Common technical document (CTD – ICH)

-Regulatory Requirement on Dossier of Medicinal Products-
Common Technical Document (CTD – ICH)
Quality Overall Summary (QOS)

1. 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, Director
Bureau of Pharmaceutical Sciences
Therapeutic Products Directorate, Health Canada

2. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 20072 |
Outline
Common Technical Document (CTD – ICH)
Quality Overall Summary (QOS)

3. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 20073 |
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 data
Incorporates relevant ICH guidelines
It is organized into five sections:
All “modules” harmonized except Module 1 – regional specific
Raw data per regional requirements

4. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 20074 |
Module 1
Regional
Administrative
Information
Nonclinical
Overview
Quality
Overall
Summary Clinical
Summary
Module 3
Quality
Module 4
Nonclinical
Study Reports
Module 5
Clinical
Study Reports
Clinical
Overview
Nonclinical
Summaries
Not Part of
CTD
CTD
Module 2
NDS
Result was the CTD Triangle

5. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 20075 |
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

6. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 20076 |
Module 2 - CTD Summaries
2.1Overall CTD ToC
2.2CTD Introduction
2.3Quality Overall Summary
2.4Non-Clinical Overview
2.5Clinical Overview
2.6Non-Clinical Written and Tabulated Summaries
2.7Clinical Summary

7. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 20077 |
2.2CTD Introduction
General introduction to the pharmaceutical, including
Pharmacologic class
Mode of action
Proposed clinical use
Typically 1 page

8. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 20078 |
2.3Quality 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

9. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 20079 |
2.3Quality 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

10. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200710 |
2.4Nonclinical 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

11. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200711 |
2.4Nonclinical 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

12. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200712 |
2.5Clinical 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

13. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200713 |
2.5Clinical 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

14. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200714 |
2.6Nonclinical 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

15. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200715 |
2.6Nonclinical 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

16. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200716 |
2.7Clinical 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)

17. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200717 |
2.7Clinical 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

18. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200718 |
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

19. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200719 |
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

20. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200720 |
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

21. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200721 |
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.

22. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200722 |
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

23. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200723 |
Benefits 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

24. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200724 |
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

25. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200725 |
Quality Overall Summary (QOS)
Japan
Primary review document
Canada
Basis for review template

26. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200726 |
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

27. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200727 |
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

28. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200728 |
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)

29. Training Workshop on Pharmaceutical Development
with a Focus on Paediatric Medicines / 15-19 October 200729 |
Thank you