Pharmacovigilance evmpd submission
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Pharmacovigilance evmpd submission



The impact on information flow, safety and labelling documents, document granularity, naming of documents and metadata, the preparation and submissions of XEVMPD dossiers

The impact on information flow, safety and labelling documents, document granularity, naming of documents and metadata, the preparation and submissions of XEVMPD dossiers



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Pharmacovigilance evmpd submission Pharmacovigilance evmpd submission Presentation Transcript

  • New EU Pharmacovigilance Legislation
    The impact on information flow, safety and labelling documents, document granularity, naming of documents and metadata, the preparation and submissions of XEVMPD dossiers
    Hans van Bruggen - eCTDconsultancy
  • Aims of the New Legislation
    Clarify roles and responsibilities NCA, EMA and MAHs
    Establish a clear legal framework for post-authorization monitoring
    Minimize duplication of effort across EU
    Free up resources by rationalizing and simplifying adverse drug reaction (ADR)
    Reporting of periodic safety update report (PSUR)
    All medicinal products and Advanced Therapeutic Medical Devices
    Across EEA (EU + Iceland, Lichtenstein and Norway)
    Copyright eCTDconsultancy B.V.
    Pharmacovigilance Legislation
  • Time lines
    Dec 2010: Directive and Regulation released
    Apr/June 2011: Information to stakeholders
    Sep 2011: Publication of technical specifications
    Oct/Nov/Dec 2011: EMA offers end user training on their eSubmission tool (for SMEs)
    Nov 2011: testing environment available at EMA
    Requires registration in EudraVigilance
    Jan 2012: EMA can accept electronic submissions
    Jul 2012: EVMPD data submitted and maintain as such
    Jan 2015: Adjust technical specs to ISO IMPD standards
    Jan 2016: ISO IMPD data submitted and maintain
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Impacts
    Safety evaluation
    Product information
    Submission format
    Electronic specifications
    Roles and responsibilities
    Translations of product information in all EU languages !?
    Terminology (elements and values)
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Safety evaluation
    Improvement of signal detection
    Inclusion of literature case reports
    AE submission from studies via DSUR
    Change of content of PSUR
    Electronic PSUR submission only via EudraVigilance
    Worksharing of PSURs by NCAs and EMA
    New scientific committee “Pharmacovigilance Risk Assessment Committee” (PRAC) to be hosted by EMA
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Evaluation
    Changed definition of adverse effect
    Incomplete/invalid and consumer cases to be included as well, e.g.
    Off label use
    No relation at all
    All literature cases to be included
    Pharmacovigilance Legislation
    Likely causing:
    • Over-reporting
    • Incorrect interpretation of seriousness and applicability to labelled use
    Copyright eCTDconsultancy B.V.
  • Product information and PSURs
    SmPC and Package leaflet
    Safety sections will have to be adjusted (occurrences will increase)
    Comparison labelled vs. unlabelled will shift
    Comparison expected vs. unexpected will shift
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Electronic specifications
    Based on a XML Schema Definition (=XSD)
    Mandatory elements
    Non-mandatory elements
    “If you like” (very little) or “If applicable” (mostly)
    Product information to be provided as single PDF files
    Likely in accordance with QRD template
    CP: in English per MAA or per procedure #?
    DCP/NP/MRP: in all EEA languages (concatenated/language)
    Substance information in addition to SSI in attached PDF
    To be submitted as a ZIP file (<60 MB per submission!!!)
    No tools available yet
    Validation criteria under development
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Potential sources for data
    Cover letter
    Application form, in accordance with
    Trade registries, GMP certificates, QP for batch release, Declaration QPPV, Etc.
    Product information
    32S1, 32P1, 32S21, 32P31, 32P21 on excipients, 32P51
    Change control databases
    Registration tracking databases
    EV codes (IDs) by EMA for MAH and manufacturers
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Portals
    EMA Web portal, provide data in XSD format as per technical specification
    EMA interface “Webtrader” for single case entry
    Third party software packages, software currently in use to capture individual safety case reports
    Adjust PV system interface with EMA systems
    Most likely, MAH responsible for maintaining accounts
    Disable accounts when people leave the company!
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Roles and responsibilities
    Reporting of product information with PV relevance
    Permanently keep PI up to date in all EEA languages (<15 days after approval ! Under review)
    Generate a PV System Master File and keep it up to date
    And also still in eCTD EU M1 !!
    RMP for all medicinal product of the company
    List products under surveillance by EMA and NCAs
    Surveillance statement to be included in PI
    Include phone no. in SmPC and PIL for ADR contacts, medical information requests, or product complaints
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Infrastructure
    Central office (CO)
    To have LOs
    Providing data
    Reviewing the submission
    Local offices (LO)
    To provide national information to CO
    To inform CO when products are approved
    To share national product information with CO
    To inform CO about changes in the MAH details
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Terminology (elements and values)
    Details on the medicinal product
    Name of the medicinal product
    Therapeutic indication (MEDRA), therapeutic area(s) (ATC code!)
    Substance preferred name (controlled vocabulary version 1.0)
    Detailed description of active substance, adjuvants and excipients (structured substance information version 1.0)
    Details on the marketing authorization holder
    Name, address and contact details of the MAH
    Code number of QPPV as in Eudravigilance database
    Information (incl. location) of the PV master file
    Designation of additional monitoring, obligatory for biological products; for others only if applicable
    Details on the MA and its status
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Terminology (elements and values)
    Strength of the active substance
    Pharmaceutical dosage form
    Route(s) of administration
    Description of packaging information
    Electronic copies of SmPC, PIL, Label
    Information on MAH for batch release, conditions of approval (=specs that might be different across the EEA!)
    Product information in all EU languages!
    Naming convention of documents?
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • ISO Identification Medicinal Product (IDMP)
    Must be used by Jan 2015
    Medicinal Product ID
    Pharmaceutical Product ID
    Substance ID
    Controlled vocabularies for:
    Dosage form
    Route of administration
    Packaging components
    Units of presentations
    Units of measurement
    Description of manufacturing process to be submitted too
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Challenges in process
    Obtaining the relevant information
    What is the authoritative source
    Central vs. local offices
    Regulatory Affairs vs. Pharmacovigilance vs. other disciplines
    Who is responsible for maintaining the source information
    Can this information be reused across eCTDs, NEES and submission and tracking tools?
    Who is responsible for the XEVMPD submissions?
    What values to be used
    How can vendors develop tools if cannot get an account?
    Impact on class labelling and reimbursement/pricing due to clustering based on MEDRA indications
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Operational challenges
    Coping with inconsistencies in guidelines; e.g.:
    Country code: ISO 3166-1 vs. eCTD M1 specs
    Dosage form: controlled vocabulary vs. ones selected for eCTD
    Single value vs. multiple values
    Uncertainty for language of values for non-CP products
    Are all substances and excipients listed in the SSI?
    E.g. Magnesium stearate is not in
    Non-compendial excipients and proprietary excipients/adjuvants?
    128.000 products to be updated in EVMPD
    400.000 products to managed from scratch
    Redundancy in AS information submitted by >1 MAH
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Conclusions
    The new legislation must be adhered to before July 2012
    It is work in progress, so (slowly) moving target
    Needs dialogue between industry-agency-vendor
    Needs dialogue between company’s disciplines
    Central Office and Local Office
    EVMPD team and suppliers
    Registration Managers
    IT and Business Support
    Pharmacovigilance, Drug Safety and Epidemiology
    Pharmacovigilance Legislation
    Copyright eCTDconsultancy B.V.
  • Thank you!
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