Biopharmaceuticals overview

Product Development Rationale Overview of Biopharmaceutics Overview of Clinical Pharmacology Overview of Efficacy Overview of Safety Benefits and Risks Conclusions Literature References... 

An overview of the general principles of filtration having specific appHcation to bacterial and viral removal is given herein. The emphasis is on ensuring that the sterility and/or safety of biologicals and biopharmaceuticals be maintained. 

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. 

In addition, tests for mutagenicity and carcinogenicity are not likely required for most biopharma-ceutical substances. The regulatory guidelines and industrial practices relating to biopharmaceuti-cal preclinical trials thus remain in an evolutionary mode, and each product is taken on a case-by-case basis. An overview of the main preclinical tests undertaken for a sample biopharmaceutical... 

This chapter aims to overview the manufacturing process of therapeutic proteins. It concerns itself with two major themes (1) sources of biopharmaceuticals and (2) upstream processing. The additional elements of biopharmaceutical manufacturing, i.e. downstream processing and product analysis, are discussed in Chapters 6 and 7 respectively. 

Figure 5.5 Overview of the production process for a biopharmaceutical product. Refer to text for specific details...

Over half of all biopharmaceuticals thus far approved are produced in recombinant E. coli or S. cerevisiae. Industrial-scale bacterial and yeast fermentation systems share many common features, an overview of which is provided below. Most remaining biopharmaceuticals are produced using animal cell culture, mainly by recombinant BHK or CHO cells (or hybridoma cells in... 

Figure 6.1 Overview of a generalized downstream processing procedure employed to produce a finished-product (protein) biopharmaceutical. QC also plays a prominent role in downstream processing. Qualty control personnel collect product samples during/after each stage of processing. These samples are analysed to ensure that various in-process specifications are met. In this way, the production process is tightly controlled at each stage...

Table 7.2 Methods used to characterize (protein-based) finished product biopharmaceuticals. An overview of most of these methods is presented over the next several sections of this chapter...

Kramer J. The biopharmaceutics classification system—an overview of the current status in relation to IR and MR dosage forms. 1st International Conference on Bioavailability, Bioequivalence and Dissolution Testing, London, 2002. 

The objective of this book is to provide both an overview and practical uses of the techniques available to analytical scientists involved in the development and application of methods for protein-based biopharmaceutical drugs. The emphasis is on considering the analytical method in terms of the stage of the development process and its appropriateness for the intended application. The availability of techniques will reveal whether or not the analytical problem has a potential solution. Then will come the question of whether or not the technique is a truly appropriate solution. The theoretical considerations behind choosing the technique may be solid. However, the practicality of the method may not hold up to inspection. 

While biopharmaceuticals are typically proteins derived from the human body, most conventional drugs have been obtained from sources outside the body (e.g. plant and microbial metabolites, synthetic chemicals, etc.). Although they do not form the focus of this text, a brief overview of strategies adopted in the discovery of such non-biopharmaceuticaF drugs is appropriate, and is summarized later in this chapter. 

This section briefly overviews how biopharmaceutical substances are produced in a biopharmaceutical/biotech manufacturing facility. As the vast bulk of biopharmaceuticals are proteins synthesized in recombinant prokaryotic (e.g. E. coli) or eukaryotic (e.g. mammalian cells) production systems, attention will focus specifically upon these. 

Over half of all biopharmacuticals thus far approved are produced in recombinant E. coli or S. cerevisiae. Industrial-scale bacterial and yeast fermentation systems share many common features, an overview of which is provided below. Most remaining biopharmaceuticals are produced using animal cell culture, mainly by recombinant BFIK or CFiO cells (or hybridoma cells in the case of some monoclonal antibodies Appendix 1). While industrial-scale animal cell culture shares many common principles with microbial fermentation systems, it also differs in several respects, as subsequently described. Microbial fermentation/animal cell culture is a vast speciality area in its own right. As such, only a summary overview can be provided below and the interested reader is referred to the Further Reading section. 

An overview of the steps normally undertaken during downstream processing is presented in Figure 3.16. Details of the exact steps undertaken during the downstream processing of any specific biopharmaceutical product are usually considered highly confidential by the... 

OVERVIEW OF METHOD VALIDATION IN PFIARMACEUTICAL AND BIOPHARMACEUTICAL ANALYSIS... 

The overview material for each chapter, written by individuals with extensive knowledge and practical experience, provides invaluable insight. The properties, characteristics, and clinical application of each biopharmaceutical are discussed in... 

For readers familiar with biotechnology, biopharmaceutics, and the drug development process, and for those that focus on the application of biopharmaceuticals. Part II provides a brief overview of each class of macromolecule with respect to physiological role and clinical application. Additional detail for each FDA approved, recombinantly derived biopharmaceutical, and several other interesting therapeutic proteins, for each category of macromolecule... 

Slater, S. (1999), Biopharmaceutical Validation An Overview in Biopharmaceuticals, an Industrial Perspective, Springer-Verlag. 

Until recently, nonparenteral routes have failed to deliver sufficient quantities of ASO to be systemically therapeutic. The recent advent of novel oral delivery technologies, coupled with the increased tissue residence time for second-generation ASOs, allows oral delivery to achieve therapeutic levels for select systemic indications. This chapter will initially outline certain more conventional aspects of parenteral dosage forms, and then focus on formulation technologies that more specifically address local treatment. For the oral route, we will pass to the biopharmaceutic considerations for both local delivery to the gut and systemic delivery via absorption from solid dosage forms. Incumbent with the discussion on formulations is the need initially to overview the physico-chemical properties of ASOs, which in large part determine their biopharmaceutic characteristics. 

While this is a brief chapter, it is appropriate to overview the manufacturing of pharmaceuticals and biopharmaceuticals in the context of this book, since effective medications will not be useful unless they are available to clinicians and their patients. 

The purpose of this overview chapter is to provide perspectives in the current status and future prospects of controlled release drug delivery. This is accomplished by examining various delivery systems from a mechanistic point of view, exploring applications of these systems, and discussing relevant biopharmaceutical parameters. A major section of this book is devoted to fundamental issues and applications of transdermal and transmucosal delivery systems (Chapter 6,8,17-23). Other developing systems of future potential... 

Green J, Black, L. Overview of preclinical safety assessment for immunomodulatory biopharmaceuticals. Hum Exp Toxicol 200 19(4) 208-12. 

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