Product Development Follows Different Rules

Product development for biological pharmaceuticals might appear as a simple continuation of a research project after a sufficiently effective compound has been identified. From a scientific point of view there is no clear distinction between research and development. Until the clinical phase, product development utilizes the same basic skills and methods and - to a great extent - the experience of the same people who did the research. However, the rules change considerably as soon as innovative research turns into conservative testing of quality, safety and efficacy and into analytical and process development. 

The decision to develop a pharmaceutical product transfers an active principle or compound from the resource-limited research laboratory into a new environment. In a multi-disciplinary approach the compound is subject to a variety of analytical, pharmacological, toxicological, and clinical tests and trials. From now on methods, results, documentation and the materials created are under strict scrutiny exerted by the developing organization itself and finally by several authorities. Research activities are hardly ever subject to such surveillance and control, concerning, for example the precision and consistency of methods and results. It usually takes time for a researcher to fully acknowlewdge and accept this fact. 

Since there is no clear distinction between the research and development phase, projects quite frequently move into development while the people involved are unaware of the changed rules. This may result in neglecting essential aspects, in extra cost for the repetition of critical studies and in a considerable loss of time. 

The general aspects of product development presented in this chapter, and the following chapter on registration requirements for pharmaceutical products were mainly written for researchers and scientists who are less experienced in product development. These two chapters are also meant to prevent the often observed, overly ambitious ideas about the commercialization of research results. Unrealistic expectations about the simplicity and duration of development may lead to inappropriate management decisions which may even endanger the future of research-oriented enterprises. The success of biotechnology ventures does not only depend on good research but also on a realistic assessment of the potential products and on the ability to adopt the required skills to effectively develop research results into commercial products. 

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The ABPR approval does not affect the current EU total ban on the feeding of animal protein meals to farmed animals, which is a separate issue and remains in force until all the meat and bone meal in storage (approximately 400,000-500,000 tons) at present, awaiting incineration, does not hnd its way into the feed chain. The EU has also developed tests to differentiate the different types of animal protein meals. Such tests are needed in order to lift the ban for fishmeal and allow for traceability. However, the ABPR establishes clear safety rules for the production of meat and bone meal in case it is ever reauthorized for inclusion in feed for nonruminant species. Concurrent with the feed ban has been a ban against the export of animal protein meals. The United States was once the world s largest exporter with over a million tons exported per year now that figure is less than 300,000 tons (35). The timeline of the BSE situation follows ... 

Sinclair and Boxall [7] focused their screening method on identifying transformation products of pesticides that were more toxic than their parent. They concluded that the majority of transformation products are less toxic than their parent compound. Exceptions are products that are more hydrophobic and thus more bio accumulative than their precursor, or those with a more potent mode of action. The latter can be explained as follows (1) by the presence of a toxicophore that is formed during transformation of a propesticide into its active product, (2) the pesticide toxicophore remains intact during transformation but hydrophobicity increases, or (3) a different toxicophore is formed during the transformation. On the basis of these rules they developed a flow chart to select appropriate assessment factors that relate the toxicity of the parent compound to the predicted toxicity of the transformation product. This approach is valuable for preliminary hazard assessment and prioritization of further testing but cannot give a quantitative account of the risk associated with transformation products. 

Fig. 4-1 The stages involved in developing a process. The time intervals specified for design, installation, and operation are only tentative and, in specific cases, the real values may differ greatly from those given here. The following rule ofthumb applies forthe plant investment laboratory research 0.1 x 10 , miniplant 1 X 10 , pilot plant 10 x 10 , production plant 100 x 10 .

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