Pharmaceutical industry comparator assessment

The effectiveness of various measures to contain expenditure on medicines in the UK can only be assessed in the context of the situation in other European Union countries. Table 21.1 gives data for the total expenditure on health care as a percentage of gross domestic product (GDP), expenditure on medicines as a percentage of total healthcare spend, the national pharmaceutical industry s research and development expenditure in euro-millions, the general price index and the medicines price index nationally compared to a European price of 100, and the national pharmaceutical consumption per capita expressed as defined daily doses (DDD). These comparisons are based on OECD Health Data 2000. 

The pharmaceutical industry uses PET studies of receptor occupancy to determine the proper doses of new radiopharmaceuticals in Phase I and II clinical trials. Receptor occupancy is assessed in those receptors upon which the new drug acts. An early example was the use of C-carfentanil to measure the duration of blockade of opiate receptors by the drug nalmifene, compared to naloxone. 

As with the simple example of benzene, there are many ways to modify an API s structure. Well-established test systems, empirical data, rules of thumb " (Figure 7.2) and computer-based systems for the assessment of the properties of molecules, such as biodegradability, are available. Their careful combination allows for the theoretical design of molecules and the assessment of their properties without the need for them to be synthesized. Computer-based systems that assist human experts with the handling of complex knowledge are widely in use within pharmaceutical industries for the optimization of APIs by in silico screening.This allows for a very early and comparatively inexpensive evaluation of the environmental properties of candidates. At the same time, undesirable properties such as mutagenicity can be reduced. This can and should also be done with respect to full mineralization of APIs when they reach the environment. 

The probability and route of exposure of humans to a chemical are crucial parameters in risk assessment. By definition, in an extreme case where the probability of exposure is null, the risk is null. Thus, there is a considerable difference in the regulatory requirements for safety assessment of industrial chemicals and environmental contaminants that result in accidental exposures compared to chemicals designed for intentional exposure of the population, like cosmetics and pharmaceuticals. Each one of these categories is subjected to specific European laws. 

The recent literature on microwave-assisted chemistry has reported a multitude of different effects in chemical reactions and processes and attributed them to microwave radiation. Some of these published results cannot be reproduced, however, because the household microwave ovens employed often have serious technical shortcomings. Published experimental procedures are often insufficient and do not enable reproduction of the results obtained. Important factors required for qualification and validation, for example exact records, reproducibility, and transparency of reactions/processes, are commonly not reported, which poses a serious drawback in the industrial development of microwave-assisted reactions and processes for synthesis of fine chemicals, intermediates, and pharmaceuticals. Technical microwave devices for synthetic chemistry have been on the market for a while (cf a.m. explanations) and should enable comparative investigations to be conducted under set conditions. These investigations would enable better assessment of the observed effects. It is, furthermore, possible to obtain a better insight into the often discussed (nonthermal) microwave effects from these experiments (Ref. [138] and Chapter 4 of this book). Technical microwave systems are an important first step toward the use of microwave energy for technical synthesis. The actual scale-up of chemical reactions in the microwave is, however, still to be undertaken. Comparisons between microwave systems with different technical specifications should provide a measure for qualification of the systems employed, which in turn is important for validation of reactions and processes performed in such commercial systems. 

This chapter explored an unusually comprehensive data set of drug R D projects all over the world. Our data base enabled us to characterize several features of the potential for success of the innovation process in pharmaceuticals. Since this industry is typically characterized by the role of both larger established companies, and smaller high-tech specialist firms the so-called NBFs our analysis enabled us to assess the different performance of R D processes conducted under different governance structures most notably projects that are fully internalized by the companies vis-a-vis projects developed in collaboration with other companies. Moreover, our data enabled to assess the different specialization and the comparative performance of different types of firms, and particularly of the large drug companies with respect to the NBFs. 

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