Biopharmaceutics control systems

Fig. 7.5. The Biopharmaceutics Classification System (BCS) provides a scientific basis for predicting intestinal drug absorption and for identifying the rate-limiting step based on primary biopharmaceutical properties such as solubility and effective intestinal permeability (Pefr). BCS serves as a product control instrument. The BCS divides drugs into four different classes based on their solubility and...

Glennon, B. 1997. Control system validation in multipurpose biopharmaceutical facilities. Journal of Biotechnology 59(1-2), 53-61. 

Often, the best examples of process efficiency can be found outside the pharmaceutical and biopharmaceutical industries. Other fields such as electronics, space, and software industries have evolved their documentation, training, quality, and change control systems to the point of best in class. These industries are more time sensitive to get product to market and have often evolved their processes to be efficient and decision processes to be very quick. Process owners may expand their knowledge by investigating other industries to find best practices and apply them internally. 

Although bioadhesive drug delivery systems have been studied extensively in the past several decades, it is only recently that such systems have been used for delivering water-insoluble drugs. One such system, Spherazole CR (Spherics Pharmaceuticals, Inc., MansLeld, MA), has been used for controlled release ofthe Biopharmaceutical ClassiLcation System (BCS) Class II water-insoluble drug, itraconazole [105-107],... 

Conte, U., Colombo, P., Caramella, C., Ferrari, F., Gazzaniga, A., Guyot, J. C., Fa Manna, A., and Traisnel, M. (1988), Influence of tablet weight control systems during production on biopharmaceutical properties of the tablets, Acta Pharm. Technol., 34(2), 63-67. 

Poultry, Applying the Biopharmaceutics Classification System to Veterinary Pharmaceutical Products (in 2 Parts), Vaccine Development, Immunological Aspects of Controlled Antigen Delivery, Pharmaceutical Challenges in Veterinary Product Development 2002 In Situ Forming Injectables, Bacterial Ghosts, 19... 

Various dissolution test systems have been developed and several of them now enjoy compendial status in pharmacopeias, for example the reciprocating cylinder (United States Pharmacopeia Apparatus 3), the flow-through apparatus [European Pharmacopoeia (Pharm. Eur.) 2.9.3], or the apparatus for transdermal delivery systems, such as the paddle over disc. Hydrodynamic properties of these and other apparatus have been described only sparingly. The paucity of quantitative data related to hydrodynamics of pharmacopeial dissolution testers is lamentable, since well-controllable hydrodynamics are essential to both biopharmaceutical simulations and quality control. Here, we focus the discussion on the paddle and the basket apparatus, since these are the most important and widely used for oral solid dosage forms. A brief treatise on the hydrodynamics of the flow-through apparatus completes this section. 

A diagrammatic representation of using PAT and the Laboratory Information Management System (LIMS) controls for the manufacturing of pharma-ceuticals/biopharmaceuticals is presented in Fig. 9.6. 

To date, most approved protein-based drugs are for therapeutic or replacement therapies. They are recombinant versions of natural proteins such as insulin and erythropoietin. Their characteristics and functions are relatively well defined and known. The next phase of biopharmaceuticals, such as antibodies and vaccines, is more complex and requires more tests and characterizations. Controls for the reliability, contamination, and fidelity of expression systems will be high on the agenda in the coming decade. 

The physicochemical and other properties of any newly identified drug must be extensively characterized prior to its entry into clinical trials. As the vast bulk of biopharmaceuticals are proteins, a summary overview of the approach taken to initial characterization of these biomolecules is presented. A prerequisite to such characterization is initial purification of the protein. Purification to homogeneity usually requires a combination of three or more high-resolution chromatographic steps. The purification protocol is designed carefully, as it usually forms the basis of subsequent pilot and process-scale purification systems. The purified product is then subjected to a battery of tests, which aim to characterize it fully. Moreover, once these characteristics have been defined, they form the basis of many of the quality control (QC) identity tests routinely performed on the product during its subsequent commercial manufacture. As these identity tests are discussed in detail in Chapter 3, only an abbreviated overview is presented here, in the form of Figure 2.7. 

---