Expanded Access and Expedited Approval
of New Therapies Related to HIV/AIDS

FDA has taken several significant steps primarily in response to the HIV/AIDS crises, toward making experimental drugs intended to treat life-threatening diseases more widely available to severely ill patients, as well as toward speeding up the review and approval of the applications for these products.

Expedited Procedures

• In 1987, FDA created a "AA" priority category to classify all applications for potential AIDS therapies to ensure that these products receive the highest priority in the review process.
• In October, 1988, FDA issued interim regulations designed to expedite marketing approval of new drugs intended for life-threatening and severely-debilitating diseases, by facilitating the clinical testing and evaluation process. Under the expedited procedures, early consultation with FDA by drug manufacturers, with agreement on the proper design of clinical trials, can lead to phase 2 studies with adequate data to support approval. In some instances, the need for Phase 3 testing can be virtually eliminated.
• On December 11, 1992, FDA published the final rule to accelerate the approval of new drugs for serious and life-threatening diseases when the drug provides meaningful therapeutic benefit over existing products. Under these procedures FDA may approve drugs based on surrogate endpoints that reasonably predict that a drug provides clinical benefit. This clinical benefit is then confirmed through additional human studies that will be completed after marketing approval. The accelerated approval approach provides for removal of the drug from the market if further studies do not confirm the clinical benefit of the therapy.
• On December 12, 1995, FDA published a report, "Timely Access to New Drugs in the 1990s: An International Comparison," which documents FDA's tough standards do not delay consumer access to important new dugs, compared to other countries and that the United States has available valuable drugs as soon as, and in many cases sooner than, its counterparts around the world. Six antivirals have received approval for the treatment of HIV: two were approved in three months, three in six months and one in eight-and-a-half months.

Antiretrovirals Currently Approved
For HIV Infection and AIDS-related Conditions

Expanded Access Mechanisms

• Expanded access mechanisms are designed to make promising products available as early in the drug evaluation process as possible.
• Expanded access mechanisms include Treatment IND protocols and parallel track protocols. In addition, the ordinary development of drugs under an IND includes a variety of open studies that also provide access to drugs. FDA monitors each of these access programs on an ongoing basis.

Examples of Expanded Access Enrollment

Treatment INDs

• Final regulations were issued in May of 1987 establishing conditions under which promising new drugs and biologics that have not yet been approved or licensed may be made available to persons with serious and life threatening illnesses. Treatment INDs have generally been granted when the product is well into clinical trials or when all clinical trials have been completed, after the development of some reliable evidence that the product is effective.
• Eleven treatment IND protocols for promising AIDS-related products have been allowed to proceed since the Treatment IND regulations became effective.

Parallel Track

• The final PHS policy statement on the parallel track mechanism was published in the Federal Register on April 15, 1992. The purpose of the parallel track policy is to expand the availability of promising investigational drugs to those persons with AIDS and HIV-related diseases who are without satisfactory alternative therapy and who cannot participate in controlled clinical trials.
• Stavudine (d4T) has been the only drug submitted for consideration under the parallel track policy. The protocol was allowed to proceed on October 5, 1992. Approximately 12,000 patients received Stavudine through the parallel track mechanism. An accelerated new drug application for stavudine was approved June 17, 1994. The application received full marketing approval on December 21, 1995.
• FDA is responsible for assuring that the availability of a drug under the parallel track program does not interfere with the drug sponsor's ability to carry out well-controlled studies on the drug and does not encourage patients with other approved treatment alternatives to resort to untested investigational drugs.

Last revised March 5, 1998, Office of Special Health Issues, HF-12