Emissions

This aggregated parameter constitutes waste (90% reduction in landfill waste), emissions to water (reduced by 52%) and emissions to air. The latter are quantified in terms of contribution to global warming potential (reduced by 83%), photochemical ozone creation potential (reduced by 50%) and acidification potential (reduced by 55% in the bio-route). For example, halogenated solvents are completely eliminated in the bio-based process.

Toxicity potential

Elimination of numerous toxic solvents and reagents results in a 58% reduction, the third largest impact on the total score.

Risk potential

The risk potential is reduced by 63% for virtually the same reasons as for toxicity.

Area demand

The area demand is reduced by 50%, mainly due to lower electricity demand for the bio-route. Less area demand is the consequence of decreased transport and generation of both electricity and energy carriers, such as coal, natural gas and/or biomass. The higher process efficiency results in a 5% lower sugar demand and consequently a 5% lower area demand for the production of agricultural feedstocks.

Due to the limitations of the LCA methodology and the restriction of our analyses from basic materials to bulk active ingredient, the People component in this sustainability assessment is slightly under-estimated. Apart from reductions in risk and toxicity poten­tial, the bio-based Cephalexin also has some distinct advantages in its further downstream processing and applications. The absence of residual solvents in the formulated product, together with a much simpler impurity profile is an advantage to all patients taking these types of antibiotics. In particular, the well-known bitter taste of most penicillins and cephalosporins is no longer present in the products resulting from the green routes. Improvements in crystal properties, crystal size reproducibility and particle size distribu­tion allow more reliability and robustness in formulation processes. Of greater advantage are the absence of the bad smell of traditionally prepared products and the much longer shelf life. Virtually all the advantages and improvements as described above for Cephalexin have also been realized for the related penicillins and cephalosporins. DSM is harvesting these achievements through their recent launch of a range of brand name products: DSMPureACTIVES™. Thus, Cephalexin is marketed as Purilex™ together with Purimox® for Amoxicilln and Puridrox™ for Cefadroxil.

19.2 Summary

Renewable resource-based biotechnologies are having a threefold impact on pharmaceuticals:

1 Molecular biology, including genomics, proteomics, metabolic pathway engineering etc., is are a rich source for new cell-based medicines, i. e. biopharmaceuticals. Although renewable based, the real motive for this development is new drugs rather than rational resource employment.

2 The same and similar techniques are used to improve existing or develop new fermenta­tion processes (biosyntheses) for enzymes and existing (mainly nature-based) products.

3 To a large extent these enzymes are used to replace stoichiometric, non-catalytic chemistry.

The latter two, i. e. biosynthesis and biocatalysis, have a direct link to renewable resources and sustainability. In particular, the fine chemical industry, providing the pharmaceutical industry with its active ingredients, has experienced the effects. This chapter shows how biocatalysis, and to a lesser extent biosynthesis, have changed the character of the manu­facturing processes for the world largest semi-synthetic antibiotics. Cephalexin is shown as a learning example. In fact, these penicillins and cephalosporins have led the way to full acceptance and development of biocatalysis as the strongest tool for environmentally compatible processes for a great number of other fine chemicals for pharmaceuticals (although competition-driven economic issues were the initial, underlying motive). For penicillins and cephalosporins the results were impressive: improvements of a factor 2 or more have been achieved in all sustainability parameters, such as energy consumption, emissions, resource consumptions, land area use and toxicity potential. Ozone-depleting agents and halogenated solvents and reagents were completely eliminated from all manu­facturing processes. Improved product quality, in particular, product smell and taste, was found to be an additional bonus. As development times for these biocatalytic processes are still relatively long compared to pressurizing time-to-market demands in the research for new drugs, full exploitation has not been achieved in modern medicinal chemistry.

Alongside the development of these biocatalytic processes for the antibiotics, a semi­quantitative methodology has been worked out for the assessment of sustainability poten­tial. Based on the three principles of sustainability, People, Planet and Profit, a rational set of parameters for all three groups has been developed. All parameters are defined in terms of improvements (decrease, increase, etc.) relative to an existing situation or existing process. All principles of LCA are used to arrive at meaningful and broadly applicable definition of parameters and their metrics.

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