Raw materials intended to be used for Gene, Cell and Tissue therapies: legal and regulatory considerations
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raw materials – ancillary products – placing on the EU market – free circulation – restrictions of use – harmonisation


This paper offers some insights on the European regulatory situation with respect to raw materials used in production of gene, cell and tissue therapy products, including advanced therapy medicinal products. By focusing on the existing EU and French rules, the purpose of this paper is to review the content and scope of the measures restricting their placing on the market and/or use, the legal implications and hence key challenges ahead. Also known under the specific term ‘ancillary products’ in France, raw materials are subject to a fragmented regulatory environment that could indirectly hinder innovation in this rapidly evolving area. Taking account of contamination risk that could originate from such materials, the question as to whether it is necessary to assure their quality and safety by means of one or various regulatory instrument(s) does not arise. Nevertheless, it is vital that, in a sector as innovative as this one, an appropriate and more predictable regulatory regime applies in Europe, which requires undertaking a constructive work aimed at harmonising the rules in relation to production of and trade in raw materials intended to be used for advanced therapies while ensuring the EU objective of public health protection: a work already in progress.
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Regulation (EC) n°1394/2007 of the European Parliament and the Council on advanced therapy medicinal products [2007] OJ L324, 10.12.2007 (ATMP Regulation)

Directive 2001/95/EC of the European Parliament and of the Council of 3 December 2001 on general product safety [2002] OJ L 11, p 4-17 (General Product Safety Directive)

Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use [2001] OJ L311, Annex 1 (Medicinal Product Directive)

Point of part 1 of Annex I to Directive 2001/83/EC

Directive 2004/23/EC of the European Parliament and of the Council on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells [2004] OJ L102 (Human Tissues and Cells Directive)

Council Directive 93/42/EEC of 14 June 1993 concerning medical devices [1993] OJ L 169, p 1

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Commission Regulation (EC) n°668/2009 of 24 July 2009 implementing Regulation (EC) n°1394/2007 of the European Parliament and of the Council with regard to the evaluation and certification of quality and non-clinical data relating to advanced therapy medicinal products developed by micro, small and medium-sized enterprises [2009] JO L 194, p 7

Point 3.2 (7) Annex 1 to Directive 2001/83/EC

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European Medicines Agency, guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells, London, 13 April 2012, point 5.1.2

Part IV of Annex 1 to Directive 2001/83/EC, as amended, lays down specific requirements applying to ATMPs and their starting materials, but not to raw materials.

French law n° 98-535 on the increase of sanitary supervision and sanitary control of products for human use, JO n° 151 of 2 July 1998 – legislative file available online at www.senat.fr/dossier-legislatif/ppl96-369.html

Case C-219/11, Brain Products GmbH v. BioSemi VOF [2012] paras 28 and 29 - Not yet published

Symposium, Raw Materials for production of cell-based and gene therapy products, EMA/EDQM, Strasbourg - France, 3 April 2013

Nolte A., Welcome Introduction European Medicines Agency, p 1, Paper presented at the Symposium on raw materials for production of cell-based and gene therapy products, Strasbourg, 3 April 2013

Salmikangas P. and Celis P., ‘Current challenges in the development of novel cell-based medicinal products’, Regulatory Rapporteur, Vol. 8, No 7/8, July/August 2011: p 4-7

Alliance for advanced therapies, consultation paper in response to the European Commission Public Consultation on Regulation (EC) n°1394/2007 on advanced therapy medicinal products, 29 March 2013, p 3, online publication 22 May 2013 at http://ec.europa.eu/health/human-use/advanced-therapies/developments/

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