Pharmacovigilance evmpd submission


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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

  1. 1. New EU Pharmacovigilance Legislation<br />The impact on information flow, safety and labelling documents, document granularity, naming of documents and metadata, the preparation and submissions of XEVMPD dossiers<br />Hans van Bruggen - eCTDconsultancy<br />
  2. 2. Aims of the New Legislation<br />Clarify roles and responsibilities NCA, EMA and MAHs<br />Establish a clear legal framework for post-authorization monitoring<br />Minimize duplication of effort across EU<br />Free up resources by rationalizing and simplifying adverse drug reaction (ADR)<br />Reporting of periodic safety update report (PSUR)<br />Scope<br />All medicinal products and Advanced Therapeutic Medical Devices<br />Across EEA (EU + Iceland, Lichtenstein and Norway)<br />Copyright eCTDconsultancy B.V.<br />Pharmacovigilance Legislation<br />2<br />
  3. 3. Time lines<br />Dec 2010: Directive and Regulation released<br />Apr/June 2011: Information to stakeholders<br />Sep 2011: Publication of technical specifications<br />Oct/Nov/Dec 2011: EMA offers end user training on their eSubmission tool (for SMEs)<br />Nov 2011: testing environment available at EMA<br />Requires registration in EudraVigilance<br />Jan 2012: EMA can accept electronic submissions<br />Jul 2012: EVMPD data submitted and maintain as such<br />Jan 2015: Adjust technical specs to ISO IMPD standards<br />Jan 2016: ISO IMPD data submitted and maintain<br />Pharmacovigilance Legislation<br />3<br />Copyright eCTDconsultancy B.V.<br />
  4. 4. Impacts<br />Safety evaluation<br />Scope<br />Product information<br />Submission format<br />Electronic specifications<br />Portals<br />Routing<br />Roles and responsibilities<br />Translations of product information in all EU languages !?<br />Infrastructure<br />Portals<br />Terminology (elements and values)<br />Pharmacovigilance Legislation<br />4<br />Copyright eCTDconsultancy B.V.<br />
  5. 5. Safety evaluation<br />Improvement of signal detection<br />Inclusion of literature case reports<br />AE submission from studies via DSUR<br />Change of content of PSUR<br />Electronic PSUR submission only via EudraVigilance<br />Worksharing of PSURs by NCAs and EMA<br />New scientific committee “Pharmacovigilance Risk Assessment Committee” (PRAC) to be hosted by EMA<br />Pharmacovigilance Legislation<br />5<br />Copyright eCTDconsultancy B.V.<br />
  6. 6. Evaluation<br />Changed definition of adverse effect<br />Incomplete/invalid and consumer cases to be included as well, e.g.<br />Overdose<br />Off label use<br />No relation at all<br />All literature cases to be included<br />Pharmacovigilance Legislation<br />6<br />Likely causing:<br /><ul><li>Over-reporting
  7. 7. Incorrect interpretation of seriousness and applicability to labelled use</li></ul>Copyright eCTDconsultancy B.V.<br />
  8. 8. Product information and PSURs<br />SmPC and Package leaflet<br />Safety sections will have to be adjusted (occurrences will increase)<br />PSUR<br />Comparison labelled vs. unlabelled will shift<br />Comparison expected vs. unexpected will shift<br />Pharmacovigilance Legislation<br />7<br />Copyright eCTDconsultancy B.V.<br />
  9. 9. Electronic specifications<br />XEVPRM<br />Based on a XML Schema Definition (=XSD)<br />Mandatory elements<br />Non-mandatory elements<br />“If you like” (very little) or “If applicable” (mostly)<br />Product information to be provided as single PDF files<br />Likely in accordance with QRD template<br />CP: in English per MAA or per procedure #?<br />DCP/NP/MRP: in all EEA languages (concatenated/language)<br />Substance information in addition to SSI in attached PDF<br />To be submitted as a ZIP file (<60 MB per submission!!!)<br />No tools available yet<br />Validation criteria under development<br />Pharmacovigilance Legislation<br />8<br />Copyright eCTDconsultancy B.V.<br />
  10. 10. Potential sources for data<br />eCTD<br />Envelope<br />Cover letter<br />Application form, in accordance with<br />Trade registries, GMP certificates, QP for batch release, Declaration QPPV, Etc.<br />Product information<br />RMP<br />DDPS<br />32S1, 32P1, 32S21, 32P31, 32P21 on excipients, 32P51<br />Change control databases<br />Registration tracking databases<br />EV codes (IDs) by EMA for MAH and manufacturers<br />Pharmacovigilance Legislation<br />9<br />Copyright eCTDconsultancy B.V.<br />
  11. 11. Portals<br />EMA Web portal, provide data in XSD format as per technical specification<br />EMA interface “Webtrader” for single case entry<br />Third party software packages, software currently in use to capture individual safety case reports<br />Adjust PV system interface with EMA systems<br />Most likely, MAH responsible for maintaining accounts<br />Disable accounts when people leave the company!<br />Pharmacovigilance Legislation<br />10<br />Copyright eCTDconsultancy B.V.<br />
  12. 12. Roles and responsibilities<br />Reporting of product information with PV relevance<br />Permanently keep PI up to date in all EEA languages (<15 days after approval ! Under review)<br />Generate a PV System Master File and keep it up to date<br />And also still in eCTD EU M1 !!<br />RMP for all medicinal product of the company<br />List products under surveillance by EMA and NCAs<br />Surveillance statement to be included in PI<br />Include phone no. in SmPC and PIL for ADR contacts, medical information requests, or product complaints<br />Pharmacovigilance Legislation<br />11<br />Copyright eCTDconsultancy B.V.<br />
  13. 13. Infrastructure<br />Central office (CO)<br />To have LOs<br />Providing data<br />Reviewing the submission<br />Local offices (LO)<br />To provide national information to CO<br />To inform CO when products are approved<br />To share national product information with CO<br />To inform CO about changes in the MAH details<br />Pharmacovigilance Legislation<br />12<br />Copyright eCTDconsultancy B.V.<br />
  14. 14. Terminology (elements and values)<br />Details on the medicinal product<br />Name of the medicinal product<br />Therapeutic indication (MEDRA), therapeutic area(s) (ATC code!)<br />Substance preferred name (controlled vocabulary version 1.0)<br />Detailed description of active substance, adjuvants and excipients (structured substance information version 1.0)<br />Details on the marketing authorization holder<br />Name, address and contact details of the MAH<br />Code number of QPPV as in Eudravigilance database<br />Information (incl. location) of the PV master file<br />Designation of additional monitoring, obligatory for biological products; for others only if applicable<br />Details on the MA and its status<br />Pharmacovigilance Legislation<br />13<br />Copyright eCTDconsultancy B.V.<br />
  15. 15. Terminology (elements and values)<br />Strength of the active substance<br />Pharmaceutical dosage form<br />Route(s) of administration<br />Description of packaging information<br />Electronic copies of SmPC, PIL, Label<br />Information on MAH for batch release, conditions of approval (=specs that might be different across the EEA!)<br />Product information in all EU languages!<br />Granularity?<br />Naming convention of documents?<br />Pharmacovigilance Legislation<br />14<br />Copyright eCTDconsultancy B.V.<br />
  16. 16. ISO Identification Medicinal Product (IDMP)<br />Must be used by Jan 2015<br />Medicinal Product ID<br />Pharmaceutical Product ID<br />Substance ID<br />Controlled vocabularies for:<br />Dosage form<br />Route of administration<br />Packaging components<br />Units of presentations<br />Units of measurement<br />Description of manufacturing process to be submitted too<br />Pharmacovigilance Legislation<br />15<br />Copyright eCTDconsultancy B.V.<br />
  17. 17. Challenges in process<br />Obtaining the relevant information<br />What is the authoritative source<br />Central vs. local offices<br />Regulatory Affairs vs. Pharmacovigilance vs. other disciplines<br />Who is responsible for maintaining the source information<br />Can this information be reused across eCTDs, NEES and submission and tracking tools?<br />Who is responsible for the XEVMPD submissions?<br />What values to be used<br />How can vendors develop tools if cannot get an account?<br />Impact on class labelling and reimbursement/pricing due to clustering based on MEDRA indications<br />Pharmacovigilance Legislation<br />16<br />Copyright eCTDconsultancy B.V.<br />
  18. 18. Operational challenges<br />Coping with inconsistencies in guidelines; e.g.:<br />Country code: ISO 3166-1 vs. eCTD M1 specs<br />Dosage form: controlled vocabulary vs. ones selected for eCTD<br />Single value vs. multiple values<br />Uncertainty for language of values for non-CP products<br />Are all substances and excipients listed in the SSI?<br />E.g. Magnesium stearate is not in<br />Non-compendial excipients and proprietary excipients/adjuvants?<br />Biosimilars?<br />128.000 products to be updated in EVMPD <br />400.000 products to managed from scratch<br />Redundancy in AS information submitted by >1 MAH<br />Pharmacovigilance Legislation<br />17<br />Copyright eCTDconsultancy B.V.<br />
  19. 19. Conclusions<br />The new legislation must be adhered to before July 2012<br />It is work in progress, so (slowly) moving target<br />Needs dialogue between industry-agency-vendor<br />Needs dialogue between company’s disciplines<br />Central Office and Local Office<br />EVMPD team and suppliers<br />Labelling<br />Registration Managers<br />CMC-RA<br />IT and Business Support<br />Pharmacovigilance, Drug Safety and Epidemiology<br />Pharmacovigilance Legislation<br />18<br />Copyright eCTDconsultancy B.V.<br />
  20. 20. Thank you!<br />For more information please visit<br />or mail to:<br />