sales in excess of $1 billion. Their number has increased steadily, from 27 in 1999 to 51 in 2001, 76 in 2003, and then levelled off. Sales of the top 20 blockbuster drugs are reported in Table 6. The APIs of 12 of them are "small" (LMW) molecules. Averaging a MW of 477, they have quite complex structures. They typically show three cyclic moieties. 10 of them exhibit at least one N-heterocyclic moiety. Five of the top 10, up from none in 2005, are biopharmaceuticals. The largest-selling non-proprietary drugs are paracetamol, omeprazole, ethinylestradiol, amoxicillin, pyridoxine, and ascorbic acid. The innovator pharma companies require mainly custom manufacturing services for their proprietary drug substances. The demand is driven primarily by the number of new drug launches, the volume requirements and the industry's "make or buy" strategy. A summary of the pro's and con's for outsourcing from the pharma industry's perspective is given in Table 7. As extended studies at the Stern Business School of the New York City University have shown, financial considerations clearly favor the "buy" option. Teva and Sandoz are by far the largest generics companies (see also chapter 6.3.2). They differ from their competitors not only in sales revenues but also because they are strongly backwards integrated and have proprietary drugs in their portfolios. They also vie for the promising biosimilars market. Several thousand small or virtual pharma companies focus on R&D. albeit on just a few lead compounds. They typically originate mostly from academia. Therefore, their R&D strategy is more focused on the elucidation of the biological roots of diseases rather than developing synthesis methods. Agrochemicals Agrochemical companies are the second largest users of fine chemicals. Most products have a "pharmaceutical heritage". As a consequence of an intensive M&A activity over the past 10–20 years, the industry now is more consolidated than the pharmaceutical industry. The top 10 companies, led by Syngenta, Switzerland; Bayer Cropsciences, Germany: Monsanto, USA; BASF Crop Protection, Germany, and Dow Agrosciences, USA have a share of almost 95% of the total 2,000,000 tons / $48.5 billion pesticide output in 2010. Since the 1990s the R&D effort is focused mainly on gene modified (GM) seeds. At both Monsanto and DuPont's seed subsidiary, Pioneer Hi-Bred, GM seed businesses already account for more than 50% of total sales. 100 new LMW agrochemicals have been launched in the period 2000–2009. However, only 8 products achieved sales in excess