substance2.3.P Drug Product2.3.A Appendices2.3.R Regional Information


2.4 Nonclinical Overview - Content

An integrated and critical assessment of the pharmacologic, pharmacokinetic, and toxicologic evaluation

Discuss relevant guidance; any deviations from guidance should be discussed and justified

Nonclinical testing strategy should be justified, including GLP status of submitted studies

Discuss associations with quality characteristics, clinical trial results, effects with related products

Typically 30 pages


2.4 Nonclinical Overview - Format

2.4.1 Overview of Nonclinical Testing Strategy2.4.2 Pharmacology2.4.3 Pharmacokinetics2.4.4 Toxicology2.4.5 Integrated Overview and Conclusions2.4.6 List of Literature Citations


2.5 Clinical Overview - Content

Highest level summary and analysis of clinical data and overall clinical development plan

Overview of the clinical part of the dossier with succinct discussion and interpretation

Critical analysis of clinical data for efficacy and safety, as well as other relevant information (e.g. pertinent animal data or quality issues)

Typically 30 pages


2.5 Clinical Overview - Format

2.5.1 Product development rationale2.5.2 Overview of Biopharmaceutics2.5.3 Overview of Clinical Pharmacology2.5.4 Overview of Efficacy2.5.5 Overview of Safety2.5.6 Benefits and Risks Conclusions2.5.7 References


2.6 Nonclinical Written and Tabulated Summaries - Content

Integrate information across studies and across speciesPrimarily text, with examples of tables and figuresExposure in test animals should be related to exposure

in humans given maximum intended dosesAge, gender, and metabolite-related effectsIn vitro studies first, then in vivoOrdered by species, route, durationTypically 100-150 pages


2.6 Nonclinical Written and Tabulated Summaries - Format

2.6.1 Introduction2.6.2 Written Summary of Pharmacology2.6.3 Tabulated Summary of Pharmacology2.6.4 Written Summary of Pharmacokinetics2.6.5 Tabulated Summary of Pharmacokinetics2.6.6 Written Summary of Toxicology2.6.7 Tabulated Summary of Toxicology


2.7 Clinical Summary - Content

Provides factual summary and support for conclusions and critical issues identified in the Clinical Overview

Comparison of results across studies with integration of clinical information

Analysis of all relevant information for dosing recommendations

Typically 50-400 pages (excluding tables)


2.7 Clinical Summary - Format

2.7.1 Summary of biopharmaceutic studies and associated analytical methods

2.7.2 Summary of clinical pharmacology (including clin micro characterization studies)

2.7.3 Summary of clinical efficacy2.7.4 Summary of clinical safety2.7.5 References2.7.6 Synopses of individual studies


Submission of CMC Information in CTD Format

3.2.S3.2.S.1

3.2.S.2

3.2.S.3

3.2.S.4

3.2.S.5

3.2.S.6

3.2.S.7

DRUG SUBSTANCEGeneral Information

Manufacture

Characterization

Control of Drug Substance

Reference Standards or Materials

Container Closure System

Stability


Submission of CMC Information in CTD Format (cont’d)

3.2.P3.2.P.1

3.2.P.2

3.2.P.3

3.2.P.4

3.2.P.5

3.2.P.6

3.2.P.7

3.2.P.8

DRUG PRODUCTDescription and Composition of the Drug Product

Pharmaceutical Development

Manufacture

Control of Excipients

Control of Drug Product

Reference Standards or Materials

Container Closure System

Stability


Submission of CMC Information in CTD Format (cont’d)

3.2.A3.2.A.1

3.2.A.2

3.2.A.3

3.2.R

APPENDICESFacilities and Equipment

Adventitious Agents Safety Evaluation

Excipients

REGIONAL INFORMATION


Submission of CMC Information in CTD Format

The CTD Quality Module is unique in that it is a combination of historical development and future commitments that apply to the commercial, post-approval production period.


Impact of the CTD

The ICH CTD represents one of the most ambitious and successful international harmonization activities undertaken

It will significantly reduce time and resources needed by industry to compile applications for global registration


Benefits of the CTD

More “reviewable” applicationsComplete, well-organized submissionsMore predictable formatMore consistent reviewsEasier analysis across applicationsEasier exchange of informationFacilitates electronic submissions



U.S. information source not used for decisionModule M3 reviewed serves as a basis for decision and

action

EUSame as aboveCan be used for reviews



Japan Primary review document

CanadaBasis for review template



The Quality Overall Summary (QOS):Is part of a drug submission organized according to ICH’s

Common Technical Document (CTD) Guideline (i.e., Module 2.3)

ICH’s CTD-Q structure (including the QOS) has been formally adopted by Canada for various drug submission types, e.g.: Clinical Trial Applications (CTAs)

• Phase I, Phase II/III, BA Studies



The Quality Overall Summary (QOS) (cont’d):New Drug Submissions (NDSs)Abbreviated New Drug Submissions (ANDSs)Drug Master Files (DMFs)

Provided the ‘Open’/‘Closed’ portions are submitted in separately bound dossiers


Quality Overall Summary – Chemical Entities (QOS-CE) Template

Health Canada’s (QOS-CE) Template:Was developed to manage the submission workload and to

assist sponsors in the preparation of the Quality SummaryPromotes efficiencies in submission preparation and in the

review processAvailable for various submissions types (CTAs x3, NDSs

and ANDSs, etc.)Entirely compatible with ICH’s QOS (e.g., can be

considered an acceptable replacement for the QOS as defined by the CTD-Q)


Thank you

Common technical document (CTD – ICH)

Health & Medicine

Transcript of Common technical document (CTD – ICH)