Biopharmaceutical

The three main sources of competitive advantage in the manufacture of high value protein products are first to market, high product quaUty, and low cost (3). The first company to market a new protein biopharmaceutical, and the first to gain patent protection, enjoys a substantial advantage. The second company to enter the market may find itself enjoying only one-tenth of the sales. In the absence of patent protection, product differentiation becomes very important. Differentiation reflects a product that is purer, more active, or has a greater lot-to-lot consistency. 

Table 1. Unit Values and Relative Production Quantities for Selected Approved Biopharmaceuticals, 1990—199T...

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. 

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). 

L. Shargeland A. B. C. Yu, Applied Biopharmaceutics and Pharmacokinetics, 2nd ed., Appleton-Centaiy Ctofts,No-rwalk, Conn., 1985. 

Membrane-retained components are collectively called concentrate or retentate. Materials permeating the membrane are called filtrate, ultrafiltrate, or permeate. It is the objective of ultrafiltration to recover or concentrate particular species in the retentate (eg, latex concentration, pigment recovery, protein recovery from cheese and casein wheys, and concentration of proteins for biopharmaceuticals) or to produce a purified permeate (eg, sewage treatment, production of sterile water or antibiotics, etc). Diafiltration is a specific ultrafiltration process in which the retentate is further purified or the permeable sohds are extracted further by the addition of water or, in the case of proteins, buffer to the retentate. 

U. Gundert-Remy and H. Mufler, eds.. Oral Controlled Release Products Therapeutic and Biopharmaceutic Assessment, Wissenschafdiche VedagsgeseUschaft mbH, Stuttgart, Germany, 1990. 

Four column systems are available from Amersham Pharmacia Biotech that can be used to pack SEC media for various applications at the laboratory scale. These include C, XK, SR, and HR column systems. All of the laboratory-scale columns are constructed with borosilicate glass tubes. Columns for larger scale process applications include INdEX, BPG, EineLINE, BPSS, and Stack columns. The larger scale columns are constructed to meet stringent validation requirements for the production of biopharmaceuticals. Each of the column types are described. 

The EineLINE series of columns was designed to meet the stringent demands of hygiene required in the production of biopharmaceuticals. These stainless-steel-based columns employ a hydraulic flow adaptor and may be operated at... 

BioProcess stainless-steel columns are fixed bed height columns designed for the most stringent requirements in the routine production of biopharmaceuticals. Wetted materials include stainless steel, polypropylene, and EPDM. The BPSS series may be operated at pressures up to 3 bar (0.3 MPa) and are supplied with sanitary fittings of 10 or 22 mm i.d. The available column sizes and specifications for the BPSS column series are given in Table 2.18. 

APPLICATION OF SIZE EXCLUSION-HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY FOR BIOPHARMACEUTICAL PROTEIN AND PEPTIDE THERAPEUTICS... 

Biopharmaceutical Product Development, Eli Lilly and Company, Indianapolis, Indiana 4618S... 

Niazi, S. Textbook of Biopharmaceutics and Clinical Pharmacokinetics Appleton-Century-Crofts New York, 1979 p 158. 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

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

Summary of Biopharmaceutic Studies and Associated Analytical Methods Summary of Clinical Pharmacology Studies Summary of Clinical Efficacy Summary of Clinical Safety Literature References Synopses of Individual Studies... 

Biomimetic polymers in pharmaceutical and biomedical sciences. Eitropean Journal of Pharmaceutics and Biopharmaceutics, Vol. 58, 2, (September 2004), pp. (385-407), ISSN 0939-6411... 

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