Commercial Cell Therapy Experience Using Mycoplasma NAT For Product Release: Five-Year Review

Autologous cell therapy products are patient-specific therapies that use cells harvested from a single patient to treat that same patient. Final product release tests that require minimal sampling, produce rapid valid results, and are inexpensive to use is critical because each lot of final product requires testing prior to implantation in the patient.

Rapid detection of mycoplasma is essential for product release testing of autologous cell therapy products such as MACI® (autologous cultured chondrocytes on porcine collagen membrane). Developing and validating a mycoplasma nucleic acid amplification test (NAT) for MACI presented many unique challenges.

The short six-day product shelf life was one major hurdle to overcome because results needed to be available on the same day as final product assembly and release. Application of a risk-based approach during development mitigated most design and process flaws prior to validation. Automation improved reliability and shortened the time to result.

Diligent research coupled with previous regulatory interactions for a rapid sterility test yielded a solid validation study to support using a mycoplasma NAT as an alternative method. Domestic and international compendia are now evaluating including NAT as an official method for mycoplasma detection. Five years of commercial experience and thousands of mycoplasma release tests yielded relatively few invalid tests.

Even so, invalid tests can become consequential if they result in delays or the inability to release the product to a surgeon who has a patient waiting for treatment. Optimization of PCR amplification and evaluation of orthogonal methods were two solutions to potentially reduce the invalid test rate even further.

It is critical to track and trend results after implementation and revisits the original risk assessment periodically as part of the analytical method lifecycle to maintain robust method performance.