Reducing research risk

Consequently, multinational pharmaceutical companies are supporting more research in third-world diseases. In the lead are major manufacturers such as GlaxoSmithKline (GSK), Novartis, AstraZeneca, and Sanofi-Aventis, which have established separate neglected-disease R&D units. These corporate initiatives do not expect to make a profit, but seek to conduct R&D in a way to avoid large losses. This "no profit–no loss" approach, says Moran, requires a new research model. Large pharmaceutical companies traditionally have obtained promising drug leads from research organizations and biotech companies and then stepped in to underwrite late-stage clinical development.

The partnership approach encourages pharmaceutical manufacturers to be more involved in relatively low-cost, early-stage research to identify and run preliminary tests on promising compounds. The more expensive and risky task of conducting clinical trials and seeking product registration in multiple countries is assumed largely by the nonprofit partner, which benefits from local research networks and experience negotiating national regulatory requirements.

The collaborative models differ. Some PPPs are establishing their own laboratories to conduct research without any industry partner, often contracting out clinical research, product formulation, and manufacturing to separate entities. Contract research organizations are involved in more than one third of PPP projects and most often are asked to handle specific tasks such as animal testing and local clinical trial monitoring.

An "industry mindset" is an important characteristic of these collaborative organizations. Medicines for Malaria Venture president Chris Hentschel, who comes from the biotech industry, explained at the Brookings conference that being able to drop unsuccessful projects is key. "If they're not meeting milestones, we have to kill them," he said, "and we operate exactly like industry in that way."

Scaling up

Manufacturability is another important consideration for identifying potentially successful products, noted Jerald Sadoff, president of the AERAS Global Tuberculosis Vaccine Foundation and formerly with Merck. Most projects fail because they can't be made at an acceptable cost or in a reliable way for millions of doses. The PPPs have expertise in the field, he said, but experience in good manufacturing practices (GMP) reporting and data management comes from industry.

Consequently, most collaborative projects rely on a large pharmaceutical partner to handle the manufacturing and packaging of final drug products. Actual production often is outsourced to a developing-country partner, frequently a local generic-drug manufacturer. Lynn Marks, senior vice-president of the GSK Medicine Development Center, noted that voluntary licensing of products allows manufacturing in low-cost plants in developing countries to "get outside our cost structure."

Fairly sophisticated generics firms in India, China, and South Africa have considerable expertise in formulation chemistry, low-cost scale-up, and product distribution in Africa and Asia. Some of these larger generic manufacturers also are moving more into R&D as PPPs provide opportunities to expand from basic productions to new drug development.

More efficient and innovative formulations and manufacturing approaches may be one beneficial outcome of the search for new treatments. For example, iOWH is partnering with researchers at the University of California, Berkeley and a spin-off company, Amyris Biotechnologies, to develop a large-scale, low-cost commercial microbial drug production process for artemisinin, the key ingredient in new antimalarials. Berkeley scientists are refining the production process, Amyris is developing a large-scale industrial fermentation process needed for commercialization, and iOWH will perform the testing to demonstrate bioequivalence of microbially produced artemisinin with the natural product.