Semisynthetic artemisinin achieves WHO prequalification

Contact:
Elena Pantjushenko, PATH, 650.392.2537, epantjushenko@path.org.

South San Francisco, United States, May 10, 2013—Semisynthetic artemisinin, a key ingredient in the most effective malaria treatments, has been prequalified by the World Health Organization (WHO), PATH’s Drug Development program announced today.

WHO’s decision means semisynthetic artemisinin has been evaluated and accepted for use in the manufacture of active pharmaceutical ingredients and finished pharmaceutical products. Prequalification also creates a simplified process for manufacturers using semisynthetic artemisinin in their products to obtain regulatory acceptance, possibly accelerating the availability of malaria treatments on the market.

Semisynthetic artemisinin was created through a nine-year, cross-sector partnership led by OneWorld Health, which affiliated with PATH in 2011 to establish PATH’s Drug Development program. Large-scale production was launched last month by the project’s development and manufacturing partner, pharmaceutical company Sanofi. Artemisinin is the key ingredient in artemisinin-based combination therapies, recommended by WHO as a first-line treatment for uncomplicated malaria caused by the parasite Plasmodium falciparum.

The global supply of artemisinin, which is derived from the sweet wormwood plant, has not always kept pace with the demand. The addition of non-plant-derived artemisinin will strengthen the capacity of the supply chain, and should contribute to price stability and ultimately ensure greater availability of treatment.

“WHO’s decision to prequalify semisynthetic artemisinin paves the way for a more reliable supply of the top malaria treatment—an essential step toward our goals of achieving greater health equity and, ultimately, eliminating malaria altogether,” said Steve Davis, president and CEO of PATH. “Malaria still kills 660,000 people every year, most of them young children in Africa. Increasing access to treatment will mean more young lives saved.”

Sanofi submitted a master file to WHO’s Prequalification of Medicines Programme in 2012 as part of the project’s regulatory strategy. The company provided information showing that semisynthetic artemisinin is comparable to plant-derived artemisinin and demonstrating adherence to good manufacturing practices at Sanofi’s facility. WHO acceptance of semisynthetic artemisinin signals that these standards have been met. WHO’s prequalification process helps ensure the quality, safety, and efficacy of medicines purchased by countries and procured by international agencies for use in resource-limited settings.

The development of a commercial-scale alternative manufacturing process to produce a complementary source of artemisinin was led by OneWorld Health and funded by the Bill & Melinda Gates Foundation, building on pioneering synthetic biology work by Dr. Jay Keasling at the University of California, Berkeley (UC Berkeley). The project involved a team of public and private partners, including Sanofi and synthetic biology innovator Amyris, Inc., to take the project from laboratory research to commercialization.

“WHO acceptance of semisynthetic artemisinin is an incredible milestone,” said Dr. Ponni Subbiah, program leader of PATH’s Drug Development program. “As part of our strategy, we needed to ensure comparability of this product with plant-derived artemisinin, as well as minimize the regulatory burden on active pharmaceutical ingredient manufacturers wanting to use this material. WHO prequalification offers a clear path to a stronger artemisinin supply chain and more robust access to malaria treatments.”

Sanofi plans to produce 35 tons of semisynthetic artemisinin in 2013. That should expand to an average of 50 to 60 tons per year by 2014, corresponding to between 80 and 150 million artemisinin-based combination therapy treatments. The manufacturing of the main intermediate, artemisinic acid, is performed by Huvepharma in Bulgaria, which Sanofi has chosen as the contract manufacturing organization. Sanofi is committed to producing semisynthetic artemisinin using a no-profit, no-loss production model.

Read more about WHO’s prequalification of semisynthetic artemisinin at http://www.who.int/prequal/info_press/documents/PQ_non-plant_derived_artemisinin_1.pdf (PDF 96 KB).

The partnership for semisynthetic artemisinin is led by OneWorld Health (now PATH’s Drug Development program), with funding from the Bill & Melinda Gates Foundation. The project began in 2004, and partners include Sanofi, UC Berkeley, and Amyris. The novel use of synthetic biology technology is based on pioneering inventions from UC Berkeley, Amyris, the National Research Council Canada Plant Biotechnology Institute, and GenoClipp Biotechnology BV. The chemistry expertise and the industrial experience and capacity of Sanofi helped bring this project from small laboratory experiments to production on the factory floor.

PATH’s Drug Development program was established through its affiliation with OneWorld Health, a nonprofit drug development organization. The program works to develop and ensure the availability and accessibility of safe and effective new medicines for diseases disproportionately affecting people in developing countries. For more information, please visit http://sites.path.org/drugdevelopment/.