The Common Technical Document- Quality (CTD-Q)
George Wade EMEA February 2008
with thanks to Dr. Jean-Louis Robert, Chairman CHMP/CVMP Quality Working Party
CTD : what is it?
IT IS : A common harmonised FORMAT for applications for preparing marketing authorisations in the three ICH regions. a TEMPLATE for presenting data in the dossier.
IT IS NOT: A statement of data requirements for applications
CTD : regulatory sources
Notice to Applicants , Eudralex Vol. 2B : NTA Guidance June 2006 : Structure is defined here. http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol2/b/ctd_06-2006.pdf Q&A Document http://www.ich.org/LOB/media/MEDIA620.pdf Location issues ( Quality ) - see CPMP/ICH/4680/02 ICH Updates http://www.ich.org
Diagrammatic Representation
1 Regional Administrative Information
not strictly part of CTD
Non-clinical Overview Module 2 ( Summaries) Quality Overall Summary 2.3 Non-clinical Written and Tabulated Summaries
Clinical Overview Clinical Written Summary
3 Quality
4 Non-clinical Study Reports
5 Clinical Study Reports
CTD-Q basic structure
MODULE 1 Admin and Regional Specific Information Dont forget molecular structure aspects re: Similarity (1.7)
although these are outside the main quality/safety/efficacy benefit-risk evaluation for an authorisation.
MODULE 2 CTD Summaries Quality Overall Summary (2C) - QOS MODULE 3 Main body of Quality Data
i.e. The Q dossier will be basically modules 2.3 & 3
Module 1: Administrative Regional Information
1.1 Table of Contents 1.2 Application forms 1.3 Product Information, SPC/Labelling/ Package Leaflet 1.4.1 Expert declarations & signatures for the QOS 1.5 Specific Requirements for types of application bibliographic, generic, biosimilar, informed consent etc. 1.6 Environmental Risk Assessment (GMO? ) 1.7 Orphan issues, structural similarity 1.8, 1.9 Pharmacovigilance and Clinical Trials
Module 2: Quality Overall Summary
This is probably what EU assessors will read first Quality Overall Summary
Written text summary following the outline and scope of the Body of Data, Module 3 . Not required to be critical No formal tabulated summary structure Key parameters of the active substance & product which may have an impact on efficacy or safety should be emphasised Relevant tables/figures could be incorporated External Drug Master File (ASMF Open part ) will be summarised here. Closed/Restricted part should be in the ASMF itself.
Module 3: CTD-Q ( guideline )
Note : Same structure for NCE & Biotech products Scope of the guidance , i.e. format 3.1 Table of Contents helpful to assessors 3.2 Body of Data 3.2.S Drug Substance External Drug Master File ( ASMF ) should also follow this structure for both the Open and Closed/Restricted parts. 3.2.P Drug Product 3.2.A Appendices A.1 Facilities and equipment ( biotech) A.2 Adventitious Agents contamination A.3 Excipients ( novel )
Scope
Addresses the format/structure of applications for MAs of active substances and their corresponding drug products. NTA Guidance : The text following the section titles is intended to be explanatory and illustrative only i.e. It merely indicates the location where information has to be provided. The actual content of these sections in the dossier should include relevant information described in existing CHMP- and CHMP-ICH guidelines The section Regional Information addresses information unique to this region
Example of a network: Polymorphism
Cross reference between section P2 (Pharm. Development) and relevant sections in S (Drug Substance) and in P (Drug Product) S 1.3 Properties of the active substance S.2 Manufacture S 3.1 Studies on Polymorphism (experimental data) S 4.1 Specifications relating to control of physical forms S.4.3 Analytical methods used S 4.5 Justification of Specifications
P 2: Influence of the polymorphic forms on product characteristics dissolution, stability , etc. P 5.1 Product Specifications, need to control polymorphs? P 5.6 Justification of Specifications
Body of Data 3.2.A: Appendices
A 1 Facilities and Equipment: applies for Biotech. products A 2 Adventitious Agents Safety Evaluation: applies for NCEs and Biotech; including TSE requirements viral inactivation studies, etc.
Body of Data 3.2.R : Regional
Process Validation scheme, manufacture of product Medical Devices, if included in the presentation of the product, CE-mark info. etc. Certificates of Suitability , where relevant (e.g. generics ?) Materials of animal and/or human origin
issues
Implementation not equal in all regions? Nothing to do with e-CTD ( although the e-CTD is of course based on the agreed CTD structure ) In EMEA, for publication purposes (EPARS) we still prefer to avoid drug
Drug substance becomes Active Substance Drug Product becomes Medicinal Product
Conclusions
Benefit for industry Format: yes, better utilisation of global resources Content: identical within the 3 regions but can it lead to an expectation of more data ? Benefit for regulators Format: yes, easy to evaluate in general Content: same as before really, no change. Benefit for the patient Expedited evaluation is a benefit, especially with a positive conclusion and early marketing.
