• cellular products;
  • quality control;
  • release;
  • specifications

Harvest, production, storage and release of cellular products are regulated by international guidelines like the EU guidelines 2004/23/EC or 2006/17/EC. In addition, worldwide effective guidelines exist with the FACT-JACIE standards. As cellular products such as haematopoietic progenitor cells (HPC) are usually applied to critically ill patients requirements for release must be well defined and high.

The determination of criteria for release requires a prior definition of specifications of parameters for the product. Such specifications and the question of product release with parameters out of specification will be addressed here exemplarily for autologous and allogeneic HPC grafts.

The harvest of cellular products must be preceded by an examination of the healthy donor or in case of an autologous transplantation of the patient. Apart from the medical history and the clinical condition of the donor, results of the testing of infectious disease markers (IDM) (HCV, HBV, HIV1,2 and syphilis at the minimum) are decisive for the judgment on the donor’s eligibility for donation. In case of an autologous donor, even positive test results for the IDM do not necessarily exclude a donation. After harvest and processing of the cellular product, the processing records must be complete and parameters like the content of the active pharmaceutical ingredient, i.e. CD34+ cells for HPC grafts, the content of possible cellular contaminants such as CD3+ cells in the allogeneic setting or tumour cells in the autologous setting, are relevant and need to be specified. For CD34+ cells, a minimum amount of 2 × 106 cells/kg of body weight for autologous or 4 × 106 cells/kg of body weight for allogeneic grafts is required. This may sometimes only be achieved by more than one harvest. Regarding CD34+ cells, the quality of the cells defined by viability and optional by analysis of clonogenic growth has to be evaluated. Such parameters need to be measured especially after manipulations such as cryopreservation or selection or depletion procedures. In addition, microbial contaminations, i.e. potential contaminations by aerobe or anaerobe bacteria or fungi for HPC products, have to be detected. Cellular grafts undergoing incubation steps need to be examined for contaminations by mycoplasma or viruses in addition. Furthermore, incubation or activation steps of cellular products require examinations regarding functionality, genomic stability and potential malignant transformation of the cultivated cells.

The final decision to release a cellular product in case of parameters being out of the specifications should be guided by the consideration that benefits outweigh potential risks for the recipient when administering the product. Furthermore, the type of the product, HPC or other product like donor lymphocyte infusions, and its importance in a given medical situation of the patient, the documented urgent medical need, will influence the decision of release.