In 2012 Congress will be revisiting Prescription Drug User Fee Act (PDUFA). In an effort to prepare the FDA is asking for comments and holding hearings on this law to ensure it is up to date.
In 1992, Congress passed the first PDUFA to meet urgent patient demands for more timely approvals of life-saving medicines. It was created in response to a perilous bottleneck of new drug approvals in the early 1990s that left patients waiting – and sometimes dying –while an understaffed and underfunded FDA struggled to review new drug applications.
Since its enactment, PDUFA has helped the FDA for nearly 20 years to fulfill its central mission – to promote and protect the public health and safety – by allowing the Agency to keep pace with the rapid increase in the number and complexity of drugs and biologics entering the review pipeline.
The PDUFA program has also enabled FDA to hire additional staff to review applications for new drugs and biologics. As a result of this growth in staff, FDA’s Human Drug Review Program went from 1,913 employees in 1989 nearly 3,000 by 2007. Using this growth of drug review staff, FDA saw the median time needed to review a new drug application (NDA) or biologics license application (BLA) reduced significantly, from 29 months in 1989 to 13 months in 2006. Moreover, this growth in staff also facilitated a median review time of just six months for “Priority-review” products – drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists.
PDUFA has also increased the efficiency of the NDA review process, with the approval rate for priority new molecular entities (NMEs) going from an approval rate of 46 percent in 1992 to 79 percent approval of priority NDAs and BLAs by 2007.
As David E. Wheadon, M.D., Senior Vice President of the Pharmaceutical Research and Manufacturers of America (PhRMA) noted, “the beneficiaries of PDUFA are the tens of millions of Americans who rely on innovative medications to improve and extend their lives. In his recent remarks at a public meeting, he urged FDA and members of Congress to reauthorize PDUFA—which is up for renewal in 2012—because it has allowed patients to “have earlier access to more than 1,100 new drugs and biologic medicines and since its passage, FDA reviewers had approved:
– 90 new medicines for cancer;
– 139 medicines for metabolic and endocrine disorders;
– 125 anti-infective medications;
– 138 medicines for neurological and psychiatric disorders; and
– 126 medicines for cardiovascular and renal disease.
Improving Safety
The 2007 reauthorization of PDUFA added important new safety-related elements that were incorporated into the user fee legislation. These user fees (totaling $225 million), were used to support drug safety measures. New safety measures included:
– Lifting previous statutory time limits on post-approval activities;
– Enabling FDA to use PDUFA funding for regulatory activities throughout the life of a drug or biologic; and
– Expanding the list of post-market safety activities for which PDUFA fees could be used to include a) adverse event data collection; b) the development of improved tools for assessing potential safety problems; and c) implementing and enforcing new regulatory authority to require post-approval safety studies, new clinical trials, labeling changes, and REMS.
Even though some critics suggest that the PDUFA user fee program in 1992 – and its reauthorizations in 1997, 2002, and 2007 – resulted in weakened FDA safety standards and/or oversight, PhRMA noted that “this has not proven to be the case.” In fact, as the above new measures detail, “additional funding provided under PDUFA III & IV has allowed the FDA to ensure patient safety more effectively by extending surveillance of new medications into the post-market period.”
PhRMA
PhRMA summarized these vast improvements in medicine for patients and physicians as evidence for the need to continue “supporting a strong, vibrant and science-based FDA.” This support is essential for PhRMA because the organization has the core mission to work with FDA to discover, develop and deliver innovative medicines to patients, and to establish a partnership with FDA that advances the public health by providing timely, scientifically sound regulatory decisions. Accordingly, PhRMA stressed that the PDUFA has advanced public health with respect to both patient safety and bringing new innovative medicines forward.
In response to FDA’s call for comments, PhRMA agreed with the Agency that increased focus on patient safety and post-market surveillance under PDUFA IV “is the right thing for patients, and should be retained.” They did not agree however, with the implementation of certain provisions under the Food and Drug Administration Amendments Act of 2007 (FDAAA), particularly risk management and mitigation strategies (REMS).
PhRMA specifically disagrees with REMS because it “has led to a breakdown in FDA’s review process and has eroded some of the positive progress derived from earlier PDUFA agreements.” Instead, they call for “new, more efficient systems and processes to address this breakdown in order to deliver safe and effective new medicines to patients without unnecessary delays.”
PhRMA also asserted that “more transparent, science-based standards for benefit-risk assessments and drug approvals are needed,” standards that “need to be consistently applied across the FDA and communicated clearly.” In order to adequately use these standards, PhRMA recognized that “FDA staff must be given resources for carrying out their jobs and training, which allows them to perform their critical tasks efficiently and effectively.”
Discussion
No one is more aware of the need for and use of resources than America’s biotechnology and pharmaceutical companies, organizations that are committed to serving the public health. These companies serve public health by “researching, developing, manufacturing, and delivering innovative, safe and effective medicines to treat devastating illnesses such as cancer, diabetes, and Alzheimer’s disease.” This support is overwhelming, especially since these activities require significant investments of time, money, and talent.
Industry’s commitment to public health is financially demonstrated by the fact that in 2009, biopharmaceutical companies invested an estimated $65.3 billion in the research and development of new medicines, up from $63.7 billion spent on innovative R&D in 2008. This kind of investment has led to even clearer results in science and medicine as demonstrated by the fact that more than 2,900 medicines are being tested in clinical trials or being reviewed by FDA today, up from 1,800 in 1999.
Although money is not the only thing these companies use to demonstrate their commitment to public health, the financial part of making patients healthier is tremendous considering “only one out of thousands of promising molecules makes it through pivotal clinical trials to the patient.” As a result, “this attrition rate is one reason that R&D costs are so great in the drug industry.
Despite such odds, drug companies “assume great risk in hopes of bringing great benefits to patients.” Accordingly, it is this great risk, and most certainly an altruistic passion to help people that cause the drug industry to take such a “huge stake in doing whatever they can to facilitate timely approval of safe and effective innovative medicines to address the unmet medical needs of patients.”
In this regard to money, it is also important to keep in mind that “PDUFA user fees have provided – and continue to provide – the FDA with the critical resources necessary to expedite access to new medicines for patients in need.” FDA at this point overwhelming depends on these fees from industry because the Agency has a “chronic shortage of appropriated funding that has been well documented.” For example, while the CDC and NIH received $6.5 billion and $31.2 billion respectively in appropriated funding in FY 2010, FDA’s budget authority was only $2.4 billion. As PhRMA correctly points out, although PDUFA user fees have helped, they are clearly no substitute for adequate appropriations to resource the agency to fulfill its critical public mission.”
Recommendations
PhRMA acknowledged the need to bring PDUFA back to its original intent—bringing innovative new treatments and life-saving new medicines to patients faster—for two specific reasons. First, “FDA itself has conceded that its ability to review new drug applications in a timely manner has decreased by the addition of new processes and the implementation of the requirements in FDAAA, particularly REMS. Second, evidence from the FY 2008 PDUFA Performance Report showed that FDA did not meet a variety of procedural and processing goals such as responding to meeting requests, scheduling meetings, and providing sponsors with meeting minutes, or conducting special protocol assessments, all of which impact our ability to bring needed new medicines to patients.
These kinds of weaknesses in the FDA will hinder science and advances in industry, which will only hurt patients. As a result, PhRMA asserted that “systems and processes must be in place to allow FDA to assess effectively the safety and efficacy of new medicines, including strategies to mitigate risk and enhance benefit, while adhering to the timely goals that have marked FDA’s success under previous PDUFA programs.” To guarantee FDA’s future progress, PhRMA recommended that the PDUFA V:
– Ensure transparent, science-based review/approval standards (e.g. clinical trials and post market surveillance);
– Provide FDA with adequate resources, personnel and staff training, and ensure the best use of FDA resources through enhanced management; and
– Support FDA’s ability to perform its critical review and subsequent monitoring of new medicines in a timely/efficient manner so industry can continue to serve patients.
Conclusion
Ultimately, PhRMA vigorously endorses a reauthorization of PDUFA in 2012 because its
“18-year term has paralleled the most productive and innovative generation of new drug development in history.” Particularly, PDUFA has created novel vaccines, breakthrough cardiovascular and psychiatric drugs, and targeted cancer therapies, which have addressed unmet medical needs. Their overwhelming support is also based on the lives of countless children, adults, and aging Americans who have been enriched and extended by the hundreds of novel therapeutics that have passed through the FDA’s regulatory pathway since PDUFA’s inception in 1992.
Accordingly, this success must not be hindered by inadequate funding of the FDA, otherwise this landmark era of breakthrough medical advances will end, and so will the lives of thousands of patients.
Fortunately for Americans, pharmaceutical research and biotechnology companies are devoted to inventing medicines that allow patients to live longer, healthier, and more productive lives, and they are leading the way in the search for new cures. Consequently, to ensure that industry can meet its goals, the reauthorization of PDUFA must give FDA “new, more efficient systems and processes so that the agency can deliver safe and effective new medicines to patients without unnecessary delays.”