FDA - Industry MDUFA III Reauthorization Meeting

September 13, 2011, 8:30 am - 1:00 pm

FDA Switzer Building, Washington, DC

Room 1007


To discuss MDUFA III reauthorization.


Malcolm Bertoni Office of the Commissioner (OC)
Ashley Boam Center for Devices and Radiological Health (CDRH)
Nathan Brown Office of Chief Counsel (OCC)
Kate Cook Center for Biologics Evaluation and Research (CBER)
Christy Foreman CDRH
Bill Hubbard FDA Consultant
Toby Lowe CDRH
Tracy Phillips CDRH
Don St. Pierre CDRH
Ruth Watson Office of Legislation (OL)
Nicole Wolanski CDRH
Barbara Zimmerman CDRH
Francisco Vicenty CDRH
Hans Beinke Siemens (representing MITA)
David Fisher Medical Imaging Technology Alliance
John Ford Abbott Laboratories (representing AdvaMed)
Elisabeth George Phillips (representing (MITA)
Donald Horton Laboratory Corporation of America Holdings (representing ACLA)
Tamima Itani Boston Scientific (representing MDMA)
Mark Leahey Medical Device Manufacturers Association
Joseph Levitt Hogan Lovells US LLP (representing AdvaMed)
John Manthei Latham and Watkins (representing MDMA)
David Mongillo American Clinical Laboratories Association
James Ruger Quest Diagnostics (representing ACLA)
Patricia Shrader Medtronic (representing AdvaMed)
Janet Trunzo Advanced Medical Technology Association

Meeting Start Time: 9:00 am

Industry 1 provided a response and counter-proposal to the proposal offered by the Agency on August 24, 2011. Industry reiterated that their intent from the beginning of these negotiations has been to achieve a process that is efficient and ultimately reduces total time from submission to final decision. Industry stated their view that the single biggest barrier to bringing down total time was changing expectations from the Agency throughout the review. Industry proposed that implementation of more structured pre-submission meetings, additional guidance documents, and other process improvements will give applicants a better understanding of the requirements prior to submission of their applications.

In addition to process improvements, Industry proposed maintaining the quantitative performance metrics in place for MDUFA II, while adding a new quantitative performance metric for average total time.


Industry indicated that Pre-Submissions are very important to their members. They highlighted the importance of applicants understanding the requirements prior to submission of an application. Industry proposed that the Agency schedule the requested Pre-Submission meetings or teleconferences within 45 calendar days of request for 98% of qualified submissions. Industry’s proposal included similar aspects to the Agency’s Pre-Submission proposal, such as the Agency providing initial feedback to the applicant prior to the meeting, and guidelines for finalizing meeting minutes, with modified timelines and process details.

There was discussion about the nature of feedback provided in Pre-Submission meetings. Industry indicated that their intent was for this interaction to provide clear expectations for the applicant early in the process, especially when guidance documents did not reflect FDA’s latest thinking; Industry further proposed that changes to the feedback given during the pre-submission would require high-level management concurrence. There was discussion regarding situations where questions or issues not raised during the pre-submission would still be necessary for FDA to raise after review of a subsequent submission, such as questions based on the data submitted or driven by discrepancies or issues observed in the submission, or when new information is learned from a source outside of the submission that materially affects safety and effectiveness. Industry indicated that the concern arises when data are discovered from an outside source, such as an animal study, outside of the submission and then applied to the device submission. The Agency emphasized that it would not be able to ignore new information that materially affects safety and effectiveness, even if it was not discussed during the pre-submission. Industry indicated that their intent is to identify as much as possible during the initial communication and that modifying the expectations without an established threshold based on evidence or literature is problematic. FDA noted that in a Pre-Submission, often the Agency is providing advice and feedback on an early concept of a design, and additional questions may arise based on subsequent review of a full data set. Industry indicated their willingness to consider suggested edits from the Agency.

The Agency also expressed concern with having an unlimited time frame for the validity of the advice given during a Pre-Submission. If an applicant does not submit a related submission for several years following the Pre-Submission, the Agency is concerned that the technology, test methods, and scientific knowledge will have progressed during that time and the original advice may no longer be valid. Industry indicated that their proposal contemplated flexibility for the Agency to modify the established expectations based on new scientific data or if new issues arose.

Industry proposed that the applicant would be responsible for initially drafting the meeting minutes to document a Pre-Submission meeting. The Agency would then have an opportunity to edit, followed by a short period to work out discrepancies and finalize.

There was discussion about workload uncertainty, since Industry proposed removing the limits on the number of Pre-Submissions that would be subject to goals that the Agency had proposed. Industry indicated their willingness to have a fee for Pre-Submissions, but did not want limits on the number of Pre-Submissions that would be subject to goals. The Agency noted that having no limits would require a significant level of resources to make sure the Agency could accommodate the requests and provide a reasonable and timely response to industry. The Agency stated that introducing a new aspect of the program, such as goals for Pre-Submission meetings, creates significant uncertainty as to how many requests will be received and the rate of growth. In addition, the Agency noted that the Pre-Submission meeting allows for an early discussion of questions or concerns, but does not include a review of data or resolution of issues that are found during the review.  

Performance Goals

Industry proposed maintaining the MDUFA II performance goals for FDA Days while adding an average total time goal. The intent of the total time goal was to capture the anticipated efficiencies from many of the process improvements such as pre-submissions, refuse to file/refuse to accept, enhanced guidance, etc. Industry noted that although it expects efficiencies to be realized from these process improvements, it was not proposing to reduce the current FDA day goals under MDUFA II. Both industry and FDA acknowledge that the total time goal is the outcome of program enhancements. Industry indicated that maintaining MDUFA II performance goals for FDA Days should allow for an easier transition for the Agency. In addition to adding the average total time goal to the MDUFA II FDA Day goals, Industry’s proposal included features discussed in previous proposals, such as an Early Interaction, a Substantive Interaction at a point when the reviewer has completed a complete review of the submission, and use of Interactive Review. Industry pointed out that during MDUFA II negotiations, Interactive Review discussions envisioned early interactions, substantive interactions and timely reviews. The proposal included progressively lower total time goals each year, to correspond with Industry’s desire to achieve a downward trend in total time during the course of MDUFA III. Additionally, Industry’s proposal included a performance goal targeted at reducing the number of review cycles per submission for 510(k) submissions in order to encourage Interactive Review. Industry proposed that review cycles for 510(k) submissions should be kept to an average of 1.5 and that 50% of all 510(k) submissions should be completed in a single cycle.

Industry stated that they understood the Agency’s concern regarding being held to goals that included applicant time, which the Agency does not control; but Industry stated that the efficiencies realized from the process improvements would allow for total times to drop. Furthermore, industry stated that since it was not asking for FDA to reduce the FDA review days under the MDUFA II goals, it is unwilling to place limits on applicant time. Industry expressed that the proposed average total time goal was intended to provide an incentive for every application to be completed more quickly. The Agency expressed concerns that Industry’s proposal did not address issues discussed previously in negotiations, such as the need for separate goals for PMAs that are taken to an Advisory Panel and those that are not, the current challenges in managing with a two tier goal structure for FDA days, the concern that maintaining the two tier goal structure will make it more difficult to reduce total time, and the lack of Agency control over the Industry portion of total time to decision. The Agency indicated its commitment to reducing total time to decision, as an important outcome for both Industry and the public health, but expressed concern that FDA could meet its part of the commitment and the total time could still increase. The Agency also indicated concern about potential unintended consequences of the proposed goal.

Industry introduced performance goals for CLIA Waivers, which did not have performance goals under MDUFA II. Industry’s proposal included similar features to those of other submission types, such as the Substantive Interaction goal, FDA Days goal, and average total time goal. Industry also proposed that the Agency would develop a revised CLIA Waiver guidance document addressing industry concerns with the current guidance.

The Agency expressed concerns that the CLIA Waiver goals were overly aggressive. The Agency has expressed willingness to establish goals for CLIA Waiver reviews as long as they can be achieved with current resources, to avoid potential CLIA statutory implications. If additional resources would be needed to meet performance goals, the Agency would have to consider legal implications of charging user fees for a program that is to be funded through the CLIA statute. Additionally, the Agency expressed concern that Industry’s proposal for a new CLIA guidance document potentially involved policy issues, which would be outside the purview of user fee negotiations.

Industry’s proposal did not allow for additional review time for combination product submissions and companion diagnostic submissions as the Agency had previously proposed. Industry expressed its view that it is the Agency’s responsibility to coordinate consultations between Centers to meet the goals for these submissions. The Agency responded that the concern was not only coordination within the Agency, but that combination products tend to be more complex and raise different and more complicated review issues, which are especially difficult to manage within the short 510(k) time frames.

Process Improvements

Industry proposed elements to be added to the third party review program, including training, certification, periodic recertification, and increasing the scope of the program. Industry proposed that the Agency draft guidance and implement the proposed changes. The Agency noted that Industry’s proposal would require additional resources dedicated to the third party program to fund the development of those enhanced efforts.

Industry proposed changes to the Agency’s proposal for an independent assessment of review process management, including shorter timelines than proposed by the Agency, adding an assessment of the effectiveness of the Reviewer Training program, and clarifying that the Agency would implement a corrective action plan based on the results of the assessment. Industry also proposed that the same independent contractor return to evaluate the effectiveness of the Agency’s corrective actions. FDA expressed concerns that given the proposed timeline, there would be little time to evaluate and implement prior to the reassessment. Industry noted that given the potential limitations on time, the assessment should initially report out on priority items instead of the full scope of corrective actions.

Industry proposed implementation of a submission tracking system to allow applicants to check the status of their submissions. This had been proposed by Industry previously and Industry noted that their previous proposal was aggressive, but they wanted to emphasize the importance of FDA being able to communicate quickly to the applicant the status of the application.

The proposal areas discussed at the August 31, 2011 meeting were not discussed in detail at this meeting, though they remained in Industry’s proposal. These areas included: Scientific and Regulatory Review Capacity, Training, Performance Reports, and Guidance Document Development.


There was discussion on the details of the proposal, including the definition of an FDA Decision for purposes of goals. Industry’s proposal removed withdrawals from the definition for both PMA and 510(k) submissions. There was also discussion regarding the different methods for a reviewer to communicate with an applicant, specifically for a 510(k) review: Interactive Review (which may occur by telephone or email, does not require management concurrence, and does not put the file on hold), “telephone hold” (which may be done by telephone or email, requires management concurrence, and puts the file on hold), and Additional Information letter (which is a formal letter that requires management concurrence, and puts the file on hold). Industry indicated that there was confusion between an Interactive Review communication and a “telephone hold” communication, as it was unclear to the applicant if or when the file was put on hold. The Agency explained the processes; a formal letter is sent anytime a submission is put on hold, including via a “telephone hold,” and these processes are outlined in a guidance document.

The Agency also noted the apparent conflict between Industry’s expressed desire for more Interactive Review and for more management oversight. The Agency explained that Interactive Review is the form of communication that receives the least management oversight.

Next Meeting

The next meeting will take place September 29, 2011.

Meeting End Time: 12:30 pm

1 For purpose of these minutes, industry refers to AdvaMed, MITA and MDMA unless otherwise specifically noted.