Bio-pharmaceutical product

The first hurdle encountered during the development of alfalfa as a recombinant protein production system was the relative inefficiency of the available expression cassettes. A study in which a tomato proteinase inhibitor I transgene was expressed in tobacco and alfalfa under the control of the cauliflower mosaic virus (CaMV) 35S promoter showed that 3-4 times more protein accumulated in tobacco leaves compared to alfalfa leaves [5]. Despite the low efficiency of the CaMV 35S promoter in alfalfa, bio-pharmaceutical production using this system has been reported in the scientific literature. Such reports include expression of the foot and mouth disease virus antigen [6], an enzyme to improve phosphorus utilization [7] and the anti-human IgG C5-1 [8]. In this last work, the C5-1 antibody accumulated to 1% total soluble protein [8]. 

Historically, the cost of recombinant bio-pharmaceutical production has not been a limiting factor, as drug manufacturers can easily pass the cost on to the consumers. Whilst this is still true in some cases, an in-... 

A number of examples from biochemical engineering are presented in this chapter. The mathematical models are either algebraic or differential and they cover a wide area of topics. These models are often employed in biochemical engineering for the development of bioreactor models for the production of bio-pharmaceuticals or in the environmental engineering field. In this chapter we have also included an example dealing with the determination of the average specific production rate from batch and continuous runs. 

There are three levels of equivalence for classifying products, each submitted to an identical maximum level of public financing chemical equivalence, pharmacological equivalence and therapeutic equivalence. The first level entails establishing groups for the same active ingredient, which at the same time include both generics and brand-name pharmaceuticals whose patent has expired. This is the system applied in Sweden, Denmark, Norway and Spain. It encompasses bio-equivalent products with identical qualitative or quantitative composition, pharmaceutical form, dose, administration method and presentation . 

Solubility, dissolution rate, and intestinal permeability, are the major bio-pharmaceutic factors that affect the rate and extent of absorption of an oral drug product. Particularly for water insoluble drugs that have generally high membrane permeability (BCS Class II), dissolution, and dose are the most critical factors affecting the rate and the extent of oral absorption. 

Clean rooms are environmentally controlled areas within the pharmaceutical facility in which critical manufacturing steps for injectable/sterile (bio)pharmaceuticals must be undertaken. The rooms are specifically designed to protect the product from contamination. Common potential contaminants include microorganisms and particulate matter. These contaminants can be airborne, or derived from process equipment, personnel, etc. 

Validation can be defined as the act of proving that any procedure, process, equipment, material, activity or system leads to the expected results . Routine and adequate validation studies form a core principle of GMP as applied to (bio)pharmaceutical manufacture, as such studies help assure the overall safety of the finished product (Box 3.1). 

FDA home page. A key reference for regulatory issues (United States) for (bio)pharmaceutical development and production. Also contains information on approved products. 

Kinetic fluid energy Homogenisation Emulsification Dispersing Cell-cracking up to 1500 foodstuffs cosmetics pharmaceutical products chemical products bio-products... 

Amidon, G L, H. Lennernas, V. R Shah, and J. R. Crison. 1995. A theoretical basis for bio pharmaceutic drug classi cation The correlation iafvitro drug product dissolution anid vitro bioavailability. Pharmaceutical Research. 12 413-420. 

Cover Figure Raman spectra of two polymorphs of Cimetidine are shown on the cover Cimetidine is a pharmaceutical product that has six polymorphic forms and each form has a distinctive Raman spectrum as shown in Figure 4 25 of Chapter 4 (with permission of Ref 47). The particular polymorphic or crystalline form of a compound can be very important since the bio- availability and patent positions often depend upon the form Raman spectra can be used to easily identify the polymorphic form. 

Some compounds are employed in only one of these areas, for example, the parabens (esters of 4-hydroxybenzoic acid) are used as preservatives in some types of cosmetic and pharmaceutical products, whereas chlorhexi-dine salts are utilized in all three areas. The collective term biocide (bios, life cido, to kill) is used widely nowadays to denote a compound used in one or more of these fields [2],... 

The performance qualification (PQ) phase of validation follows the development of the sterilization specifications and of the sterilizer parameters which will deliver them. The purpose of PQ in steam sterilization of pharmaceutical products, equipment, laboratory media, and SIP systems is to confirm that the sterilization specification consistently achieves its intended purpose. The process is run using the parameters derived from process development on (usually) three separate occasions and tested for compliance with a variety of predetermined acceptance criteria. As a subset of PQ, the purpose of bio-validation is to confirm that the lethality expected from the process does not significantly deviate from what is expected. Biovalidation is a test of consistency. If the acceptance criteria are not achieved, there may be need for more process development. 

The decision tree shown in Fig. 3 may be used to help choose the spore substrate used in bio-validation of aqueous pharmaceutical products. To use this decision tree, it is essential to have some knowledge of the effects of product on the resistance of spores as mentioned before, this requires special equipment and experience. 

In all circumstances water is the preferred substrate for bio-validation of aqueous pharmaceutical products. Where water would give deceptive results, it should not be used. 

GL Amidon, H Lennernas, VP Shah, JR Crison. A Theoretical basis for a bio-pharmaceutic drug classification the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 12 413 120, 1995. 

Key phases of successful product development place emphasis on close, collaborative, and productive interactions of the interdisciplinary sciences within a bio-pharmaceutical group. 

All fermentation or bioprocesses start with the selection of the cell type. The choice is dependent on the product synthesized, the amount of product needed, the purity of the required product, and of course the cost. A bio-pharmaceutical such as an antibiotic, antibody, or protein that is directly injected into a human requires a highly pure product, whereas food products require intermediate purity, while commodity products such as ethanol produced for alternative fuel usage do not require as stringent sterile methodology. The advantages and disadvantages of the major classes or cell types are summarized in Table 1. 

Fischer, R. Stoger, E. Schillberg, S. Christou, P. Twyman, R.M. Plant-based production of bio-pharmaceutical. Curr. Opin. Plant Biol. 2004, 7, 152-158. 

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