March 20, 2012

Congress Acts to Speed FDA Drug Reviews

Holland & Knight Alert
Michael J. Werner

Congress is taking steps to ensure that drugs and biological products reach the market sooner. Provisions included in the draft FDA user-fee legislation unveiled by the House Energy and Commerce Committee last week would expand drug developers’ access to FDA’s “accelerated approval” program.

These provisions had originally been introduced in the Faster Access to Specialized Treatments Act, HR 4132, co-sponsored by Rep. Stearns (R-Fla.) and Towns (D-N.Y.). The inclusion of these provisions in the user fee bill significantly improves their chances of enactment.

According to its supporters, these provisions are based on the successful drug development and approval model used for the early products to treat HIV/AIDS that came to market in the 1990s. During that time, FDA created its accelerated approval program. Under accelerated approval, drugs for serious and life threatening conditions could get to market sooner by showing an effect on a surrogate clinical endpoint that would predict a likely clinical benefit. However, developers were required to perform post-market testing.

Drug developers, patients and other stakeholders have argued that Congress needs to expand the applicability of the accelerated approval program — particularly for rare disease products — as well as take steps to emphasize the program’s importance and encourage its use.

The provisions in the House user fee bill are the following:

Fast Track

At the request of a sponsor, FDA must expedite the review of a drug if alone or in combination with other drugs it treats a serious or life-threatening disease or condition and demonstrates the potential to address unmet medical needs for such a disease or condition. If the drug is designated a fast track product, FDA must “take such actions as are appropriate to expedite the development and review of the application for approval of such product.”

If FDA determines the fast track product may be effective, it can begin review of portions of an application for approval — before the sponsor submits a complete application.

Accelerated Approval

The bill allows FDA to approve a product for a serious or life-threatening disease or condition, including a fast track product, if it determines, “taking into account the severity or rarity of the disease or condition and the availability of alternative treatments,” that the product has an effect on either of the following:

  • a surrogate endpoint that is reasonably likely to predict clinical benefit
  • a clinical endpoint, including an endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit

The bill says that the evidence to support that an endpoint is reasonably likely to predict clinical benefit may include “epidemiological, pathophysiologic, pharmacologic, therapeutic or other evidence developed using, for example, biomarkers, or other scientific methods or tools.”

However, approval of a product under accelerated review is subject to the following requirements:

  • the sponsor must conduct appropriate post-approval studies to verify and describe the predicted effect of the product on irreversible morbidity or mortality or other clinical benefit
  • the sponsor must submit copies of all promotional materials related to the product, at least 30 days prior to dissemination of the materials during the preapproval review period and following approval, for a period that the FDA commissioner determines to be appropriate

FDA can withdraw approval made pursuant to this section for any of the following reasons:

  • the sponsor fails to conduct any required post-approval study of the product
  • a study required to verify and describe the predicted effect on irreversible morbidity or mortality or other clinical benefit of the product fails to verify and describe such effect or benefit
  • other evidence demonstrates that the product is not safe or effective under the conditions of use
  • the sponsor disseminates false or misleading promotional materials with respect to the product

Moreover, FDA is required to develop and disseminate to physicians, patient organizations, pharmaceutical and biotechnology companies, and others a description of the accelerated approval and fast track processes. FDA is also required to establish a program to encourage the development of surrogate and clinical endpoints, including biomarkers, and other scientific methods and tools that can assist the agency in determining whether the evidence submitted in an application is reasonably likely to predict clinical benefit for serious or life-threatening conditions for which there exist significant unmet medical needs.


FDA is required to issue draft guidance to implement these provisions within one year and final guidance must be issued a year after that. FDA must also amend any regulations governing accelerated approval to bring them into line with these new provisions. The guidance must take into account issues arising under the accelerated approval and fast track processes for drugs designated for a rare disease or condition.

Independent Review

The Department of HHS is required to contract with an independent entity “with expertise in assessing the quality and efficiency of biopharmaceutical development and regulatory review programs,” to evaluate FDA’s application of these processes and the impact of such processes on the development and timely availability of innovative treatments for patients suffering from serious or life-threatening conditions. This review must include consultation with “regulated industries, patient advocacy and disease research foundations, and relevant academic medical centers.”

FDA’s View

While FDA has tentatively agreed to this statutory language, Dr. Janet Woodcock, director of the Center for Drug Evaluation and Research, testified last week on this topic and noted that the legislation will not change the current evidentiary standard for drug approval. Rather, she said, it simply provides “clarity” to the accelerated approval process.

Dr. Woodcock also said that FDA plans to issue guidance soon that explains the use of accelerated approval for rare and orphan-disease drugs.

The House bill is still in draft form and the Senate has not yet released any similar language. Thus, how the provisions will look if and when they are enacted remains unclear. Stakeholders still have time to raise concerns or questions.

Congress is expected to complete its work on FDA matters by July 2012.

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