Biopharmaceutics, defined

Bioavailability depends not only on having the drug in solution, but also on the drug s permeability. A jejunal permeability of at least 2-4 x 10 4cm/s, measured in human subjects by intubation, is considered high [97]. For many drugs and other substances, this permeability corresponds to a fraction absorbed of 90% or better. Amidon et al. [97] thus proposed a Biopharmaceutics Classification System (BCS) for drugs based on the above definitions of these two parameters. Table 3 defines the BCS and includes some drugs representative of each class. 

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 (Chapter 6). 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 that aim to characterize it fully. Moreover, once these characteristics have been defined, they form the basis of many of the QC identity tests routinely performed on the product during its subsequent commercial manufacture. As these identity tests are discussed in detail in Chapter 7, only an abbreviated overview is presented here, in the form of Figure 4.5. 

Biopesticides, encapsulation of, 16 458 Biopharmaceuticals, 9 54 Biophotolysis, 13 849 Biopile, 3 769 defined, 3 758t Bioplas microcarrier, 5 353t Biopolishing, 3 30 10 304 24 622 Biopolymer extraction, 10 787-788 Biopolymers, 20 444. See also Proteins... 

According to a biopharmaceutic expert, the term bioavailability may be defined as the rate and extent to which the ingredient is absorbed from the drug product into the body or to the site of action. It is measured by blood, serum or plasma levels or from urinary excretion data. 

One challenge that remains in biopharmaceutics research is that of correlating in vitro drug-release profiles with the in vivo pharmacokinetic data. TVIVC has been defined by the... 

In contrast to vitamin and mineral products, which are chemically well-defined, the biopharmaceutical quality and behavior of botanical dosage forms marketed as dietary supplements are often not well documented. In most cases,... 

It is important for development scientists to familiarize themselves with the regulatory process, which defines the development stages of a biopharmaceutical. Along this path there are several checkpoints that must be passed before reaching the next plateau. These checkpoints (or phases) affect all groups within... 

Methods development starts with a relatively high number of techniques to characterize and test samples. The number of protocols is often reduced once the critical parameters and the methods that identify them have been defined. The analyst must evaluate the initial techniques with respect to their purposes. If the goal is to generate research data, the practicality of the method and its limitations are not of primary concern if the goal is to use the technique as part of a test procedure, it has to be evaluated in terms of its potential to meet full validation. Critical procedures (e.g., release testing) that cannot be validated will bring a project to an expensive halt. For these reasons, this chapter provides basic principles as well as limitations of capillary electrophoresis (CE) as applied to the analysis of real biopharmaceutical molecules. 

The MS techniques described previously for characterization of the final recombinant protein product can be applied at all stages during process development. MS might be used upstream to define clone selection, processing format, and purification steps, and downstream to characterize the final product, ascertain lotto-lot reproducibility, determine stability, and define the formulation of biopharmaceutical molecules. Presented here are some examples found either in the literature or from our own experience in which MS has been found to be a useful or necessary tool. Potential limitations of MS methods are discussed, and when appropriate, other analytical methods are mentioned that can be alternatives to MS and are also efficient tools for biopharmaceutical development. 

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. 

Impurities that cause the greatest concern are those that are toxic, defined by the US Pharmacopeia (USP) as impurities that have significant undesirable biological activity [ 1 ], and host cell contaminants in biopharmaceuticals that have potential risks of allergic reaction or other immunopathological effects [2]. 

Solubility and permeability, which together largely define absorption, are the two pillars of the Biopharmaceutics Glassification Scheme (BCS). 

Diaz, D. and O Brien, P.J. (2006) Defining the sequence of events in cerivastatin toxicity using a high-content multi-parametric cytotoxicity assay. European Biopharmaceutical Review,... 

Since risk analysis plays an important role in public policy decision making, efforts have been made to devise a means by which to identify, control, and communicate the risks imposed by agricultural biotechnology. A paradigm of environmental risk assessment was first introduced in the United States by Peterson and Arntzen in 2004. In this risk assessment, a number of assumptions and uncertainties were considered and presented. These include (1) problem formulation, (2) hazard identihcation, (3) dose-response relationships, (4) exposure assessment, and (5) risk characterization. Risk assessment of plant-made pharmaceuticals must be reviewed on a case-by-case basis because the plants used to produce proteins each have different risks associated with them. Many plant-derived biopharmaceuticals will challenge our ability to define an environmental hazard (Howard and Donnelly, 2004). For example, the expression of a bovine-specihc antigen produced in a potato plant and used orally in veterinary medicine would have a dramatically different set of criteria for assessment of risk than, as another example, the expression of a neutralizing nonspecihc oral antibody developed in maize to suppress Campylobacter jejuni in chickens (Peterson and Arntzen, 2004 Kirk et al., 2005). 

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