In a workshop led by Thermo Fisher Scientific, Joseph Granchelli, Ph.D., manager of applications and technical support, introduced the company’s new department, “Customer Applications and Compliance Support,” which encompasses the company’s materials and regulatory compliance groups.
Dr. Granchelli noted that as cell therapy production moves into automated, single-use disposable process streams, one over-arching concern relates to the potential for polymeric materials used to make the single-use bags, connectors, and tubing, for example, to be resorptive, reactive, or additive and to adulterate the final product. Further confounding this issue at present is a lack of clarity and standardization on how and when to test for these effects, what to look for, and what the results mean. Regulatory bodies have not established specifications for how much testing may be required and how to go about doing it.
The presentation focused on the potential for single-use materials to be additive and, specifically, on two problems. The first is extractables—compounds forced to migrate from a molded product under highly exaggerated conditions, such as exposure to “aggressive” solvents, extreme temperatures, sterilizing irradition, high pressure, the presence of stabilizers, colorants, and plasticizers, for example, and factors related to packaging that can lead to off-gassing. The second concern is leachables—materials that migrate into the final product or an intermediate at typical or somewhat exaggerated conditions.
Dr. Granchelli presented a risk-based approach that involves assigning a risk for each component to the final product and, where there may be risk, determining if extractable/leachable data is already available and otherwise performing the appropriate assays. He described how vendors can help with this approach if they have already tested their single-use products under a range of conditions and can make the data available to customers.