Guidance for Industry: Fixed Dose Combination and Co-Packaged Drug Products for Treatment of HIV
HHS Secretary Tommy G. Thompson today announced an expedited review process to ensure that the United States is providing safe, effective drugs to developing countries under the President's $15 billion Emergency Plan for AIDS Relief. U.S. Global AIDS Coordinator Randal L. Tobias said the new process will enable his office to ensure the quality of drugs purchased by the United States for developing countries under the President's Emergency Plan for AIDS relief. Under the new guidance to be proposed next week by HHS' Food and Drug Administration (FDA), the United States will be able to provide life-saving drugs at lower prices to millions of people in Africa and the Caribbean.
Secretary Thompson and Ambassador Tobias said drug patent issues that apply in developed nations should not impede purchase of these drugs for developing countries. The FDA guidance will apply to new products that combine already-approved individual HIV/AIDS therapies into a single dosage, known as fixed dose combinations (FDC), as well as to new co-packaging of existing therapies. Drugs that are approved by FDA under the process described in the guidance will meet all FDA standards for drug safety, efficacy, and quality, said Acting FDA Commissioner Lester M. Crawford.
The expedited review process, combined with the work of local drug regulatory authorities in the affected countries, will provide a mechanism to ensure that safety, efficacy and quality standards are met and maintained by companies providing drugs for the President's Emergency Plan for AIDS Relief. President Bush has pledged $15 billion for this initiative to address the global HIV/AIDS pandemic in developing nations, through prevention, care and treatment programs that include the purchase of HIV/AIDS drugs.
"We are clearing the way to quickly deliver quality, life-saving HIV/AIDS drugs to people who desperately need them in developing countries," Secretary Thompson said. "We are committed to ensuring that President Bush's Emergency Plan for AIDS Relief is providing medical care as effectively and efficiently as possible. Fixed dose combination products and co-packaged products are an important tool in improving the quality of health care in developing nations."
"The President has made clear that his goal is to put effective treatment into the hands of those who need it in the hardest-hit developing nations, and to provide these life-saving services as widely as possible," said Ambassador Tobias. "At the same time, we must apply real discipline to ensure that the products we provide in poor nations are safe and effective. The new expedited process provides us with a solid foundation for purchasing drugs that work. With FDA review, we will have a gold-standard assurance that a combination product will be safe and effective."
The guidance will outline four scenarios for review of different FDC and co-packaged products. Some of the scenarios could permit approval in as little as two to six weeks after submission of a high quality application. For companies making products where another firm owns the U.S. patent rights, FDA could issue a tentative approval when it finds the product meets the agency's normal safety and efficacy standards.
Ambassador Tobias commended Secretary Thompson for developing the new guidance. "The Office of the U.S. Global AIDS Coordinator would recognize this 'tentative approval' by FDA as evidence of the safety and efficacy of AIDS drugs to be purchased under the President's Emergency Plan for AIDS Relief. We can then use these drugs in developing countries, where international patent agreements permit them to be purchased," he said. "What is most important is that we must only purchase products that have undergone scientifically rigorous safety and efficacy review. This initiative on the part of FDA will enable just that."
Control of HIV/AIDS generally requires use of several different drugs simultaneously. Combination products would bring together different HIV/AIDS drugs in a single medication or co-package, thereby facilitating patients' compliance with often complicated drug regimens.
To obtain approval of new products, manufacturers could cite existing clinical data to demonstrate the safety and effectiveness of the individual drugs in the new combined product -- and new data to show effectiveness of the new combination could be developed quickly. FDA pledged to work with companies in assuring that necessary data are developed rapidly if the companies do not already have access to such data.
Secretary Thompson urged manufacturers of brand-name and generic drugs alike to work with FDA and submit applications. "HHS has opened the door to rapid review of new combination products," he said. "This means companies will have new incentives to develop easy-to-use products at lower prices. It also means we will provide a sound scientific basis to Ambassador Tobias for the very substantial purchases that the President's Emergency Plan will be making on behalf of millions of people in the hardest hit nations. This is essential - to skirt the safety and efficacy issues would be wrong and dangerous."
Acting FDA Commissioner Crawford also announced that FDA is evaluating whether the agency can waive or reduce user fees, normally charged to companies making new drug applications, for products reviewed under this rapid review process.
"FDA recognizes the public health importance of these products and is evaluating the circumstances under which it may grant user fee waivers for sponsors developing products under this guidance. FDA intends to expedite the development process for these products as much as is practicable. FDA intends to maximize the many benefits, including the potential to limit the development of drug resistance, while preventing serious risks such as overlapping toxicities and the potential for inappropriate combinations to increase the amount of virus in the body, " Dr. Crawford said.
The guidance will include a list of currently approved drugs for which FDA believes there exist clinical safety and efficacy data supporting combination use. There are more than 20 unique anti-HIV medications approved in the United States.
The draft guidance will be open for a 60-day comment, but it is effective and active immediately. A fact sheet on this issue is available at http://www.hhs.gov/news/press/2004pres/20040516a.html.