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.

Presented by John Duguid, Executive Director, Research & Development at Vericel Corporation

John Duguid is Executive Director, Research & Development at Vericel Corporation in Cambridge, MA, where he is the CMC technical lead for their commercial-stage regenerative medicine autologous cell therapy products. Previously in his role as Principal Scientist, Mr. Duguid was responsible for developing, validating, and transferring molecular biology assays for rapid microbiology and cellular gene expression, managing complex projects to implement process improvements, and using statistical process control data monitoring in support of these products. He has been with the cell therapy manufacturing facility at Vericel (previously Genzyme) since 1995. Before R&D, Mr. Duguid managed Quality Control cell therapy operations at Genzyme for over ten years, where he designed and implemented a comprehensive cGMP[1]compliant raw material program controlling hundreds of parts and participated in 16 vendor audits, directing four as lead auditor. He also represented QC during ten FDA inspections and numerous audits from international regulatory authorities as a subject matter expert in material inspection and release, biopsy accessioning, endotoxin testing, mycoplasma testing, analytical methods, flow cytometry, laboratory failure investigations, assay validation, and data management. Prior to Genzyme, Mr. Duguid worked in analytical research at Abbott Laboratories’ Pharmaceutical Products Division in North Chicago, IL and then as a scientific consultant for Massachusetts biotechnology companies at Arthur D. Little in Cambridge, MA. He received his Bachelor of Science degree in Chemistry from the University of Michigan, Ann Arbor in 1986 and taught analytical chemistry at Northeastern University in 2000. As a professional in the pharmaceutical and biotechnology industries for over 20 years, Mr. Duguid has technical and management experience spanning all phases of the product lifecycle from early R&D through cGMP commercial operations.

Followed by Lori Daane, Sr. Director of Scientific Affairs at bioMérieux

Lori Daane is the Sr. Director of Scientific Affairs at bioMérieux and has over 30 years’ experience in clinical, environmental and industrial microbiology.  She is a technical expert on rapid and alternative methods and provides scientific support to the Healthcare Business in North America. Prior to joining bioMérieux, Lori worked for 11 years at Celsis in a variety of technical roles including VP of Scientific Affairs and Reagent Development where she helped develop and launch a number of new & improved products.  Lori received her Ph.D. from the University of Minnesota in Microbial Ecology studying the influence of earthwork activity on microbial gene transfer in the environment. She performed postdoctoral research at Rutgers University focusing on phytoremediation of polyaromatic hydrocarbons and at the Los Alamos National Laboratory studying microbial communities associated with cryptobiotic soil crusts. She also holds a Master’s degree in Limnology and a Bachelor’s degree in Medical Technology.

Followed by Mike Brewer, Director, Global Principal Consultant, Regulatory, BioProduction at Thermo Fisher Scientific

Michael Brewer is the Director, Global Principal Consultant, Regulatory for the BioProduction Group (BPG) at Thermo Fisher Scientific. In this role, Michael is responsible for providing global support to BioProduction customers and serving as the regulatory thought leader and expert across all technology areas within BPD.   Prior to moving to this role, he lead the team responsible for product applications including Microbiology, Analytical Sciences and Quality control. The products are fully integrated, solutions for Glycan profiling, Bacterial and Fungal identification, Mycoplasma and Viral detection and host cell DNA and protein quantitation. Michael has over 30 years of experience in the Biopharma industry, including, Scios, Synergen and Amgen in a variety of roles including Discovery Research, Analytical Sciences and Quality Control. Prior to joining Thermo Fisher Scientific, he lead a group at Amgen that developed qualified, validated and implemented molecular methods for host cell DNA quantitation, contaminant (Mycoplasma, Virus and Bacteria) detection, contaminant identification, strain typing and genotypic verification of production cell lines.

Sponsored by bioMérieux and Thermo Fisher Scientific

About bioMérieux

With more than 50 years of pioneering diagnostics, the people of bioMérieux understand the challenges you face when it comes to ensuring product quality and are proud to offer the most comprehensive portfolio of solutions for microbiology Quality Control of biopharmaceuticals and ATMPs.  Choosing the right microbiology diagnostic can boost efficiency with in-processes testing and automation simplifies the testing processes, reduces human error, and helps ensures data integrity. Rapid, simple, at-line testing of key parameters allows in-process tests to be performed closer to the production environment and provides certainty that your manufacturing process is secure.

About Thermo Fisher Scientific

Thermo Fisher Scientific Inc. (NYSE: TMO) is the world leader in serving science, with annual revenue of approximately $40 billion. Our Mission is to enable our customers to make the world healthier, cleaner and safer. Whether our customers are accelerating life sciences research, solving complex analytical challenges, increasing productivity in their laboratories, improving patient health through diagnostics or development and manufacture of life-changing therapies, we are here to support them. Our global team delivers an unrivaled combination of innovative technologies, purchasing convenience and pharmaceutical services through our industry-leading brands, including Thermo Scientific, Applied Biosystems, Invitrogen, Fisher Scientific, Unity Lab Services, Patheon and PPD. For more information, please visit www.thermofisher.com