There were so many interesting and significant developments related to the various missions of the U.S. Food and Drug Administration (FDA) during the last week or so of September 2022 that we decided to create a summary roundup for our readers! 

First, and most vital for the agency’s continuing operations, was the news that members of the House and Senate reached agreement on reauthorizing the four largest FDA user fee programs for their next five-year cycle. The legislation was signed into law by President Biden on September 30, literally the final day of the government’s FY2022 fiscal year. Although these critical programs were reauthorized so that the agency can continue to collect application and facility fees from members of the regulated industry – and FDA moved quickly to publish the FY2023 fee rates during the first week of October and to issue invoices for annual programmatic fees – none of the policy riders or substantive amendments to the Federal Food, Drug, and Cosmetic Act (FD&C Act) were included in the final deal. We previously wrote about those proposed changes to the Act (see here) and expect that at least some, if not all, of them will be revived by legislators in the future; indeed Chair of the House Energy and Commerce Committee Frank Pallone (D-NJ) stated his intent to push for certain policy changes that were voted for by House members earlier in the year, as have other key lawmakers.          

Moving away from legislative activity, the agency released several important guidance documents during the final days of September, as well as a long-awaited proposed rule to modernize the definition of “healthy” for food products. Each of these weighty developments is summarized briefly below.

Updated Guidance and Policy on COVID-19 Diagnostic Test Submissions

FDA released a revised guidance document laying out its plans for future COVID-19 diagnostic and serology tests on September 27, 2022. Following up on the practice from its 2021 revised policies (we wrote about those here) and given the evolution of the pandemic, the agency again further narrowed the universe of tests that would be prioritized for review under the Emergency Use Authorization (EUA) pathway. In particular, FDA stated that it generally intends to focus its efforts on EUA requests “from experienced developers” for these types of products:

• Tests that are likely to have a significant benefit to public health (e.g., those that employ new technologies);

• Tests that are likely to fulfill an unmet need (e.g., diagnosing infection with a new variant or subvariant of the coronavirus);

• Supplemental EUA requests for previously authorized tests when the request is intended to update the test in order to meet one of those first two goals; and

• Tests for which the EUA request is from (or supported by) a U.S. government stakeholder, such as tests funded by the Biomedical Advanced Research and Development Authority (BARDA) or the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx).

The agency is requesting that other newly developed tests be submitted for review using traditional medical device marketing pathways, such as 510(k) notification or de novo classification, rather than the EUA pathway. This directive makes good practical sense for diagnostic developers too, and would likely be their least burdensome path to market at this point in the pandemic arc, in light of FDA’s existing preparations for the end of the federal COVID-19 public health emergency and the need to transition medical countermeasures currently being sold under EUAs to some form of non-EUA authorization if they intend to be kept in commercial distribution (see our prior post about Transition Plans for devices here).

Final Guidance on Clinical Decision Support Software

Clinical decision support (CDS) functionality in software has been somewhat of a challenge for the agency and other stakeholders since well before passage of the Cures Act in 2016, in part due to the increasing complexity and huge variety of products that fall within the scope of “software as a medical device” (SaMD). As we discussed in a previous post (see here), three years ago – almost to the day – FDA published a revised CDS guidance that incorporated the various digital health reforms that were included by Congress in the Cures Act, and it requested feedback in response.

After several years of development, at the end of September a finalized version of the CDS guidance was released by FDA, and the “final” result is quite shocking. Breaking totally from the previous two versions of the guidance, the final guidance focuses solely on the interpretation of the 21st Century Cures Act language that exempts some types of CDS software functionality from regulation as medical devices (see 21 U.S.C. § 360j(o)(1)(E)), although it also provides numerous examples of non-device CDS and device software functions. Perhaps most importantly, the agency eliminated the extensive discussion and application of the SaMD risk categorization and risk analysis method established by the International Medical Device Regulators Forum (IMDRF) as well as any discussion of considerations for CDS software functions intended for patient or caregiver use, both of which had been significant components of the 2019 draft. Ultimately, the final version of the CDS guidance is probably closer to what it should have been originally—a straightforward explanation of device vs. non-device CDS functions with many examples to guide industry decision making. Still, it is odd that FDA chose to make substantial changes to the format and content of the guidance and then to finalize it without seeking additional comments from stakeholders.

FDA is hosting a webinar and answering questions about the final CDS guidance on October 18, 2022 beginning at 1 pm EST; advance registration is not necessary. You can learn more and participate in the webinar here. The agency also created a downloadable graphical version of the guidance, which can be found here.

Draft Guidance on Software Assurance for Medical Device Manufacturers

FDA also recently released a new draft guidance titled Computer Software Assurance for Production and Quality System Software, which is intended to supplement the agency’s General Principles of Software Validation (issued in January 2002) but also to supersede the portion of that prior guidance with respect to validation of process equipment and quality system software.

The new draft guidance discusses risk-based approaches for identifying critical software used in production and quality processes for medical devices, as well as when and what type of testing should be conducted to provide adequate assurance that such systems are operating within established parameters. FDA also provides various examples of applying the risk-based analysis for various production and quality software, regardless of the type of manufacturing facility in which they are deployed.

In general, the draft guidance on software assurance gives device manufacturers a more detailed explanation of the agency’s expectations for verification and validation activities for production and quality software. Previous guidances lacked such production-specific information in favor of general descriptions of software validation, which apply to software device products as well as production and quality system software, making such previous attempts at agency guidance less educational for regulated industry. Inspectional observations relating to process validation are common, according to FDA’s Inspection Dashboard, and many manufacturers have been caught unaware of production and quality system software validation requirements (e.g., validation of production-related calculations inputted into an Excel spreadsheet).

From that perspective, the draft guidance should help manufacturers understand when and how to perform software assurance testing. However, it is important to note that the guidance creates a burden on manufacturers to perform additional risk-based assessments of their production and quality system processes to determine which software functions must undergo assurance testing. Comments on the draft guidance should be submitted no later than November 14, 2022 to the electronic docket.

Draft Guidance on Electronic Submissions Under the OMUFA Program

Although not as closely followed as the CDS guidance or the agency’s prioritization policies for COVID-19 diagnostics, another impactful document was recently released by FDA in relation to the new Over-the-Counter Monograph User Fee Program (OMUFA), which we last discussed about a year ago.

The new OMUFA draft guidance describes the different types of submissions that can be made to the agency under the program, referred to as over-the-counter (OTC) monograph submissions, and how to make such submissions electronically as is now required by law. Because this guidance on Providing Over-the-Counter Monograph Submissions in Electronic Format is the first draft on this brand-new topic, stakeholder comments to FDA are strongly encouraged in order to improve the document and make it more useful for industry members who will be making OTC monograph submissions. Comments should be filed to the docket no later than November 28, 2022 to ensure they are considered during the agency’s work on a final version.

Modernized Criteria for Labeling a Food Product as “Healthy”

FDA’s release of proposed regulations to update the implied nutrient content claim “healthy” caps off a review and information collection process that was initiated in 2016, including with a public meeting convened to hear from various constituencies. It is worth remembering that from a business standpoint these labeling rules are aimed more at processed and convenient foods (rather than at whole foods such as fruits and vegetables that are typically not labeled with obvious statements like “healthy” because distributors assume we consumers know that already), and accordingly the comprehensive nature of the new proposal makes it a significant step forward for evidence-based nutrition labeling – one of the missions of FDA’s modern food program. 

In conjunction with the publication of the proposed rule on September 28, 2022, the agency’s press release included statements from Secretary of Health and Human Services Xavier Becerra, FDA Commissioner Robert Califf, and Susan Mayne, the director of FDA’s Center for Food Safety and Applied Nutrition (CFSAN), highlighting the whole-of-government approach and coordination that the executive branch is taking with respect to the wide-ranging challenge of how to improve Americans’ dietary habits. In particular, the press release emphasizes that “more than 80% of people in the U.S. aren’t eating enough vegetables, fruit and dairy. And most people consume too much added sugars, saturated fat and sodium. The proposed rule is part of the agency’s ongoing commitment to helping consumers improve nutrition and dietary patterns to help reduce the burden of chronic disease and advance health equity.” Dr. Califf notably called out FDA’s work in nutrition science as a way to reduce the burden of chronic diseases during a July hearing in front of a Senate Appropriations subcommittee on food safety.

In comparison to the existing regulation defining the claim “healthy” for foods, which is focused solely on the levels of individual nutrients in the food, the proposed revisions would require a food to contain a meaningful amount of food from at least one of the food groups  (e.g., fruit, vegetable, dairy) recommended by the national Dietary Guidelines and to also adhere to specific limits for various nutrients, such as saturated fat, sodium and added sugars. These nutrient-specific limits are based on a percent of the Daily Value (DV) for the nutrient in question. In addition, for any product to be labeled as “healthy” it would need to meet the sodium limit of 10% of the DV per serving. FDA provides cereal as an example and notes that to be labeled under the new rules, a cereal product would need to contain ¾ ounces of whole grains and no more than 1 gram of saturated fat, 230 milligrams of sodium, and 2.5 grams of added sugars. These criteria would make it impossible for most cereals marketed directly to children to be labeled as healthy without undergoing major nutritional reformulations first.

To that end, the proposed rule lays out plans for a three-year compliance deadline for industry after the rule is finalized and becomes effective, which FDA also states will be 60 days after official publication of the final rule. The agency is also requesting feedback on whether a compliance date that is three years after the effective date would give companies sufficient time to analyze products and revise labeling, especially in light of newly proposed record-keeping requirements for foods where the food group equivalent(s) are not apparent based on the label of the food. For foods that fall into this category, manufacturers would be required in order to create and maintain records verifying that each product bearing the “healthy” claim meets the food group equivalent requirements.

Comments on the “healthy” proposed rule are due by December 22, 2022 and should be submitted to the same docket as earlier feedback to the agency on this topic.