Role of the blood service in cellular therapy Paolo Rebulla * , Rosaria Giordano Centre of Transfusion Medicine, Cellular Therapy and Cryobiology, Department of Regenerative Medicine, Foundation Ca’ Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milan, Italy article info Article history: Received 21 September 2011 Accepted 18 October 2011 Keywords: Cellular therapy Stem cells Regenerative medicine Transfusion medicine Good manufacturing practices abstract Cellular therapy is a novel form of medical or surgical treatment using cells in place of or in addition to traditional chemical drugs. The preparation of cellular products e called advanced therapy medicinal products e ATMP in Europe, requires compliance with good manufacturing practices (GMP). Based on long-term experience in blood component manufacturing, product traceability and hemovigilance, selected blood services may represent ideal settings for the development and experimental use of ATMP. International harmonization of the protocols and procedures for the preparation of ATMP is of para- mount importance to facilitate the development of multicenter clinical trials with adequate sample size, which are urgently needed to determine the clinical efficacy of ATMP. This article describes European regulations on cellular therapy and summarizes the activities of the ‘Franco Calori’ Cell Factory, a GMP unit belonging to the department of regenerative medicine of a large public university hospital, which acquired a certification for the GMP production of ATMP in 2007 and developed nine experimental clinical protocols during 2003e2011. Ó 2011 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved. 1. Introduction Although blood transfusion may obviously represent a form of cellular therapy, evident technological, operational and regulatory differences exist between the traditional and well-established procedures used for the preparation of red blood cells, platelets, fresh frozen plasma, cryoprecipitate and peripheral blood stem cells with closed multiple bag or apheresis systems and the more recently developed protocols aimed at the therapeutic use of highly purified and thoroughly characterized cell sub-populations, frequently consisting of stem and progenitor cells obtained from multiple sources. The latter, which include bone marrow, adipose tissue, placental blood, amniotic fluid and other tissues [1e4], typically require sophisticated manipulations, including magnetic or immune-mediated fractionation, washing, ex-vivo expansion and cryopreservation by dedicated staff operating in expensive clean rooms e currently termed ‘Cell Factories’ e under the rules of good manufacturing practices (GMP) [5]. Because of their long experience in managing aseptic procedures for the collection, testing, labeling and distribution of labile blood products and their active involvement in hemovigilance programs including long-term product traceability and recipient look back, selected blood services with adequate resources may represent a convenient setting for the development of novel products for cellular therapy. However, this development requires specific professional training and formal qualification based on GMP. The European framework for the full transition from classical transfusion medicine into the exciting new and broader field of cellular therapy is represented by the recent regulations related to the so called ‘Advanced Therapy Medicinal Products e ATMP’. At the global level, most institutions, scientific societies and organizations involved in the development and clinical use of ATMP have formed the ‘Alliance for Harmonization of Cellular Therapy Accreditation e AHCTA’, with the objective of creating a single set of quality, safety and professional requirements for cellular therapy including haemato- poietic stem cell (HSC) transplantation (AHCTA mission statement). The aim of this article is to provide a brief overview of the European regulation of cellular therapy and to describe the programs recently developed in a public university hospital blood transfusion service primarily devoted to cellular therapy. 2. European regulation for cellular therapy All regulatory documents and procedures relevant for ATMP are available at the website of the European Medicines Agency (EMA) [6]. The regulatory framework for ATMP is established in ‘Regula- tion (EC) No 1394/2007 of the European Parliament and of the * Corresponding author. Tel.: þ39 02 5503 4021; fax: þ39 02 5458129. E-mail address: prebulla@policlinico.mi.it (P. Rebulla). Contents lists available at SciVerse ScienceDirect Biologicals journal homepage: www.elsevier.com/locate/biologicals 1045-1056/$36.00 Ó 2011 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.biologicals.2011.10.007 Biologicals 40 (2012) 218e221