Over the years, and particularly in the 1970s and the 1980s, one of the loudest complaints about the FDA’s drug approval process was that it took too long to get a drug approved. A drug could have literally sat under review for years – and this was following years of drug development and clinical testing by the company. The median approval time in the early 1990’s was 20 months, with some drugs taking much longer to review and approve. Why the delay? Not enough staff, inconsistencies between divisions, a lack of standardized clinical trial requirements, all supported a large bureaucratic process. In addition, there was no incentive to complete reviews in any given time frame. If a reviewer felt that there was insufficient information to establish safety or efficacy, they could request more testing in nearly an arbitrary manner. Clearly the FDA had reached new bureaucratic heights; the review machine was cumbersome and needed tuning.
Congress’s solution was to strengthen the FD&C law (the law for your reference) by passing another amendment entitled: the Prescription Drug User Fee Act of 1992, or PDUFA (‘puh doo fa’). (Follow the link to the FD&C law above and go to the âlist of significant amendments at the bottom to get to the PDUFA amendment. You can also get to it through the PDUFA link). In short, PDUFA allowed the FDA to collect fees from sponsors for the review of their applications. The fees are paid directly to FDA (but not sent with the application to the division doing the actual review). In turn, the FDA was required to meet stringent review time criteria with the objective of speeding up the review process. PDUFA was set to sunset in 1997, 2002 and 2007. However, it was subsequently renewed in each of those years to give us PDUFA II, PDUFA III and PDUFA IV respectively. PDUFA V was signed into law on July 9 2012. To monitor the PDUFA funds, the FDA is required to report to Congress exactly how the money is spent. To do so, four times per year for a 2 week period, the FDA takes a real time accounting of the amount of time spent performing activities that are supported by PDUFA funds (mainly reviewing investigational/new drug applications).
As we’ve seen from recent news stories (and some not so recent), the FDA is currently under scrutiny for inadequate review of the application for some new drugs and biologics resulting in recalls and products with a poor safety profile ending up on the market! It also appears that there are more frequent reports of contamination in the nationâs food supply sometimes with deadly outcome.Â To be sure, we can not rely on the public criticism only to assess FDAâs performance. The reality is that the agency always needs more resources than it gets and it is regularly the case that it ends up with unfunded mandates at each budget cycle.
One of the main features of PDUFA is the collection of user fees by the agency. There are three types of fees collected from users.
- Application fees – fees collected for new applications of drugs or uses of drugs
- Annual establishment fees – fees collected annually for manufacturing establishments
- Product fee (also Renewal fees) – annual fees on each product falling under PDUFA regulations
These fees are collected by the FDA, but the money doesn’t go to the reviewing office.
PDUFA is now in its fifth incarnation being known as the Food and Drug Administration Amendments Act of 2012. The current incarnation of PDUFA incorporates new changes, as each of the renewals has done in the past. Generally, Congress uses the amendment negotiations to add a mandate (frequently without additional funding) designed to address a current problem. For amendment V, one of the main concerns during the negotiations was the shortage of drugs and measures the FDA was required to take action to try to mitigate this problem. You can find more information on user fees on the FDA website and the CFR. They can be quite expensive. To help small companies that might not be able to afford this, the PDUFA fee schedule provides for waivers of these fees under particular circumstances. New companies, for example, get a break if it is their first application, the manufacturer employs fewer than 500 people, and if the manufacturer makes less than $10 million in annual revenue.
The program is continually evaluated for performance and reports are submitted to congress. Visit the PDUFA website for examples of detailed reports on the successes and failures of PDUFA, including the most recent one for FY 2013. Note that there are separate performance and financial reports for each year (2013 financial report available). You should also be able to access the user fee rates for the 2013 fiscal year from this link. The average number of review cycles to BLA approval has dropped pretty consistently, as have overall review times. Industry is generally happy with the result. Andrew von Eschenbach a recent past Commissioner of the FDA was quoted as saying “In the last 14 years, three consecutive user fee programs — PDUFA I, II and III — have brought enormous public health gains to our and, indeed, the world’s consumers, by helping FDA make increasingly complex medications available to patients faster than was ever possible before without sacrificing quality.”
In addition to improvements in submission review times, PDUFA negotiations also often lead to improvements in FDA responses to public health issues as a consequence of âpromptingâ by congress. For example the PDUFA V negotiations resulted in increased activity on the part of the FDA to minimize drug shortages. See the following: