Biopharmaceutics essentials

Human blood plasma contains over 700 different proteins (qv) (1). Some of these are used in the treatment of illness and injury and form a set of pharmaceutical products that have become essential to modem medicine (Table 1). Preparation of these products is commonly referred to as blood plasma fractionation, an activity often regarded as a branch of medical technology, but which is actually a process industry engaged in the manufacture of speciaUst biopharmaceutical products derived from a natural biological feedstock (see Pharmaceuticals). 

As the twentieth century came to a close, the job market for computational chemists had recovered from the 1992-1994 debacle. In fact, demand for computational chemists leaped to new highs each year in the second half of the 1990s [135]. Most of the new jobs were in industry, and most of these industrial jobs were at pharmaceutical or biopharmaceutical companies. As we noted at the beginning of this chapter, in 1960 there were essentially no computational chemists in industry. But 40 years later, perhaps well over half of all computational chemists were working in pharmaceutical laboratories. The outlook for computational chemistry is therefore very much linked to the health of the pharmaceutical industry itself. Forces that adversely affect pharmaceutical companies will have a negative effect on the scientists who work there as well as at auxiliary companies such as software vendors that develop programs and databases for use in drug discovery and development. 

Several key issues have to be addressed in the downstream processing of biopharmaceuticals regardless of the expression system. The removal of host cell proteins and nucleic acids, as well as other product- or process-related or adventitious contaminants, is laid down in the regulations and will not differ between the individual expression hosts. The identity, activity and stability of the end product has to be demonstrated regardless of the production system. The need for pharmaceutical quality assurance, validation of processes, analytical methods and cleaning procedures are essentially the same. 

Although their ability to carry out post-translational modifications renders their use desira-ble/essential for producing many biopharmaceuticals, animal cell-based systems do suffer from a number of disadvantages. When compared with E. coli, animal cells display a very complex... 

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. 

The buccal mucosa does serve as an alternative route for administering compounds systematically however, to ensure particular compounds are candidates for delivery across this biological tissue, preclinical screening is essential. While in vivo human permeability studies are ideal, due to their costs and associated issues, it is necessary to perform such screening in vitro. Assessment of compound permeability across porcine buccal mucosa has been widely used and can provide the preclinical biopharmaceutical scientist with much information relating to permeability, routes of transport, and effects of various chemical penetration enhancers. 

The successful application of CE technology has resulted in dramatic growth of CE as an essential tool for protein characterization, R D, and QC of therapeutic biomolecules. CE methods have clearly been shown to be superior over traditional slab-gel methods. Many biopharmaceutical companies have adopted CE techniques in QC environments for determination of product purity, identity and consistency needed for the release of protein products. The success of validation per ICH guidelines has moved CE technology to a position of greater prominence and ensures the quality release of therapeutic proteins and antibodies. 

Kasim N.A., M. Whitehouse, C. Ramachandran, M. Bermejo, H. Lennemas, A.S. Hussain, H.E. Junginger, S.A. Stavchansky, K.K. Midha, V.P. Shah, G.L. Amidon, G.L. (2004). Molecular properties of WHO essential dmgs and provisional biopharmaceutical classification. Molecular Pharmaceutics 1 85-96. 

Water is an essential component of many excipient interactions, whether chemical, physical, or physiological/biopharmaceutical. 

Finally, knowledge of excipient mechanical and physical properties is essential to creating a robust formulation that manufactures tablets that meet specifications in a time- and material-efficient manner. Excipient selection must also take into consideration API stability and biopharmaceutical performance of the dosage form. Uneducated selection of excipients will likely lead to numerous formulating iterations that require much time and material, which are luxuries that product development scientists do not have in the competitive pharmaceutical environment. 

Currently, many biopharmaceuticals, which are proteins in many cases, are produced in many bioindustry fields, and the measuring of the concentrations and bioactivities of these products is thus becoming essential in bioindustry. We have added a new section for Biorecognition assay in Chapter 11, and we explain the fundamental aspects of biorecognition and its application for the measurement of bioproducts at low concentrations. In this edition, we have included some examples and some new problems to assist in the progress with learning how to solve problem. 

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