Drug manufacturers, law-makers, and consumer groups all found much to praise in the passage of the Food and Drug Administration Amendments Act of 2007 (HR 3580), which President Bush signed into law in late September. The long-debated measure grants the agency new and far-reaching powers for drug safety oversight while seeking to balance the interests of industry and consumers.
But much will depend on how the FDA implements the roughly 200 provisions contained in the 156-page piece of legislation, which also renews the collection of user fees from prescription drug-makers and gives the agency new authority to impose marketing restrictions based on emerging safety concerns and require manufacturers to conduct additional post-market clinical trials.
Implementing requires FDA to issue new rules and guidelines, a process that could take months or years. “The act continues essential and successful programs that will enhance FDA’s ability to more efficiently and effectively regulate drugs, biological products, and medical devices,” FDA Commissioner Andrew von Eschenbach said. “It really represents an important addition to the FDA’s authority.”
The law renews for another five years the Prescription Drug Fee User Act (PDUFA) and the Medical Device User Fee Act (MDUFA), both of which expired at the end of September. PDUFA allows FDA to hire additional staff to speed up the review of applications for new drugs and biological products. Annual industry user fees under PDUFA will jump to $392.8 million, a 28.6 percent increase of $87.4 million, with much of the increase ($225 million over five years) devoted to strengthening FDA’s widely criticized drug safety and post-marketing surveillance activities.
The agency will use the funds to hire more employees and expand use of its Adverse Events Reporting System to collect and aggregate safety data and expand surveillance and information management tools using epidemiological data from pharmacy and insurance databases. The new law calls for a database of 25 million patients by 2010 growing to 100 million by 2012.
Because the user fee measure was a must-pass piece of legislation, it attracted numerous other safety-related bills and proposals drafted during the three years after Vioxx had been withdrawn from the market. The final version also represented a compromise between House (HR 2900) and Senate (S 1082) versions that passed earlier in the summer. “This is not a perfect bill, and compromises were made to assure its passage,” said Sen. Edward Kennedy (D-Mass.). “No drug is completely safe,” said Rep. Joe Barton (R-Tex.), noting the measure strives to “ensure that the balance between benefit and risk remains in equilibrium.”
Under the new measure, FDA can require manufacturers to develop a Risk Evaluation and Mitigation Strategy (REMS) process for new drugs and biologics and limit their distribution if there are health risk concerns. The agency can also require manufacturers to conduct additional post-market clinical studies and change labels and prescribing literature if safety problems are detected. While FDA can fine companies for noncompliance (up to $10 million), it does not have the power to review or approve label changes.
“Since its original enactment in 1992, PDUFA has been a resounding success for FDA, pharmaceutical research companies, taxpayers, and, most importantly, patients,” said Billy Tauzin, president and chief executive of Pharmaceutical Research and Manufacturers of American (PhRMA), the branded drug trade association.
Other provisions include:
Direct-to-consumer advertising: The law allows the FDA to hire additional staff to review direct to consumer (DTC) advertising prior to broadcast and provides incentives for manufacturers to voluntarily submit their ads for review. But the agency was not given authority to block ads for drugs that have serious safety concerns; instead, the FDA can levy fines up to $500,000 for false and misleading advertising without having to get court approval, as had previously been the case.
Clinical trials disclosure: The measure requires manufacturers to post registry information at the National Library of Medicine’s ClinicalTrials.gov database for clinical trials of drugs, biologics, and devices, and post results from Phase 2 and later clinical trials after drugs have been approved for marketing.
Pediatric research and exclusivity: Because of the cost and difficulty of conducting pediatric clinical studies, about two-thirds of drugs prescribed for children have not been studied and labeled for pediatric use, placing children at risk of being exposed to ineffective treatment or incorrect dosing. Under the new law, manufacturers who conduct studies on new pediatric uses of their patented drugs will receive six additional months of market exclusivity.
The Senate version of the legislation would have allowed only three months and for drugs having $1 billion or more in annual sales. In reauthorizing the Best Pharmaceuticals for Children Act for another five years, the measure also encourages pediatric research on products that have gone off-patent. In reauthorizing the Pediatric Research Equity Act, manufacturers must submit a pediatric assessment of their products.
Conflicts of interest: The number of FDA advisory board members receiving conflict of interest waivers must be reduced starting next year by 5% annually for the next five years. FDA rules finalized in May, 2007 would block individuals with $50,000 or more in stocks, annual research and consulting fees, and other income from a company or competitor whose product is being considered from serving on scientific and other advisory committees. If the amount held is less than $50,000, the person could be granted a waiver to participate in the meeting but would not be allowed to vote, provided the need for his or her expertise outweighed the potential conflict. The earlier House and Senate versions differed, with the House allowing one waiver per panel meeting and the Senate seeking no restrictions.
Reagan-Udall Foundation: The FDA will establish a private-public nonprofit corporation to advance the agency’s Critical Path Initiative with the goal of modernizing product development, accelerating innovation, and enhancing product safety. The foundation will also identify unmet needs and award research grants.
Not included in the final measure is language that would have directed the FDA to establish regulatory and scientific pathways to evaluate and approve follow-on biological drugs, or so-called “biogenerics,” leaving that battle to be fought, most likely, next year.
About the Author
Contributing editor Ted Agres, MBA, is a veteran science writer in Washington, DC. He writes frequently about the policy, politics, and business aspects of life sciences.
This article was published in Drug Discovery & Development magazine: Vol. 10, No. 11, November, 2007, pp. 10-12.
Filed Under: Drug Discovery