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Regulatory considerations in production of a cell therapy medicinal product in Europe to clinical research

The development of new drugs using stem cells has become a clinic alternative for the treatment of different diseases such as Alzheimer’s, diabetes and myocardial infarction. Similar to conventional medicines, stem cells as new medicinal products for cell therapy are subjected to current legislation concerning their manufacture process. Besides, their legality is determined by the Regulatory Agencies belonging to the Member State of the European Union in which they are being registered. With the evolution of therapy that uses cells as medicines, there is a need to develop the appropriate legislative and regulatory framework capable of ensuring their safety and effectiveness. However, few works have been published regarding the regulations that these products must comply through production and commercialization processes. The present work is focused on the description of key events during clinical development and cell production of stem cells as drugs. Such as the regulations, requirements and directives involved in the production of cell therapy medicinal products, from the clinical design stage to its commercialization in Europe.

Isolation and characterization of the environmental bacterial and fungi contamination in a pharmaceutical unit of mesenchymal stem cell for clinical use.

Design and implementation of an environmental monitoring program is vital to assure the maintenance of acceptable quality conditions in a pharmaceutical manufacturing unit of human mesenchymal stem cells. Since sterility testing methods require 14 days and these cells are only viable for several hours, they are currently administered without the result of this test. Consequently environmental monitoring is a key element in stem cell banks for assuring low levels of potential introduction of contaminants into the cell products. The aim of this study was to qualitatively and quantitatively analyze the environmental microbiological quality in a pharmaceutical manufacturing unit of human mesenchymal stem cells production for use in advanced therapies. Two hundred and sixty one points were tested monthly during one year, 156 from air and 105 from surfaces. Among the 6264 samples tested, 231 showed contamination, 76.6% for bacteria and 23.4% for fungi. Microbial genuses isolated were Staphylococcus (89.7%), Microccocus (4.5%), Kocuria (3.2%) and Bacillus (2.6%). In the identification of fungi, three genuses were detected: Aspergillus (56%), Penicillium (26%) and Cladosporium (18%). The origin of the contamination was found to be due to personnel manipulation and air microbiota. For all sampling methods, alert limits were set and corrective measures suggested.