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International Conference on Harmonisation – Common Technical (PDF)

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					                    Johannesburg workshop
                          February 2009




   International Conference on
Harmonisation – Common Technical
            Document
               -
What is the CTD and Why Use it?

                         Emer Cooke
                         EMEA           1
       Topics to be addressed

ICH Objectives
CTD background and rationale
Specific EU experience
From the NTA to the CTD to the NTA
Specific focus on approach for generic
applications
Benefits of CTD for regulators


                                         2
               ICH Objectives

Objective: to improve efficiency of new drug
development and registration process
Quicker access of patients to new medicines
Avoidance of unnecessary delays in global
development
Avoidance of duplication of animal and human
studies
Better economical use of applicant and
regulatory resources
Accomplished through the development and
implementation of harmonised guidelines and    3
standards
            CTD Background and
                Objectives

Common format acceptable for submission in
ICH regions
Seen as a logical follow up to first phase of
ICH (40 harmonised guidelines in 1997)
No rational reason for format differences
Facilitation of exchange of Information
between regulators
Logical presentation order to facilitate review
Facilitation of electronic solutions
                                              4
                   CTD Scope

Organisation of information in the dossier
Not intended to indicate what type of
documents are needed (gaps/not applicable)
Provides for regional specific administrative
information
Originally intended for New Active substance
applications (human only)
At discretion of region with respect to other
types of applications (generics, herbal,
veterinary etc.)
Defacto industry standard                       5
                                                                Module 1:
                                                                Not Part of the CTD
                               Module 1
                                 Regional                       Content to be determined
                               Information                      by EU, US, JP authorities
                                   1.0


                           CTD Table of Contents
                                   2.1

                             CTD Introduction
                                   2.2
Module 2                     Nonclinical            Clinical
                              Overview             Overview
                                2.4                   2.5
                 Quality
                 Overall      Nonclinical            Clinical                Module 2-5
                                                                                CTD
                Summary       Summaries             Summary
                  2.3            2.6                   2.7




           Module 3          Module 4                  Module 5
                              Nonclinical                 Clinical
            Quality          Study Reports             Study Reports
             3.0                  4.0                       5.0



                                                                                       6
      CTD A modular presentation

Module 1 (not part of CTD) administrative and
prescribing information, application forms,
some specific local requirements (e.g for EU
justification that the product meets generic
defintion)
Module 2 – summaries and overviews of
Quality, non-clinical and Clinical
Module 3: Quality Data
Module 4: Non-clinical data study reports
Module 5: Clinical data study reports
                                            7
       Common application format:
            EU experience
Legislation on regulation of pharmaceuticals
dates back to 1965
Objective was a single market for
pharmaceuticals based on a common assessment
approach
Quickly realised that the basis for
harmonisation and cooperation was a common
format
Legislation outlining a common outline in 1975
First “Notice to Applicants” NTA in 1986
                                            8
                 What is the Notice To
                  Applicants (NTA)?
    EU Legislation says « …. Application …. shall be
    presented …taking account of guidance published by EC
    in …. Notice To Applicants….. »

NTA = Regulatory Guidance Document
    Facilitate the interpretation and application of
    Community legislation - “Soft Law”
    Harmonised view of EC, Member States, EMEA
    CONSENSUS document
    Agreed format for the presentation of dossier
                                                        9
                  NTA-CTD Relationship ?

                            “Rules governing
         “CTD”                 medicinal
         5 Modules
                           products in the EU”

                            9
                                8
                                    7
                                        6
                                            5                      Volume 2
              Volume                            4                    NTA
                2B                                  3
2C
         2A                                             Volume 1




     NTA”
     “
                                                                          10
            Where does the CTD fit in
              the EU framework ?
European Commission Publication:
  “Rules governing medicinal products in the EU”

        Volume 1     = Community legislation
        Volume 2     = NTA= CTD +
        Volume 3     = Guidelines - Q, S, E
        Volume 4     = GMP
        Volume 5-8 = Veterinary
        Volume 9     = Pharmacovigilance
        Volume 10    = Clinical Trials
  http://ec.europa.eu/enterprise/pharmaceutical11
  s/eudralex/eudralex en.htm
               Notice to Applicants (NTA)
                       and CTD ?
 Volume 2 = NTA
        * Volume 2A: Info on Procedures for MA
                        (guidance, interpretation)
      2B   * Volume 2B: Presentation and content of a
                       MA dossier (format template)
2C
     2A

           * Volume 2C: Regulatory guidelines

 First published in 1986 - Regularly updated

 http://ec.europa.eu/enterprise/pharmaceuticals/eud
                                                12
    ralex/vol2 en.htm
              CTD = NTA - Volume 2B                     2B

               Presentation & Content
                                      2C               2A




         “CTD”        Original EU format for submission
           5                    of applications
         Modules
                                    4 parts
                                       ⇓
                     Replaced by new format based
                            on      CTD - 5 Modules
                     «4 parts may be presented as 5 modules»
         Volume 2B
2C
         2A


                        Revised NTA incorporating CTD:
     NTA”
     “
                        published 29 June 2001      13
      NTA CTD implementation in
              Europe

Since July 2003 :
CTD has been Mandatory for EU, MHLW
(Canada, CH)
Hihgly recommended for US (FDA)

EU Legislation was specifically changed in 2001



                                                  14
             CTD implementation
               European Scope
Applicable to all types of EU procedures:
- Centralised procedure
- Decentralised (MR) procedure
- National procedures


Applicable to all types of products:
- NCEs
- Generics
- Biologicals, biotech, biosimilars
- Herbal medicinal products                 15
- OTC products
          Regional (EU) specific
               Information

Requirements for content of EU application:


Administrative and Scientific information
 * required by EU legislation
 * but not reflected in CTD        Module 1




                                              16
                 Module 1 of
                Volume 2B (CTD)

1.1   Overall Table of Contents
      (complete application; modules 1-5)
1.2   Application Form = current IA-form

1.3   SPC, Labelling & Package Leaflet

1.4   Experts

1.5   Specific Requirements

Annex      Environmental Risk Assessment    17
     Specific information relevant for
         generics/biosimilars- 1

CTD does not indicate what studies are required for
successful approval,

Indicates appropriate organisation for the information
included in the application

If no information is available or required under a
specific heading, that section of the application should
be marked “not applicable” or “not relevant” whilst
retaining the section title and numbering

Justification for absence of a study should be provided
in the QoS, the NCoS or the CoS
           Specific information for
            generics/biosimilars 2

For generic and biosimilar applications the non-
clinical/clinical overviews/summaries should focus on
particular issues concerning the basis for the
application

Module 2 should include the Quality Overall Summary,
Non-clinical Overview and Clinical Overview.

Non-clinical and Clinical Summaries can be provided,
but they are only mandatory if new additional studies
have been provided
              Generic and Biosimilars

Module 1.5:
Generics: to contain summary document on:
          Active substance(« same »)
          Overall S/E profile in comparision to
          reference medicinal products
          Details related to Bio-availability , Bio-
          equivalence



                                                       20
              Generic and Biosimilars

Module 1.5:

Biosimilars: to contain summary document on:
           Similar biological mp, as and
           meanufacturing process
           Comparision with relative attributes of
           reference medicinal products
           Comparability details (table)


                                                     21
             CTD Overall Benefits

 7 years international experience – defacto
industry standard
Common format for applications, to be used in the
3 Regions (and beyond)
Resource saving for industry     Single dossier and
Possible simultaneous submissions
Implementation of electronic CTD (e-CTD)
More consistent assessment
Easier sharing between regulators
Accelerate availability of medicines              22
               Conclusion

A common application format is the
cornerstone of a harmonised regulatory
system
The CTD is the logical “standard” to adopt

   THANK YOU VERY MUCH FOR YOUR
             ATTENTION!
Back-Up Slides
              ICH Structure

ICH Steering Committee
ICH Coordinators
ICH Expert Working Groups (EWG)
Secretariat (IFPMA)




                                  25
                   ICH Structure

The six parties: Committed to implementation of
                     guidelines

  Regulators :   EC (EU), MHLW (JP), FDA (US)
  Industry:       EFPIA, JPMA, PhRMA


  Observers: EFTA, Health Canada, WHO


  Secretariat: IFPMA
                                                  26
  Expert Working Groups

SAFETY
SAFETY                   EFFICACY
                         EFFICACY




QUALITY
QUALITY             MULTIDISCIPLINARY
                    MULTIDISCIPLINARY



   STEERING COMMITTEE
  Monitors and Facilitates EWGs
Steps of ICH Harmonisation


         STEP 5--Implementing
         Guidelines in ICH Regions

               STEP 4--Adopting
             Harmonised Guidelines

      STEP 3--Consulting with Regional
    Regulatory Agencies—Comment Period

      STEP 2--Agreeing on Draft Text


  STEP 1--Building Scientific Consensus

				
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