• <div class="header-image" style="background-image: url(/live/image/gid/4/2441_V5N9Header.rev.1508162078.jpg);">​</div><div class="header-background-color"/>

Debate Over the Priority Review Voucher

March 17, 2017
The FDA serves as the gatekeeper of pharmaceutical innovation in the United States, ensuring the efficacy and safety of drugs through careful regulatory supervision. Founded in 1906 with the passage of the Pure Food and Drugs Act, the FDA is responsible for guaranteeing the integrity of America’s food and pharmaceutical industries. Succeeding legislation, from the Hatch-Waxman Act to the FDA Modernization Act, have enshrined the modern-day regulatory pathway a drug must successfully navigate in order to be taken to market. [1]

<a href="http://www.raps.org/uploadedImages/Site_Setup/Regulatory_Focus/News/2015/03/Drug-Development-Failure-and-Success(1).jpg" target="_blank">Source</a>Source

The process begins with the submission of an Investigational New Drug (IND) application. The drug must then make it through three phases of clinical trials, with the trial data summarized in a New Drug Application (NDA). [2] It can take over twelve years for a drug to complete the IND-NDA pipeline, delaying consumer access to potentially life-saving drugs for a decade or more.

<a href="http://www.raps.org/uploadedImages/Site_Setup/Regulatory_Focus/News/2015/03/2015-priority-voucher-system-figure(1).jpg" target="_blank">Source</a>Source

The need to expedite the drug approval process led to the proposal of a priority review voucher system in March 2006 by David Ridley, Henry Grabowski, and Jeffery Moe of Duke University. They articulated a legislative framework in which pharmaceutical companies seeking approval for a neglected or rare tropical disease could receive a voucher for priority review, shortening the typical review period by four months for any drug of the company’s choice. This framework became law in 2007 as a provision of the FDA Amendments Act, and it has since evolved to include rare pediatric diseases with the Creating Hope Act of 2012. [3]

In recent years, the efficacy of the priority review voucher has come into question by the FDA, which perceives the voucher system to be inefficient and flawed. On the other hand, consumer advocacy groups and the pharmaceutical industry continue to champion the priority review voucher as essential to promoting drug discovery in rare tropical and pediatric diseases.

Support for the Priority Review Voucher

One of the major arguments in favor of priority review is the temporal imperative of disease. Many patients cannot afford to wait years for the approval of a potentially life-saving drug or treatment; the drug review process could prove fatal for these individuals. Consumer advocacy groups like Kids v. Cancer are at the helm of this crusade. Nancy Goodman, the executive director of Kids v. Cancer, established the foundation after her ten-year old son died from a rare pediatric brain cancer.[4]

Support for the priority drug review voucher amongst pharmaceutical companies is also predicated on the promise of better financial performance. Expedited approval saves companies hundreds of millions of dollars in expenses pertaining to staffing and compliance during the regulatory pipeline.[5] Additionally, because priority review shortens the timeline for approval, companies can take their drugs to market faster. This shortened review period takes on even greater significance considering the fixed patent timeline. Pharmaceutical companies file for patent protection for their molecules before beginning the regulatory process; the countdown to patent expiration begins before firms even have the opportunity to begin making profit. As such, by reducing the regulatory period by four months, a firm’s drug enjoys an additional period of market exclusivity before patent expiry, allowing pharmaceutical companies to recoup their R&D costs before the arrival of generic competitors. [6] Once a company submits a treatment for a tropical or pediatric disease for FDA approval, the company is eligible to receive a priority review voucher, which can be used to expedite the approval process for any drug of the company’s choice. As such, companies are incentivized to create needed drugs for rare tropical and pediatric diseases, which can allow them to shorten the approval process for another of their promising drugs. Bill Gates, who has come out in support of the priority review voucher, voices this idea quite succinctly: “If you develop a new drug for malaria, your profitable cholesterol-lowering drug could go on the market a year earlier.” For now, this incentive remains largely theoretical, as it can take a decade or longer to develop a drug. New treatments catalyzed by the voucher system will not be evident for several more years. [7]

The priority review voucher system has inspired extensive congressional support, passing both the House and Senate in 2007 with a near unanimous vote. The system has been so popular among lawmakers for primarily two reasons. First, the granting of vouchers has no budgetary implications; Congress does not need to allocate additional funding or grants for drug discovery. Another, comparatively cynical, reason is the fact that passing the priority review system allows congressmen to say they’re taking action to address unmet tropical and pediatric diseases without proposing more comprehensive legislation to alleviate R&D costs in the pharmaceutical industry. [8]

Opposition to the Priority Review Voucher

The chief opponent of the priority drug review voucher is the FDA itself. Considering that Congress promulgated the priority review system with minimal FDA oversight, the Department holds serious reservations about the efficacy of priority review in its current form.

First, no requirement exists mandating that treatments up for priority review be novel. Essentially, companies can be awarded vouchers for drugs that have been approved and sold in international markets, but not yet in the United States. For example, Novartis was awarded the first priority review voucher in 2009 for its combination malaria drug. While it was a treatment targeting a tropical disease, the drug had already been licensed and in active use outside the United States for almost a decade prior. Essentially, firms can take already developed drugs for tropical or pediatric diseases in international markets and submit them for approval in the U.S. to receive a review voucher, a perversion of the program’s motivation to encourage new drug development. [9]

Additionally, pharmaceutical companies do not need to guarantee that their drugs will be sold at affordable prices. Because the priority review system lacks the means to establish and enforce price controls, firms can be granted vouchers for drugs that may not be accessible to patients. Janssen, for example, was awarded a voucher for Sirturo, a treatment for multidrug resistant tuberculosis. However, it has been reported that Sirturo is prohibitively priced in many international markets, reducing access to this potentially life-saving drug. [10] Indeed, this prohibitive pricing undermines the temporal imperative of disease, one of the key purposes of the priority review system. What is the purpose of a voucher system to accelerate drug development if patients at the end of the pipeline can’t afford the needed treatment? <a href="https://faculty.fuqua.duke.edu/~dbr1/voucher/voucher-prices" target="_blank">Source</a>Source

To receive a priority review voucher, a company needs only to submit a drug for a pediatric or tropical disease for FDA approval; there is no stipulation that the drug had to be developed by the company itself. This oversight, along with the ability to transfer a priority review voucher to another firm, has created a shadow market around the voucher system. Knight Pharmaceuticals, for instance, received a voucher for Impavido, a drug it acquired which treats leishmaniosis, a rare infectious disease transmitted by sandflies. Knight played no role in the development process, as R&D was conducted by the World Health Organization in collaboration with public and private partners. However, because its drug fulfilled the necessary requirement of treating a tropical disease, Knight was able to receive a priority review voucher after spending $10 million to get Impavido through the approval process. However, the company’s true intent for the drug was revealed when it sold its priority review voucher to Gilead Sciences for $125 million, netting Knight Pharmaceuticals a $115 million profit. [11] Knight isn’t alone in the market for priority review vouchers, as Askelepion Pharmaceuticals, BioMarin, and United Therapeutics have all sold their vouchers for a combined $662 million. [12]

Perhaps most fundamentally, the FDA opposes the priority review system for its inherent impact on the Department’s mission. Redeeming a voucher limits  the FDA’s autonomy, forcing it to prioritize a drug which may not combat a key health issue per its existing prioritization process. Indeed, FDA officials believe that the program has “adversely [affected] the agency’s ability to set its public health priorities by requiring FDA to provide priority reviews of new drug applications that would not otherwise qualify if they do not treat a serious condition or provide a significant improvement in safety or effectiveness.” Moreover, by shortening the approval pipeline from ten to six months, the FDA has expressed concerns that this window is insufficient to guarantee drug safety, given these tight timelines are already straining agency resources. While drug companies must pay a fee of around $2 million to redeem a voucher, the FDA argues that there is insufficient time to use the money to hire and train additional, long-term employees for accelerated reviews. [13]

What’s next?

The priority review voucher system for rare tropical and pediatric diseases was reauthorized by Congress in December 2016 with the 21st Century Cures Act, extending the program’s lifeline to October 1st, 2020. [14] While priority review will continue for another four years, questions remain about the effectiveness of the voucher system, as the Government Accountability Office’s March 2016 study was inconclusive, finding that “insufficient time has elapsed to determine whether the 3 year-old program has been effective.” [15] Additionally, there have even been complaints that the voucher system isn’t providing sufficient incentive for drug makers to begin early-stage research, considering the uncertainties and exorbitant cost of R&D.

With discussion circulating in Congress about adding generic drugs to the priority review voucher, the FDA’s concerns with the program will once again be raised. [16] It appears that, without undermining the basis of the program, Congress might assuage the FDA’s concerns by either provide additional funding for the FDA to hire more permanent staff for expedited review or increase the existing fee to redeem a voucher. Additionally, amending the voucher system to include stipulations on pricing and a requirement that firms partake in some aspect of the drug’s development seem to be stipulations that will further ensure the voucher system fulfills its stated mission: to promote the discovery of novel treatments for patients suffering from rare pediatric and tropical diseases.

References

  [1] https://www.fda.gov/AboutFDA/WhatWeDo/History/

  [2] https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/

  [3] http://priorityreviewvoucher.org/

  [4] http://www.npr.org/sections/health-shots/2016/09/29/495904450/are-golden-tickets-that-speed-drugs-through-fda-worthwhile 

  [5] http://www.sabin.org/updates/blog/priority-review-vouchers-closer-look

  [6] http://www.raps.org/Regulatory-Focus/News/2015/07/02/21722/Regulatory-Explainer-Everything-You-Need-to-Know-About-FDA%E2%80%99s-Priority-Review-Vouchers/

  [7] http://www.sabin.org/updates/blog/priority-review-vouchers-closer-look

  [8] http://blogs.sciencemag.org/pipeline/archives/2016/03/03/closer-looks-at-priority-review-vouchers

  [9] https://www.statnews.com/2015/11/28/priority-review-vouchers-rare-diseases/

  [10] https://www.statnews.com/2015/11/28/priority-review-vouchers-rare-diseases/

  [11] https://www.statnews.com/pharmalot/2016/06/09/congress-vouchers-rare-diseases 

  [12] http://www.raps.org/Regulatory-Focus/News/2015/07/02/21722/Regulatory-Explainer-Everything-You-Need-to-Know-About-FDA%E2%80%99s-Priority-Review-Vouchers/ 

  [13] http://www.fiercebiotech.com/r-d/priority-review-voucher-program-fda-hates-it

  [14] http://raps.org/Regulatory-Focus/News/2016/11/28/26242/Regulatory-Explainer-21st-Century-Cures-Redux-and-What-it-Will-Mean-for-FDA/

  [15] http://www.gao.gov/products/GAO-16-319 

  [16] https://www.bna.com/lawmakers-revise-bill-n57982084911/ 

Student Blog Disclaimer
  • The views expressed on the Student Blog are the author’s opinions and don’t necessarily represent the Penn Wharton Public Policy Initiative’s strategies, recommendations, or opinions.

PENN WHARTON PPI
RESOURCE SPOTLIGHT:

  • <h3>The World Bank Data (U.S.)</h3><p><img width="130" height="118" alt="" src="/live/image/gid/4/width/130/height/118/484_world-bank-logo.rev.1407788945.jpg" class="lw_image lw_image484 lw_align_left" srcset="/live/image/scale/2x/gid/4/width/130/height/118/484_world-bank-logo.rev.1407788945.jpg 2x, /live/image/scale/3x/gid/4/width/130/height/118/484_world-bank-logo.rev.1407788945.jpg 3x" data-max-w="1406" data-max-h="1275"/>The <strong>World Bank</strong> provides World Development Indicators, Surveys, and data on Finances and Climate Change.</p><p> Quick link: <a href="http://data.worldbank.org/country/united-states" target="_blank">http://data.worldbank.org/country/united-states</a></p><p>See all <a href="/data-resources/">data and resources</a> »</p>
  • <h3>NOAA National Climatic Data Center</h3><p><img width="200" height="198" alt="" src="/live/image/gid/4/width/200/height/198/483_noaa_logo.rev.1407788692.jpg" class="lw_image lw_image483 lw_align_left" srcset="/live/image/scale/2x/gid/4/width/200/height/198/483_noaa_logo.rev.1407788692.jpg 2x, /live/image/scale/3x/gid/4/width/200/height/198/483_noaa_logo.rev.1407788692.jpg 3x" data-max-w="954" data-max-h="945"/>NOAA’s National Climatic Data Center (NCDC) is responsible for preserving, monitoring, assessing, and providing public access to the Nation’s treasure of <strong>climate and historical weather data and information</strong>.</p><p> Quick link to home page: <a href="http://www.ncdc.noaa.gov/" target="_blank">http://www.ncdc.noaa.gov/</a></p><p> Quick link to NCDC’s climate and weather datasets, products, and various web pages and resources: <a href="http://www.ncdc.noaa.gov/data-access/quick-links" target="_blank">http://www.ncdc.noaa.gov/data-access/quick-links</a></p><p> Quick link to Text & Map Search: <a href="http://www.ncdc.noaa.gov/cdo-web/" target="_blank">http://www.ncdc.noaa.gov/cdo-web/</a></p><p>See all <a href="/data-resources/">data and resources</a> »</p>
  • <h3>HUD State of the Cities Data Systems</h3><p><strong><img width="200" height="200" alt="" src="/live/image/gid/4/width/200/height/200/482_hud_logo.rev.1407788472.jpg" class="lw_image lw_image482 lw_align_left" srcset="/live/image/scale/2x/gid/4/width/200/height/200/482_hud_logo.rev.1407788472.jpg 2x, /live/image/scale/3x/gid/4/width/200/height/200/482_hud_logo.rev.1407788472.jpg 3x" data-max-w="612" data-max-h="613"/>The SOCDS provides data for individual Metropolitan Areas, Central Cities, and Suburbs.</strong> It is a portal for non-national data made available through a number of outside institutions (e.g. Census, BLS, FBI and others).</p><p> Quick link: <a href="http://www.huduser.org/portal/datasets/socds.html" target="_blank">http://www.huduser.org/portal/datasets/socds.html</a></p><p>See all <a href="/data-resources/">data and resources</a> »</p>
  • <h3>Federal Reserve Economic Data (FRED®)</h3><p><strong><img width="180" height="79" alt="" src="/live/image/gid/4/width/180/height/79/481_fred-logo.rev.1407788243.jpg" class="lw_image lw_image481 lw_align_right" data-max-w="222" data-max-h="97"/>An online database consisting of more than 72,000 economic data time series from 54 national, international, public, and private sources.</strong> FRED®, created and maintained by Research Department at the Federal Reserve Bank of St. Louis, goes far beyond simply providing data: It combines data with a powerful mix of tools that help the user understand, interact with, display, and disseminate the data.</p><p> Quick link to data page: <a href="http://research.stlouisfed.org/fred2/tags/series" target="_blank">http://research.stlouisfed.org/fred2/tags/series</a></p><p>See all <a href="/data-resources/">data and resources</a> »</p>
  • <h3>MapStats</h3><p> A feature of FedStats, MapStats allows users to search for <strong>state, county, city, congressional district, or Federal judicial district data</strong> (demographic, economic, and geographic).</p><p> Quick link: <a href="http://www.fedstats.gov/mapstats/" target="_blank">http://www.fedstats.gov/mapstats/</a></p><p>See all <a href="/data-resources/">data and resources</a> »</p>
  • <h3>The Penn World Table</h3><p> The Penn World Table provides purchasing power parity and national income accounts converted to international prices for 189 countries/territories for some or all of the years 1950-2010.</p><p><a href="https://pwt.sas.upenn.edu/php_site/pwt71/pwt71_form.php" target="_blank">Quick link.</a> </p><p>See all <a href="/data-resources/">data and resources</a> »</p>
  • <h3>USDA Nutrition Assistance Data</h3><p><img width="180" height="124" alt="" src="/live/image/gid/4/width/180/height/124/485_usda_logo.rev.1407789238.jpg" class="lw_image lw_image485 lw_align_right" srcset="/live/image/scale/2x/gid/4/width/180/height/124/485_usda_logo.rev.1407789238.jpg 2x, /live/image/scale/3x/gid/4/width/180/height/124/485_usda_logo.rev.1407789238.jpg 3x" data-max-w="1233" data-max-h="850"/>Data and research regarding the following <strong>USDA Nutrition Assistance</strong> programs are available through this site:</p><ul><li>Supplemental Nutrition Assistance Program (SNAP) </li><li>Food Distribution Programs </li><li>School Meals </li><li>Women, Infants and Children </li></ul><p> Quick link: <a href="http://www.fns.usda.gov/data-and-statistics" target="_blank">http://www.fns.usda.gov/data-and-statistics</a></p><p>See all <a href="/data-resources/">data and resources</a> »</p>
  • <h3>Federal Aviation Administration: Accident & Incident Data</h3><p><img width="100" height="100" alt="" src="/live/image/gid/4/width/100/height/100/80_faa-logo.rev.1402681347.jpg" class="lw_image lw_image80 lw_align_left" srcset="/live/image/scale/2x/gid/4/width/100/height/100/80_faa-logo.rev.1402681347.jpg 2x, /live/image/scale/3x/gid/4/width/100/height/100/80_faa-logo.rev.1402681347.jpg 3x" data-max-w="550" data-max-h="550"/>The NTSB issues an accident report following each investigation. These reports are available online for reports issued since 1996, with older reports coming online soon. The reports listing is sortable by the event date, report date, city, and state.</p><p> Quick link: <a href="http://www.faa.gov/data_research/accident_incident/" target="_blank">http://www.faa.gov/data_research/accident_incident/</a></p><p>See all <a href="/data-resources/">data and resources</a> »</p>
  • <h3>National Center for Education Statistics</h3><p><strong><img width="400" height="80" alt="" src="/live/image/gid/4/width/400/height/80/479_nces.rev.1407787656.jpg" class="lw_image lw_image479 lw_align_right" data-max-w="400" data-max-h="80"/>The National Center for Education Statistics (NCES) is the primary federal entity for collecting and analyzing data related to education in the U.S. and other nations.</strong> NCES is located within the U.S. Department of Education and the Institute of Education Sciences. NCES has an extensive Statistical Standards Program that consults and advises on methodological and statistical aspects involved in the design, collection, and analysis of data collections in the Center. To learn more about the NCES, <a href="http://nces.ed.gov/about/" target="_blank">click here</a>.</p><p> Quick link to NCES Data Tools: <a href="http://nces.ed.gov/datatools/index.asp?DataToolSectionID=4" target="_blank">http://nces.ed.gov/datatools/index.asp?DataToolSectionID=4</a></p><p> Quick link to Quick Tables and Figures: <a href="http://nces.ed.gov/quicktables/" target="_blank">http://nces.ed.gov/quicktables/</a></p><p> Quick link to NCES Fast Facts (Note: The primary purpose of the Fast Facts website is to provide users with concise information on a range of educational issues, from early childhood to adult learning.): <a href="http://nces.ed.gov/fastfacts/" target="_blank">http://nces.ed.gov/fastfacts/#</a></p><p>See all <a href="/data-resources/">data and resources</a> »</p>
  • <h3>Congressional Budget Office</h3><p><img width="180" height="180" alt="" src="/live/image/gid/4/width/180/height/180/380_cbo-logo.rev.1406822035.jpg" class="lw_image lw_image380 lw_align_right" data-max-w="180" data-max-h="180"/>Since its founding in 1974, the Congressional Budget Office (CBO) has produced independent analyses of budgetary and economic issues to support the Congressional budget process.</p><p> The agency is strictly nonpartisan and conducts objective, impartial analysis, which is evident in each of the dozens of reports and hundreds of cost estimates that its economists and policy analysts produce each year. CBO does not make policy recommendations, and each report and cost estimate discloses the agency’s assumptions and methodologies. <strong>CBO provides budgetary and economic information in a variety of ways and at various points in the legislative process.</strong> Products include baseline budget projections and economic forecasts, analysis of the President’s budget, cost estimates, analysis of federal mandates, working papers, and more.</p><p> Quick link to Products page: <a href="http://www.cbo.gov/about/our-products" target="_blank">http://www.cbo.gov/about/our-products</a></p><p> Quick link to Topics: <a href="http://www.cbo.gov/topics" target="_blank">http://www.cbo.gov/topics</a></p><p>See all <a href="/data-resources/">data and resources</a> »</p>
  • <h3>National Bureau of Economic Research (Public Use Data Archive)</h3><p><img width="180" height="43" alt="" src="/live/image/gid/4/width/180/height/43/478_nber.rev.1407530465.jpg" class="lw_image lw_image478 lw_align_right" data-max-w="329" data-max-h="79"/>Founded in 1920, the <strong>National Bureau of Economic Research</strong> is a private, nonprofit, nonpartisan research organization dedicated to promoting a greater understanding of how the economy works. The NBER is committed to undertaking and disseminating unbiased economic research among public policymakers, business professionals, and the academic community.</p><p> Quick Link to <strong>Public Use Data Archive</strong>: <a href="http://www.nber.org/data/" target="_blank">http://www.nber.org/data/</a></p><p>See all <a href="/data-resources/">data and resources</a> »</p>
  • <h3>Internal Revenue Service: Tax Statistics</h3><p><img width="155" height="200" alt="" src="/live/image/gid/4/width/155/height/200/486_irs_logo.rev.1407789424.jpg" class="lw_image lw_image486 lw_align_left" srcset="/live/image/scale/2x/gid/4/width/155/height/200/486_irs_logo.rev.1407789424.jpg 2x" data-max-w="463" data-max-h="596"/>Find statistics on business tax, individual tax, charitable and exempt organizations, IRS operations and budget, and income (SOI), as well as statistics by form, products, publications, papers, and other IRS data.</p><p> Quick link to <strong>Tax Statistics, where you will find a wide range of tables, articles, and data</strong> that describe and measure elements of the U.S. tax system: <a href="http://www.irs.gov/uac/Tax-Stats-2" target="_blank">http://www.irs.gov/uac/Tax-Stats-2</a></p><p>See all <a href="/data-resources/">data and resources</a> »</p>