Prescription Drug User Fee Act Research Articles

Building on the successes of patient-focused drug development: a call for new policies to maintain momentum.

Since its commencement as part of the Food and Drug Administration's (FDA) Prescription Drug User Fee Act (PDUFA) V in 2012, patient-focused drug development (PFDD) has become an integral part of the drug development paradigm. FDA encourages the development and use of Patient-Experience Data (PED) as it provides important information on the patients' needs and perspectives and inform regulatory decision-making. While the FDA is required to fill out a table which includes a list of various types of Patient Experience Data (PED) and if such data was reviewed by FDA as part of a drug application, there is still a need to understand how FDA uses PED in its regulatory decision-making. This article examines whether new policies are needed to ensure the full potential of PFDD.

Cost benefit analysis and the FDA: measuring the costs and benefits of drug approval under the PDUFA I-II, 1998–2005

This paper examines the Food and Drug Administration’s regulation of drug safety. In one of the most sophisticated cost-benefit analyses to date, (Cost-benefit analysis of the FDA: The case of the prescription drug user fee acts, The Journal of Public Economics, 92, 1306–1325.) argue that between 1998 and 2005 the FDA’s drug submission process under the Prescription Drug User Fee Act (PDUFA) increased social surplus by $14–31 billion. However, this conclusion is based upon inappropriate data that underestimate the welfare costs of drugs that were withdrawn from the market due to their harmful side effects. Once appropriate epidemiological data are used to calculate the welfare costs of a single drug, Vioxx, which was withdrawn from the market after it was found to cause heart attacks, PDUFA I-II are found to have caused a net reduction in social welfare of between $1-201 billion. This indicates that statistically infrequent regulatory mistakes may have large social welfare implications that can counteract the benefits of years of accurate regulatory decisions. Thanks to Sarah Bernhardt, Romit Bhattacharya, Stephen DeCanio, Marco Giani, Colin Jennings, John Meadowcroft, and Tariq Thachil for helpful comments and suggestions. Special thanks to the helpful comments offered by two anonymous referees.

Industry update, December 2022.

Industry update, December 2022.

History, status, and politicization of the FDA.

The Center for Drug Evaluation and Research (CDER) performs an essential role in public health by ensuring, evaluating, and monitoring the safety and efficacy of drugs before they are sold in the US. Before approving new drug applications, CDER ensures that therapeutic benefits of both prescription and over-the-counter drugs (brand name and generic) provide more health benefits than the potential risks. First passed by Congress in 1992, the Prescription Drug User Fee Act (PDUFA) allowed the Food and Drug Administration (FDA) to collect fees from drug manufacturers to fund new drug approvals. The law allowed the FDA to expedite drug approvals, but possibly lowered standards for safety and brought potential conflicts of interest within the FDA and pharmaceutical industry. To examine the conflicts of interest, we conducted a review using the Excerpta Medica database, US National Library of Medicine National Institutes of Health Database (PubMed), Scopus, and Google. Our search yielded Vioxx (rofecoxib) and Exondus-51 (eteplirsen) as examples of consequence when the FDA and pharmaceutical industry are too closely aligned. We further examine how the pharmaceutical industry may indirectly influence the FDA by lobbying to Congress or directly by hiring ex-FDA commissioners.

The Prescription Drug User Fee Act: Much More Than User Fees.

The Prescription Drug User Fee Act (PDUFA) is due for reauthorization in 2022. Beyond creating the user fee program which now generates a majority of the Food and Drug Administration (FDA) Human Drugs Program budget, PDUFA has made numerous additional changes to FDA policy during its 29-year history. FDA's budgetary dependence on user fees may advantage the industry in negotiating favorable policy changes through PDUFA. The full texts of all prior PDUFA reauthorization bills and all submitted public comments and meeting minutes for the 2022 reauthorization were reviewed. Provisions affecting FDA regulatory authority and processes were identified. PDUFA legislation has instituted a broad range of changes to FDA policy, including evidentiary standards for drug approval, accelerated pathways for approval, industry involvement in FDA decision-making, rules regarding industry information dissemination to providers, and market entry of generic drugs. Negotiations over the 2022 reauthorization suggest that industry priorities include increased application of real-world evidence, regulatory certainty, and increased communication between FDA and industry during the drug application process. The need for PDUFA reauthorization every 5 years has created a recurring legislative vehicle through which far-ranging changes to FDA have been enacted, reshaping the agency's interactions and relationship with the regulated industry. The majority of policy changes enacted through PDUFA legislation have favored industry through decreasing regulatory standards, shortening approval times, and increasing industry involvement in FDA decision-making. FDA's budgetary dependence on the industry, the urgency of each PDUFA reauthorization's passage to maintain uninterrupted funding, and the industry's required participation in PDUFA negotiations may advantage the industry.

Analysis of the Real-Time Oncology Review (RTOR) Pilot Program for Approvals of New Molecular Entities.

The United States Food and Drug Administration (FDA) Oncology Center of Excellence (OCE) established the Real-Time Oncology Review (RTOR) pilot program in 2017 to streamline the review process for oncology drug applications with the applicant and the Agency agreeing upon a piecemeal strategy and timeline for module components. The Prescription Drug User Fee Act (PDUFA) review clock does not officially start until the final component is submitted. Participation requires careful planning of time and resources due to the multiple submissions and interactions with the FDA. Applicants must also meet certain criteria regarding the clinical trial design and development program to be eligible for RTOR. Publicly available databases (Drugs@FDA) and documents were searched for all RTOR applications, which revealed a total of 28 approved applications that participated from February 2018 to August 2020. Initial marketing applications were further reviewed to identify any potential advantages or limitations from participation in the pilot program. These four case studies demonstrated an individualized RTOR process reflecting the program’s pilot status. The FDA approved 3 out of the 4 applications approximately three to four months before the PDUFA goal date. The time savings is not guaranteed as other parts of the review may influence the overall timeline. However, the optional biweekly teleconferences increased communication and collaboration between the applicant and the FDA. The full impact of RTOR on applications remains undetermined as the number of approved applications that have participated in the pilot program is still relatively small.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43441-021-00296-7.

Opportunities and challenges for applying model-informed drug development approaches to gene therapies.

As part of the US Food and Drug Administration (FDA)’s Prescription Drug User Fee Act (PDUFA) VI commitments, the Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER) are conducting a model‐informed drug development (MIDD) pilot program. Sponsor(s) who apply and are selected will be granted meetings that aim to facilitate the application of MIDD approaches throughout the product development lifecycle and the regulatory process. Due to their complex mechanisms of action and limited clinical experience, cell and gene therapies have the potential to benefit from the application of MIDD methods, which may facilitate their safety and efficacy evaluations. Leveraging data that are generated from all stages of drug development into appropriate modeling and simulation techniques that inform decisions remains challenging. Additional discussions regarding the application of quantitative modeling approaches to drug development decisions, such as through the MIDD pilot program, may be crucial for both the sponsor(s) and regulatory review teams. Here, we share some perspectives on the opportunities and challenges for utilizing MIDD approaches for product review, which we hope will encourage investigators to publish their experiences and application of MIDD in gene therapy product development.

Tumor Growth Dynamic Modeling in Oncology Drug Development and Regulatory Approval: Past, Present, and Future Opportunities.

Model‐informed drug development (MIDD) approaches have rapidly advanced in drug development in recent years. Additionally, the Prescription Drug User Fee Act (PDUFA) VI has specific commitments to further enhance MIDD. Tumor growth dynamic (TGD) modeling, as one of the commonly utilized MIDD approaches in oncology, fulfills the purposes to accelerate the drug development, to support new drug and biologics license applications, and to guide the market access. Increasing knowledge of TGD modeling methodologies, encouraging applications in clinical setting for patients’ survival, and complementing assessment of regulatory review for submissions, together fueled promising potentials for imminent enhancement of TGD in oncology. This review is to comprehensively summarize the history of TGD, and present case examples of the recent advance of TGD modeling (mixture model and joint model), as well as the TGD impact on regulatory decisions, thus illustrating challenges and opportunities. Additionally, this review presents the future perspectives for TGD approach.

Model‐Informed Drug Development: Current US Regulatory Practice and Future Considerations

Model-informed drug development (MIDD) refers to the application of a wide range of quantitative models in drug development to facilitate the decision-making process. MIDD was formally recognized in Prescription Drug User Fee Act (PDUFA) VI. There have been many regulatory applications of MIDD to address a variety of drug development and regulatory questions. These applications can be broadly classified into four categories: dose optimization, supportive evidence for efficacy, clinical trial design, and informing policy. Case studies, literature papers, and published regulatory documents are reviewed in this article to highlight some common features of these applications in each category. In addition to the further development and investment in these established domains of application, new technology, and areas, such as more mechanistic models, neural network models, and real-world data/evidence, are gaining attention, and more submissions and experiences are being accumulated to expand the application of model-based analysis to a wider scope.

Emerging Role of Organ-on-a-Chip Technologies in Quantitative Clinical Pharmacology Evaluation.

The recently enacted Prescription Drug User Fee Act (PDUFA) VI includes in its performance goals “enhancing regulatory science and expediting drug development.” The key elements in “enhancing regulatory decision tools to support drug development and review” include “advancing model‐informed drug development (MIDD).” This paper describes (i) the US Food and Drug Administration (FDA) Office of Clinical Pharmacology's continuing efforts in developing quantitative clinical pharmacology models (disease, drug, and clinical trial models) to advance MIDD, (ii) how emerging novel tools, such as organ‐on‐a‐chip technologies or microphysiological systems, can provide new insights into physiology and disease mechanisms, biomarker identification and evaluation, and elucidation of mechanisms of adverse drug reactions, and (iii) how the single organ or linked organ microphysiological systems can provide critical system parameters for improved physiologically‐based pharmacokinetic and pharmacodynamic evaluations. Continuous public‐private partnerships are critical to advance this field and in the application of these new technologies in drug development and regulatory review.

Commentary on Fit-For-Purpose Models for Regulatory Applications

Model-based analyses have been applied to influence various drug development and regulatory decisions in the last 2 decades. Applied models range from empirical models to highly complex mechanistic models. “Fit-for-purpose” has been the principle to determine the level of model complexity. While numerous case studies have been published to highlight the impact and value of model-based analyses, more experience and lessons are being accumulated to address new challenges and create more opportunities. The inclusion of Model-Informed Drug Development in the Prescription Drug User Fee Act (PDUFA) VI represents a new landmark for the field of quantitative clinical pharmacology.

Rucaparib: a new treatment option for ovarian cancer

ABSTRACTIntroduction: Approximately 50% of high-grade serous ovarian cancers present a deficiency in the pathways involved in homologous recombination (HR). PARP inhibitors prevent single-strand DNA damage repair and determine a progression of the defect towards double-strand breaks, which results in a process known as ‘synthetic lethality’.Areas covered: In this review, the authors discuss the efficacy and toxicity of rucaparib either as a single agent or as a maintenance treatment for ovarian cancer. This includes the NGS Foundation Medicine evaluation of the role of this drug in the treatment algorithm of ovarian cancer. Moreover, perspectives on the future development of this drug are presented.Expert opinion: The FDA has approved this drug for the treatment of recurrent BRCA-mutated ovarian cancers, which were previously treated with at least two chemotherapies and has accepted the supplemental new drug application for maintenance use in patients who respond to platinum-based chemotherapy via the Prescription Drug User Fee Act (PDUFA) on 6 April 2018. European Medicines Agency (EMA) approval in the same setting is awaited. The possibility of using PARP inhibitors as a maintenance therapy, as a front-line therapy to combat recurrence, and in combination with anti-angiogenic agents and immune-therapies appears to be of particular interest.

The Prescription Drug User Fee Act: Cause for Concern?

The Prescription Drug User Fee Act (PDUFA) was originally enacted into law in 1992. PDUFA provides the Food and Drug Administration (FDA) with needed revenue in the form of various fees paid by drug and biologic manufacturers. The FDA utilizes this revenue to streamline the review and approval process for medications. Since the enactment of PDUFA, the median approval time for priority new drug applications and biologics license applications has reduced significantly. The FDA views PDUFA as a successful program that provides a consistent revenue stream to the agency, improves access to medications for patients, and allows industry to have a more predictable product review timeline. However, critics of PDUFA cite concerns including the potential for a lack of FDA independence and medication safety issues involving drugs approved after the existence of PDUFA.

User fee act, pending legislation focus on drug costs.

The October 1 start of the federal government’s 2018 fiscal year marked the beginning of the fifth renewal of the Prescription Drug User Fee Act (PDUFA) and the first-ever reauthorization of user fee acts for biosimilar products and generic drugs. The first version of PDUFA was enacted in 1992 to

A Cautionary Note on Measuring the Duration of FDA Drug and Device Reviews

The Prescription Drug User Fee Act (PDUFA) created rewards for the Food and Drug Administration (FDA) if it can meet goals related to the duration of the 'formal review stage' of the drug development process. Later, the Medical Device User Fee and Modernization Act (MDUFMA) set up a similar scheme for medical devices. This short note assembles some evidence showing that FDA has in recent years changed its patterns of interaction with drug and device sponsors: Some interactions or steps that previously would have been carried out during the formal review stage are now very often carried out prior to that stage. In light of these changes, it could well be that the main driver causing shorter durations of the formal review stage is not an increase in review efficiency, but rather that sponsor submission of the formal application — which is the marker in time identifying the start of the formal review stage — is happening later in the new-product development process. Sponsors are likely quite willing to submit their formal applications later so long as the development process ends no later, and indeed a sponsor may be very happy to do so if it means that its product will undergo only one 'cycle' of FDA review, since a sponsor's reputation in the medical marketplace can be damaged whenever a product does not succeed on the first cycle of FDA review. The FDA's increased interaction with sponsors prior to application submission thus may have caused a real gain in reducing needless negative shocks to sponsor reputations, but it may also mean that the much-touted success of PDUFA and MDUFMA in increasing the speed with which drugs secure FDA approval has become partially illusory or false; both of these effects, however, would be difficult to verify through observation. In the limit, continued changes in the pattern of FDA-sponsor interaction could turn the formal review stage into something of a formality, with measurements of FDA's performance during the formal review stage in turn becoming mostly meaningless.

US Prescription Drug User Fee Act (PDUFA): An Introduction for the Pharmaceutical Physician

Originally enacted to address the delays in US Food and Drug Administration (FDA) new drug review due to chronic understaffing and outdated systems, the Prescription Drug User Fee Act (PDUFA) of 1992, with its 5-year reauthorization cycle, enabled rapid rigorous review and ushered in a new era of continuing program innovation, evaluation, and improvement. This has resulted in a scientifically and financially strong program with transparent stakeholder engagement as a routine way of doing business. The enhancements to the process of human drug review, conducted in the FDA Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER), originally focused on the FDA review of a new drug application, have evolved and expanded to include extensive communication and consultation between drug sponsors and FDA throughout drug development, advances in regulatory science applied to drug development and regulatory oversight, strengthening and innovating approaches to post-market safety, increasing patient focus and modernizing supporting informatics. These enhancements, identified and supported in successive rounds of user fee negotiation with regulated industry, have enabled the USA to sustain global leadership in drug innovation, and earlier patient access to safe and effective new medicines.

U.S. Food and Drug Administration: Review for the Emergency Physician of Approval Process and Limitations.

U.S. Food and Drug Administration: Review for the Emergency Physician of Approval Process and Limitations.

Drug Safety and the Cost of Monitoring: The Role of REMS in Risk Management.

The mission of the US Food and Drug Administration (FDA) can be viewed as a pendulum that swings between protecting public health and patient safety and promoting the public health through the drug review and approval process. Two decades of legislation have by and large provided the FDA with additional resources under the successive reauthorizations of the Prescription Drug User Fee Acts (PDUFA) to provide a necessary infusion of funds to hire medical experts, scientists, and epidemiologists, among other disciplines, to expedite review of new drug and biologic applications. However, a renewed attention to potential adverse drug experiences, culminating in the Vioxx withdrawal, has resulted in the passage of the Food and Drug Administration Amendments Act of 2007 (FDAAA). Under this act, the FDA was authorized to impose postapproval requirements on the biopharmaceutical industry through the imposition of risk evaluation and mitigation strategies (REMS) and postmarketing trial (PMT) requirements to improve drug safety. Despite the extensive dialogue between stakeholders and lawmakers in the development of the FDAAA, there remains some uncertainty as to the exact impact of REMS on not only operational costs for both industry and health care professionals but also product sales and prescribing habits in the 5 years since its implementation. Recognizing that in the past 2 years, the use of REMS has shifted markedly, we sought to provide greater clarity on the duration of REMS requirements and impact of REMS on drug sales. While in absolute terms, the use of REMS may be declining, the REMS experience has provided an important, perhaps even critical, step in the development of current risk management strategies aimed at improving patient safety.

Congress Speeds Funds to FDA to Continue Pace of Drug Approvals

Back to table of contents Previous article Next article Government NewsFull AccessCongress Speeds Funds to FDA to Continue Pace of Drug ApprovalsLeslie SinclairLeslie SinclairSearch for more papers by this authorPublished Online:6 Jul 2012https://doi.org/10.1176/pn.47.13.psychnews_47_13_4-bAbstractBoth houses of Congress have taken steps to ensure that the Food and Drug Administration (FDA) has the funds to evaluate and approve new medications.The Prescription Drug User Fee Act (PDUFA)—enacted in 1992 and renewed in 1997, 2002, and 2007—is set to expire in September. It authorizes the FDA to collect “user fees” from companies that produce human drug and biological products. The program has been a success, giving the FDA the staff it needs to move drug candidates along more quickly and reducing approval times dramatically by increasing the number of drug reviewers available.Sen. Tom HarkinThat success may be why Congress is sparing no time to ensure that the system keeps working. On May 24, the Senate passed the FDA Innovation and Safety Act (S 3187) by a vote of 96-1; the bill included reauthorization of PDUFA. It was sponsored by the bipartisan team of Sens. Mike Enzi (R-Wyo.) and Tom Harkin (D-Iowa). Sen. Bernie Sanders (I-Vt.) cast the lone vote against approval, saying that the legislation did not go far enough: “The most pressing prescription drug issue in our country today is that Americans pay, by far, the highest prices in the world for their medicine, and millions of people cannot afford the medications their doctors prescribe. I voted against this bill because it does far too little to address this crisis while it perpetuates a prescription-drug system that continues to fail the American people,” Sanders said.On May 30, the House approved by a vote of 387-5 the FDA Reform Act of 2012 (HR 5651), which included reauthorization of PDUFA. The act was introduced by a bipartisan group consisting of Reps. Fred Upton (R-Mich.), Henry Waxman (D-Calif.), Joseph Pitts (R-Pa.), Frank Pallone Jr. (D-N.J.), Joe Barton (R-Texas), and John Dingell (D-Mich.).Both the Senate and House bills also reauthorized the Medical Device User Fee and Modernization Act and established new user-fee statutes, the Generic Drug User Fee Act (GDUFA) and the Biosimilars User Fee Act (BsUFA).The GDUFA calls for the generic-drug industry to pay $299 million annually in user fees for the next five years to enable the FDA’s Office of Generic Drugs to hire the scientific expertise needed to provide timely approval of generic medicines, just as the PDUFA has done for new drugs. According to the Generic Pharmaceutical Association, a manufacturers’ organization, the new fees also will boost spending for generic manufacturing facility inspections, which are required before new generics can be approved.The BsUFA will provide fees for approval of a new class of products created as part of the Patient Protection and Affordable Care Act. Biosimilar drugs, according to the FDA, are those that may be demonstrated to be “biosimilar” if data show that, among other factors, the product is “highly similar” to an already approved biological product. The FDA will require licensed biosimilar and interchangeable biological products to meet exacting standards of safety and efficacy.Overall, the Senate and House bills are comparable, and analysts say they will raise $6.4 billion in user fees for the FDA over five years. Congress is expected to resolve differences between the two bills in time to deliver a final version to President Obama before the July 4 congressional recess.Even those who will be paying the fees say the arrangement works. The drug-company trade group Pharmaceutical Research and Manufacturers of America (PhRMA) said in an April press release that the PDUFA program has enabled the FDA to better keep pace with the rapid increase in the number and complexity of new medicines entering the review pipeline.“PDUFA has facilitated the hiring of hundreds of additional review staff at the FDA, helped reduce review times for new drug applications and biologics license applications, improved the efficiency of the review process for priority new molecular entities, and, perhaps most importantly, provided patients with access to more than 1,100 new medicines over the past 18 years,” the organization said. ISSUES NewArchived

The COPD Pipeline XV

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