On May 9, after two weeks of floor consideration, the United States Senate voted by an overwhelming 93-1 to pass S.1082, the Food and Drug Administration Revitalization Act (FDARA).
FDARA is the most comprehensive FDA-related legislation considered by Congress in recent memory. It encompasses four critical reauthorizations to the prescription drug and medical device industries, would establish important new regulatory authorities affecting the food industries, and addresses many other important regulatory issues in a manner that has secured unusually broad bipartisan support.
Committee Consideration of FDARA
Following the April 18 committee markup in the Senate Committee on Health, Education, Labor and Pensions, Chairman Edward M. Kennedy (D-MA) worked closely with the committee Ranking Member Mike Enzi (R-WY) and other members of the committee to develop a manager’s substitute amendment for floor consideration.
PDUFA IV
The reauthorization of the Prescription Drug User Fee Act (PDUFA) alone provides for more than $392 million in user fees annually for essential drug review and approval activities, in addition to $150 million in new fees over 5 years dedicated to post-market drug safety activities, and more than $6 million annually for the review of direct-to-consumer (DTC) television advertisements.
As in previous reauthorizations, the legislation incorporates performance goals that are memorialized in a letter from the Secretary of Health and Human Services to Congress relating to the timeliness of NDA and BLA review. The performance goals also newly address postmarket safety in a comprehensive fashion by authorizing the use of fee revenue to enhance safety surveillance, validate epidemiology best practices, and improve FDA’s information systems.
It is notable that with user fees currently comprising greater than half of the agency’s resource base for human drug reviews, PDUFA has been criticized as allegedly enabling inappropriate sponsor influence on agency decisions. Under PDUFA IV, that ratio will rise to over 70 percent of the resource base for drug reviews.
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Original Titles of the Committee-Reported S.1082, FDA Revitalization Act
Title I
Prescription Drug User Fee Amendments of 2007 (PDUFA IV)
Title II
Enhancing Drug Safety and Innovation Act of 2007
Subtitle A - Risk Evaluation and Mitigation Strategies
Subtitle B - Reagan-Udall Foundation for the FDA
Subtitle C - Clinical Trials
Subtitle D - Conflicts of Interest
Subtitle E - Database for Authorized Generic Drugs
Title III
Medical Device User Fee Amendments of 2007
Title IV
Pediatric Medical Products
Subtitle A - Best Pharmaceuticals for Children Amendments of 2007
Subtitle B - Pediatric Research Improvement Act
Title V
Other Provisions |
Drug safety
Title II authorizes a system of Risk Evaluation and Mitigation Strategies (REMS) for select drugs. While most REMS requirements are not novel, sponsors may be newly required to conduct post-approval clinical studies or trials, or to comply with mandates, specific timeframes, and dispute resolution procedures for labeling changes. Sponsor failure to comply with required labeling changes or other REMS requirements, such as the conduct of required studies, communication plans, or compliance with restrictions on distribution, would be subject to civil and criminal penalties.
Title II also creates a Reagan-Udall Foundation to provide FDA with a resource base for Critical Path Initiative activities relating to all industries regulated by FDA, including modernizing veterinary, food, food ingredient, and cosmetic product development as well as pharmaceutical, biologics and medical device development.
It is notable that the Senate did not divide the pre-market and post-market functions of the Center for Drug Evaluation and Research (CDER), or mandate “one-size-fits-all” REMS on all newly approved drugs. However, the legislation authorizes FDA to disclose “trade secret or confidential commercial or financial information” in the event of a public health emergency.
The drug safety title also includes a provision creating a clinical trials registry within the National Institutes of Health for all Phase II, III and IV clinical trials for drugs and devices. The clinical trials registry must include links to patient labeling and published results of the trials, but, in contrast to previous iterations of the legislation, does not create a separate clinical trials results database. Instead, FDARA provides for a feasibility study to determine the best methods of publicly disseminating clinical trials results after approval of the drug or device. The legislation also authorizes civil monetary penalties and withholding of federal funds for failure to register a clinical trial.
Pediatric Drug Exclusivity
The Senate also placed a high priority on reauthorizing pediatric exclusivity. Sponsors would be newly required to develop appropriate formulations for specific age groups and make labeling changes within FDA’s requested timeframes. A new FDA advisory committee would track and oversee Written Requests for pediatric studies, and sponsors declining Written Requests would newly specify their reasons for declining and indicate why pediatric formulations cannot be developed. Most controversially, exclusivity would be limited to 3 months for any active moiety with $1 billion in gross annual sales for all drug products with such active moiety. The FDA would designate an outside, independent organization to evaluate sales figures. The legislation further precludes any pediatric extension of extant exclusivity or patents later than 9 months prior to the expiration of such period or such patents. There is concern that linking and abridging exclusivity rights based on product sales is a precedent that could subsequently affect orphan exclusivity, Hatch-Waxman exclusivities, and any new exclusivity enacted in the future.
Conflicts of Interest
The legislation requires candidates for FDA advisory committees to disclose all information relating to current investments, current and past employment, current and past consulting relationships, current and past contracts and grants, and current patents or royalties. Serving advisory committee members would have to disclose all financial interests relevant to the matter at hand prior to an advisory committee meeting.
MDUFMA II
Despite a late start to negotiations on the MDUFMA II package, FDARA reauthorizes medical device user fee provisions, providing for collection of $287 million in fees through FY12 and an annual 8.5% increase in fees. Although individual device user fees are reduced in the reauthorization, the FDA revenue stream is stabilized by the creation of four new categories of fees, including an establishment registration fee and an annual periodic report filing fee. After debate on the topic, FDARA continues to tie device user fees to a $205.7 million congressional appropriation trigger. MDUFMA II also further reduces the user fees for small businesses, and streamlines and expands the third party inspection process.
Floor Consideration of FDARA
Follow on Biologics
On May 2, Senators Kennedy, Enzi, Hatch, Clinton and Schumer engaged in a colloquy calling for committee deliberations on follow on biologics legislation on a separate track culminating in a June 13 HELP Committee markup. Chairman Kennedy stated “that the conference report on the FDA Revitalization Act will include a pathway to follow-on biologics that has been reported out of the HELP Committee and that is acceptable” to Senators Clinton and Schumer, the sponsors of follow on biologics legislation. Ranking Member Enzi concurred, stating “I am committed to moving a bipartisan bill through the HELP committee in the near future with the goal that it can be joined with the conference on the FDA Revitalization Act.”
Human Food and Pet Food Safety
On that same day, the Senate voted 94-0 to adopt a human and pet food safety amendment sponsored by Senator Dick Durbin (D-IL) that establishes an early warning and notification system for human food and pet food, creates an adulterated food registry for imported and domestically produced food, authorizes civil fines of companies that fail to promptly report contaminated food products, and strengthens food import inspections.
Drug Importation
On May 7, after extensive debate on Senator Dorgan’s (D-ND) drug importation amendment, the Senate voted 49-40 in favor of an amendment sponsored by Senators Cochran (R-MS) and Carper (D-DE) requiring the Secretary of Health and Human Services certify that drug importation would “pose no additional risk to the public’s health and safety” and “result in a significant reduction in the cost of covered products to the American consumer.” Following adoption of the Cochran-Carper amendment, the Senate voice voted in favor of the Dorgan amendment, which authorizes importation of drugs from Australia, Canada, the European Union, Switzerland, Japan, New Zealand, and other countries determined by the Secretary.
Amendments Agreed To By Unanimous Consent
On May 8, the Senate agreed by unanimous consent to accept a number of other amendments as part of the FDA Revitalization Act, including an amendment offered by Senator Roberts (R-KS) that requires new DTC advertisement disclosures about serious drug risks if FDA determines such an ad would be false or misleading without the disclosure, eliminates a provision allowing for a 2 year moratorium on DTC ads as part of a drug REMS, and also provides for enhanced civil monetary penalties against failure to comply with adding a necessary disclosure, or for otherwise disseminating a false or misleading ad. (see box)
Other Amendments Agreed To on the Floor
On May 2, Senator DeMint (R-SC) offered an amendment agreed to by unanimous consent that requires the sponsors of the drug Mifeprex (mifepristone, also known as RU-486) to provide an assessment of its REMS requirements earlier than other drug sponsors. On May 9, the Senate agreed by a vote of 64-30 to an amendment offered by Senator Grassley (R-IA) that authorizes civil monetary penalties against violations of the new REMS requirements authorized under Title II of FDARA. That same day, the manager’s substitute amendment to S.1082 passed the Senate by a recorded vote of 93-1.
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Amendments Agreed To by Unanimous Consent
Brownback/Brown: establishes a priority drug review process to encourage treatments of tropical diseases.
Inhofe: amends Head Start to require parental consent for nonemergency intrusive physical exams.
Landrieu: allows baby turtles as pets so long as seller uses effective methods to treat salmonella.
Levin: requires FDA to determine whether certain substances create any health risks and mislead consumers.
Murkowski: modifies provisions relating to provider or pharmacist experience or certification for prescribing or dispensing certain drugs (frontier REMS).
Hatch: concerns antibiotic access and innovation; addresses enantiomer drugs.
Stabenow: revises the process for FDA consideration of citizen petitions.
Casey/Specter: sense of the Senate on orphan diseases in children.
Feingold: concerns FDA annual reports.
Obama: calls for an Institute of Medicine report on genetic tests.
Roberts: authorizes new penalties for improper DTC advertising.
Enzi: concerns counterfeit resistant technologies, food facilities, seafood, and patents.
Enzi/Kennedy: requires color certification reports.
Enzi: modifies pediatric testing and medical products provisions.
Reed/Isakson: calls for a report on labelling for indoor tanning devices. |
Analysis
The Senate legislation is a remarkable bipartisan accomplishment in an otherwise frequently partisan political environment. The sponsors intended FDARA to be a consensus-driven, bipartisan effort to restore public confidence in the FDA and in the regulated prescription drug and food industries. The collaboration between Chairman Kennedy and Senator Enzi on drug safety in particular was driven by an expressed intent to respond to public fears that, as former FDA Commissioner Frank Young testified last week to the House of Representatives, “FDA is wounded.”
Attention will now shift to the House of Representatives, where Committee on Energy and Commerce Chairman John Dingell (D-MI-15th) and Subcommittee on Health Chairman Frank Pallone (D-NJ-6th) are currently convening hearings on FDA-related issues, including PDUFA, prescription drug safety, follow on biologics, and the medical device user fees.
The key questions are how Chairman Dingell and Chairman Pallone will decide to move the FDA-related reauthorization bills - whether separately or in combination - and how such House-passed legislation will ultimately be reconciled in a timely manner with the Senate-passed omnibus bill.
A complete summary of S.1082, the FDA Revitalization Act, is available from the Foley Hoag Life Science Government Strategies practice.
Download the Foley Hoag May 11, 2007 Life Sciences Government Strategies Alert (.pdf)