Vice President Dan Quayle and HHS Secretary Louis W. Sullivan, M.D., today announced that four initiatives are being implemented by the Food and Drug Administration to speed access to new drugs and improve the drug review process.
These initiatives follow through on FDA's commitment made last November, as recommended by the President's Council on Competitiveness, to provide earlier access to important new drugs, ease unnecessary regulatory burdens and strengthen U.S. competitiveness," said Vice President Quayle, who chairs the Council.
These actions will save both lives and money and reduce human suffering. They will substantially improve FDA's ability to respond vigorously to the nation's health needs by allowing important new drugs to be approved months or even years earlier than was previously possible," Secretary Sullivan said.
FDA Commissioner David A. Kessler, M.D., said that the changes will streamline the drug development process without sacrificing rigorous oversight. "While drug reviews will be accomplished faster, patients can be assured that only drugs that are both safe and effective will be approved," he said.
The four initiatives reported today are:
Proposed rules are being published to accelerate the approval of new "breakthrough" drugs. They will allow these therapies to be approved at the earliest time in their development at which safety and effectiveness can be reasonably established. Under these new procedures, in making an approval decision, FDA will use "surrogate endpoints" that indicate that a drug is effective and then further confirm its effectiveness through additional human studies that will be carried out after marketing approval. "We used surrogate endpoints in approving the AIDS drug ddI. ddI was approved in just months -- not years, as would normally have been the case," Dr. Kessler said.
Under the new procedures time to approval could be reduced by as much as one to three years for "breakthrough" drugs.
Experimental therapies will be made available to AIDS patients as early as possible in the drug development process -- a departure from the current practice of making investigational drugs available initially only through controlled clinical studies. This "parallel track" policy, an effort of the National Institutes of Health and FDA, will be published in the Federal Register this week. It will permit access to these drugs by those patients with AIDS who are unable to participate in the controlled clinical trials. The new policy, initially aimed at AIDS, may be evaluated for other serious diseases.
Safety Testing Harmonization.
Through guidance based on consensus among the European Community, Japan and the United States, safety data based on animal testing in one of the participating countries will now be accepted by the others. This will eliminate the need to duplicate valid animal testing, and will reduce the time currently required for long-term testing by six months or more. "As a result, safety data developed in accordance with one country's standards will be accepted by another, and drug sponsors will no longer face the burden of performing multiple studies on new drugs to meet varying national requirements. This will cut the time and resources currently required for such testing," Dr. Kessler said.
Outside Expert Reviews.
To reduce the backlog of new drug applications, FDA is undertaking an external review program to use qualified experts from outside the government to review certain routine types of applications. FDA has solicited a proposal for a pilot external review. A contract to manage and conduct this review is being negotiated with the MITRE Corporation. A notice appeared Friday, April 3, in Commerce Business Daily soliciting additional qualified organizations to participate in this program. Although FDA will retain final approval authority, the expert reviewers will assume much of the burden of analyzing the data in these applications.
Both FDA and NIH are agencies of the Public Health Service within HHS.
FDA is announcing a proposed regulation for accelerating the approval of "breakthrough" drugs for patients with serious illnesses when a drug provides a meaningful therapeutic benefit over existing therapy. Reliance on "surrogate endpoints" could allow a drug to be approved months or even years earlier than if an endpoint such as significant damage or death from the diseases were used.
Such therapies would be approved at the earliest time in their development at which safety and effectiveness could be reasonably established by relying for evidence of effectiveness on a drug's effect on surrogate endpoints, such as laboratory measurements or physical signs, that do not represent patient benefit in themselves but are thought to correspond to a real benefit. Under the regulation, the drug's sponsor could be required to commit to post-marketing human studies to confirm that the drug's effect on the surrogate endpoints was an indicator of its clinical effectiveness.
Accelerated approval could also be used if FDA determined that a drug, effective for the treatment of a disease, could be used safely under a restricted distribution plan. Here, too, the sponsor could be required to commit to perform post-marketing studies.
All drugs or biological products approved under this proposal would have to meet the statutory standards for safety and effectiveness.
The procedures would also allow for a streamlined withdrawal process if the post-marketing studies did not verify the drug's clinical benefit, if there was new evidence that the drug product was not shown to be safe and effective, or if other circumstances arose that FDA believed necessitated expeditious withdrawal of the drug or biologic.
A new policy, called "parallel track," is intended to make promising new investigational drugs for AIDS and other HIV-related diseases more widely available as early as possible in the drug development process. Under this policy, promising new drugs may be made available to people with advanced HIV-related diseases who have no satisfactory alternative therapy, while the controlled studies necessary to establish the effectiveness and safety of the drugs are being performed. Patients with AIDS and other HIV-related diseases, who are without satisfactory alternative therapy and who cannot participate in the controlled clinical studies, now have a potential alternative means of obtaining promising therapies.
The public Health Service is also prepared to work with interested patient groups, physicians and sponsors to develop comparable programs for other life-threatening diseases when there is significant support for doing so.
Under this policy, sponsors of experimental therapies for AIDS and other HIV-related diseases may submit proposals for parallel track studies either to the AIDS Research Advisory Committee of the National Institute of Allergy and Infectious Diseases or to the FDA. FDA will determine if sufficient evidence exists that the drug is reasonably safe, if there is promising evidence that the drug may be effective in the patient population and if the proposal meets additional criteria set forth for the parallel track program.
If safety concerns arise with an experimental drug in the parallel track program, the studies may be stopped by the use of a "clinical hold" mechanism.
All drugs in the parallel track program will be distributed under a study protocol so that data, particularly as they pertain to side effects and safety, will be collected in these expanded access studies. However, most of the data essential for market approval will come from controlled clinical trials.
Harmonized and Streamlined Safety Testing Requirements for Drugs
The FDA is announcing the availability of new draft guidance that will streamline testing in animals for the safety of investigational drugs. This guidance is one of a series of consensus agreements among the European Community, Japan and the United States to harmonize scientific requirements and technical standards for drug approval. These guidelines will reduce the time and resources currently required for this testing -- in some cases by half -- and can thus be expected to reduce by six months or more the overall time required for drug development. They should also reduce the number of animals used for testing.
As a result, animal testing data developed in accordance with one country's standards can be accepted for review by another, the drug sponsors will no longer face the burden of performing repetitive studies, such as for cancer and reproductive toxicity, to meet varying national requirements.
FDA will make this draft guidance available for public comment shortly trough an announcement in the Federal Register.
External Review Program For New Drugs
The FDA is beginning an "external review" program that provides for qualified experts from outside the government to review certain applications for new drugs and biologics. In general, these will be drugs and biologics whose review is not expected to pose major problems -- for example, those similar to ones already approved. Although the FDA will retain the approval authority in determining that the drug or biologic meets the statutory requirements of safety and effectiveness and will carry out the usual supervisory reviews, the contract reviewers will relieve much of the burden of the initial analysis of data in these applications.
New drug applications (NDAs) or supplements in areas in which FDA has an application backlog, such as for anti- allergy, anti-infective, anti-inflammatory or analgesic drugs, or product licensing agreements (PLAs) for biologics, will be reviewed under this program. The FDA, contract reviewers, and if necessary, the drug sponsor will communicate regularly to review the progress and identify problem issues that may arise during the review. The contract reviewers will submit a comprehensive written report containing a recommendation on approval or nonapproval of the drug, 120 days after receiving the NDA or PLA. The FDA will then asses the quality, completeness and validity of the data review and if necessary, present the data to an FDA expert advisory committee. The sponsor will be notified by FDA 180 days after initiation of the review as to whether or not the drug is approvable.
The FDA has solicited a proposal for a pilot external review. On April 1, a sole source notice for this review was published in the Commerce Business Daily (CBD); FDA plans to award the contract to the MITRE Corporation. In addition, a notice seeking competitive bids from interested firms for the ongoing program was published in the CBD on April 3. The first review of an NDA or PLA is expected to begin this summer.