The most important outcomes are steps that are intended to improve FDA’s ability to recruit, hire and retain scientific staff, measures to improve the agency’s financial transparency and accountability, and extensions of ongoing efforts to integrate patient perspectives and real-world data into regulatory decision making.
Completion of the goals letter, expected in March, and review by HHS and the White House over the summer, will mark the end of the first phase of the PDUFA reauthorization process. But it only will launch the start of the much more arduous portion of the PDUFA reauthorization journey: congressional approval.
I. Fixing HR
FDA’s ability to meet user fee review goals, and to go beyond them by implementing new regulatory ideas and proactively supporting product development, depends almost entirely on its ability to recruit, retain and develop talented and dedicated staff.
At the start of PDUFA VI negotiations, PhRMA and BIO told FDA that industry would not support increases in user fees to hire new staff unless CDER demonstrated that it had put procedures in place that would fill staffing holes and provide confidence it could hire to fill new positions funded by PDUFA VI. According to industry negotiators, CDER and FDA have met the challenge, in part by taking some steps that are common in the private sector, such as hiring external head hunters.
Unlike previous user fee agreements, which paid for FTEs even if they were never hired, the agency will only receive the additional money if it meets recruitment and retention goals. FDA has also agreed to hire an external organization to assess and continuously evaluate its hiring and retention efforts.
Other nuts-and-bolts activities covered in PDUFA VI include improving the reliability of the electronic filing process for new drug applications, steps to improve the management of meetings between FDA and sponsors, and revamping a formula that is used to increase user fee payments based on estimated workload.
II. Breakthroughs and Biomarkers
Some of the new hires will work on improving FDA’s review of products that combine drugs and devices, and on the breakthrough therapies program. The breakthrough process is resource-intensive, and the largest allocation of new staff in PDUFA VI, about 60 employees, will be dedicated to breakthrough reviews. PDUFA VI will also include additional money and mandates for FDA to review drug development tools, including surrogate endpoints, biomarkers and patient-reported outcomes (PROs).
Alas. industry dropped attempts to establish review time goals for biomarker qualification.
Advancing FDA’s patient-focused drug development (PFDD) initiative is another priority for patient groups as well as for industry and FDA. FDA has already started expanding PFDD by encouraging patient groups to hold their own meetings modeled on meetings the agency has held. PDUFA VI will include a series of guidance documents that are intended to lead to PFDD version 2.0, which could include establishing standards for conducting and analyzing patient-preference research, and taking steps to formally integrate patient preferences into regulatory decisions.
FDA created structured benefit-risk frameworks during PDUFA V, and will expand their use in PDUFA VI.
Advancing the use of real-world evidence to make regulatory decisions will be another major emphasis of PDUFA VI. This will include enhancing the Sentinel Initiative, a system that allows investigators to monitor and query electronic medical records, health claims databases and other sources. Projects under consideration for Sentinel include monitoring the safety of biosimilars, and broadening its focus from safety to efficacy.
Biopharmaceutical companies are looking to PDUFA VI to open legal avenues to communicating with payers and possibly other parties about real-world data on off-label uses of approved drugs.
Finalization of the draft PDUFA VI goals letter will set in motion a series of reviews by HHS and the White House Office of Management and Budget that are slated to be completed by September. Following publication of the draft agreement in September, and a final public meeting in October or November, the deal should be formally submitted to Congress in mid-January.
PDUFA VI AT A GLANCE
* Improve FDA recruitment, hiring, retention: Implement HR improvements, hire outside HR contractors, contract for external analysis and monitoring of progress
* Funding for about 200 additional full-time employees (FTEs): Funding contingent on FDA meeting recruitment, retention goals
* Increased funding for breakthrough reviews: Largest portion of new FTEs
* Modification of the “workload adjustor” formula used to increase user fee payments based on anticipated submissions: Annual user fee increases expected to be smaller; FDA to gain more predictable funding
* Patient-focused drug development 2.0: Issue a series of new guidance documents on patient-focused drug development
* Research on the integration of real-world evidence into product reviews: Expand Sentinel Initiative, a system for postmarket monitoring and querying of electronic health records, insurance claims and other records to track medical product safety; Implement other efforts to use real-world evidence to study and communicate about safety and efficacy
* Increased funding for review of drug development tools: Add resources to qualify surrogate endpoints, biomarkers, patient-reported outcomes; Expand use of benefit-risk framework to guide drug development activities; Enhance FDA capacity to analyze innovative clinical trial designs
* Increased transparency regarding spending PDUFA funds
* Information technology improvements: Increase reliability of the electronic submissions system, upgrade CDER's IT system