On the one year anniversary of implementation of the Prescription Drug User Fee Act (PDUFA V), what element has shown the most promise?

Contributors Respond

Andrew J. Emmett

Andrew J. Emmett

Managing Director, Science & Regulatory Affairs, BIO

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The one year anniversary of PDUFA V represents an important milestone to reflect on the positive impact that FDA’s human drug review program is having for patients and biomedical innovation. 

The passage of PDUFA V highlighted a number of unifying policy themes, such as strengthening the patient voice in drug development, carefully balancing and articulating benefits and risks in regulatory decision-making, and enhancing FDA’s scientific capacity.  However, one key theme stands out and cuts across several major PDUFA programs: Enhancing Communication between FDA and industry to help promote the development and approval of innovative new therapies for patients.

A centerpiece of PDUFA V is a novel program for the review and evaluation of New Molecular Entities (NMEs).  Historically, 80% of all NMEs are ultimately approved by FDA, but this can often take several review cycles.  The NME Review Program seeks to improve FDA-Sponsor communication and transparency at key points in the FDA review, such as the mid-cycle communication and late-cycle meeting, to increase the likelihood of a first-cycle approval.  To accommodate this additional interaction, the agreement also adds a two-month "filing period" to the start of the review process. Potential issues that could delay an approval can now be raised and proactivelyaddressed earlier in the review, thereby leading to fewer review cycles and timely patient access to these therapies. 

It is also critically important to promote robust, interactive scientific communication during drug development.   

For instance, PDUFA V includes a new program to enhance communication by creating a new liaison office that Sponsors can contact to help seek answers from the review division regarding simple scientific questions or other procedural issues.  Under the program, FDA also trains staff and will issue guidance on best practices for effective FDA-Sponsor communication during the drug development phase.

As part of the Food and Drug Administration Safety and Innovation Act (FDASIA) which reauthorized PDUFA V, Congress also enacted a new “Breakthrough Therapy” designation for new treatments that have demonstrated promising early clinical results.  Upon designation, FDA will provide timely advice to, and interactive communication with, the Sponsor regarding the development of the drug to ensure that the design of the clinical trials is as efficient as practicable.  

It is absolutely critical to facilitate communication and coordination between the private and public sectors.  In enacting these programs, Congress, FDA and industry acknowledge that robust communication is good medicine for patients.  These three elements of PDUFA V offer the promise to usher in a new era of collaborative scientific engagement to help foster the development of a new generation of medicines.  By embracing a culture of timely, interactive communication, PDUFA V helps put patients first.

Richard Pops

Richard Pops

Chairman and Chief Executive Officer, Alkermes

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Others will cite certain provisions, such as late-cycle review meetings and enhanced accelerated approval, as promising elements of PDUFA V.  I agree and also would highlight a more significant accomplishment, which was one of our explicit goals at the outset of the negotiation. PDUFA V established an entirely new and collaborative tone of engagement between FDA and industry. This new approach replaced a more adversarial stance and has resulted in important benefits for all stakeholders during the complex process of drug development.

In previous reauthorizations of PDUFA, once the legislative language was negotiated and signed into law, industry and FDA tended to head back to their respective corners and wait for the next five-year cycle to pass.  There was little ongoing dialog during the implementation phase – what was going well?  What could be improved upon?  Have we really impacted the process of new drug approval through our actions?  This past approach didn’t serve anyone well.  FDA was given significant new requirements;, industry provided significant incremental funding; and all parties experienced delays and inefficiencies in the review process.  Most importantly, innovation suffered and patients missed opportunities for timely access to new medicines. 

With the implementation of PDUFA V, there is a major shift in how FDA and industry interact.  The parties meet more frequently to assess the performance of PDUFA V and actively engage in making sure key objectives are being met.  For this reason, I see the most promising aspect of PDUFA V to be the collaborative engagement of FDA and industry, particularly alignment with the mutual objective of supporting innovation and getting valuable new medicines to patients as quickly as possible.

It is a remarkable accomplishment in today’s political environment that PDUFA V emerged as a truly bipartisan piece of legislation with widespread support.  This collaborative spirit will continue to be mutually beneficial as we implement PDUFA V. 

Rebecca D. Kush, Ph.D.

Rebecca D. Kush, Ph.D.

Founder, President & CEO, CDISC

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The most promising element of PDUFA V is a newfound commitment to incorporating patients’ views into the regulatory process. This commitment is the impetus of the provisions that create a comprehensive benefit-risk framework and the Patient-Focused Drug Development (PFDD) initiative, both of which are grounded in the idea that people with chronic conditions are their own experts. One cannot underestimate the knowledge that informed patients have about their conditions. 

Even before the PDUFA V negotiations between industry and FDA, the patient community has strongly advocated for FDA to create a process to better incorporate patients’ views on benefits and risks. While science has been – and should always be – the main factor in approval decisions, there will always be an inherent value judgment to determine whether benefits of a drug outweigh the potential risks.

An important component of the benefit-risk framework is that it will capture patients’ perspectives, which will be used by FDA reviewers to incorporate into their decisions. Furthermore, the framework will lend transparency and credibility to the process so that patients can understand why a product was or was not approved.

Another newly created tool to capture patients’ perspectives on benefit-risk is the PFDD initiative, which is comprised of 20 disease-specific meetings between FDA and patients. One of the most promising aspects of PFDD is that it will help create a methodology to incorporate patients’ views into FDA’s decision-making processes. This initiative will impact the regulation of products for all conditions, not just the 20 diseases being discussed at the meetings.

These provisions of PDUFA V are leading FDA toward a new era of drug regulation that elevates the views of patients with chronic diseases and disabilities. 

Steven Grossman, JD

Steven Grossman, JD

Deputy Executive Director, Alliance for a Stronger FDA

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One particular element of PDUFA that has been the focus of promising progress during the past year is the commitment that FDA would work with an open, consensus-based standards development organization (i.e. CDISC)  to develop standards/terminology for specific therapeutic areas (TA).  

When FDA reviewers receive data in a standard format, a) they can begin their reviews sooner (since they readily understand what they receive and do not need to perform additional programming); b) they can use sophisticated tools to see graphic displays of the data (which need data in standard formats); and, c) they can essentially perform higher quality reviews on higher quality data.

To help address this PDUFA V goal, CDISC has increased its resources and expertise through partnerships and collaborations, redesigned its standards development process based upon lessons learned from prior TA standards development projects, and will offer a new tool to make the standards more readily accessible.  Specifically, CDISC and the Critical Path Institute (C-Path) formed an initiative called the Coalition for Accelerating Standards and Therapies (CFAST); CFAST collaborators include the FDA, TransCelerate Biopharma, National Cancer Institute Enterprise Vocabulary Services, Association of Clinical Research Organizations, the Innovative Medicines Initiative and others depending upon the TA. These groups are working together in the development of TA standards, which augment the existing suite of global foundational CDISC standards that support research from protocol and data collection through analysis and reporting, including electronic submissions to FDA. 

The first therapeutic area standards project initiated under CFAST is Asthma, which is currently available for public review. Standards for Diabetes and Multiple Sclerosis were also initiated early this year. Updates on the progress of all CDISC TA Standards can be found on the CDISC website

The therapeutic areas are prioritized through the CFAST Therapeutic Area Program Steering Committee with scientific input from the CFAST Scientific Advisory Committee. These groups include representatives of the major stakeholders, which have brought significant resources and expertise to progress CFAST. 

To make the standards electronically accessible and to ensure coordination among all TA standards development activities, CDISC will launch a Shared Health and Research Electronic Library (CDISC SHARE) at the International Interchange in November 2013, and the first release should be ready by Q1 2014.  An explanatory video on SHARE is available for more information on this tool, which will benefit from widespread support.

The promise of data standards after PDUFA is in streamlining the entire research process, from protocol through analysis and reporting. Using standards from the start in therapeutic area research facilitates aggregation of results data. An example is C-Path’s Alzheimer’s database with data from over 6,000 patients, which researchers can use in modeling activities to support research for new and better therapies.

FDA has indicated, in a recent position statement, that they will publish guidance in the near future that will require study data in conformance with CDISC standards. 

Sascha Haverfield, Ph.D.

Sascha Haverfield, Ph.D.

SVP, Scientific & Regulatory Affairs, PhRMA

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Reauthorizing PDUFA is the core of what has become an every 5-year cycle for Congressional review of the overall goals and underlying laws governing the safety and approval of drug products.  The latest iteration—the year-old FDA Safety Innovation Act, known as FDASIA—has the rare virtue of being both transformational and evolutionary. 

In a very real sense, the most promising aspect of FDASIA/PDUFA V is how it demonstrates the ongoing ability of Congress, FDA, and stakeholders to work together to promote public health and innovation. Commitment to a strong, scientifically-based FDA has never been higher or better expressed by such a broad array of constituencies.  

This is all the more remarkable when compared with the general difficulties of Congress in finding consensus on most areas of government responsibility and more specifically in the broad disagreements about the role and future of most regulatory agencies. Not FDA, however, for which there is strong consensus that its effectiveness is a national priority.   

In the face of this broad bipartisan, bicameral, consensus about the promise of FDA, it is troubling that the very same Congress is having so much difficulty funding FDA at a level commensurate with its responsibilities.   The difficulty is not with FDA itself. The agency and its broad vital mission have the support and encouragement of the authorizing committees that passed FDASIA/PDUFA V. House and Senate appropriators support FDA, too.  The agency does exceptionally well in the competition for funds within the Agriculture/FDA appropriations process.

The problem for FDA is that its resource needs are growing rapidly at a time when macro-budgetary issues are impacting every federal agency and activity. Domestic and defense discretionary spending are being squeezed inordinately by lower spending caps and sequestration and by Congress’ inability to reach agreement on entitlement and revenue changes.  FDA has endured additional cuts because even its non-appropriated funding, through user fees, has been subjected to sequestration.

The situation is exacerbated by the current government shutdown in which 45% of FDA staff has been furloughed. While carry over from user fees is allowing some critical drug review functions to continue in the short-term, the FDA drug review process cannot keep pace if the shutdown continues for more than a few days. Further,  FDA cannot accept any new drug applications that require submission of a user fee. Meantime, the shutdown is causing a change in focus and preventing long-term planning.


So, the greatest promise of FDASIA/PDUFA V is as a statement of broad consensus among key players that FDA is heading in the right direction. Its programs and processes for the safety and approval of drugs can be improved through discussion, debate and good will, not rancor and attacks.  To fully realize that promise, the Alliance works every day to advocate for the resources FDA needs to serve the American people.

Ryan M. Hohman, JD

Ryan M. Hohman, JD

Managing Director, Policy & Public Affairs, FOCR

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The integration of the patient perspective into drug development and the regulatory process is a key component of the PDUFA V agreement.  Despite the financial challenges posed by sequestration, the FDA has made progress in this effort over the past year.

The severity of a disease and currently available treatment options are significant factors in the FDA’s assessment of whether the benefits of a new medicine outweigh the risks. An initiative in PDUFA V aims to gain patients’ perspective on both factors through twenty public disease-specific meetings on Patient-Focused Drug Development.  FDA held four of these meetings in FY13 and has another scheduled in December.

As important stakeholders in the drug development and review process, patients provide an essential perspective to the consideration of the benefits and risks of medicines.  Patient input can identify areas of unmet medical need, provide critical insights on the impact of a disease and its manifestations, and uniquely inform the development of outcome measures that are meaningful to patients.  Systematic consideration of the views of patients – their perception of the acceptable balance of known and possible risks and benefits – has the potential to add crucial perspective when drug developers and regulators are faced with difficult benefit-risk decisions.

A fully-integrated, structured approach to benefit-risk assessment has great potential to advance the Agency’s efforts to achieve greater consistency and predictability in the regulatory review and decision-making process, and can facilitate the enhanced consideration of the patient perspective in benefit-risk assessments.  Such an approach can also facilitate greater understanding of FDA’s regulatory decisions by patients, caregivers, healthcare professionals, biopharmaceutical companies and other stakeholders. 

We fully support FDA’s efforts to advance patient-focused drug development, and look forward to continuing the dialogue on how the Agency can best incorporate patient perspectives into regulatory decision-making.

We also look forward to working with FDA to elevate the regulatory science initiatives which are a critical component of PDUFA V but which unfortunately have not been advanced due to the sequestration of user fees paid by industry.