To date, the industry struggles to detect and classify contaminants in cell and gene therapies (CGTs). Key contaminants found within CGT therapies include—but are not limited to—bacteria, mycoplasma, viral, peptides/proteins, cytokines, growth factors, antibiotics, beads, serum, dead cells, unwanted mammalian cells, non-viable particulates, endotoxins, pyrogens, and bioburden. The lack of standards surrounding many of the potential contaminants is largely due to the novel nature in which these components are being utilized, according to a PLOS One article (1). In addition, the lack of standards for CGT comes from the naivety of the industry, with prior drugs often using endpoint sterilization as a highly successful method to reduce the contamination risk, especially in the pharmaceutical industry. This leaves the burden, or potential opportunity, for the CGT developer to develop their own analytical method based on knowledge and risk within their individual therapies. As a result, detecting any contamination in the final product after the therapy has been produced leads to high manufacturing failure rates and increases in manufacturing costs.
Unfortunately, sterilization methods cannot be adopted for the final product in CGT due to the living nature of the product. Sterilization by filtration, heat, radiation, or chemical would render the product ineffectual. Therefore, manufacturing requires highly controlled environments to limit the contamination risk. However, even with all these controls, there remains a high chance of contamination, no more than from entry to the cleanroom of personnel and materials (2,3). As a result of this risk, regulators are adamant about the use of good manufacturing practices (GMPs) as stated in 21 Code of Federal Regulations Parts 210 and 211. Even with GMPs in place, there are many causes of contamination and, as such, there remains an expectation that final product testing for contamination is conducted on every batch due to the potentially fatal consequence of administering a contaminated product.
David Smith, PhD, Vice President of Technical Operations, Ori Biotech
Courtney LeBlon, PhD, Director of Technical Operations, Ori Biotech