HHS Proposes Rapid Process for Review of Fixed Dose Combination and Co-packaged Products
Expedited Review Process Will Assure the President's Emergency Plan for AIDS
Relief That These Drugs Are Safe and Suitable for Purchase
Date: May 16, 2004
Contact: HHS Press Office
(202) 690-6343
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.
HHS FACT SHEET
Secretary of Health and Human Services Tommy G. Thompson, Global AIDS
Coordinator Randall Tobias, and Acting Food and Drug Administration (FDA)
Commissioner Lester Crawford, announced an expedited pathway for FDA to
review low-cost, safe and effective fixed dose combination (FDC-creating one
pill out of two or three individual drugs), co-packaged(putting two or more
pills into single packaging for distribution) and single ingredient HIV
therapies for use under the President's Emergency Plan for AIDS Relief.
What drugs can be reviewed through this pathway?
- Brand-Name Fixed-Dose Combination and Co-Packaged HIV Therapy Drugs.
Today's action encourages the development and provides expedited review for
applications from brand-name companies (research and development based
companies that hold the original patent for the individual drugs used to
make up the FDC) for FDC and co-packaged HIV therapy drugs composed of drugs
previously approved by FDA.
- Non-Brand-Name Fixed-Dose Combination and Co-Packaged HIV Therapy
Drugs. FDA will also provide expedited review for applications from non
brand-name companies for FDC and co-packaged HIV therapy drugs composed of
drugs previously approved by FDA. Non-brand-name companies can submit
applications on their own or develop partnerships with brand-name companies.
- Non-Brand-Name Single Ingredient Drugs. Today's action also
provides expedited review from non-brand-name companies for generic forms of
already approved single-ingredient HIV therapy drugs.
What scientific information is required from Applicants?
- Existing Clinical Data. FDA's expedited review process for FDCs or
co-packaged drugs encourages companies to rely on existing data, including
published literature, to support labeling for the combined use of already
approved drugs rather than developing new clinical data. Normally, it takes
a company 3-4 years to develop this information. FDA's guidance provides a
list of currently approved drugs for which the agency believes there are
sufficient clinical data. In addition FDA will consider the following types
of information in lieu of new clinical data:
- Peer-reviewed scientific literature reports of clinical studies.
FDA's guidance provides a list of drugs currently approved by FDA for which
there are sufficient clinical data.
- Reference to a company's own relevant data including data already
submitted to FDA.
- Cross-reference to another company's data (for which the applicant
has obtained the reference rights).
- Reliance on FDA's findings of safety and effectiveness for an
approved drug product.
- Chemistry. For co-packaged brand-name products, only data showing
that the drugs are stable in the new package will be needed. For new FDCs
information showing that the combined drugs do not react with one another
will be necessary. If a manufacturer has never submitted a description of
the manufacturing process to FDA, additional information would be needed.
- Bioavailability Study. A bioavailability study is needed to show
that the blood levels of the products when used in combination are at levels
comparable to that achieved by the drugs used alone.
- Manufacturing Inspection. Plants manufacturing these products will
have to pass an FDA quality inspection.
What are the time frames for review?
- Once FDA receives a completed application, it anticipates completing
review of FDCs within 6 weeks. Review of applications for co-packaged
products consisting of individually approved components with new combination
labeling could be completed more quickly. FDA will provide technical
assistance to those not familiar with the FDA process. FDA will also
provide basic technical assistance to manufacturers who do not currently
market a product, but wish to develop a product.
What will FDA review cost companies submitting applications?
- For new drugs, FDA typically charges a user fee of over $500,000.
Congress has provided the Agency with authority to grant waivers of these
fees when appropriate. To minimize the cost of submitting an application
for review, FDA anticipates waiving fees for products proposed for use under
the President's Emergency Plan for AIDS Relief.
How much will the drugs cost?
- The process announced today does not directly relate to price. The
Global AIDS Coordinator will create a competitive process to procure the
lowest price in the future. Nonetheless, this pathway should significantly
increase the number of companies and products that will compete for the
Coordinator's procurement. It has been claimed that some HIV/AIDS therapies
may cost as low as $140 per year. All companies with products are
encouraged to participate in this process and compete in the procurement.