Philadelphia (July 24)—Rapid microbial testing in biopharmaceutical manufacturing is an important tool in potentially reducing process risk and manufacturing costs due to loss of production material. At the Pharmaceutical Technology Annual Conference*, Amy McDaniel, associate director of the QC Microbial Science and Technology Department at Wyeth Biotech (Madison, NJ), discussed the company’s evaluation and implementation of rapid microbial testing at Wyeth’s facility in Andover, Massachusetts.†††
Wyeth evaluated and used a viability-based technology, solid-phase cytometry, in mammalian cell-culture manufacturing. Viability-based technologies use techniques that are linked to the viability of the microbial cells or the potential for the cells to grow. Other technologies for rapid microbial testing are growth-based, cellular component–based, and nucleic acid–based.
In evaluating the potential benefits of rapid microbial testing, Wyeth took several factors into consideration. “During the cell-culture process, manufacturing decisions are made based on retrospective microbiology data. Samples are removed and tested in the quality control microbiology laboratory,” said McDaniel. “Because of the time to results for the bioburden assay, typically 3–7 days, the process proceeds at risk.” This situation is true for both the batch-refeed and pooling portions of a typical cell-culture manufacturing process.
In a batch-refeed process, 80% of the contents are removed, and new media is added every 2–3 days. Processing continues during microtesting and results delivery. If one batch is contaminated, subsequent batches will be lost. A similar problem arises at the beginning of the purification process, in which batches from several bioreactors are fed into a single purification step. Again, if a batch from one bioreactor is contaminated, the pooled batches will be lost.† Therefore, a method for detecting microbial growth more quickly would reduce lost batches and be more cost-effective.
Following a review with the US Food and Drug Administration to discuss the potential change to the testing method and validation protocol, Wyeth evaluated rapid microbial testing in its mammalian cell-culture processing facility using the “ScanRDI” (AES Chemunex, Ker Lann, France) system. The system uses a three-step process of membrane filtration, direct fluorescent labeling of active cells, and laser scaning for microbial testing. The system allowed return of microtesting results in 4 h compared with 3–7 days typically required when using a traditional membrane system.
“Rapid microbial testing can be considered PAT-like,” says McDaniel. “Although it does not involve in-line, at-line, or on-line testing, the reduction in time to 4 h to receive microtesting results makes it ‘near’ real time,” she says. “Also, it improves control of the process by being able to make proactive decisions on refeed and harvest.”
Wyeth also evaluated rapid testing in cleaning validation and is the process of implementing the ScanRDI system for detecting bioburden in rinsewater or swab recovery solutions from clean-in-place validation samples.*The 2007 Pharmaceutical Technology Annual Conference was held in Philadelphia, Pennsylvania July 24–26. Read more.