Priority review voucher
The priority review voucher in the United States is an expedited review granted by the Food and Drug Administration (FDA) to the developer of a treatment for neglected diseases. The system was first proposed by Duke University faculty David Ridley, Henry Grabowski, and Jeffrey Moe in their 2006 Health Affairs paper: "Developing Drugs for Developing Countries." In 2007 Senators Sam Brownback (R-KS) and Sherrod Brown (D-OH) sponsored an amendment to the FDA Amendments Act of 2007. President George W. Bush signed the bill in September 2007.
The priority review is an incentive for companies to invest in new drugs and vaccines for neglected tropical diseases. A provision of the Food and Drug Administration Amendments Act (HR 3580) awards a transferable “priority review voucher” to any company that obtains approval for a treatment for a neglected tropical disease. Sponsored by Senators Sam Brownback (R-KS), and Sherrod Brown (D-OH), this provision adds to the market based incentives available for the development of new medicines for developing world diseases such as malaria, tuberculosis and African sleeping sickness.
Prior to approval, each drug marketed in the United States must go through a detailed FDA review process. In 1992, under the Prescription Drug User Act (PDUFA), FDA agreed to specific goals for improving the drug review time and created a two-tiered system of review times – Standard Review and Priority Review.
Standard Review is applied to a drug that offers at most, only minor improvement over existing marketed therapies. The 2002 amendments to PDUFA set a goal that a Standard Review of a new drug application be accomplished within a ten-month time frame.
A Priority Review designation is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. A Priority Review means that the time it takes FDA to review a new drug application is reduced. The goal for completing a Priority Review is six months.
Priority Review status can apply both to drugs that are used to treat serious diseases and to drugs for less serious illnesses. The FDA goal for reviewing a drug with Priority Review status is six months.
The distinction between priority and standard review times is that additional FDA attention and resources will be directed to drugs that have the potential to provide significant advances in treatment. Such advances can be demonstrated by, for example:
evidence of increased effectiveness in treatment, prevention, or diagnosis of disease; elimination or substantial reduction of a treatment-limiting drug reaction; documented enhancement of patient willingness or ability to take the drug according to the required schedule and dose; or evidence of safety and effectiveness in a new subpopulation, such as children. A request for Priority Review must be made by the drug company. It does not affect the length of the clinical trial period. FDA determines within 45 days of the drug company’s request whether a Priority or Standard Review designation will be assigned. Designation of a drug as “Priority” does not alter the scientific/medical standard for approval or the quality of evidence necessary.
The statute authorizes the FDA to award a priority review voucher to the sponsor (manufacturer) of a newly approved drug or biologic that targets a neglected tropical disease. The provision applies to New Drug Applications (NDAs), Biological License Applications (BLAs) and 505(b)(2) applications. The voucher, which is transferable and can be sold, entitles the bearer to a priority review for another product.
Under current Prescription Drug User Fee Act targets, the FDA aims to complete and act upon reviews of priority drugs within six months instead of the standard ten-month review period. Actual FDA review timelines, however, can be longer than the target PDUFA review periods, particularly for new products that haven’t previously been approved. Economists at Duke University, who published on this concept in 2006, estimated that priority review can cut the FDA review process from an average of 18 months down to six months, shortening by as much as a full year the time it takes for the company’s drug to reach the market.
For a company with a top selling drug with a net present value close to $3 billion, the Duke researchers calculated the accelerated approval could be worth over $300 million. At this level, the voucher would be expected to offset the substantial investment and risk required for discovery and development of a new treatment for a neglected disease. If the time saved from gaining a priority review is much shorter, however, the value of the voucher will be significantly less. In fact, in 2006, median standard review times were 12 months, suggesting that a voucher could cut six months from the standard review period.
An intangible benefit of the voucher is the value created for a company if the faster review provides them "first mover advantage," allowing the voucher holder's product to be introduced ahead of a similar, competing product. By taking advantage of existing market forces, patients in the developing world can have faster access to lifesaving products that may not otherwise be developed. And sponsors of neglected disease drugs can be rewarded for their innovations.
Companies that use the voucher will be required to pay a supplemental priority review user fee to ensure that the FDA can recoup the costs incurred by the agency for the faster review. The additional user fee also aims to ensure that the new program will not slow the progress of other products awaiting FDA review.
The tropical diseases that will benefit include the following:
- Blinding trachoma.
- Buruli Ulcer.
- Dengue/dengue haemorrhagic fever.
- Dracunculiasis (guinea-worm disease).
- Human African trypanosomiasis.
- Lymphatic filariasis.
- Soil-transmitted helminthiasis.
- Any other infectious disease for which there is no significant market in developed nations and that disproportionately affects poor and marginalized populations.
News and reaction
|“||But some of the highest-leverage work that government can do is to set policy and disburse funds in ways that create market incentives for business activity that improves the lives of the poor. Under a law signed by President Bush last year, any drug company that develops a new treatment for a neglected disease like malaria or TB can get priority review from the Food and Drug Administration for another product they've made. If you develop a new drug for malaria, your profitable cholesterol-lowering drug could go on the market a year earlier. This priority review could be worth hundreds of millions of dollars.||”|
First, the priority review voucher might be too small. Diseases with incredible burdens might merit more resources. The Advance Market Commitment, proposed by Michael Kremer and colleagues, calls for creating a $3 billion market for neglected diseases with high burdens, such as malaria, tuberculosis, and HIV/AIDS.
Second, the priority review voucher might be too large, if it rewards research which would have been done anyway, or research with low value. Aidan Hollis of the University of Calgary notes that "firms which are developing very profitable products will be rewarded even more". While some treatments for neglected diseases are lucrative, this is generally not the rule, which is why the diseases are neglected.
Third, the priority review voucher encourages innovation, but does not pay for access to existing therapies. Funding from governments or foundations might be needed to purchase treatments for poor people. Aidan Hollis of the University of Calgary has commented that the proposal does not address "the access problem, but helps to increase incentives through creating distortions in markets in developed countries".
Fourth, the priority review voucher might tie up FDA resources. Fortunately, however, the law includes an extra fee paid by manufacturers to the FDA and requires that voucher bearers provide FDA with a year notice before using a voucher.
Fifth, priority review might not be safe. Priority review should not, however, be confused with accelerated approval or fast track. Priority review does not omit safety or efficacy studies or require approval within a given time frame. It sets a target of 6 rather than 10 months for FDA review. Nevertheless, if the FDA feels pressure to meet deadlines faster, it might be more likely to err. Carpenter and colleagues (2008) report that new molecular entities approved in the two months before the first review deadlines showed a higher rate of postmarketing safety problems than drugs approved at other times. Nardinelli and colleagues (2008) of the FDA, however, wrote that they were not able to replicate the findings and that the findings might be driven by HIV-AIDS therapies. Following the Nardinelli piece, Carpenter acknowledged several errors in their data set and demonstrated errors in the FDA's and Nardinelli's data; Carpenter and colleagues report that the original associations between last-minute approvals and safety problems hold.
Extension to Europe
Writing in The Lancet, David Ridley and Alfonso Calles Sánchez proposed extending the voucher to the European Union. The proposed EU voucher would provide priority regulatory review through the European Medicines Agency, as well as accelerated pricing and reimbursement decisions by EU member states.
Extension to rare pediatric diseases
In 2012, President Obama signed into law the FDA Safety and Innovation Act which includes Section 908 the "Rare Pediatric Disease Priority Review Voucher Incentive Program". The act extends the voucher program to rare pediatric diseases, but only on a trial basis. One year after the third pediatric voucher is awarded, no other pediatric vouchers may be awarded. The extension to rare pediatric diseases was championed by Nancy Goodman of Kids v Cancer.
The pediatric voucher program includes several changes that had been sought for the neglected-disease voucher program, but apply only to pediatric vouchers. First, the pediatric treatment developer can ask the FDA in advance for an indication of whether the disease qualifies as a rare, pediatric disease. Second, the pediatric voucher can be transferred an unlimited number of times, whereas the neglected-disease voucher can only be transferred once. Third, the pediatric voucher user needs to notify FDA 90 days prior to using the voucher, rather than 1 year for the neglected-disease voucher. Fourth, the pediatric voucher winner risks having the voucher revoked if the treatment is not marketed within a year. Fifth, the pediatric voucher winner must report to FDA about use of the pediatric treatment within five years of approval.
- Ridley DB, Grabowski HG, Moe JL (2006). "Developing drugs for developing countries". Health Aff (Millwood) 25 (2): 313–24. doi:10.1377/hlthaff.25.2.313. PMID 16522573.
- H.R. 3580
- Bill Gates - Bill & Melinda Gates Foundation
- Carpenter D, Zucker EJ, Avorn J (March 2008). "Drug-review deadlines and safety problems". N. Engl. J. Med. 358 (13): 1354–61. doi:10.1056/NEJMsa0706341. PMID 18367738.
- Nardinelli C, Lanthier M, Temple R (July 2008). "Drug-review deadlines and safety problems". N. Engl. J. Med. 359 (1): 95–6; author reply 96–8. doi:10.1056/NEJMc086158. PMID 18596282.
- Ridley DB, Sánchez AC (September 2010). "Introduction of European priority review vouchers to encourage development of new medicines for neglected diseases". Lancet 376 (9744): 922–7. doi:10.1016/S0140-6736(10)60669-1. PMID 20833303.
- Jack, Andrew (30 April 2008). "FDA to aid tropical disease research". Financial Times.
- Hollis, Aidan (5 April 2005). "Optional Rewards for New Drugs for Developing Countries" (PDF). Submissions: Commission on Intellectual Property Rights, Innovation and Public Health (CIPIH). World Health Organization. — critique of Priority Review Voucher
- Duke faculty information page about the Priority Review Voucher
- BVGH information page on the Priority Review Voucher
- SEC. 524. (21 USC §360n) Text of the amendment
- Duke University video about the voucher