Biopharmaceuticals product design

Both pre-clinical and clinical trials are underpinned by a necessity to produce sufficient quantities of the prospective drug for its evaluation. Depending on the biopharmaceutical product, this could require from several hundred grams to over a kilo of active ingredient. Typical production protocols for biopharmaceutical products are outlined in detail in Chapter 3. It is important that a suitable production process be designed prior to commencement of pre-clinical trials, that the process be amenable to scale-up and, as far as is practicable, that it is optimized (Figure 2.9). The material used for pre-clinical and clinical trials should be produced using the same process by which it is intended to undertake final commercial-scale manufacture. 

While some culture media are formulated to promote cell multiplication (growth media), others only maintain cell structural and metabolic integrity (maintenance media), but do not stimulate cell division. Media prepared with highly purified compounds and with known composition are designated chemically defined media. These are particularly attractive for biopharmaceutical production, because they are less vulnerable to contamination and quality control is easier. Nevertheless, these media can be expensive. 

The optimal preclinical development of a biopharmaceutical product has benefited from experience. This is because the strategy for designing programs is... 

For products that are prepared extemporaneously at a regular basis or even for a limited stock, a product specific documentation (product file) is needed. This will include specifications, instructions, and records but also a pharmaceutical assessment of safety data, toxicity, biopharmaceutical aspects, stability, and product design. The product file should also include a product review as soon as a product is used repeatedly or over longer periods. 

Table 1 Biopharmaceutic considerations in drug product design...

Obviously, not all conditions are met, but by every compound we keep this direction in mind, it is easier to sift through many possibilities offered. It requires testing a range of selected compounds in in vitro and in vivo animal studies and thus, preformulation work gets combined with biopharmaceutic studies to identify product design issues. 

Purpose. As biopharmaceutical products are large and complex molecules and no single test method is sufficient, product analysis uses multiple, different analytical methods strategically designed to be complementary with respect to selectivity and specificity [4, 27]. More sensitive test methods allow proof of greater removal of a putative risk factor [12], and the more key parameters that can be measured assure that process variability is understood and controlled [66]. However, it is important... 

Dnring the period since World War II, collaborations between biochemists, applied microbiologists, and chemical engineers have evolved in several complementary directions, as their joint efforts have led to the successful development of innovative processes based on biochemical transformations that take place in creatively designed fermenters and bioreactors. This equipment has been tailormade to satisfy not only the safety, sanitation, and microbiological constraints imposed by the FDA and its counterparts in other nations, but also the labile and shear-sensitive nature of animal and plant cells. The equipment used in traditional facilities for manufacturing biopharmaceutical products consists of stainless steel bioreactors/fermenters, tanks, piping, valves, and so on, that are quasi permanent installations. 

Although the terms in Table 18.2 to describe the solubility of an active substance are still used in many handbooks, from a clinical view they are no longer used. The principle of solubihty in perspective is now used. That is, the solubihty of an active substance is connected to the dose that should be administered to the patient. Thus, solubility in perspective is not a pure physico-chemical characteristic of the active substance. For example, the solubility will not cause any problems when an active substance with a low solubility has to be given to a patient as a solution at a very low concentration. In Chap. 17 Product design and in Chap. 16 Biopharmaceutics this concept will be explained in more detail. 

GPP touches upon the processes assessment of the physician s prescription or formulation design in the Documentation paragraph a pharmaceutical assessment of therapeutic rationale, safety data, toxicity, biopharmaceutical aspects, stability and product design should be carried out, before preparation takes place. No further details are established however. 

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... 

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