US FDA says its upcoming accreditation scheme pilot to streamline the agency's review of companies' conformance to standards is an important part of the effort to modernize and globally harmonize pre-market reviews. But questions about what manufacturers will tangibly gain from the program, what the costs will be and the challenges of incorporating specific standards still need to be answered.
The agency convened a workshop May 22-23 at its Maryland headquarters to discuss the Accreditation Scheme for Conformity Assessment (ASCA) for medical devices. The ambitious program was hatched in the most recent MDUFA IV user-fee negotiations, and FDA has committed to getting it off the ground by fiscal year 2020. (Also see "Industry Supports US FDA Conformity Assessment Concept, But Questions Abound" - Medtech Insight, 28 Aug, 2017.)
Device firms contract with third-party testing labs to assess conformance to some standards, or, in some cases, firms have in-house testing labs they use for the same purpose.
"We are trying to hone in on what it is that FDA would like to see in a test report … so we can streamline our regulatory practices," FDA's Scott Colburn says.
The goals of ASCA are to better align how testing laboratories address FDA's regulatory expectations in their reports to manufacturers, and increase the agency's confidence in declarations of conformity to standards, which device-makers include in pre-market submissions to support the case for clearance.
Under the proposed program, FDA would formally qualify select accreditation bodies into the program. The accreditation bodies could then accredit testing labs, and testing labs could be formally recognized by FDA under the ASCA program. The accreditation and recognition milestones would be based on existing standards for testing laboratories adjusted to better meet FDA regulatory expectations. The idea is to provide more assurance to the agency that the testing reports provided to manufacturers by the labs appropriately address key issues.
The ASCA program is also intended to open lines of communication between FDA and the testing labs, so they can discuss evolving standards issues, and identify opportunities for training to ensure different stakeholders are on the same page.
FDA has tentatively selected three standards in the IEC 60601 series addressing the safety and essential performance of medical electrical equipment, and four standards in the ISO 10993 series addressing biocompatibility to incorporate into the pilot program, with the idea of adopting more standards into the program if the pilot is successful.
Device companies frequently declare conformity to consensus standards as part of 510(k) submissions to save time by avoiding the need to submit independent testing data. Scott Colburn, director of FDA's Center for Devices and Radiological Health standards program, noted at the start of the workshop that there is an average of seven standards cited per 510(k) submitted to FDA.
But FDA reviewers are sometimes left with questions about the conformity declarations, based on concerns about the standard being relied on, the possibility of variations in the application of the standard compared to what FDA has formally recognized, or other gaps in information. That often leads to reviewers requesting the actual testing lab reports to support the declaration and then questions to sponsors, either in the form of interactive review or as formal "additional information" requests. All of this adds up to review delays.
That's where FDA hopes the ASCA program could come into play.
"We are trying to hone in on what it is that FDA would like to see in a test report … so we can streamline our regulatory practices," Colburn said on May 22. "Hopefully, through the ASCA program, we will have more predictability. Increasing consistency and predictably, that is really what … this program is about."
CDRH Director Jeff Shuren emphasized the role of ASCA in the center achieving its goal of a majority of novel technologies reaching the US first or in parallel with other markets. (Also see "FDA's US-First Strategy: Device Center Sets Three-Year Goals" - Medtech Insight, 17 Jan, 2018.) "In order to get there, we need to have our programs ... as efficient and as consistent and predictable as optimally possible. ASCA can play a critical role," Shuren said.
"If we can improve the time to market, sometimes we are OK with spending more money," Philips Healthcare's Elisabeth George, says.
The agency also sees ASCA as highly connected to efforts to better harmonize FDA requirements with other authorities around the world. The reliance on third parties to perform conformity assessments for international standards would move the US system a step closer, for instance, to Europe's notified body approach, even while still relying on a centralized clearance/approval process.
Shuren highlighted plans to have ASCA work alongside the recently proposed alternative 510(k) route – technically an expansion of the abbreviated 510(k) program – that will allow companies to rely more on consensus standards and performance criteria, rather than comparisons to a predicate device, to gain clearance. (Also see "Proposed FDA Guidance Would Provide Alternate Route For 510(k) Applications" - Medtech Insight, 11 Apr, 2018.)
ASCA and the alternative 510(k) program, with a greater reliance on accredited conformance to global standards, can help support development of the Medical Device Single Review Program, he said. (Also see "Single Marketing Application Review For Multiple Jurisdictions On Horizon" - Medtech Insight, 6 Apr, 2017.)
In addition, the combined programs can help provide "more of a market place for national and international standards," Shuren said. They might provide a framework for FDA to work with other countries to "drive a friendly cycle of generation of more standards that are fit for purpose for regulatory needs," he noted.
Value To Device-Makers?
Despite FDA's ambitions, testing lab officials at the meeting questioned whether the program will provide enough bang for the buck for manufacturers, and, thus, make it worth it for testing labs to participate.
"One of the key things to figure out, from manufacturers' point of view, is what is the value of the program," one testing lab official asked during the workshop, echoing a repeated inquiry over the course of the two-day meeting.
Testing labs will likely need to invest extra resources to become accredited and recognized under ASCA. They would likely look to sell their services to device-maker clients at a premium, officials suggested. But for that approach to work, the organizations will need to be convinced that manufacturers would see a big enough advantage to pay more.
FDA's Colburn said he can't promise a specific impact to manufacturers, but he expects it will be positive. "I think we will see a natural lowering of some of the regulatory burden," Colburn said. "I wish I could make a promise. That is a metric that we will be looking at."
Shuren cited one tangible efficiency impact, estimating that pre-market review times of declarations for certain standards could go from "11 hours down to 15 minutes" by relying on an ASCA-accredited review.
That type of adjustment, Colburn said, would "put our resources into areas that we are most concerned about with patient safety."
Angela Krueger, acting deputy director for engineering and science review in FDA's Office of Device Evaluation, says she sees a real opportunity to cut back on the "volumes and volumes of data" that come in when reviewers feel compelled to ask for full testing lab reports to just "a handful of pages."
"That is where we see a lot of the payoff, from the pre-market perspective, both in terms of resources for industry and FDA, and for getting innovative products to market," Krueger said.
Device industry representatives who were involved in the MDUFA negotiations that established the ASCA pilot provision showed support for the approach during the workshop, arguing that is expected to reduce review times.
"The bottom line is, we are hoping for shorter review times," said Jamie Wolszon, an associate VP for AdvaMed. "[People are asking,] how many less hours or days would the reviews need to be for buy-in to the program, and I don't, we didn't talk about that granularity. It was the idea of tracking review times – looking to see how often questions were being asked for the standards that are participating in the program."
Elisabeth George, who represented the Medical Imaging & Technology Alliance at the workshop, said the ASCA program is a long-term bet for the industry. She suggested the pilot process, slated to run through 2022, will be crucial for determining how best to use ASCA to meaningfully improve predictability and efficiency down the road.
"Industry was excited ... because we could see the ultimate future of this," George said, recalling the 2016 negotiations with FDA.
But George – who is VP of global government affairs, standards & regulations at Philips Healthcare – acknowledged that there were not enough device-manufacturer representatives attending the workshop to help make that case during the various breakout sessions and in informal discussions. "I have already communicated to my colleagues that I am embarrassed by how few manufactures are here," she said.
Meanwhile, there was little doubt among workshop attendees that the ASCA program would add some cost to the system – and there was some angst about that.
"60601-1 is a beast," FDA's Alford Taylor says. The consensus is, "there is potential value here, but it is going to be really hard to realize it."
"The one concern that comes up [is that] not every manufacturer is a big, multi-faceted manufacturer making millions of dollars," said Fred Freedman of the Dental Trade Alliance.
FDA's Colburn acknowledged the point, but emphasized that FDA would be focused on minimizing additional requirements to testing labs that are already are accredited underISO 17025:2017, the standard for testing and calibration labs.
The goal is to have the ASCA accreditation standards for labs be "a very close mapping of what you do today. Maybe a few tweaks," Colburn said. The idea is not to make it more difficult … but to provide the key elements to us." A primary goal will simply be to open the line of communications between FDA and testing labs so FDA can better understand labs' output, and labs can be keyed in to the agency's thinking on various standards, he stressed.
Beyond that, the hope is that the extra cost will be worth it, as a result of the extra predictability gained.
"We know sponsors do a ton of effort to try to predict that magic date of when they get their clearance or approval, and there are millions and millions of dollars that go into that date being shifted a week, one way or the other," Colburn said.
Philip's George agreed that she likes the tradeoff. "If we can improve the time to market, sometimes we are OK with spending more money," she said. "I know that may make some small manufacturers cringe to hear that: sometimes it is worthwhile to spend a little to get a lot."
A Steep Climb Ahead
But based on the discussions at the workshop, perhaps the biggest challenge to getting ASCA off the ground is mapping out detailed "schemes" that will be necessary to establish meaningful accreditation for the selected standards to support FDA review.
IEC 60601 (Medical Electrical Equipment):
- 60601-1: Base standard/Basic safety and essential performance
- 60601-1-2: Collateral electromagnetic/Compatibility for all devices
- 60601-1-8: Collateral alarms for all devices
ISO 10993 (Biological Evaluation of Medical Devices):
- 10993-4: Hemolysis and complement activation
- 10993-5: Cytotoxicity
- 10993-10: Irritation and sensitization
- 10993-11: Acute systemic toxicity/Material-mediated pyrogenicity test
According to George, MDUFA negotiators envisioned incorporating three standards into the pilot program, but FDA has proposed at least seven, in addition to the potential for a more device-specific standard to be added to the mix. (See box, "ASCA Standards.")
Not only is the number ambitious, but consensus at the workshop was that the specific standards selected would be very challenging due to their complexity.
Discussions on the biocompatibility standards during workshop breakout sessions appeared to be the most productive in terms of getting down to detailed, line-item considerations for creating the schemes, based on a debriefing session at the workshop. The 60601 standards, particularly the base "-1" standard, and the "-1-2" standard relating to electromagnetic disturbances, appeared to cause the most challenges and head-scratching during the meeting.
"60601-1 is a beast," noted Alford Taylor Jr., associate director for engineering and quality management in the FDA device center's Office of Science and Engineering Laboratories (OSEL). The consensus from the breakout sessions on that standard that he helped moderate, Taylor said, was, "Yes, there is potential value here, but it is going to be really hard to realize it."
When the group was asked if it is an appropriate standard to include, "there was silence, but no one said no," Taylor conveyed. "No one that works with the standard thinks it shouldn't be in the pilot, but it will take a lot of work."
"I am hoping we can pick up the pace in the 60601 world, compared to biocompatibility," noted Brian Fitzgerald, a senior technical advisor in OSEL.
The next step for FDA is to write draft guidance documents, incorporating input from the workshop and follow-up discussions, that will lay out the accreditation process for both accreditation bodies and testing laboratories. Those are due, according to the MDUFA IV commitment letter, by Sept. 30, 2019, and expected to be finalized within a year to align with the official start of the pilot by the end of FY 2020.
FDA's Colburn suggested the agency's goal is to stay ahead of those dates. The agency is already ahead of schedule, having committed to hold the workshop before the end of the current fiscal year.
George, from Philips, said participants should be aware the guidance documents are likely to be relevant for the pilot program, but new documents will likely be necessary if it becomes a long-term program after 2022, when the current MDUFA program expires.
"We know that it is going to take awhile. We know that we have to start with a pilot," George said. "It is going to be slow at first."