Characterization of Alternatives to Animal-Derived Raw Materials “ Animal-Free ” May Not Mean “ Problem-Free ”

Raw material selection, testing, and control strategies are an integral part of the preparation of a well-characterized biological product (1, 2). Animalderived raw materials may be used in cell culture, fermentation, purification, and/or formulation of biopharmaceuticals. Because any animal-derived component could carry a theoretical risk of prion (3) or other adventitious agent transmission (4–6), it is desirable to replace those components with equivalent materials that are not derived from animal sources. Such raw materials can be derived from bacteria, yeast, fungi, or various types of plants. Often it is possible to find a microbial or plant-derived component that meets or exceeds the desired functionality of the original animal component. However, because the alternatives to animal-derived raw materials come from various sources, they may have very different impurity profiles, and their impurities could present additional risks (7). Therefore, it is incumbent upon users of such materials to understand productand process-related impurities associated with the new component and the potential impact those impurities may have on the safety, purity, and efficacy profile of a biopharmaceutical product. The first step is to thoroughly understand the vendor’s manufacturing process by performing a vendor audit. Next, a strategy should be developed for characterizing each component biochemically and functionally to ensure that it does not affect the approved process. The biochemical and functional assays used depend upon the source of the component and what perceived risks related to it are found during searches of the scientific literature. The final step may require demonstrating clearance of the component through the process (during the course of process validation) and developing a scheme for routine monitoring of cleaning effectiveness. All raw materials must be appropriately characterized and qualified for the process to be in compliance with cGMPs. A number of regulatory guidance documents are available (8–21) that discuss how the characterization/qualification should be performed and documented. PRODUCT FOCUS: THERAPEUTIC