US regulators are touting the success of a regulatory review program that they say has been responsible for approving dozens of drug products intended for use in developing countries-and in particular Africa-to help fight AIDS.
The drug approvals are part of a signature plan shepherded through Congress in 2004 by President George W. Bush known as the President's Emergency Plan for AIDS Relief (PEPFAR). That plan committed tens of billions of dollars toward fighting AIDS in low-resource environments, and is based on five core goals:
- the formation of nationwide programs that address AIDS systematically, as opposed to on an emergency basis
- improving the capacity of governments to respond to AIDS and other health crises
- improving prevention, care and treatment measures for AIDS and other health crises
- integration of local programs into broader health and development programs
- investment in innovation and operations research to maximize outcomes and improve service
Integrated into those goals is the US Food and Drug Administration (FDA), which lends its considerable regulatory capacity to assist local regulators in being able to tentatively approve antiretroviral drugs.
"Some resource-constrained low- and middle-income African countries have lacked sufficient expertise to conduct registrations efficiently," Beverly Corey, FDA's senior regional advisor for Sub-Saharan Africa, said. And without the capacity to properly review those applications, local populations could be subject to lengthy waits or-worse-unsafe medications.
The solution to this has been tentative approvals, which can be thought of as a sort of regulatory assistance clearinghouse method of reviewing products.
Tentative approval allows FDA to review single entity, fixed-dose combination, or co-packaged products for approval, even if the product(s) is still under patent protection in the US. FDA then works with other entities, such as the World Health Organization (WHO), to communicate its decisions to local regulators to assist with the process of local registration in respective countries.
The pathway has by some standards been a marked success. Between 3 December 2004 and 8 November 2012, FDA said it had approved 155 such applications, "thereby making them available for use" under the PEPFAR program. That averages out to over 19 antiretroviral medications each year.
Of those, 128 have been abbreviated new drug applications (ANDAs), used to approve generic medicinal products already approved in the US. The remaining 27 were for new drug applications (NDAs).
Other groups, including the Global Health Technologies Coalition (GHTC), a group supported by the Bill and Melinda Gates Foundation, argued in a report issued in May 2012 that FDA's activities in this area-and even in the US alone-have facilitated development and access to dozens of new medicines around the globe for use in neglected diseases like AIDS.
Regulators, Corey explained, are also involved in efforts to boost the regulatory capacity of local officials as well. "One necessary way to address delayed access to medications is to bolster the expertise of African regulators so that they can conduct timely reviews of drug applications. After all, the FDA approval or tentative approval is just one step. Then the therapies must be registered (or approved) by competent drug regulatory authorities in the countries of use."
Corey also highlighted some recent regulatory developments, including a recent training program collaboration led by FDA at the Kilimanjaro School of Pharmacy intended to teach regulators and academics from 17 African nations about the review of generic drug applications (ANDAs) and PEPFAR drug reviews.
Corey said she hopes that the training course could "Eventually be turned into a teaching module for use in academic curricula throughout Africa [and] support a cadre of regulatory affairs professionals to work in government agencies."
"This would further the availability and the manufacture of quality, safe and effective drug products for the African population," she concluded.
A Sustained Effort
Carey's discussion of the PEPFAR program is part of what one might call a sustained effort on the part of FDA to make the case for improving regulatory capacity abroad.
Carey is a member of FDA's Office of International Programs (OIP), which has also made the case for its successes in recent months. In October 2012, a trio of OIP's top regulatory officials-Charles Preston, Mary Lou Valdez and Katherine Bond-argued that strengthening regulatory capacity of international regulators should be a top priority for the agency.
The group was writing in the medical journal Public Library of Science Medicine (PLoS Medicine), and called the difference between high- and low-resource regulatory systems a "significant gap."
"We propose that strengthening regulatory systems in low- and middle-income countries must become a global health priority, and explain the imperative in terms of globalization and the rapid scale up of medicines to the developing world," they wrote.
While much of the article talked about the benefits of strengthened regulatory capabilities abroad, and in particular how such developments could cut down on substandard and counterfeit medicines, they too brought up PEPFAR as a potential model for broader agency use.
The program, they said, was instrumental in allowing foreign regulators not only to build their own capabilities, but also to focus their attention on other pressing issues that might otherwise be lost among in the fight against AIDS.
"Systems in many low- and middle-income countries are not equipped to perform such assurance functions," they noted. "A global dialogue is beginning. Discussions of expanded market access for exports, increased trade opportunities emanating from science-based regulation and regulatory coherence, and more sustainable economic development, should also be included, as they will provide further incentives for countries to come to the table."
"As the challenges of globalization mount, and efforts to provide medical products to low- and middle-income countries scale up, there is no better time to put regulatory system strengthening squarely on the global health and development agenda."