Biotechnologies protein product development

At the moment, most of these more exotic bacteria are mainly used in expression for fundamental studies. Considering the speed of developments in biotechnology, their application for industrial or pharmaceutical protein production might become even more important very soon. 

Additional future innovations likely to impact upon pharmaceutical biotechnology include the development of alternative product production systems, alternative methods of delivery and the development of engineered cell-based therapies, particularly stem cell therapy. As mentioned previously, protein-based biotechnology products produced to date are produced in either microbial... 

While some potential therapeutic proteins can be isolated and purihed from natural sources, it may be impractical to extract a sufficient amount for therapeutic purposes. This is the case for tissue plasminogen activator (tPA). While its therapeutic potential was quickly recognized, the protein was present naturally in such small amount that it was not possible to obtain quantities sufficient for chnical evaluation. Advances in biotechnology, including the development of recombinant DNA engineering, permitted production of recombinant tPA in sufficient quantities to evaluate its effects on occluded coronary arteries and to eventually develop a product. 

Bioassays may be the most important assays since they are often the only available tools for determining the correct tertiary structure of complex protein products and the activity of even more complex biotechnology products. Bioassays are also the most problematic assays, and the variability may be 50% for animal-based bioassays. New developments in sensor technologies may improve both the speed and accuracy of bioassays [9]. The development of hematopoietic stem cells for in vitro assays has the potential to increase both the accuracy and the speed of bioassays [10]. 

Based on these mechanisms a new frontier in the application of enzymes to biotechnology, including the development of synthetic enzymes (synzymes)82,83 will be exploited. Research on structure-function relationships between ribozymes and abzymes will lead to the development of a number of sequence specific catalysts, which will control expression of a specific gene or its products, and eventually to application as pathogen controls in agriculture and to clinical use. Sequence specific abzymes may also facilitate research on the primary structure determination of protein. 

Over the past two decades many biotechnology-derived products have been approved in the United States. A selected list of these products is provided in Table 6.2. The products include recombinant endogenous-replacement proteins, cytokines, monoclonal antibodies, and fusion molecules. Other chapters in this book give more detailed product-class-specific descriptions of the preclinical development programs for many of these molecules. 

In the early days of biotechnology product development, the focus was on quality issues [4] or process-related impurities.The concerns at that time were for carryover of other cellular proteins and DNA and for contamination with endotoxins, chemicals, and viruses. Of course, these concerns still exist, but methods for purification and assays for evaluation of clearance have alleviated the need for the safety assessment scientist to focus on contaminants instead they are now asked to focus on the pharmacological activity of the molecules. An ICH guidance (Q6B Specifications Test Procedures and Acceptance Criteria for Biotechnological/Biological Products) addresses the specific issues related to the manufacturing process [6], Other product-related issues such as impurities do need to be considered by the safety assessment scientist, for... 

Gerald W. Becker, SSCI, West Lafayette, Indiana, Biotechnology-Derived Drug Product Development Regulatory Considerations in Approval of Follow-On Protein Drug Products... 

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