A lingering concern is always the very simple question: "Is it safe?" However, answering that question for therapies based on living cells is not simple because biological safety (biosafety) is largely relative; for cellular-based therapies (CBTs) it is perhaps best discussed in terms of biosafety risk. Such risks can be assessed only after considering numerous factors, such as the source of the cells or tissue, preparation methods, the intended recipient, where in the body the cell-based therapy will be implanted, and the method of cell delivery. This article provides an overview of biosafety issues facing cell- and tissue-based products and discusses a systematic, practical approach for addressing them.
Given the inability to completely assess risks that may be lurking in a product derived from living sources and the inability to inactivate or eliminate unknown threats inherent in living cells, it is obvious that providing an absolute assurance of biosafety is not possible. Consequently, a systematic, risk-based approach to biosafety must be employed that considers the unique characteristics of the product in relation to the condition of the recipient.1 Such an approach requires an ongoing biosafety risk assessment throughout all stages of development — before, during, and after administration of the product.
ELEMENTS OF A BIOSAFETY PROGRAMA comprehensive program for assessing, minimizing, and monitoring risks to biosafety includes the following elements, which are also illustrated in Figure 1:
1. Qualification of materials used in product manufacturing
2. Final product release testing
3. Preclinical pharmacology and toxicology
5. Clinical monitoring
Qualification of materials used in product manufacturing
Federal regulations mandate establishment of a quality control unit as part of good manufacturing practices (GMP).2 This is particularly important for cell- and tissue-based products, since the manufacturing process entails the use of source and ancillary materials of differing complexity, variability, and risk for introduction of adventitious agents. FDA has made it clear via conference presentations, mass mailings to IND sponsors and guidance documents that developers of gene therapies and cell- or tissue-based products must have a qualification program in place prior to initiating clinical studies.3-7