Novel cell and cell-based therapies require stringent manufacturing, testing and oversight to ensure integrity, function, and above all else, patient safety upon administration. Tissue-derived cellular products are considered to be manufactured products and are regulated as such. Thus, you must ensure that your cell manufacturing process is aligned to current Good Manufacturing Practice requirements. (Note the “current”. This means that these are evolving requirements, so you must stay up-to-date!) In the United States, human cells, tissue and cellular- and tissue-based products (HCT/Ps) are regulated by the Center for Biologics Evaluation and Research (CBER), a division of the U.S. Food and Drug Administration (FDA).
When manufacturing cell and cell-based products, a production facility under strict Quality Control must be used. Ideally, this facility includes the cell manufacturing suites, the storage space for raw and finished product and any laboratory/testing areas. Thus, (1) facility design, access and maintenance, (2) equipment purchase, installation and operational qualification (I/OQ), use and maintenance and (3) raw material specifications, purchase, use and storage must all be carefully controlled. For cell and cell-based therapies, terminal sterilization of the final product is often not possible. As such, quality by design (QbD) is highly important in cell therapy, with stringent testing conducted on the tissue Donor (our next blog post in this series will cover this topic) to preclude risk of contamination at the source. In addition, facility and equipment standards and monitoring must be instituted to ensure aseptic processing of cell and cell-based products. To this end, closed systems and single-use disposables should be used whenever possible to minimize risk of contamination. Therefore, a cGMP manufacturing facility must include clean rooms which control for temperature, humidity, pressure and air particulates, preventing any contamination of manufactured product due to the environment, materials, human handlers and cross-contamination from other products manufactured in the same facility. As such, there should be uni-directional flow of materials and people through these areas and personnel must follow proper gowning procedures. Facilities and equipment requirements are defined under US FDA 21CFR§211 and 21CFR§1271.
As mentioned above, stringent Quality Control systems must be in place to qualify all reagents and processes and to institute Standard Operating Procedures (SOPs) to ensure quality and consistency in manufacturing processes and the end product.
|Facility and Quality Control considerations for cGMP cell manufacturing.|