1. Best Archival Practice in the Regulation of Medicines: Work on the Guidelines for Agencies for Medicinal Products Ph.D. Arian Rajh Agency for Medicinal Products and Medical Devices Ph.D. Hrvoje Stančić, associated prof. Department of Information Sciences, Faculty of Humanities and Social Sciences, Zagreb

2. Agenda 1.Making medicinal products dossiers digital – past, present and future processes with resources related to authorization of medicines 2.Toward preservation of digital dossiers 2

3. Making medicinal product dossier digital Medicinal product dossier – basic business resource for marketing authorization of medicines Medicinal product dossier consists of – administrative records – dossier summaries – quality records – nonclinical studies – clinical studies Dossiers were submitted in paper – hard to track product lifecycle and manage dossiers – problems with large volume – deviations from standard formats 3 Picture 1: Archives of large agencies can hold > 10 linear kilometres of paper dossiers

4. Making medicinal product dossier digital Solution was to make dossiers e-born – facilitates communication between applicant and agency – easier to manage lifecycle deleted, appended and new documents in the dossier are promptly visible – cheaper to store – easier to check validity and adherence to standard one global standard – eCTD – electronic Common Technical Document – covers ICH regions (EU, Japan, USA) and many non-ICH countries – supported by specifications, expected to become an ISO standard – consists of sequences, structure of directories and files, XML backbone plus additional format – NeeS – Non-eCTD electronic Submission – easy to publish for smaller pharma companies without large IT budgets – same structure and naming conventions as in eCTD, but without XML (unsupported lifecycle) 4 Picture 2: eCTD structure

5. Making medicinal product dossier digital It became serious after Reykjavik agreement – in February 2005 Heads of EU agencies reached decision on target date (2009) when all EU agencies start receiving eCTDs – leaders: European Medicines Agency (EMA) for products approved via centralised procedures, Nederland, Portugal, GB, Ireland, Austria, Hungary… – digital dossier implementation support group from 2000 onwards Telematic Implementation Group on electronic Submission (TIGes) – European group responsible for implementation of eCTD and production of guidance – from 2009 EU agencies are working with eCTDs, with more or less success… complex workflows, lack of records management systems and business intelligence maintenance and preservation issues 5

6. Toward preservation of digital dossiers Preparations for target date included… – designing eCTD related processes, creating standard operative procedures – education of medicinal products assessors – non-EU countries have to adjust XML in eCTD because they were not included in eCTD specifications Current efforts include planning – submission via one centralised gateway for all EU agencies – 2-way communication between applicants and agencies – work sharing between agencies – preservation issues brought with 2010 archive survey conducted by French agency and Croatian visit to French agency idea of gathering special group for archiving question was suggested to TIGes 6

7. Toward preservation of digital dossiers Ad-hoc drafting guidance group Best Archiving Practice – adopted by the TIGes in 2011 – supported by EMA – first meeting held on 25 October 2011 – co-chairs: Cecile Levy-Lombard (France), Arian Rajh (Croatia) – members: Austria, Belgium, Croatia, Denmark, EMA, Estonia, Finland, France, Greece, Hungary, Luxembourg, Malta, Nederland, Slovenia, Sweden – members are TIGes delegates – working methods web meetings face-to-face meetings if needed 7

8. Mission/mandate – to prepare Best archiving practice document for publication by the TIGes – to facilitate referent framework for establishing long-term preservation policy for electronic submissions, including common archival requirements defined responsibilities and provided recommendations on archival issues that should fit organisational and national requirements Referent framework should rely on following standards – Recent eCTD specifications and Guidance for Industry on providing regulatory information in eCTD format – Standards issued by International Council of Archives (ICA) – ISO 14721 OAIS – ISO 30300 Management systems for records – ISO 15489 Records management – ISO 19005 PDF – ISO 23081 Records management processes - Metadata for records – Model Requirements for Electronic Records Management Toward preservation of digital dossiers 8 Picture 3: Archival package defined by OAIS (Blue book, figure 4-15)

9. Toward preservation of digital dossiers Results – Ad-hoc guidance drafting group on Best archiving practice is composed. – Creating model(s) of archival packages based on OAIS information model – Identification of mandatory archival metadata for electronic submissions – Preparing Best archiving practice guidance Deliverables – Model and composition of archival packages are designed. – Recommendations on PDF versions and other issues submitted to TIGes. – Mandatory archival metadata for archival packages and format of metadata that can be exchanged between digital archives agreed. – Draft and final version of guidance produced. 9

10. Toward preservation of digital dossiers Decisions that must be made before drafting guidance – linked to production of OAIS-based model that allows national and organisational differences in archiving What to preserve? – eCTD dossiers, invalid eCTD sequences, records produced by agencies (Marketing authorizations, Assessment reports) For how long? – different procedures – national authorizations, centralised procedure, procedures that include more agencies – different national retention periods Specific issues – how to facilitate future migrations, benefit of deriving archival package from submitted package – how to protect packages, which algorithms to use (MD5, SHA) – metadata issues, to single out preservation metadata and to prescribe storage of metadata – PDF issues (compliance to PDF/A standards) 10

11. Thank you for your attention! Best archival practice in the regulation of medicines: Work on the guidelines for Agencies for medicinal products Ph.D. Arian Rajh Agency for medicinal products and medical devices arian.rajh@halmed.hr Ph.D. Hrvoje Stančić, associated prof. Department of Information Sciences, Faculty of Humanities and Social Sciences, Zagreb hrvoje.stancic@zg.t-com.hr 11