FDA - Industry MDUFA III Reauthorization Meeting

August 9, 2011, 2:15 - 5:00 pm

FDA White Oak Building 1, Silver Spring, MD

Room 4101-5


To discuss potential workload and performance impacts of the Institute of Medicine’s report on 510(k)s and the draftguidance on 510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device.


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)
Natalia Comella CDRH
Christy Foreman CDRH
William Hubbard FDA Consultant
Elizabeth Hillebrenner CDRH
Toby Lowe CDRH
Thinh Nguyen OC
Tracy Phillips CDRH
Michael Ryan CDRH
Don St. Pierre CDRH
Ruth Watson Office of Legislation (OL)
Barbara Zimmerman CDRH
Susan Alpert Representing AdvaMed
David Fisher Medical Imaging Technology Alliance (MITA)
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 (MDMA)
Jim Ruger Quest Diagnostics (representing ACLA)
Patricia Shrader Medtronic (representing AdvaMed)
Janet Trunzo Advanced Medical Technology Association (AdvaMed)

Meeting Start Time: 2:15pm

The Institute of Medicine’s (IOM’s) Report on 510(k)s

FDA discussed the potential impacts of the recommendations in the IOM report on future 510(k) program workload. FDA asked the IOM two questions: (1) Does the current 510(k) clearance process optimally protect patients and promote innovation in support of public health? (2) If not, what legislative, regulatory, or administrative changes are recommended to optimally achieve the goals of the 510(k) clearance process?

FDA noted that there has been some criticism about the makeup of the IOM committee; however, as part of the process to answer these questions, the IOM held three public meetings with input from the venture capital Community (Fischell, Makower, and PWC), the device industry (Alpert, Burlington, Feigal, Hutt, Phillips), academia (Fu, Hall, Kessler, Redberg), patient and consumer advocacy groups (Allina, Vaughan), those with a global regulatory perspective (Jefferys, Trunzo), and from a post-market perspective (Masoudi, Peterson, Resnic, Varosy).

After the public process, the IOM had internal deliberations which resulted in the following recommendations to FDA:

  • The FDA should obtain adequate information to inform the design of a new medical device regulatory framework for Class II devices so that the current 510(k) process, in which the standard for clearance is substantial equivalence to a previously cleared device, can be replaced with an integrated premarket and postmarket regulatory framework that effectively provides a reasonable assurance of safety and effectiveness throughout the device life cycle. Once adequate information is available to design an appropriate medical device regulatory framework, Congress should enact legislation to do so.
  • The FDA should develop and implement a comprehensive strategy to collect, analyze, and act on medical device postmarket performance information.
  • The FDA should review its postmarket regulatory authorities for medical devices to identify existing limitations on their use and to determine how the limitations can be addressed.
  • The FDA should investigate the viability of a modified de novo process as a mechanism for evaluating the safety and effectiveness of Class II devices.
  • The FDA should develop and implement a program of continuous quality improvement to track regulatory decisions on medical devices, identify potential process improvements in the medical device regulatory framework, and address emerging issues that affect decision-making.
  • The FDA should commission an assessment to determine the effect of its regulatory process for Class II devices on facilitating or inhibiting innovation in the medical devices industry.
  • The FDA should develop procedures that ensure the safety and effectiveness of software used in devices, software used as devices, and software used as a tool in producing devices.
  • The FDA should promptly call for PMA applications for or reclassify Class III devices that remain eligible for 510(k) clearance.

FDA offered preliminary perspectives on the IOM’s recommendations. CDRH does not believe that the 510(k) process should be eliminated; however, CDRH remains open to additional proposals and approaches for continued improvement of the 510(k) process as well as for any of our other device programs. FDA plans to continue review of the report and to solicit input from stakeholders regarding the recommendations in the report consistent with FDA’s commitment to use a public process to vet the IOM’s recommendations. FDA opened an official public docket so that they can receive comments on the IOM report and is looking for dates to hold a public meeting this fall, to discuss the IOM recommendations in greater detail with industry, patients and the health care community.

With respect to the report’s potential impact on workload or performance, FDA indicated that the main IOM recommendation was not specific enough to analyze for potential impacts in the event it were to be implemented. And, even if the recommendation was considered for implementation, it would be a lengthy process that would likely not impact performance in MDUFA III. FDA plans to review the public input and then announce by the end of October what, if any, recommendations the agency would adopt. FDA is already in the process of implementing the last recommendation (calling for PMA applications for or reclassifying Class III devices that remain eligible for 510(k) clearance), with a targeted completion by the end of 2012.

Industry asked how FDA will balance IOM’s recommendations for changing the current system with IOM’s main recommendation for eliminating the current system. FDA reiterated that the Agency does not believe the 510(k) program should be eliminated; it works well for most devices. FDA acknowledged that some increasingly complex devices stretch the boundaries of the program, and FDA is looking for ways to better address them. Industry pointed out that the report suggested substituting the 510(k) process with the de novo process, and asked if this would increase workload due to the de novo process requirement to develop special controls. FDA explained that, based on discussions with IOM, the agency understood this proposal to be a way of piloting a new regulatory framework, and was not intended to be a comprehensive approach.

Industry asked FDA to comment on workload impacts of the seven items that FDA referred to the IOM but on which IOM declined to comment. FDA replied that there are no current plans to implement these recommendations. Industry asked whether FDA is considering consolidating indications for use and intended use. FDA replied that the forthcoming 510(k) paradigm guidance document retains both distinct concepts and terms. Industry indicated that the IOM’s recommendations were so far outside the scope that the report does not provide meaningful answers to the questions FDA asked. Industry also expressed concern with the IOM’s statement that the 510(k) program is not designed to address safety and effectiveness, and encouraged FDA to rebut this contention. FDA noted that the IOM acknowledged that there is not a public health crisis relating to the 510(k) program. FDA further indicated that the agency plans to address this issue in its formal response in October.

Draft Guidance--510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device

FDA discussed the potential impacts of the draft 510(k) modifications guidance on future 510(k) program workload. FDA first issued guidance on 510(k) device modifications in 1997 to clarify when a new 510(k) is needed and to ensure consistency between review branches. FDA recently published an updated version in draft to provide added clarity in certain sections, reflect new technology, and coordinate with current software policies. The updated document utilizes the same logic scheme and regulatory basis (21 CFR 807.81) as the previous version, but in a slightly different format. FDA removed the flowchart to emphasize the text of the document, which contains important explanatory language. FDA explained that simply following the flowchart, without reading the accompanying text, could result in the wrong decision.

The updated guidance also differs from the previous version in that it stresses known and potential points of confusion (based on actual cases, warning letters, and conversations with industry), and clarifies application of the device modification standards to newer technologies such as software and nanotechnology. The document further clarifies FDA’s interpretation of changes that “could significantly affect safety or effectiveness” as described in the regulations. This includes changes intended as improvements. A manufacturing section has been added to the guidance based on 807.81(a)(3)(i), which gives “manufacturing processes” as an example of changes that could significantly affect safety or effectiveness and require a new 510k. FDA interprets this to apply to devices that typically include manufacturing information in 510(k)s (e.g., wound dressings and contact lenses). The updated document also contains many examples to illustrate FDA’s interpretation of the regulations. FDA noted that the guidance document contains no new policies; rather, it provides additional clarity on how FDA currently interprets existing regulations. FDA would appreciate comments, including additional examples, as the agency prepares the final guidance.

Industry inquired as to how to apply the updated draft guidance to ultrasound transducers. Previously, a company would submit one 510(k) for a given transducer and a single ultrasound device. The submitter would then use “letters to files” for other cleared ultrasound devices with which the same transducer could be used. Under the new draft guidance, Industry asked whether companies would need to submit separate 510(k)s for each transducer/ultrasound device combination. FDA clarified that the agency does not interpret the regulations to require separate 510(k)s in this case, and asked Industry to submit this example to the docket for consideration for inclusion in the final guidance. FDA indicated that adding more examples to the final version of the guidance might provide greater clarity.

Industry brought up an example of material changes, which often impact entire product families. FDA clarified that a change in supplier would not necessarily require a new 510(k); however, a change in formulation for a patient-contacting material raises biocompatibility issues that could impact safety and effectiveness. FDA also noted that manufacturers sometimes change materials in a given device to the same material used in another device of the same type, but with a different design. FDA indicated that in some cases the materials can impact performance and therefore must be evaluated in the given device design.

Industry also brought up a sterilization example, stating that previously changes could be made to sterilization methods and documented with a letter to file if the Sterility Assurance Level (SAL) remained unchanged. FDA explained that this is an example in which the previous flowchart needed to be considered along with the explanatory text of the guidance; the flowchart raised the SAL, but the guidance text noted the relevance of whether the methods could impact materials. For example, a change in methods could impact plasticizers in materials and consequently impact performance.

Industry suggested that there could be a large increase in submissions when this draft guidance is implemented. Some individual manufacturers suggested the increase may be around 20%. One trade association obtained input from ten member companies suggesting the increase may be 300% based on comparison of their annual projections of submissions under the previous and updated versions of the guidance. Industry stated that these estimates were preliminary and additional input from members would be forthcoming. FDA did not believe that estimate was correct, and asked whether the 300% estimate is based on each change counted individually or each planned submission (which often include multiple changes). FDA asked for specific examples of types of changes that drove this increase. FDA suggested that some examples may be the result of an incorrect interpretation of the new draft guidance, and further clarification and additional examples in the final version may resolve some misperceptions.

Industry questioned why the guidance did not indicate the type of 510(k) (i.e., Special, Traditional, Abbreviated) for each example. FDA explained that this guidance is only intended to address the threshold question of whether a change requires a 510(k) or not; the 510(k) paradigm guidance addresses types of 510(k).

Industry and FDA agreed that training of industry members and FDA reviewers and supervisors on the appropriate interpretation of this guidance document is important. Industry also pointed out the importance of training FDA investigators who look at design history files during inspections. FDA is currently in the process of developing internal training and will work with Industry on external training.

Industry and FDA discussed how to move forward in determining the impact of this guidance on workload. Industry reiterated their assessment that workload could dramatically increase. FDA reiterated its concern that potential misinterpretation of the draft guidance may be driving estimates about increased workload; FDA noted the need for additional details behind Industry’s preliminary estimates. FDA indicated they are willing to talk to companies during the comment period. In particular, FDA would like to talk through examples of changes that companies think previously did not require a submission but now do, as well as any areas of confusion. FDA is open to suggestions for new wording, additional examples, and any other means of improving the document.

Next Meeting

The next meeting will take place August 24, 2011.

Meeting End Time: 5:00pm