Assessment of biotechnology products for therapeutic use.

Biotechnology products for therapeutic use include a very diverse range of products, including growth factors, cytokines, hormones, receptors, enzymes, clotting factors, monoclonal antibodies, vaccines, DNA vaccines, gene transfer products, cell therapies and tissue/organ grafts. While some of these products are regulated as medicinal products, the regulatory status of others such as some cell therapies and tissue/organ-based products differs globally and falls within the borderline between the practice of medicine, medical devices and medicinal products. The unclear regulatory status of some products can add to the complexity of the safety assessment of such products. Conventional non-clinical testing paradigms and guidelines for small molecule development are often not relevant for biotechnology products. Guidelines relating to the non-clinical safety evaluation of biotechnology products, gene transfer products and cell therapy products are available and represent a set of general guiding principals to be applied on a case-by-case basis. The quality, safety and efficacy of biotechnology products for therapeutic use are intricately linked, far more so than for conventional medicinal products, leading to the need for increased communication between those responsible for ensuring product quality and those responsible for non-clinical safety testing. Safety issues include microbiological safety (due to the use of biological materials either during the manufacturing process or as an integral part of the products), pharmacological/ biological toxicity (due to excessive primary pharmacology or undesirable secondary pharmacology), immunogenicity and potential tumourigenicity (for example, for growth factors, immunosuppressive monoclonal antibodies and cell therapy products). Genotoxicity and intrinsic chemical toxicity are less of a problem for biotechnology products.