Biopharmaceuticals definitions

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. 

Biopharmaceuticals are subjected to strict regulations to monitor and quantitate impurities to maintain product safety, quality, integrity, and efficacy.4 The following are definitions that relate to purity ... 

Yazdanian, M., Briggs, K., Jankovsky, C., and Hawi, A., The "high solubility" definition of the current FDA guidance on biopharmaceutics classification system may be too strict for acidic drugs, Pharm. Res., 21, 293, 2004. 

For a facility manufacturing biopharmaceuticals, appropriate designs according to biosafety level (BSLl to BSL4 refer to Exhibit 9.6 for biosafety definitions) have to be implemented. 

As used herein, biotechnology medicines or products of pharmaceutical biotechnology are afforded a much broader definition. Unlike the term biopharmaceutical , the term... 

Table 1.3. A summary of the definition of the terms biologic , biopharmaceuticaf and biotechnology medicine as used throughout this book. Reprinted from European Journal of Pharmaceutical Sciences, vol 15, Walsh, Biopharmaceuticals and Biotechnology, p 135-138, 2002, with permission from Elsevier Science...

Pharmaceutical and biopharmaceutical clinical trials fall within the domain of clinical research as provided by these descriptions. The primary focus of this book concerns clinical trials conducted during the development of new drugs, one of the categories in this definition (see Becker and Whyte, 2006, for discussions of clinical trials for medical devices and Piantadosi, 2005, for discussion of clinical trials for surgical procedures). 

The basic principles of toxicology are applicable across product classes. It is the specific attributes of the product that have the greatest influence on the successful practice of biopharmaceutical toxicology (see Table 3.2). This focus on product attributes has defined the case-by-case approach. Table 3.3 provides a further definition of the case-by-case approach (see Table 3.3). 

Typically these studies cost from 1.5 to 3 million to conduct. Based on the perceived probability of a significant QT interval effect (based on preclini-cal studies, class effects, and ECG data from phase 1 studies) a decision must be made whether to conduct the definitive QT study prior to proceeding with a proof-of-concept study in patients, or whether to delay this study until the proof of concept (POC) has been demonstrated. Of note, for many biophar-maceutical products it would not be possible nor ethical to dose to steady state in healthy volunteers, to dose at two to four times anticipated therapeutic exposures, or to use a crossover design with reasonable washout periods. Thus a QT study performed with a biopharmaceutical may need to vary from the usual design and the E14 guidance, and may present great challenges for subject or patient recruitment. 

With the transfer of most biopharmaceutical INDs from CBER to CDER in 2003, there has been an increased tendency to apply the small-molecule paradigm for evaluation of QT liability to biopharmaceutical product candidates, and to request information on hERG assays or plans for definitive clinical QT studies. This does not seem reasonable based on the postmarketing safety data for biopharmaceuticals, nor on scientific grounds as discussed above. If these investigations become routinely required, they will only add significant time and costs to the process of biopharmaceutical product evaluation and have little ultimate impact on patient safety. 

A specific definition of what constitutes a peptide is difficult to find. Most people involved in developing biopharmaceuticals would define a peptide as... 

Several tools that are useful in the planning and management of biopharmaceutical projects are identified in Table 27.8. Definitions can be found in the Project Management Institute s (PMI) A Guide to the Project Management Body of Knowledge (5) and within the tutorial and help sections of Microsoft Project . 

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