药物分析学报

抽象的

Development of Test Method for Pharmaceutical and BioPharmaceutical Products

Hideharu Shintani

Biological products are mostly macromolecular entities that are considerably larger than most chemical products. With the exception of synthetic oligonucleotides or peptides, living cells-complex metabolic factories produce them. The target molecule(s) must be isolated from a biochemical milieu consisting of chemical entities relatively similar to the desired product. As such, it may be difficult to completely eliminate impurities derived from the host system. The purified target may comprise several structurally heterogeneous forms, some or all of which might be active. Compared to traditional chemical drugs, biological materials are highly labile, and unable to tolerate high temperatures or undue chemical or physical stress. Higher-order biological products (e.g., cells and tissues) may have a very short window of viability. It requires numerous complex analytical methods to provide an effective physiochemical profile of biotechnology products.
This paper has presented several factors to consider when selecting the analytical methods to assess the identity, purity, impurities, concentration, potency, stability, and (in some cases) comparability of biotechnology products. Since no single method can provide data on all key product parameters, orthogonal analytical methods should be used to increase confidence in the quality of product. Methods used under good laboratory practice (GLP) or CGMP quality practices must be validated for their intended use. The strategies for qualifying and/or validating biomolecular methods should be based on the type of method, the nature of the product, and the parameter to be evaluated with the data. Laboratories that adopt validated methods (e.g., compendial methods) must experimentally verify the suitable performance of these methods in the user environment. In order to provide a complete product development record, all of these activities must be adequately documented to demonstrate how, when, and by whom they were conducted.
As has been noted, "Some data are worthless; some data are priceless. The conditions and procedures used to find data ultimately determine their value". All decisions regarding the control of the process and the quality of the product are based on data generated by analytical tests. If there are design flaws in the test methods, unrecognized sources of method variation, or a method is chosen that cannot support the specification requirements, the data will inevitably be inadequate, inaccurate, or unreliable. So, while it is certainly critical to understand the process by which a biological or biotechnological product is produced, it is equally vital to understand the methods of analysis that are applied to the product. Otherwise, it will be very difficult to distinguish between those data that are priceless and those that are worthless.