CTD CTD and Regional Requirements

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CTD CTD and Regional Requirements Powered By Docstoc
					Creating Quality Applications in a
Changing Regulatory Environment


Diane J. Zezza, Ph.D.
Eli Lilly and Company
September 8, 2003
Today’s Regulatory Environment

•Regulatory environment is dynamic!

•Strategic Initiatives and Change at FDA
  •   Improving innovation
           – Reduce delays by avoiding multiple cycles of review
           – Improve quality and efficiency of review process through quality systems
             approach
           – Facilitate new product development by providing clearer guidance




Diane Zezza, Ph.D.                                                                      2
PDA Conference September 8, 2003    Eli Lilly and Company
Today’s Regulatory Environment

Strategic Initiatives and Change at FDA
•21st Century Regulation of Pharmaceutical
Manufacturing
           – Ensure regulatory review, compliance and inspection policies are based
             on state-of-the-art science
           – Do not impede adoption of new technological advances
               • New guidances enhance consistency and coordination of drug
                 quality regulatory programs (i.e. Part 11, dispute resolution, aseptic
                 processing, comparability protocols, PAT)
               • Collaborations to promote innovative approaches to drug
                 development
               • Streamline and improve its internal processes
               • Improve international standards for drugs through efforts supporting
                 global harmonization and collaboration


Diane Zezza, Ph.D.                                                                        3
PDA Conference September 8, 2003    Eli Lilly and Company
Today’s Regulatory Environment

Strategic Initiatives and Change at FDA


  •   Critical Challenges Facing Agency
           – Efficient risk management, better informed consumers, patient and
             consumer safety, counterterrorism, a strong FDA




Diane Zezza, Ph.D.                                                               4
PDA Conference September 8, 2003   Eli Lilly and Company
Today’s Regulatory Environment
Strategic Initiatives and Change at FDA

• CBER/CDER Consolidation
           – To CDER:
               – Monoclonal antibodies, cytokines, growth factors, enzymes,
                 interferons
               – Proteins intended for therapeutic use extracted from animals or
                 microorganisms
               – Other therapeutic immunotherapies
           – Stayed at CBER:
               – Gene therapy products
               – Products composed of human/animal cells
               – Proteins used as ex vivo constituents or reagents in production


Diane Zezza, Ph.D.                                                                 5
PDA Conference September 8, 2003    Eli Lilly and Company
Challenges in Today’s Regulatory Environment

•Staying current in the changing regulatory
environment
           – New FDA and ICH guidances
           – New organizational structures
           – Changes in processes, policies

•Knowledge and evolution global regulatory
requirements
           – Adoption of CTD
           – EU: CT Directive and EU Enlargement
           – Asia Pacific: ASEAN CTD




Diane Zezza, Ph.D.                                         6
PDA Conference September 8, 2003   Eli Lilly and Company
Regulatory Challenges
•Dynamic regulatory environment

•Consolidated development timelines

•Goal: Accelerate the development of critical safe and
effective new drugs and deliver them to patients faster




Diane Zezza, Ph.D.                                         7
PDA Conference September 8, 2003   Eli Lilly and Company
Regulatory Opportunity
•Building a quality submission that is reviewable and
approvable expedites availability of important new
medicines to market




Diane Zezza, Ph.D.                                         8
PDA Conference September 8, 2003   Eli Lilly and Company
Common Technical Document
•ICH CTD Guidance provides harmonized format for
drug product applications to be submitted to global
regulatory authorities
           –   Organization of CTD
           –   Quality Section
           –   Efficacy Section
           –   Safety Section

•CTD format is supplemented with regional information

•Content is still as defined by regional requirement
           – Regional requirements, guidances, local pharmacopoeia
           – FDA Guidance for Industry: Drug Product (January 2003)


Diane Zezza, Ph.D.                                                    9
PDA Conference September 8, 2003     Eli Lilly and Company
Introduction to CTD
                                   Modular Construction

Module 1: Regional Administrative Information

Module 2: TOC and Summaries

Module 3: Quality (CMC)

Module 4: Pre-Clinical

Module 5: Clinical


Diane Zezza, Ph.D.                                               10
PDA Conference September 8, 2003         Eli Lilly and Company
CTD Organizational Structure
                                                                 1.0

                                                            Module 1
                                                          Regional
                                                        Administrative
                                                          2.1 TOC
             Module 2                                2.2 Introduction
                                                          2.4 Non-Clin 2.5 Clinical
                                             2.3              Overview     Overview
                                        Quality
                                       Summary
                                                            2.6 Non-Clin    2.7 Clinical
                                                               Summary       Summary

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

Diane Zezza, Ph.D.                                                                            11
PDA Conference September 8, 2003                   Eli Lilly and Company
Location of Regional Differences for CMC
Module 1                                   Administrative Information

Module 2                           2.3     Quality Overall Summary

Module 3                           3.2.S   Drug Substance
                                   3.2.P   Drug Product
                                   3.2.A   Appendices
                                   3.2.R   Regional Information




Diane Zezza, Ph.D.                                                      12
PDA Conference September 8, 2003            Eli Lilly and Company
  Information Assembly Order
                                    I                                              G
                                                                  A
                   B               C*  C# E                                F*     F#
                                     C’               H                D     F’

         C’            D            A         A          B C#               E’     F* A
         G             F’           I         D          E F#               B      H  I
                                              G          H  I               G      D C*
                  Japan                                  US                        EU
         A            B            C’         A            B      C#         A     B    C*
         D            E            F’         D            E      F#         D     E’   F*
         G            H            I          G            H       I         G     H     I
           Japan CTD                              US CTD                         EU CTD
Diane Zezza, Ph.D.                                                                           13
PDA Conference September 8, 2003          Eli Lilly and Company
CTD Status
•Modular format has facilitated preparation

•Harmonized format has assisted global application
compilation

•Global Health Authorities are receiving new
applications in CTD format and gaining experience

•Differences in content still exist as dictated by regional
requirements

•Not one size fits all!

Diane Zezza, Ph.D.                                            14
PDA Conference September 8, 2003   Eli Lilly and Company
Alternate Submission Strategies
•Fast Track designation
  •   Facilitate development and expedite review of drugs to treat serious
      and life-threatening conditions so that an approved product can
      reach the market experitiously

•Draft Continuous Marketing Applications:
  •   Pilot 1: Reviewable Units for Fast Track Products Under PDUFA
  •   Pilot 2: Scientific Feedback and Interactions During Development of
      Fast Track Products Under PDUFA




Diane Zezza, Ph.D.                                                           15
PDA Conference September 8, 2003   Eli Lilly and Company
Additional Opportunities
•Comparability Protocols
  • Draft Guidance CPs – CMC (excludes protein products)
  • Draft Guidance CPs – CMC for Protein Drug Products and Biologicals



•Can be submitted in new applications or as supplements

•CP describes a change, specifies studies to be performed
including analytical procedures and acceptance criteria

•Potentially allows reduced reporting category for future reporting
of CMC changes




Diane Zezza, Ph.D.                                                       16
PDA Conference September 8, 2003   Eli Lilly and Company
FDA Guidances
•Draft Guidance Good Review Management Principles
for PDUFA Products
           – Guidance to industry and FDA review staff (CBER and CDER)
           – Clarify roles and responsibilities of review staff in review process
           – Identify ways to enhance effectiveness and efficiency of the review
             process
           – Lead to greater consistency and efficiency within and across review
             divisions, and between CBER and CDER




Diane Zezza, Ph.D.                                                                  17
PDA Conference September 8, 2003    Eli Lilly and Company
Facilitation of Review and Approval Process

•Understand the requirements

•Develop a high quality submission
  •   Easy to review
  •   Complete data
  •   Application integrity

•Understanding the process

•Effective communication



Diane Zezza, Ph.D.                                         18
PDA Conference September 8, 2003   Eli Lilly and Company
Conclusions
•Regulatory environment is changing and will continue
to change – stay current

•Work to build quality submissions

•Quality submissions can accelerate the development
of critical safe and effective new drugs and deliver
them to patients faster




Diane Zezza, Ph.D.                                         19
PDA Conference September 8, 2003   Eli Lilly and Company

				
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