3 November 2006
Oseltamivir
(Tamiflu) now produced in United States for Pandemic Flu Preparedness…Are we
safer?
Amidst fears of a
bird flu pandemic, the US Department of Health and Human Services (HHS) has
been adamant that the US be self-reliant in the supply of the anti-influenza
drug oseltemivir (“Tamifllu”) for the American
public. Now through a working
partnership with Roche AG, the Swiss manufacturer of Tamiflu, and its external
contractors, the US is able to make the drug entirely on US soil. The US production facility is part of
Roche’s worldwide global production network capable of producing 400 million
treatment courses of Tamiflu annually by the end of 2006 (Roche Pharmaceuticals
Press Release, 14 September 2006, [http://www.rocheusa.com/newsroom/current/2006/pr2006091401.html]).
Oseltamivir is the
generic name for Tamiflu that is used in the treatment and prophylaxis of both
Influenza virus A and Influenza virus B. Oseltamivir is a neuraminidase
inhibitor which prevents new viral particles from being released by infected
cells. Neuraminidase cleaves terminal sialic acid residues from carbohydrate
moieties on the surfaces of infected cells. This promotes the release of
progeny viruses from infected cells (FDA Information on Tamiflu, [http://www.fda.gov/cder/drug/infopage/tamiflu/default.htm]
and Roche Tamiflu Fact Sheet, [http://www.roche.com/med_mbtamiflu05e.pdf]).
Roche AG
(http://www.roche.com/home.html) is the primary maker of Tamiflu and in early
2005, it announced a production shortage resulting from a bottleneck due to
lack of shikimic acid. Shikimic acid is a critical ingredient that is isolated
from star anise, which is an ancient cooking spice. Star anise is only grown in
four provinces in China and harvested between March and May, and also in Lang
Son province in Vietnam. The extraction process for the shikimic acid from star
anise is long, complicated, and has a low yield. Therefore, Roche is now
shifting production to a fermentation process using E. coli bacteria. This will decrease, if not eliminate,
reliance on limited and unpredictable agricultural resources. Reports have indicated that this new
fermentation production method of shikimic acid also produces much higher
amounts of this critical ingredient.
Tamiflu is hoped to
be effective in combating the next flu pandemic, assuming the virus causing the
next pandemic is susceptible to this neuraminidase inhibitor. In preparing for
this future pandemic, many countries and health organizations, including the US
and the WHO, have begun stockpiles of oseltamivir (Roche Media News, 19 April
2006, [http://www.roche.com/med-cor-2006-04-19]). Along with the US, multiple countries have begun to produce
oseltamivir. Prior to 2004 all production of this medication occurred in
Switzerland at the Roche company production facility in Basel.
"The ability to
produce Tamiflu from start to finish on US soil is a significant milestone that
will help ensure access to Tamiflu when and where it is needed," said
George Abercrombie, president and chief executive officer for Hoffman-La Roche,
Inc., the company's US pharmaceutical division (Roche Press Release, 14
September 2006). He continues,
“"This most recent expansion further demonstrates Roche's long term
commitment to serving as a responsible and collaborative partner with the U.S.
government on pandemic preparedness and response To date, HHS has ordered 21.3
million courses of Tamiflu for the U.S. Strategic National Stockpile, which
will be delivered in full this year. The total targeted U.S. stockpile is 81
million antiviral treatment courses by the end of 2008; HHS plans to purchase
50 million treatment courses and subsidize by 25 percent the states' purchases
of 31 million courses”.
Oseltamivir is the
only oral neuraminidase inhibitor licensed by the FDA to prevent and treat
influenza infection. The only other
FDA-licensed neuraminidase inhibitor drug for influenza prevention and therapy,
zanamivir (“Relenza”) is only available commercially as an inhaled drug and not
as a pill or capsule. Of note,
influenza viruses that are resistant to oseltamivir (Tamiflu) are still
susceptible to zanamivir (Relenza). The
US Department of Health and Human Services (see their pandemic flu website:
www.pandemicflu.gov) is stockpiling both oseltamivir and, to a lesser extent,
zanamivir.
If the next pandemic
influenza virus is susceptible to these neuraminidase inhibitor medications,
then we will be better prepared and safer than in the absence of this
stockpile. At the same time it is important to remember that both oseltamivir
(Tamiflu) and zanamivir (Relenza) have important caveats to their use and
effectiveness. In addition, antiviral drugs are only one part of overall
pandemic flu preparedness and response.
Shoshana Avertick,
Jordan Kanter, Stephanie Hrycaj, Igor Fogelman, Pete Harlan, and Shannon
Hibbard.
Graduate students,
Georgetown University Master of Science (M.S.) Program in Biohazardous Threat
Agents and Emerging Infectious Diseases. Biodefense Public Health
Countermeasures MICB-523.Washington, DC. Course instructor and article editor:
Daniel R. Lucey, MD, MPH. Adjunct
Professor of Microbiology and Immunology. Director, Center for Biologic
Counterterrorism and Emerging Diseases, EROne Institute, Washington Hospital
Center, Washington, DC. Website for this posting: www.BePast.org.
E-mail:Daniel.R.Lucey@Medstar.net