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 private sector's prime expertise is finding drugs, explained Moran at a conference sponsored by the Brookings Institution
in Washington, DC last April. "Where they're less interested and less expert is doing large-scale trials with pregnant women
and children in remote developing countries in diseases that they don't know about." So the new model "swaps roles round,"
she explained. "Industry moves upstream" to do high-level innovation that carries less liability risk, and public groups move
downstream to clinical development and dealing with regulatory authorities and patient groups. Lower expenditures produce
drugs at not-for-profit prices and with higher health value to patients in developing countries.
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."
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.