WP 4. GMP faciliteter för bioterapi SWECRIN Temamöte Stockholm, 1 Oct 2008 Pontus Blomberg Karolinska Universitetssjukhu

1. WP 4. GMP faciliteter för bioterapi SWECRIN Temamöte Stockholm, 1 Oct 2008 Pontus Blomberg Karolinska Universitetssjukhuset Huddinge

2. ECRIN-PPI WP4 - GMP facilities for biotherapy Starting date: March 1st, 2008 WP leader Istituto Superiore di Sanità (Italian National Institute of Health) (ISS),Rome, Italy Filippo Belardelli, Dept. of Cell Biology and Neuroscience, Director WP co-leaders: Institut National de la Santé et de la Recherche Médicale (INSERM),Paris, France Philippe Moullier, Nantes Univ. (INSERM U649)Gene Therapy Laboratory, Director Karolinska University Hospital (SweCRIN),Stockolm, Sweden Pontus Blomberg, Vecura, Clinical Research Center, Director

3. GMP- Good Manufacturing Practice • Regelverk som används vid tillverkning av läkemedel • Patientsäkerhet • Garantera kvalitet och reproducibilitet • GMP innefattar både tillverkning och kvalitetskontroll

4. GMP är mer än ett laboratorium • Byggnader och Faciliteter • Storlek, läge, materialflöden, ljus, ventilation • Organisation och personal • Utbildning, erfarenhet, tillverkning och kvalitetskontroll oberoende • Utrustning • Design, storlek, rengöring, underhåll, kalibreringar • Produktion • Skriftliga instruktioner (SOPs), Validering, produktsäkerhet • Dokumentation • genomarbetad, fullständig • Lagring och distribution • Karantän/frisläppande, förvaring, dokumentation • Kvalitet och kontroller • Specifikationer, Testning, Provtagning, Procedurer, Klagomål, Indragningar

5. GMPGreat Mountains of Paper

6. Biopharmaceuticals/Bioterapier • Rekombinanta proteiner (inkluderande antikroppar) • Peptider • DNA/RNA oligonukleotider • Vacciner • Läkemedel för avancerad terapi - e.g. genterapivektorer, celler, vävnad

7. GMP Requirement in Cell Therapy • Tissues and cells 2004/23/EC – unmanipulated cells • Amendments 2006/17/EC, 2006/86/EC • ”GMP like” system • Tissue establishments • Quality management system including personnel, equipment, materials, reception, storage, labelling, distribution, quality review • Facilities/premises - tissues and cells exposed to the environment should be carried out in GMP Grade A environment surrounded by GMP Grade D • Medicinal Products 2001/83/EC – manipulated cells • Amendent 2003/63/EC Part IV, Annex I Advanced Therapy Medicinal Products – gene therapy, cells, tissues • GMP Directive 2003/94/EC • Regulation (EC) No 1394/2007 on advanced therapy medicinal products • Valid from 30 December 2008 • Guidelines in line with the principals of GMP (Chapter 2 Article 5) • EMEA/CHMP/4108697/2006 guideline - from Sep 1, 2008

8. ECRIN-PPI WP4 GMP facilities for biotherapy Clinical trials require GMP-compliant manufacturing facilities providing clinical grade batches of medicinal products. Access to such facilities may be a bottleneck to academic institutions and biotechnology SMEs acting in the field of biotechnology and biotherapy. In particular, there is clear need for flexible academic GMP facilities providing, in a non-commercial context, small amounts of biopharmaceutical/biotherapy products for phase I-II trials in exploratory designs.

9. WP1 Management WP1 Management WP3 Financial Plan WP4 Strategy WP8 Regulatory issues WP5 Physical infrastructure WP4 GMP facilities for biotherapy WP7 Standard.-Harmon. Interdependencies between ECRIN-PPI WP4 and other ECRIN-PPI WPs or EATRIS WPs

10. WP4 GMP facilities for biotherapy • Joint ECRIN-EATRIS activity • EATRIS would be in charge of the GMP manufacturing facilities for biopharmaceuticals whenever they fit with the specialisation of the EATRIS disease-oriented translational research centres (cancer, brain, metabolism, cardiovascular and infectious diseases). • ECRIN would be in charge of ‘generic‘ GMP manufacturing facilities for biopharmaceuticals not covered by the EATRIS disease areas, and also of GMP manufacturing for cell therapy and regenerative medicine where GMP production has to be located close to the bedside, resulting in an integrated biotherapy/investigation centre.

11. WP4GMP facilities for biotherapy • Task 4.1 Joint ECRIN-EATRIS survey on existing resources and needs in terms of GMP-manufacturing facilities, both for academic institutions and for EU biotechnology SMEs. • Task 4.2 Then the cost of their construction will be evaluated, and a decision made on the location of these facilities (taking into account national support, availability of EU structural funds, cost of salaries). • Task 4.3 Evaluation of their operation costs and revenues • Task 4.4Comparison of this strategy of construction of EU infrastructures with the use of commercial facilities. A strategy for setting-up a consistent and comprehensive network of GMP facilities, avoiding duplication and covering the needs of users, will be proposed. • Task 4.5 to develop a set of standard operating procedures for the use of these medicinal products in EU clinical trials.

12. WP4GMP facilities for biotherapy Deliverables • 4.1 M12 ECRIN-EATRIS survey on existing resources (public, private, PPP) in all the EU in terms of GMP facilities for biotherapy and biopharmaceuticals • 4.2 M12 ECRIN-EATRIS survey on needs (for public institutions and for the industry, particularly biotechnology SMEs) in all the EU in terms of GMP facilities for biotherapy and biopharmaceuticals • 4.3 M18 Decision on the connection of existing GMP facilities to either ECRIN or EATRIS • 4.4 M18 Evaluation of the construction costs for relevant new GMP facilities • 4.5 M24 Proposal for the construction of GMP facilities within the ECRIN project, and for their location in the EU. • 4.6 M36 Design of these GMP facilities

13. ECRIN-WP4 Teleconference • April 22nd, 2008 • Purpose • To discuss and approve what should be a specific strategy and methodology for Task 4.1: • Joint ECRIN-EATRIS surveys on existing resources (Deliverable 4.1) and needs (Deliverable 4.2) EU-wide in terms of GMP-manufacturing facilities, both for academic institutions and EU biotechnology SMEs. • Definition of an approach to conduct the ECRIN-EATRIS survey on existing resources. • Definition of an approach to conduct ECRIN-EATRIS survey on needs (forpublic institutions and for the industry, particularly biotechnology SMEs). Identification of target groups/primary sources of information. • Geographic area to be covered by the surveys. • Definition of the methodology for obtaining contact details of the primary sources of information. • Definition of the outline of the survey on the existing resources, concerning structural and financial aspects. • Methodology to conduct the surveys.

14. Stretegi och metodologi för undersökning 1. Approach för genomförande av ECRIN-EATRIS undersökning om befintliga resurser • Fastställande av undersökningens utformning gällande struktur och ekonomi • Vilken information om de befintliga GMP faciliteterna ska inhämtas? • Teknik • Infrastruktur • Konstruction • Kapacitet • Ekonomi • Byggkostnad • Driftkostnader • Valideringskostander • Intäkter

15. Proposed Strategy and Methodology • 2. Målgrupper ECRIN-EATRIS undersökning för framtida behov • Målgrupper: • Unversitet (behöver definieras), Universitetssjukhus, Hälsoministerier, Industriministerier, Forskningsministerier, Kliniska forskningscentra, industriorganisationer, Bio - clusters • 3. Länder som ska omfattas: • Båda undersökningarna ska omfatta ECRIN/EATRIS partner länder (14 altogether) plus de som formellt ansökt • 4. Metod: • Lösenordsskyddat formulär tillgängligt på ECRINs hemsida

16. Timetable for the implementation of the activities related to 4.1 and 4.2 Deliverables • End of June 2008 - First draft of the questionnaires. • End of June 2008 - Identification of the contact details of the primary sources of information. • End of July 2008 - Establishment of contact with the GMP facilities contact points. • End of September 2008 - Design and activation of surveys on ECRIN Website. • Three months – Length of the surveys • February 2009 – Assessment of the surveys results. • March 2009 – Deliverable of the reports succeeding the assessment related to the surveys on existing resources (first-level) and needs. • Early 2010 - Design and activation of the second-tier survey on existing resources including non-certified, under construction and planned GMP facilities. • May-June 2010 - Deliverable of the reports succeeding the assessment related to the second-tier survey on existing resources.