Adaptable, modular strategy for quality control of cell-based therapies
What is ZellTherQC?
"ZellTherQC" is the title of a highly innovative R&D project initiated by 4 SMEs and 4 research institutions. The aim of the project is the development of an adaptable strategy for improved quality control (QC) of human cells, as they are used in cell-based therapies and Tissue Engineered Products (TEP). Standard operating procedures (SOPs) and handling instructions are just as much a part of the project as the development of devices and diagnostics used in the quality control of cell therapeutics.
Cell-based therapeutics represent a new and very promising alternative for chemotherapy, radiotherapy and surgery in cancer patients and for the treatment of other serious diseases, which can significantly increase the survival rate of patients. As cell therapy drugs consist of living cells, intensive quality control in the manufacturing and application process is required in order to ensure safe and effective treatment of patients. At present, the empirical success is still the central point for the definition of specifications and QC criteria in cell-based therapy concepts. An established general strategy for the quality management of therapeutic cells is still lacking. The ZellTherQC project aims to close this gap and enable manufacturers and users to improve the quality control of cell-based therapies.
What is ZellTherQC´s content?
Cell-based therapeutics are so-called ATMP (Advanced Therapy Medicinal Products), which are divided into somatic cell therapeutics, gene therapeutics and tissue engineering products (TEP) as well as mixed products. They contain or consist of living cells which are either taken from the patient himself (autologous cells, iPS) or derived from the blood/tissue of other people (allogeneic). In the laboratory, these cells are processed and manipulated ex vivo and then administered to the patient. To ensure safe and efficient use, cell therapeutics must meet high quality standards. Quality control plays a central role here.
Many different factors must be taken into account in order to create generally valid standards in quality control. This includes, on the one hand, ensuring product quality through new/improved production technology and in-process quality control (Critical Process Parameters, CPP) and on the other hand the verification of product quality on the basis of defined characteristics (Critical Quality Attributes, CQA), such as identity, conformity, purity, activity, functionality and geno-/phenotypic changes of the cells, contaminations and biocompatibility of the cell products as well as influencing factors of the culture medium.
© Sergey Nivens, Shutterstock.com
The project aims to cover the most important aspects and parameters of the quality control of cell-based therapeutics and their starting products and to orient them towards the existing regulatory framework of EMA (European Medicines Agency) and FDA (Food and Drug Administration).
The broad monitoring spectrum should be condensed to the essential parameters in order to identify meaningful quality parameters at acceptable costs. An adaptable, modular strategy for quality control of cell therapies represents a major technical advance over current systems in terms of more efficient (e.g. automated) control of critical product and process attributes. For this purpose - similar to clinical diagnostics- individual analysis methods are formulated as modules, which can be individually combined according to process and control measures (modular system) and, for example, implemented on an automated system or offered as a central service. This modular, adaptable strategy is intended to enable rapid adaptation to different cell therapeutic cell types/products and to secure a reliable quality control through monitoring along the entire process chain. It will also provide the basis for the production of cell products of consistently high quality, even on a large scale.
The joint project consists of six subprojects, which are implemented by four SMEs and four scientific institutions and emerged from the former ZIM-funded innovation network "Cell Culture 2.0". The joint project is coordinated by EurA AG.
Although the project partners involved are focused and specialized on certain problem areas, no rigid corset for quality control should and can be developed. Rather, the aim is to create a basis for a flexible, powerful and efficient range of methods.