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Common Technical Document, Basic & General Information, December 2005
The Common Technical Document (CTD)
Basic & General Information
Miriam Titulaer, Regulatory Affairs EU
Europe
Table of Content
CTD Background and Objectives
1.
2.
3.
4.
5.
Definition
Scope
Implementation
Organisation of the CTD
Information on the Structure and Content of the
CTD
6. Genzyme Europe BV experience
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1. Definition
ICH Initiative
 Agreement on the structure and format of a well-structured
presentation for applications submitted to Regulatory
Authorities in Europe, US and Japan
 Benefits:
Simplify dossier preparation(s)
Save time & resources
Facilitate Regulatory review & communication
Simplify exchange of Regulatory information
Easier preparation of e-submissions
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1. Definition
 Warnings
-
-
Does not provide information on the content of
dossier
-
Does not indicate which studies & data are required
for successful approval
Does not harmonise Assessment Procedures
(Dossier approval & amendments)
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2. Scope
Application, Procedure, Product
 Applicable for all types of marketing applications:
full, abridged (including line extensions), and
bibliographical applications
 All types of procedures
Centralised, Mutual Recognition or national
 Applicable for all types of products
NCE’s, generics, biologicals, radiopharmaceuticals,
vaccines, herbal medicinal products
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3. Implementation
 Optional
July 2001: EU, FDA, Japan (Canada, Switzerland)
 Mandatory
July 2003: EU, Japan (Canada, Switzerland)
 Highly recommended
July 2003: FDA
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3. Implementation
Variations and Line extensions
 In Europe, after 1 July 2003, new CTD format mandatory for all
variations & line extensions applications.
 There is no obligation to reformat the dossier of already authorised
products into the CTD format (cross-referencing to ‘’old’’ format
documentation is acceptable).
 Reformatting is allowed, but not recommended for the Non-clinical
and Clinical parts of the documentation.
 Reformatting is recommended for the Quality part to facilitate the
handling of variations and line extensions. Such reformatting must
involve the complete Quality parts, including Drug Master Files (if
applicable) and also include all approved variations. A signed
declaration must be provided stating that the content/data of the
Quality Module is identical to the currently approved Quality part, with
no changes to the dossier as a result of the re-formatting.
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4. Organisation of the CTD
Diagrammatic Representation
Module
1

1
CTD
Regional
Administrative
Information
2.1 and 2.2
TOC & Introduction
2.4 and 2.5
Module
2
Nonclinical & Clinical
Overviews
2.3
Quality
Overall
Summary
2.6
Nonclinical
Summary
2.7
CTD
Clinical
Summary
2.7 (1-2-3-4)
Written
Summary
Tabulated
Summary
Written & Tabulated
2.7 (5)
Synopses of Ind. Studies
Modules
3, 4, 5
3
Quality Data
4
5
Nonclinical Data
Clinical Data
Study Reports
Study Reports
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Common Technical Document?
 The CTD defines the format of an application and not the content.
Quote: “Neither the type nor extent of specific supporting data has
been addressed in this guideline, and both may depend upon regional
guidance.”
 For instance:
Module 3, Quality information, in general EU requires less detailed
equipment descriptions than US;
Module 5, Clinical data, US requires inclusion of all clinical study
report annexes.
 Note: the implementation of the CTD is a compromise, resulting in
a more elaborate dossier.
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5. Information on the Structure and Content of the CTD
Guidelines: standard format
 Information on the structure and content of the CTD is provided in the
rules governing medicinal products in the European Union: Notice to
Applicants Volume 2B: Presentation and content of the dossier, CTD,
Edition June 2004.
 It is supported by a Questions and Answers document (June 2004)
which provides further information on the use of the CTD with respect
to the different regulatory procedures/different forms of applications.
 Additional information on the organisation of the CTD is provided in the
CHMP guideline CPMP/ICH/2887/99, Topic M4, Step 5: Common
Technical Document for the Registration of Pharmaceuticals for Human
Use - Organisation of CTD.
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ICH Multidisciplinary - Adopted Guidelines
 Topic M4, Step 5 Common Technical Document for the
Registration of Pharmaceuticals for Human Use:
Organisation of Common Technical Document
(CPMP/ICH/2887/99 - released for information February
2003):
 M4 - Organisation of the Common Technical Document Rev 2
Correction February 2004 Transmission to CPMP and Release
for Information November 2003
 M4 Quality - Quality overall Summary and CTD Quality Rev 1
 M4 Safety - Nonclinical Summaries and Organisation of Module
4 Released for Information July 2003
 M4 Efficacy - Clinical Overview, Clinical Summary, Sample
Tables for Clinical Summary and Module V Rev 1
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ICH Multidisciplinary - Adopted Guidelines
CHMP Question and Answer Documents
 M4 Step 5 - General Questions and Answers.
CPMP/ICH/5552/02, Rev 2, June 2004.
 M4 Quality - Question and Answer/Location issues For Common
Technical Document for the Registration of Pharmaceuticals for
Human Use - Quality CPMP/ICH/4680/02, July 2003.
 M4 Safety Step 5 - Questions and Answers.
CPMP/ICH/5549/02, November 2003.
 M4 Efficacy Step 5 - Questions and Answers.
CPMP/ICH/5551/02, Rev. 2,June 2004.
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ICH M4 QUALITY
QUESTION AND ANSWER LOCATION ISSUES
 Intended to provide additional guidance for the preparation
of an application file in the CTD-Q format.
 It should be read in conjunction with the CTD-Q guideline
(Modules 2 and 3).
 The document also addresses the relationship between
linked CTD-Q sections for certain parameters, such as
polymorphism, impurities, or particle size.
 This document also clarifies location issues; that is, it
indicates in which CTD-Q section(s), requested information
should be placed (see section 4: Location Issues in Drug
Substance, section 5: Location Issues in Drug Product, and
section 6: Location Issues in Appendices).
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Preparing and Organizing the CTD
 Throughout the CTD, the display of information should be
unambiguous and transparent, to facilitate the review of the basic data
and to help a reviewer become quickly oriented to the application
contents.
- Text and tables should be prepared using margins that allow the
document to be printed on A4 paper.
- The left-hand margin should be sufficiently large that information is not
obscured through binding.
- Font sizes for text and tables should be of a style and size that are
large enough to be easily legible, even after photocopying.
- Times New Roman, 12-point font is recommended for narrative text.
Acronyms and abbreviations should be defined the first time they are
used in each module.
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Preparing and Organizing the CTD
 Guidance: M4 Organisation of Common Technical Document,
ANNEX: Granularity Document
Provides guidance on:
 headings in relation to document location and the section headings
within those documents.
 where in the CTD and eCTD multiple documents can be located in the
hierarchy.
 how documents should be paginated and on what the module Table of
Contents should therefore include.
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7. Genzyme Europe BV Experience
 Cholestagel®: 1st CTD stand-alone, Application filed on
August 30th, 2002
 AT, filed on February 2004.
 Myozyme (Pompe), filed on December, 2004
 Variations, line extensions, renewal applications
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7. Genzyme Europe BV Experience
CTD-format for Variations
 Module 1:
1.0 Cover Letter
1.1 Comprehensive table of content
1.2 Variation Application Form
1.3 Product Information
1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet – where
appropriate
1.4 Information about the experts: The relevant expert declaration(s) and signature(s)
must be provided, corresponding to the Overview/Summary submitted in Module 2.
 Module 2:
As mentioned in the Variation Regulation any Type II variation should be accompanied
by the relevant Overviews/Summaries updates or addenda (even if a variation is
submitted at the request of the Competent Authority/CPMP). Expert details and signature
are to be provided in Module 1.4 separated from the actual Overview/Summary.
Supportive data are to be included in Modules 3, 4 and/or 5 as appropriate and in
accordance with the EU-CTD structure.
 Documentations for Type IA/IB-Notifications also have to follow CTD-structure where
applicable.
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Genzyme Europe BV Experience
CTD-format for Renewal Applications
 Module 1:
1.0 Cover Letter
1.1 Comprehensive table of content
1.2 Renewal Application Form with annexes
1.3 Product Information:
1.3.1 SPC, Labelling and Package Leaflet
1.3.3 Specimen
1.4 Information about the expert
1.4.1. Quality
1.4.2. Clinical
 Module 2:
2.3 Quality Overall Summary – (Quality Expert Statement)
2.5 Clinical Overview (Clinical Expert Statement)
 Module 5:
 5.3.6 Reports of Post-marketing experience.
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7. Genzyme Europe BV Experience
 Recommendation to use to the CTD format as early as possible in
the global development process:
- increase harmonization
- save time and resources
 EU: Clinical Trial Applications falling under the Clinical Trials Directive
require submission of an Investigational Medicinal Product Dossier
(IMPD). The IMPD contains CMC (chemistry, manufacturing control),
Non-clinical and Clinical information which must be presented in the
format of the CTD Module 2 Quality Overall Summary and Nonclinical
and Clinical Overviews.
 FDA: IND can be submitted in the CTD format, but this is not yet
mandatory.
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