When patients are administered biological treatments created from their own bodies - autologous regenerative medicines - every second counts. Quality and purity can’t be compromised. To ensure microbial contaminants are removed during the manufacturing process, rapid microbial methods are needed for cell therapy, tissue-engineered, and gene therapy products.
Several unique rapid microbial method challenges present themselves during the manufacturing process for autologous therapies. Compared to typical pharmaceutical products, autologous regenerative medicines provide inherently a high volume of samples because each patient constitutes a unique manufacturing source. As a result, the number of aseptic manipulations associated with concurrent preparation of multiple samples increases the opportunity for false positive results. What’s the solution?
The importance of rapid microbial methods and building quality into the system
Limited product shelf-life governs manufacturing of regenerative medicines and requires same-day product release in most cases. Testing laboratories need to develop and validate methods capable of high-throughput screening to rapidly test 100% of the lots manufactured. Processing challenges include inconsistencies in the collected cells or tissues, manual sterilization processes to remove microbial contaminants, and degradation of products that cannot withstand terminal sterilization. These challenges in manufacturing regenerative medicines require building quality into the system via environmental, process, and personnel controls.
Meeting the challenge of incubation times vs. shelf life
The primary issue with the current methodology for confirming the sterility of cell therapy and tissue-engineered products is that it requires incubation times that often exceed the product shelf-life. A number of rapid microbial test technologies may address the product release requirements of autologous cell therapy products with short shelf-lives. These tests use enhanced growth-based methods with continuous monitoring and automated detection, molecular biology techniques such as PCR, or biochemical reactions to detect bacteria, fungi, or mycoplasma. In contrast to standard direct culture methods that may take weeks to complete, results for several of the indirect rapid microbial - tests are ready in less than 24 hours.
USP engaging with stakeholders in regenerative medicines
USP continues its leadership role by convening expert panels and collaborating with industry leaders. During one recent panel comprised of biopharmaceutical manufacturing leaders, the participants and USP experts developed user-requirement specifications (URS) for the different stakeholders. This collaboration led to recommendations for determining appropriate technologies in compendial rapid sterility tests as noted in an upcoming General Information Chapter <1071> RAPID STERILITY TESTING OF SHORT-LIFE PRODUCTS: A RISK-BASED APPROACH in USP-NF. This chapter will be proposed in the September–October 2018 issue of the Pharmacopeial Forum and will be open for public comment until November 30, 2018. It will contain explanations of the URS, appropriate rapid microbial testing technologies that satisfy the URS, and the risk-based approach. This will be followed by a test methods chapter based on technologies that can be advanced as compendial methods. Look to USP for continued leadership in supporting biologics manufacturing as the source for resources, standards and collaboration.
