Patent Baristas

President Bush has signed the FDA Amendments Act of 2007 into law. The Senate passed the bill, H.R. 3580, by unanimous consent on Sept. 20, a day after the House approved it in a 409-17 vote.

The massive 422-page FDA bill, the biggest overhaul to the FDA in the last decade, renews device and drug user fees for five years and strengthens product safety programs.

The new legislation pays for new safety initiatives through hefty increases to the user fees negotiated by FDA and industry. The negotiated fees are $396 million per year, plus adjustments for inflation and other factors. The new safety fees total $225 million across all five years, phased in at a rate of $25 million in fiscal 2008 with increases of $10 million per year through FY ’12.

If Congress increases appropriations for postmarket safety, the new safety user fees would be reduced, dollar for every dollar appropriated on top of inflation-adjusted current levels. FDA also is given authority to assess fees in FY ’12 to create three months of operating reserves that can be used to pay for new drug reviews during the first three months of FY ’13. This gives FDA a funding cushion should Congress once again delay reauthorizing the fees until close to their Sept. 30, 2012 expiration date.

The Act also adds transparency to FDA and industry discussions about user fee levels and agency performance goals, including a provision from the House bill that would place on the FDA Web site the minutes from all negotiations with representatives from industry and patient and consumer advocacy groups.

Safety Changes

The bill represents a change in standards for making sure that drug side effects are known and promptly dealt with since Merck’s withdrawal of the painkiller Vioxx three years ago. Now, the FDA will now be able to dictate what claims companies can make about their drugs.

In addition, the FDA will be able to force drug makers to do clinical trials even after a medicine is approved and fine them if they don’t follow through. Previously, many big clinical trials requested by tge FDA weren’t finished. Finally, there will be more money to study side effects of new medicines post-approval. Companies will pay more in fees when they submit drug applications, increasing the amount of money the FDA gets from industry by 25%.

The Act gives the FDA authority to require label changes and to set timelines for negotiations. If a company is informed that new safety information must be included in a drug’s labeling, the firm has 30 days in which to submit a change or contest the requirement. If FDA disagrees with the response, it shall begin discussions with the company. These may last for no more than 30 days.

Once the discussions have concluded, FDA can order a labeling change and the company has 15 days in which to submit a supplement containing the change, or five days in which to appeal, through a dispute resolution proceeding. The process may be accelerated if the labeling change is needed to protect public health.

Additional post-approval clinical studies and trials can be required to assess a known serious risk, signals of a serious risk or to identify an unexpected serious risk, on the basis of scientific data, including chemically-related or pharmacologically-related drugs. Post-approval studies may be required if other reports and active surveillance are insufficient to answer safety questions.

New Device Fees

The act makes important changes to device user fees, originally established five years ago under the Medical Device User Fee and Modernization Act.

Fees will still be tied to individual premarket submissions, including PMAs and 510(k)s, but in the new program these submission-specific fees will be reduced and supplemented by four new fee categories.

The act allows FDA to collect $287 million in fees from device manufacturers over fiscal years 2008 through 2012. The fees will be dedicated to increasing the speed of review of device applications and for assuring the safety and effectiveness of devices,” the legislation states.

In addition, the act authorizes congressional appropriations totaling $39 million over five years for FDA’s device center to collect and evaluate postmarket safety information – a new earmark responding to growing sentiment that FDA needs to do more to monitor the safety of marketed devices. The new act also sets annual user fee increases at 8.5%, lending predictability to the fee system.

Medical Device Review

In return for paying user fees, device manufacturers are given assurance that FDA will meet specified premarket review goals. The goals, enumerated in letters from HHS to congressional leaders, are documented in the Congressional Record and referenced in the legislation.

Slightly more rigorous than the current goals, the new set requires, for example, that FDA in 2008 make a decision on 60% of regular PMAs within 180 days – versus 50% under the current performance goals.

More significantly, the new scheme eliminates premarket review “cycle goals” pertaining to the number of days FDA has to take various interim actions, such as issuing a PMA “major deficiency letter” to a company.

In other provisions, the Act requires the agency to establish a system under which manufacturers will be required to label their devices with unique identifiers unless they receive a waiver. This is intended to facilitate recalls and other postmarket safety activities.

Title III of the act, dealing with pediatric medical devices, contains provisions relating to the development and safety of devices used in children. It authorizes $6 million a year for pediatric device development projects, and allows FDA to order companies to conduct postmarket surveillance on devices expected to be used in pediatric patients.

Penalties Capped

The $50 million cap on penalties for continuing violations adjudicated in a single proceeding has been changed to $10 million, and the provision allowing fines of as much as $1 million per day was dropped.

H.R. 3580 permits fines of no more than $250,000 per violation, not to exceed $1 million for all violations adjudicated in a single proceeding. If a violation continues after written notice to the responsible party, the same amounts can be charged for the first 30 days, doubling for every 30-day period thereafter, subject to the $10 million cap.

Clinical Trials Database

One of the biggest changes is a new requirement that drug companies list all of their clinical trials in a registry maintained by the National Institutes of Health accessible to anyone with an Internet browser. After the studies finish, the results will also have to be posted. Additionally, the legislation calls for studies on the 510(k) premarket notification process, the prevalence of device-related infections, and the safety and quality of genetic tests.

The Act expands the existing registry of clinical trials to cover more drugs. It also creates a new trial results database, as envisioned by H.R. 2900, but this would be done in a series of steps and with HHS given the regulatory authority to determine the details.

Within a year of enactment, the registry is to include the demographic and baseline characteristics of patient samples and primary and secondary outcomes for clinical trials for approved drugs. This deadline can be extended to 18 months at the discretion of HHS. Not later than three years after enactment, regulations are to be issued to further expand the database and determine whether trials for unapproved drugs should be included.

There remains the question of whether the new authorities for the FDA are self-implementing or whether they need clarification in the form of regulations or other guidance (FDA Legislative Watch).