Stakeholder Meeting on MDUFA III Reauthorization
To discuss FDA’s proposal package presented to Industry for MDUFA III.
Meeting Start Time: 1:45 pm
FDA recently presented a proposal package for MDUFA III to Industry. The goal of the package is to achieve an outcome on which all Industry participants, stakeholders, and FDA agree: timely access to safe and effective medical devices. To accomplish this goal, FDA has considered ways in which improvements to the predictability, transparency, efficiency, consistency, and accountability of the medical device review process can be made. To this end, FDA conducted several in-depth analyses of the device review program. The analysis demonstrated that performance has been strong, yet there are signs of overload. FDA is meeting most performance goals; however, more decisions are being made closer to the MDUFA deadlines and the gap between the highest and lowest performing branches has increased. FDA considers these observations to be signs of stress on the review system. Moreover, despite best efforts in designing the MDUFA II program, meeting the performance goals is not having the desired outcome of bringing safe and effective medical devices to market more quickly. FDA noted that the average total time to final decision has increased, driven by the increasing time taken by Industry to respond to requests for additional information and increasing numbers of review cycles. FDA believes a major contributor is poor submission quality. Furthermore, FDA asserted that addressing these challenges and improving efficiency of the program is a shared responsibility for FDA and Industry.
FDA outlined several key uncertainties which have the potential to impact the review program. FDA is mindful of all such uncertainties and will continue to monitor them throughout the reauthorization process. First, the user fee reauthorization legislation is considered “must pass” and therefore is an attractive target for policy riders. Second, technology is always changing and becoming increasingly complex, which can have a significant impact on what FDA is asked to evaluate. New technologies can take longer to review. Third, there is uncertainty regarding the number of applications and other submissions industry will send to FDA for review. Finally, the Budget Authority (BA) appropriation levels for upcoming fiscal years are unknown. FDA presented three financial baseline scenarios for the MDUFA III period, all of which assume maintenance of the current 1230 full-time equivalent (FTE) staff supporting the review process and a 4% annual rate of inflation applied to the total program costs, including user fees. If the BA increases 4% per year with inflation, FDA can maintain current staffing levels. If the BA is flat, FDA could lose 153 FTEs over the course of MDUFA III due to attrition that occurs when funding fails to keep pace with inflationary costs of maintaining each FTE. If the BA is reduced by 4% per year, the funding gap would be exacerbated, and FDA could lose 284 FTEs over the course of MDUFA III. FDA indicated that the program already is operating beyond capacity and are very concerned with their ability to maintain current performance under any scenario outlined above. FDA has therefore been considering and implementing additional program efficiencies and also included such initiatives in the initial proposal package.
FDA’s Initial Proposal Package for MDUFA IIII
The elements of FDA’s initial proposal package fall into four main categories: enhancing capacity, managing workload, improving interactions, and fostering innovation.
FDA reported a much higher attrition rate at CDRH compared to other Centers at FDA, which results in new reviewers and new managers. Specifically, 47% of reviewers have less than four years’ experience and 71% of branch chiefs have less than 5 years of management experience. Furthermore, CDRH has a high employee-to-front line supervisor ratio: 14:1 in ODE and 37:1 in OIVD. This creates a very challenging management situation. Additionally, there are several areas with gaps in expertise or with only one expert who is often overworked. Funds for training and professional development are limited such that new reviewers are actually trained through the review of applications, and more experienced reviewers may leave due to lack of opportunities for career development or excessive workload.
FDA developed a series of proposals to address the above concerns about the Agency’s “scientific review infrastructure.” First, FDA proposes to establish adequate review staff, targeted in areas of current bottlenecks due to lack of expertise or sufficient capacity. FDA also proposed to use expertise more appropriately by establishing teams of cross-cutting experts (e.g., in areas such as biocompatibility, sterility, and software) who meet routinely to ensure consistency, provide back-up for one another, and develop training for staff. Additionally, FDA has piloted a new reviewer training program that could be funded to support initial training of all new reviewers coming on board. FDA also proposed expanding the site visit program which allows reviewers to visit device manufacturing facilities and clinical settings where devices are used. Finally, to ensure FDA is efficient in its use of additional staff and training funds, FDA proposed a reorganization and hiring of additional managers that will put in place better management oversight, as well as development of a guidance document on good review management practices to ensure consistency and increased transparency.
FDA believes that submission quality is an issue contributing to longer review times. Therefore, FDA intends to only begin review of complete submissions. This would involve developing and publishing a set of revised checklists based on objective criteria. Only once the criteria defining a complete submission are met would the review clock start.
FDA also believes that guidance documents benefit both FDA and Industry as they make transparent FDA’s current thinking in a product area. FDA therefore proposed targeted improvements to the current guidance document development process. One important element is tracking documents under management review so that FDA can ensure each document reaches publication in a timely manner. Based on Industry’s concerns that some guidance documents are outdated, FDA also proposed to conduct reviews of all device-specific guidance documents every five years and publish technical updates when appropriate.
FDA finds the structure of the current PMA performance goals difficult to manage. Therefore, FDA proposed creating a separate category for PMAs requiring Advisory Panel review, increasing the percentage of non-Panel PMAs that will meet the current Tier 1 goal, decreasing the number of days between Tier 1 and Tier 2 goals,- and creating a single Expedited PMA goal with a shorter timeframe than a non-Expedited PMA going to Panel. For all PMAs, FDA would implement an initial review communication goal under which a major deficiency letter or status letter would be sent by a target date. Similarly, for 510(k)s, FDA would issue an additional information letter or status update by a target date. Status letters/updates would only be used in cases where outstanding issues are considered minor and can be addressed interactively. FDA believes that these early communications will lead to more timely review decisions and provide Industry with greater predictability for the process.
In many cases, FDA finds that the current review paradigm for bundled and multiplex devices leads to an unlevel playing field. The review of such submissions involves reviews of multiple datasets, all for one user fee and in the same timeframe as for submissions containing single devices with one dataset. FDA proposed increasing review times and/or user fees to account for the additional resources required.
Interactive Review (IR) is an important element of the MDUFA II legislation. Interaction does not place a file on hold but gives industry a chance to address issues “on the clock.” FDA has not tracked IR in a consistent manner so it is difficult to analyze how often it is used or its level of success. FDA therefore proposed improvements in how IR is tracked so that the program can be analyzed and improved. Additionally, FDA proposed to address IR in the good review management principles guidance document outlined above to ensure consistency across the Center with respect to when and how IR is used.
Stakeholders in the IVD product area have benefited from regular “roundtable” meetings. FDA proposed to broaden this successful program to include yearly public stakeholder meetings at the Office of Device Evaluation (ODE) Division level. This would allow more focused interactions in a forum for two-way feedback.
Fostering innovation is a strategic priority for the Agency and CDRH. FDA has proposed several strategies that they believe may assist with conducting clinical trials in the U.S. First, FDA proposed to develop and make publicly available a clinical investigator list which includes specific areas of research and inspectional history. Second, FDA proposed to make permanent and expand the current pilot outreach and training program through which staff from FDA’s Bioresearch Monitoring group and product-specific experts provide on-site training at academic research centers. The training focuses on how to conduct clinical research in a manner that addresses FDA’s expectations with respect to data quality, as well as how to successfully participate in clinical research in compliance with the regulations. This program allows FDA to communicate directly with investigators, study management staff, IRB (Institutional Review Board) members, Clinical Event Committee (CEC) members, Data Safety and Monitoring Board (DSMB) members, and new physicians who may be considering participation in clinical research. FDA also proposed to develop and implement a certification program for clinical research sites. Specifically, FDA would reach out to and partner with existing nonprofit organizations who already certify/accredit various aspects of clinical sites. The program would allow industry to identify sites and set up trials more quickly with confidence that data will be of high quality, provide assurance to patients that there is oversight such that they should feel comfortable participating in research at that site, and hopefully result in submission of higher quality data to FDA for review in marketing applications. Finally, FDA proposed the use of registries as infrastructure for addressing required post-approval studies (PAS). Such an infrastructure would allow sponsors to begin such studies more quickly and provide FDA with data on “real world” use of devices.
FDA pointed out that the proposal package described above addresses more than just performance goals. The package as a whole is intended to improve timely access to safe and effective devices.
In the context of FDA’s description of lack of expertise in some areas, stakeholders inquired about the use of third party reviewers. FDA indicated that there are some challenges associated with the third party review program, which does not directly address lack of staff expertise. The third party reviewers are trained once a year, which does not provide the same background FDA reviewers receive through regular interactions with other members of the review team and management. The program is intended for simple, lower risk devices, but has grown to include more. FDA is working to improve the existing third party review program; however, it is important to note that FDA does not see it as a means of bridging their expertise gap. FDA is attempting to address lack of expertise by sending application-specific homework assignments to advisory panel members for input and developing networks of outside experts in general cross-cutting areas, such as nanotechnology, which are not application-specific and do not require confidentiality. Stakeholders questioned how FDA determines which panel member a homework assignment is sent to. FDA looks at the backgrounds and expertise of an entire panel roster to pick the most appropriate individuals and to screen for conflict of interest. FDA often struggles to find appropriate experts that do not have real or perceived conflicts of interest. Stakeholders asked if FDA tracks problems with conflicts of interest and if data are available. FDA does keep data relating to conflicts of interest and committee membership; although conflict of interest is assessed for homework assignments, FDA does not keep specific data on this.
Following FDA’s comments regarding a high attrition rate at CDRH, stakeholders asked where people are going when they leave CDRH. FDA indicated that staff seem to move to a variety of places, including reassignments within the Agency, consulting, and industry. FDA believes people often leave due to the high workload volume.
Stakeholders expressed frustration with the speed of the guidance development process and asked what they could do to help. FDA acknowledged the process is slow but indicated the proposal described above is intended to at least help them identify more quickly when there is a roadblock in the process so that they can troubleshoot it. FDA suggested that stakeholders provide comments on the list of priority guidance documents FDA currently publishes annually. Stakeholders questioned whether a relevant standard could be just as useful in the absence of a specific guidance document. FDA confirmed that standards can be incredibly useful and therefore many FDA resources are spent supporting their development. The most useful standards are those with more specificity (such as acceptance criteria); standards with too much flexibility (such as those describing methods without acceptance criteria) do not significantly lessen the review burden.
In reference to FDA’s proposal for increased training capacity, stakeholders asked FDA to outline their priorities for who will receive what types of training. FDA indicated that their first priority is to train new reviewers (which currently comprise roughly half of the review staff). The second priority would be to offer training in specific areas of expertise to keep more experienced reviewers ahead of the latest developments in their fields, help improve performance, and prepare for the review of new technologies. Stakeholders indicated support for such training.
FDA acknowledged a letter recently received from the National Health Council, which FDA had not yet had the opportunity to review it in detail. The National Health Council outlined the two key messages for the group: a suggestion to establish a framework for benefit versus risk evaluation during the review process that includes input from the patient groups who would be using the device, and a request for clarification of how advanced diagnostics may be impacted by the user fee program. FDA agreed to consider the suggestion and question as outlined in the letter and comment at the next meeting.
Schedule of Future Meetings
The next meeting will be held on May 19, 2011.
Meeting End Time: 3:30 PM