June 27, 2012

Congress Enacts Sweeping FDA Reforms

Holland & Knight Alert
Michael J. Werner

With a final overwhelming vote in the Senate, the U.S. Congress passed an FDA user fee bill that will provide necessary funds for the agency to perform drug reviews and require it to meet performance goals, as well as other important reforms. The Food and Drug Administration Safety and Innovation Act (the “Act”) will be signed by President Obama shortly.

Many provisions in this sweeping bill change existing review and approval rules and processes - especially for rare disease products and antibiotics. It also contains provisions aimed at alleviating or preventing drug shortages.

Below is a summary of key provisions of the legislation.

User Fees

The bill codifies the negotiated agreement on user fees between the drug industry and FDA. It reauthorizes the prescription drug user fee program allowing the FDA to continue to collect fees from industry to support the review process for human drug applications from fiscal year 2013 through fiscal year 2017. Under the Act, in exchange for fee increases, FDA agrees to:

  1. meet performance goals related to timely review of drug applications
  2. increase interaction with drug sponsors during the review process
  3. expand interactions with patients, including those with rare diseases
  4. evaluate its own performance

In addition, the Act for the first time creates user fees to support reviews of biosimilars - new versions of already-marketed biologics - as well as for generic drugs.

Accelerated Approval

The Act requires FDA to facilitate the development and expedite the review of a drug designated as a “fast-track product.” These are drugs for the treatment of a serious or life-threatening disease or condition that also demonstrates the potential to address unmet medical needs.

In addition, the Act “enhances” the existing accelerated approval process and creates a mechanism whereby the FDA can expedite reviews of marketing applications for drugs that treat serious or life threatening conditions, including fast track products, at the request of the sponsor.

Under the Act, during the accelerated approval process, the FDA can approve a product if it has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit or a clinical 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 taking into account the severity or rarity of the disease or condition and the availability of alternative treatments. Accelerated approval may be subject to a sponsor being required to perform post-approval studies and submit promotional materials prior to dissemination.

FDA is required to issue draft guidance implementing this process within one year and a final guidance a year later. In addition, the legislation calls for an independent analysis of accelerated approval and its impact on the development of innovative treatments.

The Act also requires the FDA to expedite the development and review of a drug designated a “breakthrough therapy.” To achieve this designation, a drug must be intended to treat a serious or life-threatening disease or condition, and preliminary clinical evidence must indicate that it may demonstrate substantial improvement over existing therapies.

Rare Diseases

The Act contains several provisions specifically designed to promote drug development for rare diseases. For example, the accelerated approval provisions noted above require FDA to consider the “severity or rarity” of the disease or condition being treated. In addition, when developing its guidance to implement the program, FDA must specifically take into account issues relating to how the process will apply to development of products for very rare diseases for which the low prevalence of a disease makes collecting data difficult. Moreover, under the Act, FDA must ensure that opportunities exist for consultation with external stakeholders from the rare disease community and keep a list of medical experts to consult with during reviews of products for rare diseases.

It is important to note that the Act implements the provisions in the negotiated agreement between FDA and the drug industry that call for employing user fees to address rare disease issues, such as training FDA staff to better handle orphan drug applications. Moreover, FDA is expected to increase rare disease patient and advocate involvement in application reviews and add new staff for outreach to sponsors.

Moreover, the Act creates a program that provides the sponsor of a rare pediatric disease product with a voucher that entitles the sponsor to priority review of any other product (FDA must act on the application within six months). To qualify, the rare pediatric disease product cannot have an adult indication and the disease must primarily impact those up to 18 years of age. Companies that receive a voucher can use it for their own future products or transfer/sell the voucher to another sponsor.

Antibiotic Development

The Act contains provisions designed to respond to the public health emergency caused by a lack of vaccines and therapies for infectious diseases. Specifically, it creates incentives for development of new “qualified infectious disease products” (QIDPs) by providing an additional five years of market exclusivity for the product post-approval, in addition to the periods of exclusivity for which the drugs would otherwise qualify. QIDPs would also be eligible for priority review and fast track review at FDA.

The QIDPs are defined as antibacterial or antifungal drugs intended to treat serious or life-threatening infections. The HHS secretary is required to develop a list of pathogens that cause serious or life-threatening infections.

Drug Shortages

The Act contains several provisions to address drug shortages. Specifically, manufacturers of drugs that are life-sustaining, life-supporting and intended for use in the prevention or treatment of a debilitating disease or condition, including those used in emergency medical care or surgery, must notify the HHS secretary at least six months prior to discontinuance or interruption of manufacturing. The Act also authorizes the secretary to expedite establishment inspections and review of applications and supplements that could help mitigate or prevent a shortage.

The HHS secretary must assemble a task force to create a strategic plan to address shortages. The secretary must also issue an annual report on drug shortages, including information about actions taken by the secretary to prevent or mitigate drug shortages, and coordination efforts between FDA and the Drug Enforcement Administration (DEA) to prevent or alleviate drug shortages.

FDA is required under the Act to maintain a drug shortage list and provide patients, providers and the public with necessary information to prevent, mitigate and manage drug shortages. In addition, the U.S. Government Accountability Office (GAO) is required to perform a study to examine the causes of drug shortages and issue recommendations on how to prevent or alleviate a drug shortage.

The Act also attempts to address the role of DEA quotas of controlled substances in the reported shortages of those products. DEA is required to respond to quota increase requests within 30 days. In addition, DEA must report annually on its efforts to address drugs shortages.

Other Provisions of Note

The Act contained other provisions related to drug development including:

  • requiring FDA to work with other regulatory agencies to reduce duplication of studies necessary for premarket approval, without altering the current standards for premarket review of medical products; FDA must, when considering drug applications, either accept foreign clinical data or notify the sponsor of FDA’s rationale for concluding that the data are not adequate to support approval
  • requiring FDA to establish a strategy and implementation plan for advancing regulatory science
  • prohibiting FDA from issuing guidance on the regulation of laboratory developed tests unless it notifies Congress of its intent to do so 60 days prior to the issuance of the guidance

Congress and FDA had also been working on provisions to create a national uniform “track and trace” system to ensure the integrity of the drug supply chain. However, congressional negotiators could not reach agreement in time for the House and Senate user fee bill debate and these provisions were not included.

We will continue to monitor those issues as well as implementation of all FDA programs in the coming weeks and months.

Related Insights