Administrative Requirement on Dossier of Medicinal Products WHO Workshop, October 2007

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Administrative Requirement on Dossier of Medicinal Products WHO Workshop, October 2007 Sultan Ghani, Director Bureau 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 "Worldwide Dossier" ! It is a settled upon regular configuration for the "particular" introduction of synopses, reports and information Incorporates important ICH rules It is sorted out into five areas: All "modules" blended aside from Module 1 – territorial particular Raw information per provincial necessities

Module 1 Regional Administrative Information Not Part of CTD Nonclinical Overview Clinical Overview Quality Overall Summary Nonclinical Summaries Clinical Summary CTD Module 3 Quality Module 4 Nonclinical Study Reports Module 5 Clinical Study Reports Result was the CTD Triangle NDS Module 2

CTD Structure Full dossier contains 5 "Modules" - -Only Modules 2-5 are "CTD" Module 1 – district particular however constantly incorporated into finish CTD structure Module 2-All rundowns/reviews Module 3 – CMC ("Quality") Module 4 – Preclinical Module 5 - Clinical

Module 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

2.2 CTD Introduction General prologue to the pharmaceutical, including Pharmacologic class Mode of activity Proposed clinical utilize Typically 1 page

2.3 Quality Overall Summary - Content A Summary that takes after the degree and blueprint of the Body of Data in Module 3 Emphasize and talk about basic key parameters of the item Discuss key issues to coordinate data from Module 3 and different modules Typically 40 pages, barring tables, figures

2.3 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

2.4 Nonclinical Overview - Content A coordinated and basic appraisal of the pharmacologic, pharmacokinetic, and toxicologic assessment Discuss pertinent direction; any deviations from direction ought to be examined and legitimized Nonclinical testing methodology ought to be supported, including GLP status of submitted studies Discuss relationship with quality attributes, clinical trial comes about, impacts with related items Typically 30 pages

2.4 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

2.5 Clinical Overview - Content Highest level outline and investigation of clinical information and general clinical improvement arrange Overview of the clinical piece of the dossier with brief exchange and translation Critical examination of clinical information for viability and security, and in addition other applicable data (e.g. apropos creature information or quality issues) Typically 30 pages

2.5 Clinical Overview - Format 2.5.1 Product improvement basis 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

2.6 Nonclinical Written and Tabulated Summaries - Content Integrate data crosswise over reviews and crosswise over species Primarily message, with cases of tables and figures Exposure in guinea pigs ought to be identified with presentation in people given most extreme expected dosages Age, sex, and metabolite-related impacts In vitro concentrates to start with, then in vivo Ordered by species, course, length Typically 100-150 pages

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

2.7 Clinical Summary - Content Provides real outline and support for conclusions and basic issues distinguished in the Clinical Overview Comparison of results crosswise over reviews with joining of clinical data Analysis of all important data for dosing suggestions Typically 50-400 pages (barring tables)

2.7 Clinical Summary - Format 2.7.1 Summary of biopharmaceutic studies and associated scientific techniques 2.7.2 Summary of clinical pharmacology (counting clin smaller scale portrayal ponders) 2.7.3 Summary of clinical adequacy 2.7.4 Summary of clinical wellbeing 2.7.5 References 2.7.6 Synopses of individual reviews

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

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

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

Submission of CMC Information in CTD Format The CTD Quality Module is novel in that it is a blend of authentic advancement and future duties that apply to the business, post-endorsement generation period.

Impact of the CTD The ICH CTD speaks to a standout amongst the most yearning and fruitful universal harmonization exercises attempted It will essentially diminish time and assets required by industry to arrange applications for worldwide enrollment

Benefits of the CTD More "reviewable" applications Complete, efficient entries More unsurprising organization More predictable surveys Easier investigation crosswise over applications Easier trade of data Facilitates electronic entries

Quality Overall Summary (QOS) U.S. data source not utilized for choice Module M3 checked on fills in as a reason for choice and activity EU Same as above Can be utilized for surveys

Quality Overall Summary (QOS) Japan Primary audit report Canada Basis for audit format

Quality Overall Summary (QOS) The Quality Overall Summary (QOS): Is a piece of a medication accommodation composed by ICH's Common Technical Document (CTD) Guideline (i.e., Module 2.3) ICH's CTD-Q structure (counting the QOS) has been formally embraced by Canada for different medication accommodation sorts, e.g.: Clinical Trial Applications (CTAs) Phase I, Phase II/III, BA Studies

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'/"Shut" parts are submitted in independently bound dossiers

Quality Overall Summary – Chemical Entities (QOS-CE) Template Health Canada's (QOS-CE) Template: Was created to deal with the accommodation workload and to help supports in the arrangement of the Quality Summary Promotes efficiencies in accommodation planning and in the survey procedure Available for different entries sorts (CTAs x3, NDSs and ANDSs, and so on.) Entirely good with ICH's QOS (e.g., can be viewed as a satisfactory substitution for the QOS as characterized by the CTD-Q)

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