PIM Update to Vendors

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PIM Update to Vendors

• 1 December 2008

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Speakers

• Tim Buxton, EMEA, Co-chair PIM Core Team
• Andrew Marr, EFPIA, Co-chair PIM Core Team
• Claire Holmes, EMEA, PIM Project Manager
• Klaus Menges, BfArM, NCA Member, PIM Core Team
• Jill Newton, EMEA DES Team Lead

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Status

• Current acceptance of submissions
• Submissions made
• PIM Review System (PRS)
• Data Exchange Standard (DES)
• Light Authoring Tool (LAT)
• PIM DES Validation Engine (PDVE)

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Current Acceptance of Submissions

• PIM is currently in pilot
• Acceptance of PIM submissions for new
  applications is open
• Needs to be agreed by EMEA first (at least 7
  months before anticipated submission)
• Acceptance of PIM submissions for
  Post-authorisation applications is by negotiation
• Post-authorisation Procedures (PAPs) for products
  already in the pilot only
• Anticipate opening for additional products from
  beginning January 2009
• Needs to be agreed by EMEA first (at least 2
  months before anticipated submission)
• One additional product already anticipated 1Q2009

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Submissions Made

• New Applications
• Atriance GSK Approved
• Volibris GSK Approved
• NCE Pfizer Approaching Day 210
• NCE GSK Approaching Day 120
• Post-Authorisation Procedures
• Thyrogen Genzyme
• Erbitux Merck Serono
• Atriance GSK further submissions
• Volibris GSK further submissions

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Post-Authorisation Procedures Breakdown

• Type II 7
• Type 1A 1
• Type 1B 1
• Notification 61(3) 1
• Annual Reassessment 1

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Status of PRS

• Single instance of PRS hosted at EMEA
• Access by NCAs to PRS via EudraNet (VPN)
• V5.0.3 in production
• Key functionality improvements in v5.0
• Outstanding issues, also from PAP experience
• Various enhancements
• V5.1 in development
• Target date for production end December 2008
• Key functionality improvements in v5.1 e.g.
• Support of late linguistic comments
• Checking of information-only comments due to
  confidentiality to avoid disclosure to applicants
• Readability of document icons
• Long list of additional minor enhancements

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Status of the Data Exchange Standard

• Current DES Version v2.6.1
• V2.6 in production since January 2008
• Patch release v2.6.1 in July 2008
• DES History in next two slides
• Take away messages
• DES is getting more stable
• Further assistance with quality control requested
• Wider testing desirable

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DES Version History
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DES Version History
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DES 2.7 - Drivers

• Target availability end 1Q 2009
• 2 Main drivers for DES 2.7
• Increase flexibility of DES
• Lack of flexibility has been key issue in pilot
  submissions to date
• Increase usability of PIM
• Need to ease authoring/reviewing/publishing of
  information in PIM
• Additional requirement to align with upcoming QRD
  changes
• Aim to exit PIM pilot phase

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Out of Scope for DES 2.7

• DES 2.7 is a minor version change only
• Does not include
• Reference Data Model (in support of
  interoperability between telematics systems)
• ISO Standards for Identification of Medicinal
  Products (IDMP)
• Support for MRP/DCP

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DES 2.7 Scope

• DES Change Orders (DCOs) grouped into Themes
• Flexibility of the DES
• Usability
• Lifecycle Management
• Commenting
• Process/Documentation
• No technical impact on DES
• Alignment to QRD
• Others
• Mostly bug fixes

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Flexibility of the DES

• Flexibility on Element Location
• Option to include elements at different levels in
  the tree for different products
• Element sequence for sections that combine
  several elements
• Allow flexibility in order of sequence of text in
  elements
• Flexibility on use of empty lines for elements
  that are reused in different contexts e.g.
  invented_name

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Lifecycle Management

• Delta submissions vs full submissions
• Use of LCM features when generating track changes
  views (vs text comparison)
• Currently no standard way to generate track
  changes view applicant and regulator do not see
  same view
• Support for exchange of subset of languages
• Issue raised due to late linguistic review
  comments
• Should such files contain a full tree zone, or
  just the tree zone for the exchanged languages
• Permanent IDs
• Synchronisation of submissions with comments

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Commenting

• Comment Granularity
• Text layout and formatting in comment reason

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Alignment to QRD

• Advanced Therapy
• New optional sub-headings for Advanced Therapy
  products
• (Most changes affect guidance in annotated
  template only)
• SPC Guideline
• Final changes under review by Commission
• Update to standard statements
• New sub-headings

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DES Testing

• Acknowledge testing of DES is currently not ideal
  historically only DES Team and TRASYS
• Participation in testing requires
• Knowledge of the DES
• Technical ability to build files based on new DES
  version/system to build files
• Time and willingness
• Team proposals
• Involve vendors in testing
• Involve person raising DCO in resolution and
  testing

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Question to Pose

• Is there a desire for vendors to be able to test
  the DES, within a short time-frame, before each
  release is finalised?
• Major
• Minor
• Patch
• Time-frame
• Feedback desired at second vendor Webex

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Light Authoring Tool

• Single user tool with limited functionality
• Merging of database instants used to bring
  together languages
• Current production version v4.0
• Introduces significant changes in the way
  translations are handled.
• Introduces a new scheme for identifiers (IDs)
  where the initial ID given to a template/element
  is retained during the lifecycle of a product
  (i.e. across submissions and procedures).
• Introduces support for the latest DES releases
  (v2.6 and v2.6.1) and PIM Data Validation Rules
  (v2.6)
• V4.1in test
• Just released for testing
• Full support of translation requirements

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LAT Experience

• Used in two applications
• LAT supports full use of PIM
• Improvements needed to
• The application of regulator comments for
  translators
• The response to regulator comments
• The inclusion of translator comments in internal
  (-i) packages

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PIM DES Validation Engine (PDVE)

• Currently part of PRS
• Intent is to make standalone (together with API)
• Currently in redevelopment
• Will validate to rules for DES v2.6
• Earlier versions are not supported
• Ability to create PDF renditions as per PRS (full
  versions only)
• Targeted release date January 2009
• Future DES releases will be accompanied by an
  updated PDVE (if required)

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Experience

• New submissions
• Post-Authorisation Procedures (PAPs)
• Workshops on PAPs
• Items to be delivered
• Including
• What went well
• What needs to be improved

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New Submission Experience

• Applicant
• Initial submissions
• Responses to comments
• Linguistic review
• Finalisation
• EMEA
• Product Team Leader
• Secretaries
• NCAs
• Rapporteur/Co-Rapporteur
• NCA non-Rapporteur/Co-Rapporteur
• Linguistic review

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Applicant initial submission

• Constant Issue
• Lack of a stable DES was challenging
• Creation of the initial application was the
  simple part
• Use for real products identified some issues with
  the DES
• Readability guidelines affecting need for
  flexibility
• Decreasing number of issues with time
• Some more flexibility required

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Applicant responses to comments

• New part of the process
• Comments at various levels
• Reason for comments not used consistently
• Comments against comments were needed
• Provides ability to see that all comments have
  been addressed
• Some challenges related to differing
  interpretation of specification
• Were all comments (and responses) being seen?

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Applicant linguistic review

• Challenging part of the process
• Authoring process for translation
• In Word?
• In XML?
• With computer-assisted translation?
• Linguistic comments
• Viewing in context
• Late linguistic comments
• Potential impact on timelines
• Need for handling individual languages

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Applicant Finalisation

• Formatting has been more problematic than
  anticipated due to detailed QRD requirements for
  formatting the final output
• Different interpretation of specification
• Lack of access to rendition engine
• Access to LAT has improved situation
• Access to PDVE will further improve
• Reduction in requirements for formatting would
  greatly reduce workload

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Applicant - Conclusion

• PIM works!!
• Needs to be more stable
• Needs to be embedded in processes
• and regarded as routine
• A number of issues need to be addressed before
  full value is obtainable

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EMEA PTL Secretaries

• Positives
• Appreciate the ability to see in real time how
  Rap/Co-Rap are progressing
• Appreciate ability to consolidate comments more
  easily from a single location
• Automated formatting and ease of generation of
  correct PDFs
• Areas for improvement
• Increased communication for co-ordination of the
  procedure has been required
• Technical issues

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NCAs Rap/CoRap

• Learning the system and processes
• Issues of access/transparency
• e.g. promotion of comments (private, agency, EU)
• Working with external reviewers
• Positive response with handling of provision of
  comments
• Challenging to do comparisons
• Understanding the comparison functionalities
• Fine detail of comparison algorithms
• Performance is the key issue
• Varies from NCA to NCA

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Experience of BfArM

• Lot of discussions around business steps what is
  to do when
• Helpful listings of activities from EMEA
• Performance problems
• Solved by exchange of hardware at EMEA,
  configuration check at MS
• Bugs and flaws of the software, functionalities
  to be added
• Update of software during the first submission,
  preparation for post-authorisation processes in
  parallel
• Identification of additional needs
• Updating the specifications

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Regulators - Conclusion

• PIM works!!
• Efficient and sophisticated system available for
  review
• A number of issues need to be addressed before
  full value is obtainable
• Improved usability
• Eg. comparison features
• Performance key issue
• Baseline performance testing has been undertaken
• Performance targets established

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Post-Authorisation Procedures

• PIM works!!
• Same provisos as for new submissions
• It will be necessary further to define the
  process of migration of existing product
  information
• Shown to work for single applications and simple
  parallel applications
• It still needs to be demonstrated that it works
  for more complex parallel submissions
• Active products often have parallel activities
• Merge
• Split
• Reconcile two approved versions

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PAP Workshop

• Held September 2008 to
• Review the requirements for processing each
  post-authorisation procedure - progressed
  independently
• Additional requirements that may come from
  running procedures in parallel (eg merge/split)
• Determine whether the pilot should be opened for
  additional post-authorisation products and under
  what conditions
• Much better understanding of requirements gained
• PRS improvements identified
• Further guidances identified

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Addressing the Requirements

• Enhancement of PRS particularly compare
  functionality
• In PRS v5.1
• Guidance
• Guidance for PTLs on when 'merge' submissions
  should be considered
• Reviewer guidance should be provided on how to
  review merged submissions - initially, asap, as
  stand-alone guidance but then incorporated into
  the full guidance
• Applicant guidance on how to merge or to split
  submissions should be available
• NB.
• A number of the existing products have parallel
  submissions on-going
• Core Team has endorsed acceptance of newly
  proposed PAP product in pilot subsequent to
  guidances being in place

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Criteria to Move out of Pilot

• Overarching
• DES
• PRS
• LAT
• In-use Business Criteria
• Experience Breadth and Mass of Experience
• Validation of these Criteria
• Service Level Agreements
• Processes

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Overarching

• Key criteria have been defined to allow PIM to
  move out of pilot and into production
• In a state of regular operation, PIM will be used
  routinely for an unlimited number of submissions
  as a mission-critical system and approach to
  process EMEAs daily work, with no need for prior
  discussion/requests regarding the submissions
• A Road Map/Statement of Intent should be
  published by EMEA
• Full set of criteria will be published imminently
• Following slides provide an overview of key
  points of the criteria

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DES

• Stable
• One release per year in principle
• Lack of need for corrective actions
• Long-term plans clearly defined
• PDVE available
• Defined process for testing DES releases

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PRS

• Performance acceptable bandwidth in place
• Usability acceptable
• Functionality acceptable
• Role-based and procedural-based guidance
  available
• Support in place
• One planned release per year

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LAT

• Performance must be satisfactory
• Must have functionality provided
• Used in two procedures
• Guidance, user support etc. in place
• Mid-term and long-term release plans available
• One planned release per year

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In-Use Business Criteria

• Migration guidance
• Comprehensive guidances available
• Business processes supported
• Change control processes operational
• Business continuity, risk mitigation plans in
  place etc.
• Vendor support minimum of two commercially
  available tools that have been successfully used
  throughout a procedure

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Experience

• Breadth
• Procedure types, in parallel, no major issues
• Mass
• Initial MAAs 3
• Two each of PAPs (II, Ia, Ib, Extension, Renewal,
  61(3)
• Minimum of 5 applicants

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Validation of Criteria

• Proving mechanisms for the criteria are being
  established
• A plan to prove the criteria is being established

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SLAs and Processes

• A PIM Service Level Agreement must be in place
  between EMEA and its stakeholders
• National Competent Authorities
• Applicants
• 3rd party vendors
• Processes in place for
• Service support
• Service delivery
• Service management

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Plans

• More pilot applications
• EMEA roadmap

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More pilot applications

• New submissions open now
• PAPs by negotiation
• Additional one accepted
• Further desired
• Additional vendor needed to meet pilot exit
  criteria

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EMEA Roadmap

• All product information migrated to PIM by
  end-2009
• PIM strongly recommended by 2010

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Engagement with Applicants

• Publication of criteria
• Call for further involvement in pilots
• Engagement over process for migration and
  adoption of PIM use

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Take away messages

• PIM works!!!
• DES is more stable
• Better engagement with vendors is a specific
  project objective
• Wider testing desirable
• Vendor involvement in proposing and resolving
  DCOs
• Further involvement in pilot submissions wanted

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Engagement with Vendors

• Critical to success of project
• Continuing and meaningful
• This is the start of a dialogue
• Topics for next Webex to be determined based upon
  feedback from today
• Next Webex 16 December 2008
• Proposed future engagement at DIA meetings
• DIA EDM Philadelphia February 2009
• DIA Euromeeting March 2009
• DIA Annual/DIA Euro EDM
• Volunteers to host?

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Questions of Clarification

• QA based on clarifying what was presented today
• Matters of substance to be considered at next
  Webex

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