Bioscope ‘06

by Dr. Barbara Price

Drug treatments for the many.

          A concern raised by several groups developing plans in case the H5N1 avian flu virus adapts to produce a pandemic is having enough drugs available, either vaccines to confer immunity or anti-virals to treat those who become infected. As noted in an earlier Newsletter, Roche, the developer of Tamilflu (oseltamivir) is licensing other companies in several countries around the world to produce oseltamivir. Oseltamivir production is a time-consuming 10 step process, including converting shikimic acid into an epoxide then an azide (potentially explosive). And shikimic acid comes from the Chinese star anise (Illicium verum) tree, grown commercially in only four provinces in China. Thirty kg of star anise seedpods can produce 1 kg of oseltamivir by Gilead’s process, but fermentation of a special strain of E-coli is used to produce about one-third of the oseltamivir, without the supply limitations of the herb.

          This brings several points into focus, supply (extraction and fermentation for synthesis), trade, and control. If the avian flu does progress to a human pandemic, the supply of star anise will become a limiting factor because of amounts, possible adulteration (already noted by buyers), and low yields in the potentially hazardous 10-step process. Fermentation will be the way to avoid those problems, but it will introduce others in terms of E.coli strains and process and product purity. GMP is critical to both methods of producing oseltamivir. For Roche, sublicensing means guaranteeing their licensee has the technical ability and capacity and is GMP compliant. Once the reliable supply issues are solved, the next political and regulatory step is controlling the delivery of oseltamivir so the potential for drug resistant strains of flu is reduced.

          In today’s world, where diseases and drugs to treat them are global business, it is important to learn about the sources for active pharmaceutical ingredients (API) and how they are made and what standards they meet before a critical shortage requires new sources of API. While Roche is, of course, one of the world’s largest pharmaceutical companies and has sufficient resources to find and even license other companies, how do smaller companies ensure their supplies? How do smaller companies, who can produce API, learn and implement GMP without huge investments and risky potential for returns? This is one of the focal points for the International China Biopharmaceutical Symposium, ICBPS. See page 14 this issue.

Where is H5N1 in the current list of disease?

          The top 10 infectious disease killers in the world (WHO 2002) are lower respiratory infections (6.8%), HIV/AIDS (4.9%), diarrheal diseases (3.2%), TB (2.7%), malaria (2.2%), measles (1.1%), pertussis, tetanus, meningitis, syphilis, hepatitis B, and tropical diseases. Perhaps drug companies should be looking at cheaper and alternate sources for threating these diseases also.