dossier structure en
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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
Regulatory Requirement on Dossier of Medicinal Products
WHO Workshop, October 2007
Sultan Ghani, DirectorBureau of Pharmaceutical Sciences
Therapeutic Products Directorate, Health Canada
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 20072 |
OutlineOutline
Common Technical Document (CTD – ICH)
Quality Overall Summary (QOS)
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 20073 |
An Overview of the CTDAn 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 data
Incorporates relevant ICH guidelines
It is organized into five sections: All “modules” harmonized except Module 1 – regional specific
Raw data per regional requirements
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 20074 |
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
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 20075 |
CTD StructureCTD 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
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 20076 |
Module 2 - CTD SummariesModule 2 - CTD Summaries
2.1 Overall CTD ToC
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
2.7 Clinical Summary
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 20077 |
2.2 CTD Introduction2.2 CTD Introduction
General introduction to the pharmaceutical, including Pharmacologic class
Mode of action
Proposed clinical use
Typically 1 page
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 20078 |
2.3 Quality Overall Summary - Content2.3 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
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 20079 |
2.3 Quality Overall Summary - Format2.3 Quality Overall Summary - Format
2.3 Introduction
2.3.S Drug Substance
2.3.P Drug Product
2.3.A Appendices
2.3.R Regional Information
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200710 |
2.4 Nonclinical Overview - Content2.4 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
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200711 |
2.4 Nonclinical Overview - Format2.4 Nonclinical Overview - Format
2.4.1 Overview of 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
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200712 |
2.5 Clinical Overview - Content2.5 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
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200713 |
2.5 Clinical Overview - Format2.5 Clinical Overview - Format
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
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2.6 Nonclinical Written and Tabulated Summaries - Content
2.6 Nonclinical Written and Tabulated Summaries - Content
Integrate information across studies and across species
Primarily text, with examples of tables and figures
Exposure in test animals should be related to exposure in humans given maximum intended doses
Age, gender, and metabolite-related effects
In vitro studies first, then in vivo
Ordered by species, route, duration
Typically 100-150 pages
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200715 |
2.6 Nonclinical Written and Tabulated Summaries - Format
2.6 Nonclinical Written and Tabulated Summaries - Format
2.6.1 Introduction
2.6.2 Written Summary of Pharmacology
2.6.3 Tabulated Summary of Pharmacology
2.6.4 Written Summary of Pharmacokinetics
2.6.5 Tabulated Summary of Pharmacokinetics
2.6.6 Written Summary of Toxicology
2.6.7 Tabulated Summary of Toxicology
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2.7 Clinical Summary - Content2.7 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)
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200717 |
2.7 Clinical Summary - Format2.7 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 efficacy
2.7.4 Summary of clinical safety
2.7.5 References
2.7.6 Synopses of individual studies
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Submission of CMC Information in CTD Format
Submission of CMC Information in CTD Format
3.2.S
3.2.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 SUBSTANCE
General Information
Manufacture
Characterization
Control of Drug Substance
Reference Standards or Materials
Container Closure System
Stability
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200719 |
Submission of CMC Information in CTD Format (cont’d)
Submission of CMC Information in CTD Format (cont’d)
3.2.P
3.2.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 PRODUCT
Description and Composition of the Drug Product
Pharmaceutical Development
Manufacture
Control of Excipients
Control of Drug Product
Reference Standards or Materials
Container Closure System
Stability
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200720 |
Submission of CMC Information in CTD Format (cont’d)
Submission of CMC Information in CTD Format (cont’d)
3.2.A
3.2.A.1
3.2.A.2
3.2.A.3
3.2.R
APPENDICES
Facilities and Equipment
Adventitious Agents Safety Evaluation
Excipients
REGIONAL INFORMATION
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200721 |
Submission of CMC Information in CTD Format
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.
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Impact of the CTDImpact 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
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200723 |
Benefits of the CTDBenefits of the CTD
More “reviewable” applications
Complete, well-organized submissions
More predictable format
More consistent reviews
Easier analysis across applications
Easier exchange of information
Facilitates electronic submissions
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200724 |
Quality Overall Summary (QOS)Quality Overall Summary (QOS)
U.S.
information source not used for decision
Module M3 reviewed serves as a basis for decision and action
EU
Same as above
Can be used for reviews
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200725 |
Quality Overall Summary (QOS)Quality Overall Summary (QOS)
Japan
Primary review document
Canada
Basis for review template
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200726 |
Quality Overall Summary (QOS)Quality Overall Summary (QOS)
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
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200727 |
Quality Overall Summary (QOS)Quality Overall Summary (QOS)
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
Training Workshop on Pharmaceutical Development with a Focus on Paediatric Medicines / 15-19 October 200728 |
Quality Overall Summary – Chemical Entities (QOS-CE) Template
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 Summary
Promotes efficiencies in submission preparation and in the review process
Available 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)
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Thank youThank you