FDA Today | After Years of Waiting, FDA’s ISO 13485/QSR Proposed Rule Heads to White House

The wait is, at long, long last, almost over. Yesterday the Office of Management and Budget updated its website to indicate that the FDA’s proposed rule to harmonize the agency’s medical device Quality System Regulation with the ISO 13485 standard has been finished and is now under review by OMB.

Our own Laura DiAngelo has the details for you below.

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Long-sought regulation to transition device QSR to ISO 13485 heads to White House for review

The top line: FDA’s long-awaited plan to harmonize the U.S.-specific medical device quality system regulations with the international standard – ISO 13485 – has been submitted for regulatory review by the White House Budget Office.

The medical device industry has been awaiting the transition plan for several years. For the first time, it appears that the regulation has been fully drafted.

• Quick Background: The current medical device quality system regulations (QSR) are U.S.-specific. Outlined at 21 CFR 820, they set regulatory standards for facilities and controls for medical device manufacturing, packaging, storage, and installation. However, outside of the U.S. regulators have been converging around an international quality system standard, ISO 13485. For several years, the FDA has been working to harmonize its QSR with ISO 13485 in order to foster consistency for regulated industry and global quality expectations for medical devices.
• However, FDA’s plan to adopt ISO 13485 has faced repeated delays. While FDA’s Center for Devices and Radiological Health (CDRH) announced its intent to transition from the QSR to the ISO standard back in May of 2018, the planned regulation has been delayed several times. The agency’s original projected publication date for the proposed rule to effectuate the transition was April 2019, which was later pushed back to October 2020, a target date that again was not met. While the 2021 Unified Agenda of planned rulemaking listed the target date as June 2021, CDRH Director Jeff Shuren has stated that his goal was to get the proposed rule out by the end of 2021. In August of 2021, the agency started to prepare some of its staff for the impending transition – albeit without a formal regulation.
• While CDRH didn’t meet its self-imposed 2021 deadline, it came close. The proposed rule is now at the Office of Management and Budget (OMB) for administrative review. OMB, within the Executive Office of the President, is tasked with reviewing regulations from government agencies to ensure consistency and that the action is appropriate and relevant. As of January 5, 2021, the draft “Harmonizing and Modernizing Regulation of Medical Device Quality Systems” rule is now pending review at OMB.
• What does this mean? Given the scope and economic significance of the regulation, industry can expect OMB review to be extensive – and potentially lengthy. However, the rule’s submission to OMB does mean that the FDA has actually finished writing it, or at least the first version of it – a first in the years-long awaited transition. Once OMB has finished its review (and the posting at OMB shows as “cleared”) the FDA will be free to publish the proposed rule.
• Timelines are likely to be an issue. CDRH officials have previously stressed that industry should expect a long transition period for the transition from the QSR to the ISO standard, but exactly what those timelines will look like will be previewed regulation. As a reminder, the rule that is currently pending OMB review is only a proposed rule – meaning that it will propose an implementation date (or, potentially, multiple implementation dates in a phased transition) based on the publication of a final rule – which can only come after the defined notice-and-comment period. Industry should be prepared to provide feedback on the proposal upon its publication.

The timing of any transition from the QSR to ISO 13485 could pose some pandemic-related challenges.

• A note on another series of transitions: Recently, the FDA issued two draft guidances on separate transitions, and specifically the transition away from emergency authorities for Covid-19 response products. One guidance outlines the process for products authorized under an EUA, while another outlines expectations for products under enforcement discretion. Both of these documents propose a phased re-introduction of regular regulatory requirements – some of which were waived during the pandemic – based on the end of the relevant emergency authorities (which notably vary based on whether the product is marketed under EUA or enforcement discretion).
• Interestingly, QS regulation compliance is highlighted in both of those guidance documents. While the guidance documents highlight flexibilities for market authorizations (e.g., a product may remain on the market while awaiting full market authorization during the transition period), the post-market regulatory compliance requirements will snap back into place upon the effective dates. In effect, sponsors can continue to offer their product without marketing authorization while a submission is under review, but the manufacturer will need to comply with post-market regulations. There is some flexibility here, especially for non-traditional manufacturers who took up device production during the pandemic, for which the agency acknowledges these entities “may face challenges that take more time to address in transitioning to a system that fully complies with 21 CFR 820” – and will assess the need for flexibilities on a case-by-case basis.
• Depending on the timelines, this could lead to two interconnected transitions. While ideally all emergency products would be fully transitioned into full regulatory compliance well in advance of the ISO transition, that will largely depend on the trajectory of the pandemic. However, there may be a scenario in which products authorized (or marketed under enforcement discretion) need to transition from emergency authorities into full QS regulation compliance and then into ISO compliance – a concern of which CDRH is aware, and may be addressed in the proposed rule.

What we're watching and reading

• …this news that the FDA will now allow booster doses of Moderna’s Covid-19 vaccine to be administered to patients just 5 months after the full course of their initial vaccination, rather than the previous 6 months. This standardizes the dosing timing for both Pfizer and Moderna’s booster doses.
• …this news that the FDA has lost a FOIA-related lawsuit regarding documents related to its approval of the Pfizer Covid-19 vaccine, and must produce tens of thousands of pages of related correspondence per month for the foreseeable future. The news could tie up FDA’s FOIA office for months.
• …this announcement that Michael Felberbeum has been tapped as the Assistant Commissioner for Media Affairs. Felberbaum previously held the position on an acting basis.
• …this early data suggesting – suggesting – that saliva-based testing methods may be able to detect cases of Covid-19 in patients infected with the Omicron variant than nasopharyngeal-based approaches. The idea is that Omicron may be more prevalent in the throat than in the nose in the early course of the disease, and that a combination of nasal and throat swabbing could detect infections earlier. The FDA’s next Town Hall meeting on diagnostics tests is next Wednesday on the 12th and we are extremely interested in asking them about this data.
• …this ProPublica investigation into FDA inaction over a problematic heart pump device manufactured by HeartWare. The main finding: FDA failed to warn other health care agencies about problematic findings that resulted in a Warning Letter to HeartWare. CMS, the VA and others continued to pay for the device. We should note, however, that a Warning Letter to a company is not by itself grounds for a product to be withdrawn or not used.
• …this court case that’s coming as a relief to some generic drugmakers hoping to preserve a longstanding ability to “carve out” off-patent parts of a brand-name drug’s FDA-approved label.
• …this weekend’s CERSI summit, which will feature several of the FDA’s top regulatory officials (and incoming FDA Commissioner Robert Califf). I have no clue why this event is being held for 7 hours on a Sunday, but if you’re around with some free time, this is a good one to watch.
• …this new data showing that requests received by CBER for Regenerative Advanced Therapy Medicinal (RMAT) designation declined in FY2021 as compared to FY2020 – from 34 to 24.
• …this statement by Moderna's CEO that a fourth dose of its Covid-19 vaccine may be needed later this year.

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