Agenzia Italiana del Farmaco

Transcription

1 Agenzia Italiana del Farmaco European Regulation on Advanced Therapies Cristina Pintus Head of European Relations Unit and Coordinator of the Advanced Therapy Project Italian Medicines Agency

2 Proposal for a Regulation of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004 To be adopted and pubblished within the next months

3 Blood Products 2002/98/CE Medical Devices 93/42/CEE 90/385/CEE Cells and tissues 2004/23/CE Medicinal Products 2001/83/CE Advanced Therapy Medicinal Products GMP 2003/94/CE 2003/63/CE Clinical Trials 2001/20/CE

4 2001: First discussions 2002: 1 st public consultation 2003: Conference with the 25 EU MS 2004: 2 nd public consultation and conference with the 25 MS 2005: 3 rd public consultation and with the Pharmaceutical Committee 2005: Proposal adopted by the Commission See COM(2005) 567 definitive of : Report on the proposal amended by the MS rejected by the Parliament Committee May 31, 2007: Council of Ministers approval

5 8 Chapters 1. Subject Matter and Definitions 2. Marketing Authorisation Requirements 3. Marketing Authorisation Procedure 4. SPC, Labelling, Package Leaflet 5. Post-Authorization Requirements 6. Incentives 7. Committee for Advanced Therapies 8. General and Final Provisions 30 Articles 4 Attachments

6 1. Subject Matter a) Specific rules concerning the authorisation, supervision and pharmacovigilance of advanced therapy medicinal products b) Products to be released on the European market and prepared industrially or by means of industrial methods

7 Following products are exempted (article 28) Every AT medicinal product which is prepared on a non-routine basis, according to specific quality standards and used in a single MS, in a hospital, under the exclusive professional responsibility of a physician, according to a medical prescription for single patient Similar to the products described in art. 3 of directive 2001/83/EC (magistral( or officinal formula)

8 Definitions Advanced Therapy Medicinal Product Gene therapy medicinal product Cellular somatic therapy medicinal product Tissue engineering products Directive 2001/83/EC, Annex I, Part IV

9 Tissue engineered (TE) product (definition) Contains or consists of engineered cells or tissues, and has properties for regenerating, repairing or replacing a human tissue Cells or tissues can be of human or animal origin, viable or non viable.. The TE product may also contain additional substances like cellular products, biomolecules, biomaterials, chemical substances, scaffolds or matrices

10 Cells or tissues are considered engineered if they fulfil at least one of the following points: Substantial manipulation: modification of biological characteristics, physiological functions or structural properties relevant for the intended regeneration, repair or replacement Cells or tissues are not intended to be used for the same essential function in the recipient as in the donor (non homologous use: : amnion in cornea, b.marrow in heart)

11 an AT product thatcontains exclusively non- viable cells or tissues and does not act principally by a pharmacological, immunological or metabolic action is not considered an advanced therapy medicinal product

12 Annex 1 Manipulations considered non substantial: Cutting Grinding Shaping Centrifugation - Soaking in antibiotic or antimicrobial solutions Sterilization Irradiation Cell separation, concentration or purification Filtering Lyophilization Freezing Cryopreservation Vitrification

13 Combined Advanced Therapy Medicinal Product: Incorporates as an integral part of the product one or more medical devices or active implantable medical devices,, and its cellular or tissue part contains viable cells or tissues, or contains non-viable cells or tissues, able to exert an action that can be considered primary to that of the devices referred to Directive 93/42/EEC and Directive 90/385/EEC

14 2. Marketing Authorisation Requirements Donation, procurement and testing : 2004/23/EC Clinical Trials: 2001/20/EC and new GCP guidelines Production: new guidelines according to GMP principles Products combined with medical devices: 93/42/EEC Products combined with implantable medical devices: : 90/385/EEC Amendments to Regulation 726/2004/EC Directive 2001/83/EC

15 3. Registration procedure (EMEA only) ) (a) CHMP will consult a specific committee, that will give support for any specific scientific assessment of AT medicinal products: Committee for Advanced Therapies (CAT) CAT will prepare a draft opinion on the scientific assessment of AT products and will also re-examine examine any opinion

16 3. Registration procedure (EMEA only) ) (b) CHMP will issue the final evaluation based on the CAT draft opinion. In case of divergent opinions,, the CHMP will annex to its opinion a detailed explanation of the scientific grounds for the differences

17 3. Registration procedure (EMEA only) ) (c) For combined products the CHMP will take into account the evaluation of the certifying bodies of the medical device and formulate a global final opinion may request the relevant notified body to transmit any information related to the results of its assessment

18 4. SPC, labelling,, package insert Information on primary/external package Unique codes of the product and of the donation For autologous use only,, with ID code of the patient Type and source of the cells Nature of the medical device with directions and potential precautions for use and disposal See Annex II, III, IV for all details

19 5. Post-Authorisation Requirements (a) (pharmacovigilance) Measures foreseen for efficacy and adverse reactions follow-up (Regulation 726/2004 and next specific guidelines) A risk management system to identify, characterise, prevent or minimise risks related to AT products

20 5. Post-Authorisation requirements (b) (pharmacovigilance) Evaluations on the effectiveness of the risk management system if established (results of any such studies to be included in the periodic safety reports) Detailed guidelines for the specific follow up criteria and for a risk management plan will be prepared by EMEA

21 5. Post-Authorisation Requirements (c) (pharmacovigilance) In case of severe adverse reactions with a combined product, the applicant will send the report to EMEA (Eudravigilance) EMEA will thereafter inform the national competent authorities responsible for Tissue and Cell Transplantation (in Italy the CNT) and for Medical Devices (in Italy the Ministry of Health)

22 5. Traceability (a) Traceability of single products and their source substances and raw material must be documented Documentation should remain available for 30 years (after the product expiry date) at the manufacturer site to trace the product from industry (manufacturing, packaging, storing, transport and delivery) to the hospital where the product will be used.

23 5. Traceability (b) The hospital must keep trace of the product from supply to administration to patient Registries must indicate for each patient the identification of the specific product administered Directives 2004/23 and following directives on tissues and cells

24 6. Incentives (a) The applicant of an AT may ask for scientific advice from EMEA for pharmacovigilance and risk management plans and systems 90% fee reduction for SMEs and 65% for others AT product classification: within 60 days

25 6. Incentives (b) For SMEs: scientific assessment and certification for data relevant on quality and preclinical studies 50% registration fee reduction (and for first year post- registration activities) for hospitals and SMEs if they can show that the product is of particular interest for EU public health

26 7. AT Committee (a) 5 CHMP members or co-opted opted members 1 representative from each Member State 2 representatives of the physicians selected by the EU Commission 2 representatives of the patients associations selected by the EU Commission for each member there will be an alternate pubblication of names on EMEA s s website

27 7. AT Committee (b) Expertise in: Medical devices (at least 2), tissue engineering, cell therapy, biotechnology, surgery, pharmacovigilance, risk management and ethics. External experts admitted if needed 3 years mandate (renewable( renewable) ) and absence of interests/conflicts with industries of biotechnology and medical devices

28 8. General and Final Provisions (a) The Commission, after consulting the Agency,, can amend the Annexes I-IV IV Within 5 years from the entry into force of the Regulation the Commission will publish a report and an assessment of the impact of technical progress on the Regulation The Regulation enters into force the 20th day after its publication and becomes operating after 1 year

29 8. General and Final Provisions (b) The upcoming new Regulation on advanced therapy medicinal products is a lex specialis and introduces additional provisions to those foreseen in directive 2001/83/EC Amendments will be necessary to: Directive /EC Annex I Part IV and Regulation 726/2004/EC to introduce combined products containing medical devices, scaffolds, matrices and their characteristics

30 8. General and Final Provisions (c) Regulation of AT should not interfere with decisions made by MS on whether to allow the use of any specific type of human cells, such as embryonic stem cells,, or animal cells. It should also not affect the application of national legislation prohibiting or restricting the sale, supply or use of medicinal products containing, consisting of or derived from these cells.

31 8.. General G and Final Provisions (transition period) For products different from those of tissue engineering already on the national market at the date of the Regulation application: 3 years to comply For products of tissue engineering already on the national market at the date of the Regulation application: 4 years to comply For all these situations: : no fee to the Agency

32 Reference Draft proposal for a Regulation on advanced therapies Guideline on human cell-based medicinal products EMEA In public consultation until 31 July 2007, see: emea.europa.eu/pdfs/human/cpwp/ en.pdf