HHS Proposes Decennial Review of Regulations

The U.S. Department of Health and Human Services has posted a notice of proposed rulemaking that would require HHS agencies to assess their regulations periodically to determine whether a regulation is reviewable under the Regulatory Flexibility Act (RFA) of 1980. Under the proposed rule, any regulation issued by an HHS agency would become null at 10 years unless a confirmatory review is conducted, but the rule has a short time for activation, given the impending change of administration at the White House.

The Nov. 4 HHS statement asserts that federal government agencies should retrospectively re-examine the initial projections of the impact of a rule to determine whether the rule should be amended or rescinded. HHS stated that an analysis of HHS data performed by an artificial intelligence (AI) algorithm disclosed that 85 percent of the regulations issued by HHS agencies before 1990 have not been edited. HHS Secretary Alex Azar said the proposed rule would help ensure that the affected agencies are fulfilling their responsibilities “in a way that maximizes benefits, minimizes costs, and keeps up with the times.”

Several types of regulations would not be subject to the proposed rule, such as regulations issued jointly by two or more agencies. Any regulations that are exempt from rulemaking requirements under the Administrative Procedures Act would also be exempt (the RFA was an amendment to the Administrative Procedures Act).

The statement lists similar actions undertaken by every president to hold office since 1978, along with statements in support of routine regulatory review from members of the Obama and George H. W. Bush administrations. The Organization for Economic Cooperation and Development (OECD) is also among the entities that have recommended this type of review function, with OECD recommending that regulations be subject to a sunset to incentivize the review.

One of the issues that surfaced during the AI review of HHS regulations is that the U.S. Code of Federal Regulations (CFR) bears nearly 300 references to portions of the CFR that no longer exist. There are 50 references to requirements to submit paperwork in triplicate or quadruplicate, and 114 sections with no regulatory entity listed. HHS stated that a number of regulations that have been relaxed to aid in the response to the COVID-19 pandemic would also be subject to review.

HHS acknowledged the problem with the proposed rule in the event the 2020 presidential election failed to return President Donald Trump for a second term. The comment period ends Jan. 4, 2021, but HHS said that whether it finalizes the rule and the time frame for doing so “depends on the comments received during the public comment period.” Inauguration day is Jan. 20, 2021, leaving HHS with only 16 calendar days to act on the proposal once the comment period closes.

HHS Using Algorithms in Regulatory ‘Clean-up’ Initiative

The Nov. 4 HHS statement’s references to the use of AI for regulatory review were expounded on in a Nov. 17 HHS statement describing the use of a new department-wide regulatory clean-up initiative, which uses both AI and natural language processing (NLP) technologies. The intent of this program is to identify entries in the CFR that call for correction, such as the incorrect citations mentioned in the Nov. 4 HHS statement. The process used by HHS also examined the CFR for misspellings, typographical errors, and erroneous language, but the HHS statement also tabulated the CFR at approximately 185,000 pages, a testimonial to the complexity of compliance.

This regulatory clean-up program is part of a final rule that is effective Dec. 16, and which takes aim at administrative, non-substantive changes that will clean up HHS agency regulations. This final rule is based on a pilot program that employed the same algorithms to analyze a limited section of the HHS portion of the CFR. The statement describes this pilot program as having demonstrated that federal agencies can execute “a cost-effective, enterprise-wide approach to regulatory reform that could improve accountability and transparency.”

The HHS statement further emphasizes the deregulatory agenda of the Trump administration, and HHS deputy secretary Eric Hargan said HHS accounted for more than half the regulatory savings achieved by the federal government between fiscal years 2017 and 2019. Hargan said HHS is the first cabinet agency to use AI and NLP to conduct a regulatory clean-up that will eliminate “archaic, obsolete and inconsistent rules.”

HHS Announces Delayed HIT Compliance Deadlines

The Department of Health and Human Services has responded to concerns about compliance dates for healthcare IT with an interim final rule that relaxes those deadlines by nearly half a year. According to the Oct. 29 HHS press release, vendors of health IT systems have until April 5, 2021, to comply with information blocking provisions of the 21st Century Cures Act, a delay some saw as critical due to the COVID-19 public health emergency.

The Office of the National Coordinator (ONC) had released the final rule March 9, 2020, which in addition to the information blocking provisions included certification requirements for application programming interfaces (APIs). ONC director Don Rucker emphasized that this latest delay does not eliminate the rules requiring greater patient access to their health information, but is intended to allow developers to focus on the pandemic.

In April 2020, the ONC exercised enforcement discretion by adding three months to several of the compliance deadlines included in the March final rule, making the Oct. 29 delay the second such announcement this year. In addition to the delay until April 2021 for the Cures Act’s information blocking provisions, the ONC will allow developers until Dec. 31, 2022, to demonstrate that their software complies with the updated requirements for API functionality.

The Healthcare Information and Management Systems Society Inc., (HIMSS) of Chicago, said the announcement allows the health care sector to focus on the pandemic while sustaining a path forward toward greater patient access to their own information. HIMSS stated that the scope of the information blocking provisions will expand in October 2022, prior to which developers will have to demonstrate only that they are providing access to a limited number of elements initially included in the U.S. Core Data for Interoperability. This will allow developers to become more accustomed to these requirements prior to the compliance date of Oct. 6, 2022, when the full scope of a patient’s electronic health information becomes mandatorily accessible to patients.

The American Health Information Management Association (AHIMA), also headquartered in Chicago, applauded the delay in an Oct. 29 statement. AHIMA CEO Wylecia Wiggs Harris, said the additional delay “is a prudent decision, as the reallocation of resources due to the COVID-19 pandemic has made it challenging for many health information professionals to ensure their institutions are sufficiently in compliance.” Harris thanked ONC “for being cognizant of the realities health information professionals are encountering during the COVID-19 pandemic.”

CMS Resets Two DME Policies

The Centers for Medicare & Medicaid Services released two policy changes, one each for competitive bidding for durable medical equipment (DME), and the other for how items are categorized under the Medicare Part B DME benefit. Of the two, the more immediate impact on patients may be created by the Oct. 27 CMS proposal to classify all continuous glucose monitors (CGMs) as DME, providing broader coverage of CGMs than has been available up to now. At present, Medicare covers these devices only when approved by the FDA for use in making treatment decisions for those with diabetes, such as changes to insulin dosage or to diet.

The policy change would provide coverage for CGMs for more routine considerations, such as potentially hazardous overnight glucose excursions. CMS also made note of the fact that one in every three Medicare beneficiaries suffers from diabetes. The proposed rule would also expand the DME classification of external infusion pumps to permit more in-home use.

The second CMS announcement regarding DME for the week ending Oct. 30 stated that the competitive bidding program would be delayed again for most items. Two items, off-the-shelf (OTS) knee and back braces, will be subject to bidding in 2021, and CMS indicated that the bidding process may save $600 million over the three years of the bidding program for these two items.

The 2021 round of bidding had originally included non-invasive ventilators, a category the agency removed because of the COVID-19 pandemic. OTS back and knee braces were not included in previous bidding programs, but bidding for the other 13 categories was dropped because previous bidding rounds failed to deliver on the anticipated savings.

The American Association for Homecare lent its support to the changes to the bidding program, stating that the program has established a price floor for the 13 devices that will be exempt from bidding year. The statement also recommended that bidding for these products be permanently ended.

FDA Closes EUA Program to Lab-Developed Tests

The question of whether the FDA has the authority to regulate lab-developed tests (LDTs) boiled into plain view in August when the Department of Health and Human Services directed the agency to stand down on its regulation of LDTs. The predicament took another turn Oct. 7 when the FDA announced it would no longer review LDTs under the emergency use authorization (EUA) program, a change that was not well received in some quarters.

The HHS order to the FDA arrived with a reference to two executive orders from the Trump administration, but the notice also stated that developers of LDTs could voluntarily file for an EUA or a conventional premarket review. One of the more significant drawbacks described in the rescission order was that any LDTs that did not go through the FDA would not enjoy immunity from litigation under the Public Readiness and Emergency Preparedness (PREP) Act. At the time of the HHS announcement, however, there was no signal from the FDA that it would refuse to review LDT filings under the EUA program.

The FAQ page for testing stated, “we are currently in a different phase of the pandemic with respect to tests than we were previously, where many COVID-19 tests are now authorized to be run in labs.” The update states that the agency is prioritizing review of EUA requests for considerations such as public health need and availability of the product.

Among the priorities cited by the FDA are testing that would increase accessibility, such as point-of-care tests and home collection test kits, and tests that consume relatively few supplies. The statement said the FDA was declining to review EUA requests for LDTs “at this time,” suggesting the policy can be reversed if circumstances dictate.

Three members of the House of Representatives took the news as a negative, casting the FDA’s decision as “a grave mistake” that was prompted by officials at HHS. The letter described the change as reckless and as increasing the risk of false negative test results. Another concern voiced by Reps. Anna Eshoo (D-Calif.), Frank Pallone (D-N.J.) and Diana DeGette (D-Colo.) was the abruptness of the announcement, which did not allow the FDA to make changes to previously posted policy announcements.

The American Clinical Laboratory Association (ACLA) provided a brief Oct. 7 statement, making the argument that many of the LDTs that have been granted EUAs are known for reducing the reliance on supplies and for increasing testing capacity. ACLA President Julie Khani said these “are exactly the kinds of tests the FDA has stated it wants to prioritize,” adding that the FDA should continue to review LDTs under the EUA program. Khani also said the announcement “creates unnecessary confusion.”

CMS Cracking Down on CLIA Certification

Two days after the FDA announced its change in policy for LDTs, the Centers for Medicare & Medicaid Services announced it is targeting clinical laboratories that have lapsed certifications or are conducting tests not included in their certifications. The agency directed these labs to immediately cease any violative testing, although no enforcement action was spelled out in the statement.

The CMS said it has issued 171 cease and desist letters to labs since Aug. 12, 66% of which were for labs that were conducting tests that fell outside their certifications under the Clinical Laboratory Improvement Amendments (CLIA) Act. The other 34% were conducting tests with no CLIA certification at all, and recipients of the CMS letters were required to certify that they had desisted from the violative testing activity. The agency indicated that it had offered labs an expedited review process early in the COVID-19 pandemic, but said there is concern that these labs’ operations could lead to errant tests that would worsen the pandemic. However, the letters were sent with instructions on how to amend the oversights, assuming the recipient lab is interested in resuming the violative testing protocols.

FDA Revisits Intended Use Rule

The FDA’s policy for determining a manufacturer’s intended use has strained relations between the agency and industry in the past, but the agency said in a press release that the latest version clarifies that simple knowledge of off-label use does not suffice to infer intended use. The press release highlights this as a significant change despite that essentially the same language appears in the version of the rule published five years ago.

A previous version of the intended use rule was released in September 2015, and led with a discussion of the agency’s regulation of tobacco, only belatedly discussing pharmaceutical products and medical devices. The 2015 edition states that the FDA can consider any objective evidence to determine intended use, including direct and circumstantial evidence.

The text of the 2015 rule states that circumstantial evidence is often sufficient to determine a manufacturer’s intent even in the absence of express claims about off-label use. However, this portion of the 2015 rule states also that the agency would not infer intention “based solely on the firm’s knowledge” of off-label use.

Interestingly, the agency’s press release for the Sept. 22, 2020, rule states that a firm’s knowledge of an unapproved use of a medical device or pharmaceutical, “standing alone, is not sufficient to establish the product’s intended use.” The FDA said this update should provide a greater degree of certainty and predictability for regulated industry.

The statement contends that the new rule does not reflect a change in the agency’s policies, but is intended to reemphasize the FDA’s long-standing approach to the question. The preamble to this latest version provides some examples of evidence that would not be deemed adequate to infer the manufacturer’s intent. The new rule would replace the version issued in 2017, which carried its own controversies.

The Jan. 9, 2017, final rule states that the agency would rely on the totality of the evidence to determine a manufacturer’s intent, a provision that was not well received. One commenter stated that the totality of the evidence standard had not previously been discussed in connection with the intended use rule, and that this standard was not a logical outgrowth of any prior communications on the FDA’s part. Because this standard was not discussed in a draft version, its introduction in the final rule violated the Administrative Procedures Act, said Richard Samp and Mark Chenoweth of the Washington Legal Foundation. The FDA is taking comment on the draft rule through Oct. 23.

DOJ Revisits APA a Second Time

The U.S. Department of Justice expressed its views of the current understanding and use of the Administrative Procedures Act in early August, but the matter wasn’t closed as of the date of that Aug. 11 statement. This was followed quickly by an Aug. 26 statement that provided details on two executive orders that are intended to provide guidance on adherence to the terms of the APA, a question that has arisen in the context of FDA guidance and rulemaking on several occasions.

Attached to the Aug. 11 statement was a report on a summit regarding the APA, which provided some insights into the concerns held by a number of parties about the evolution of the act. One source of concern was that compliance with federal regulation adds $2 trillion in costs to the economy each year, perhaps not surprising given the staggering volume of guidance and rulemaking across the federal government.

There is also some legislative interest in bringing independent federal agencies under the umbrella of the APA, such as the Securities and Exchange Commission. However, the larger point of interest for the DOJ consists in part of thwarting the use of guidance to create novel liabilities for the private sector without going through the normal notice-and-comment process required of rulemaking. The underlying theme in this regard is the 2017 Sessions memo, and Executive Order 13891 is intended to codify that principle.

Another consideration expands on the 2018 Brand memo, which pushed back on the use of agency guidance in affirmative civil enforcement. The second Executive Order announced Aug. 26 likewise codifies the Brand memo, but also provides a set of procedures for DOJ staff regarding the review and clearance of department guidance. Going forward, DOJ will be required to post all guidance documents on a web portal set up specifically for that purpose, but also creates a process by which the public can petition for withdrawal of a guidance.

Deputy Attorney General Jeffrey Rosen said guidance broadly is helpful to regulated parties, but observed that “backdoor regulation by guidance document is improper.” Rosen stated further that the Executive Orders will ensure “that guidance documents will not be used to impose novel legal requirements as a shortcut around the rulemaking process.”

CMS Floats Coverage Policy for Breakthrough Devices

The Centers for Medicare & Medicaid Services recently unveiled a new plan to offer four years of Medicare coverage for any medical devices cleared or approved through the FDA’s breakthrough devices program. The news won raves from medical device associations, but the offer comes with a postmarket study requirement that may exceed the demands usually imposed by the FDA for breakthrough devices.

The CMS announcement describes the terms of the Medicare Coverage of Innovative Technology (MCIT) pathway as providing coverage on the same date as the FDA marketing authorization. This coverage would last four years, an offer that assumes, but does not mandate, that the sponsor of the device continues to collect data in the postmarket realm.

Following the four years of MCIT coverage, that device would have to be covered by one of the conventional Medicare coverage mechanisms. In addition to national and local coverage determinations, the CMS press release cites claim-by-claim decisions as one of the post-MCIT alternatives. However, the agency advised that a coverage with evidence development outcome may follow the fourth year of MCIT coverage, adding that participants may be incentivized to gather postmarket data.

CMS said the MCIT program is available only to breakthrough devices that fit within an existing Medicare benefit category, while coverage is limited to on-label use. Device makers are encouraged to communicate with the CMS during the four-year coverage period, but the agency also suggested that sponsors of MCIT devices communicate their interest in an NCD or LCD before the four years are up.

‘Reasonable and Necessary’ Defined

CMS also offered a definition for the term “reasonable and necessary,” which would eventually be codified in the regulation. This definition would address all coverage decisions, rather than being limited to the scope of the MCIT program.

As described in the regulatory notification, the first prong of the three-part test for whether a device or service meets the definition of reasonable and necessary is whether the device is safe and effective. The second prong stipulates that the device must not be strictly experimental or under investigation for the use in question, but the third prong is more complex and asks whether the device or service is appropriate for Medicare patients.

The process for determining appropriateness can be fairly complicated, starting with determining whether the device’s use is consistent with accepted standards of medical practice. The device or service must also be “at least as beneficial as an existing and medically appropriate alternative,” and must not exceed the patient’s need.

However, CMS is offering an alternative mechanism by which appropriateness can be determined. This approach hinges on whether private payers are covering the item or service, although the sponsor would have to demonstrate that the commercially insured individuals are more or less clinically homogenous with Medicare beneficiaries. Sponsors could entirely eliminate the other standards for appropriateness if they can meet this requirement for commercial payer coverage.

The proposal was met with enthusiasm by the trade associations, including the Advanced Medical Technology Association (AdvaMed). Scott Whitaker, AdvaMed’s president/CEO, said in an Aug. 31 press release that the proposed rule would “help ensure the patients who need these innovative technologies have access to them.” Executives from several major device makers also lent their support in the AdvaMed statement, including Mike Mussallem, CEO of Edwards Lifesciences, and John Liddicoat, executive VP for the Americas for Medtronic.

Mark Leahey, president/CEO of the Medical Device Manufacturers Association (MDMA), also supported the proposed rule, something Leahey said MDMA “has long advocated.” He said the association would continue to work with the White House, Congress and other stakeholders to “narrow the gap between regulatory and reimbursement decisions that will bolster patient care.”

HHS Orders FDA to Stand Down on LDTs

The Department of Health and Human Services issued an Aug. 19 rescission order to the FDA directing the agency to cease requiring any premarket reviews for lab-developed tests (LDTs), a change the administration said is consistent with two executive orders (EOs). The order mentions the COVID-19 pandemic, but seems intended to endure beyond the existing declaration of public health emergency.

The question of the FDA’s statutory authority to regulate LDTs has dated back at least as far as the early 1990s. In 2006, the Washington Legal Foundation (WLF) resurrected the question in a citizen’s petition that makes reference to a similar petition filed in 1992. According to the 2006 petition, the FDA waited six years to respond to the earlier petition, and WLF cited “an urgent need for FDA to comply with the Administrative Procedures Act (APA). The APA is also a timely theme, given the Department of Justice’s recent public pronouncement about whether the underlying statute is in need of a legislative update.

The HHS announcement states that the FDA is not authorized to require premarket review of any sort for LDTs absent the use of the rulemaking process. This would supplant the FDA’s use of guidances, immediately-in-effect policy declarations, and any other informal mechanisms. The notice advises, however, that LDTs practiced for testing for the COVID-19 pandemic will not enjoy immunity from product liability under the Public Readiness and Emergency Preparedness (PREP) Act without an emergency use authorization or submission of a regulatory filing under a conventional premarket review path.

At present, there are two competing legislative responses to the impasse making the rounds on Capitol Hill, such as H.R. 6102, the Verifying Leading-edge IVCT Development (VALID) Act of 2020, which has a companion bill in the Senate. While previous iterations of the VALID Act included language directed toward a pre-certification program that seemed to parallel the precert program for software as a medical device, this latest version describes a technology certification process that would ease the demands ordinarily imposed by FDA premarket review. Neither the House nor the Senate version has come up for a vote in committee, however.

Conversely, the Verified Innovation Testing in American Laboratories (VITAL) Act of 2020, sponsored by Sen. Rand Paul (R-Ky.), would place sole authority for LDT regulation under the Centers for Medicare & Medicaid Services. S. 3512 keys on laboratory staffing qualifications to ensure that tests are appropriately developed and conducted, but also has provisions related to the pandemic, such as a requirement that CMS update the related CLIA regulations to address future pandemics. This bill, too, has failed to gain enough traction to merit a vote in the committee of jurisdiction.

PTO Revisiting IPR Rules of Practice

The U.S. Patent and Trademark Office is considering an amendment to the rules of practice for several patent procedures as indicated by an entry at the electronic dashboard for the Office of Information and Regulatory Affairs at OMB. The entry is titled to reflect an examination of the rules of practice in trials before the Patent Trial and Appeal Board, the entity charged with handling inter partes reviews (IPRs). There is little additional information as to the nature of the proposed changes, however.

The IPR process has come under fairly constant fire in the years since passage of the America Invents Act, including in a 2017 article describing the process as “a patent killing field.” The authors of the article claimed that despite the numbers posted by the PTO, the IPR process proved substantially more hostile toward claims than litigation conducted in Article III courts.

The docket for this proposal lists four meetings, the first of which took place Aug. 4 with members of the Computer & Communications Industry Association. Included in the documents for that Aug. 4 meeting is a file by PTO suggesting that IPR institution rates have dropped from 87% in fiscal year 2013 to 56% to date in fiscal 2020. However, the sheer volume of petitions for IPRs rose from 220 in that first year to more than 1,500 three fiscal years later. The current total for FY 2020 is 854 petitions, 478 of which have been instituted.

DOJ Presses for Reforms of APA

The U.S. Administrative Procedure Act (APA) came into being in 1946, but by some accounts hasn’t been subjected to a serious overhaul in the intervening 74 years. However, the Department of Justice has made the argument that the time has come to revisit the language in the APA, and has bipartisan Senate legislation to back the argument.

The Aug. 11, 2020, DOJ statement includes a link to a report that summarizes the findings of a December 2019 summit on the measures that might bring the APA more into line with modern circumstances. The report, titled “Modernizing the Administrative Procedure Act,” is largely a transcription of the discussions at the summit, but the report also cites previous efforts to amend the APA due to concerns that the statute has not worn well with the passage of time.

Among these was a push for reform by the Second Hoover Commission in 1955, but another pressing consideration is the sheer cost of regulation. Deputy Attorney General Jeffrey Rosen estimated that the aggregate annual cost of federal regulation is as much as $2 trillion a year, a sum one speaker said would represent the ninth largest economy in the world if that figure represented a nation’s gross domestic product.

Multiple Legislative Proposals, No Votes

The APA has not gone untouched in the 74 years since its passage, but many of the changes, such as the 1967 Freedom of Information Act, have been additive in nature rather than attempts to substantially overhaul the APA. Several bipartisan bills have emerged in Congress recently to address the drift of the APA toward functional senescence, including the Regulatory Accountability Act of 2017 (S. 951). Among its other provisions, S. 951 would have required federal agencies to conduct public hearings preparatory to development of rules with an anticipated economic impact of $100 million or more.

Another feature of the bill is a requirement that federal agencies must disclose all data and other sources of information used in rulemaking per the Portland Cement doctrine. The administrative requirement of a cost benefit analysis for rules would also become part of the statute via S. 951. That bill never came up for a vote, however.

There is also some interest in the Independent Agency Regulatory Analysis Act (S. 869), which would subject independent federal agencies to the same requirements as other agencies. This includes the economic impact analysis requirement for rules that are estimated to impose an economic cost of $100 million, but this bill was never put to a vote in the Senate Homeland Security and Government Affairs Committee.

Despite the absence of legislation, the Trump administration has taken measures, including Executive Order 13,771, which is said to have led to a reduction in the volume of new federal rules from the average of 279 rules between 2000 and 2016 to 61 in 2017 and 2018. According to the related entry at the Office of Information and Regulatory Affairs, this executive order has eliminated more than $13 billion in costs across government in 2019 and an overall total of nearly $51 billion since 2017.

As might be expected, the Brand memo receives some attention in connection with administrative activities, given that it bans the use of federal agency guidance as an indicator of violations in civil and criminal matters pursued by the DOJ. Rosen said in his presentation that federal agencies are sometimes inclined to issue guidances in lieu of rulemaking in an attempt to avoid the relatively cumbersome rulemaking process, but as a result, private sector entities may find themselves unavoidably in conflict with one or more guidances that may be difficult to locate.

While the summit took place prior to the onset of the COVID-19 pandemic and thus might be counted as a casualty of the pandemic, DOJ’s revival of the question signals an interest in renewing the push for reform of the APA. The impending election suggests, however, that any related legislation will not emerge until December at the earliest, with calendar year 2021 perhaps a more likely target date.

FDA Releases Final Guidance for Multiple Function Devices

After a wait of two years, the FDA has concluded the draft guidance for multiple function devices with a final version that makes several substantive changes. Among these is that the list of participating centers now includes the Center for Drug Evaluation and Research (CDER), which was excluded from the draft.

One of the clear indications that the FDA took to heart some of the recommended changes is that the draft covered 18 pages while the final version spans 27 pages. The draft explicitly stated that the scope includes device constituents of combination products, a factor that prompted at least one trade group to recommend that the final version include CDER.

Conversely, the draft and final guidances both state that the FDA will offer no insight as to which functions do and do not meet the definition of a device. Both versions apply the same approach regarding the device types for which the agency currently exercises enforcement discretion regarding compliance activities.

One of the more substantial changes to the policy appears in Section V., specifically the paragraphs for separation of the device and non-device functions in design and implementation. The draft guidance makes several overarching recommendations without providing much in the way of detail. However, the final guidance offers much more insight into the agency’s thinking, such as the suggestion that documentation of a risk analysis of the impact of the non-device function may aid the agency’s understanding of the device function under review.

The final guidance briefly discusses design architecture in the context of maximizing functional separation and segregation as a means of managing risk, content that is not seen in the draft. Also missing from the draft is a recommendation that the sponsor take cybersecurity issues under consideration when considering functional separation.

One of the major changes seen in the final guidance is the addition of a flowchart depicting assessments of the impact of non-device functions on the device function under review. One element of the flowchart states that any beneficial effect the non-device function might have on device performance should be included in the premarket filing, assuming the sponsor intends to include such information in product labeling.

In the absence of a determination that there will be any impact, positive or negative, the device maker should document the rationale for such a determination per the company’s standard operating procedures.

FDA Posts New Template for COVID-19 Testing

The FDA’s Center for Devices and Radiological Health has pressed forward with more policy changes to deal with the COVID-19 pandemic in the final days of July 2020, including publication of a template for non-clinical diagnostic testing in the home and other settings. FDA commissioner Stephen Hahn praised the publication of the template as a game changer, although limited supplies might continue to crimp the volume of testing.

The FDA’s July 29 statement explains that the new template will assist test developers in drafting their emergency use authorization applications for tests that can be performed outside a clinical lab setting, such as the home, the workplace, and in educational settings. This test would be available without a prescription, and Hahn said the objective is to ensure there are tests available that would be no more complicated to use than a pregnancy test.

“These types of tests will be a game changer in our fight against COVID-19, and will be crucial as the nation looks toward reopening,” Hahn said.

The Advanced Medical Technology Association said in a July 28 statement that the daily volume of molecular diagnostic tests for COVID-19 reached one million for the week ending July 24. That number is based on a report from a registry operated by AdvaMed and several diagnostics companies, which also states that 80 million total molecular tests have been shipped in the U.S. as of July 18.

Despite the increase in molecular testing, a number of stakeholders are pressing Congress for dedicated funding and clear coverage guidelines for testing. The letter was signed by several each of medical societies, trade associations and non-profit patient organizations, but the House and Senate are at a standstill over their respective economic relief bills, which include the much-needed taxpayer funding for testing.

FDA to Resume Domestic Device Inspections

The FDA was forced to announce in March 2020 that it would suspend inspections of drug and medical device manufacturing sites because of the COVID-19 pandemic, but the agency has partially reversed that decision in a July 10 statement. FDA commissioner Stephen Hahn said the pause that had been applied to inspections did not prevent the agency from conducting mission-critical inspections, although routine surveillance inspections had been shuttered for four months.

The FDA has been tracking state and local conditions with the aid of a rating system designed to establish which locations are reasonably safe for a site inspection. This COVID-19 advisory rating system makes use of real-time data to provide a qualitative assessment of the number of cases in an area. These data are shared with the agency’s partners on the state level who handle some inspectional activities, presumably including inspections of mammography facilities.

The rating system is broken down into three levels of risk on a county-by-county basis, starting with the category of counties where inspections will only take place when those inspections are deemed mission-critical. The second tier of inspections takes into account whether the agency can send field investigators who have not identified themselves as vulnerable to poor outcomes for infection with the SARS-CoV-2 virus. The last tier is for counties that are open to a resumption of normal activities. The agency’s objective is to resume surveillance inspections the week of July 20, although the FDA said that conditions on the ground would continue to drive the level of inspectional activity.

FDA Posts Two Draft Updates

Regulatory science has not completely stagnated in the COVID-19 pandemic, a fact of life demonstrated by two draft guidances the FDA published for updates to existing guidances. One of these is a July 13 update for 510(k) submissions for devices that provide atherectomy for the peripheral vasculature, comments for which are due Sept. 11.

The scope of the draft is limited to intraluminal artery strippers that fall under the MCW product code, which includes four technologies, including rotational atherectomy devices. Sponsors can use ISO 10993 to test for biocompatibility, and ISO 14971 for risk evaluation and management. Devices that are packaged with a pre-installed internal battery will have to fulfill several performance testing recommendations, including shelf life, and the sponsor will have to determine the impact of sterilization on the battery when the battery will be left in the device during sterilization procedures.

The FDA states that it has no intention of imposing changes to the existing guidance that are not specified in this latest draft. Interestingly, the existing final guidance was issued in February 2020, less than two years after the previous draft had been published.

The second updates draft published in the month of July is the July 14 draft for clinical and non-clinical investigations into devices for treatment of benign prostatic hyperplasia (BPH), which will also limit updates to the existing to the contents of the draft. This draft will update the recommendations for devices that are covered by four product codes (KNS, PEW, PZP and NOY), and includes updates to recommended approaches to animal studies.

Among the draft recommendations is that animal studies should include both gross and histological examinations of the treated area by a pathologist who is blinded to the treatment. The draft states that animal studies of thermotherapy devices should include evaluations of how well the device limits the volume of affected tissue by checking parameters such as blood flow and tissue heterogeneity. There are also recommendations for animal studies of stents used for BPH.

Also included in the updates draft for BPH devices are recommendations for pilot and pivotal studies, including a recommendation that the sponsor make use of a randomized, controlled study design for the pivotal study. While the standard of care for the population under investigation might be the most appropriate control treatment, the FDA said the risk-benefit ratio of the investigational device should be comparable to that of the control treatment. The comment period for this draft closes Sept. 14.

FDA Sets 50% Efficacy Benchmark in Vaccine Guidance

The FDA has released a guidance for development of vaccines in response to the COVID-19 pandemic, which among other things suggests the agency will push harder to ensure that any such studies enroll pregnant women and minorities. The guidance also calls for an effectiveness rate of 50%, a benchmark which exceeds those of most recent influenza vaccines used in the U.S.

The June 30 FDA press release states that the agency may use the accelerated approval pathway for licensing a vaccine for the SARS-CoV-2 virus, but that any application would have to identify an immune response or other measure “that is reasonably likely to predict clinical benefit.” The agency left open the possibility that a vaccine could be distributed under the emergency use authorization program (EUA), but the guidance seems to suggest that the FDA is reluctant to grant an EUA authorization for the first vaccine specific to this virus.

The guidance states that issuance of an EUA prior to completion of a large randomized trial could inhibit demonstrations of effectiveness, and that such a study may be needed to clarify the effect of the vaccine on vaccine-associated enhanced respiratory disease. Conversely, the FDA said an EUA may be appropriate once the study has returned sufficient data to demonstrate safety and effectiveness, even if the manufacturer has not yet submitted all the data from that study.

Patients who are at higher than average risk of severe adverse events may be excluded from early-phase studies, but those patients may have to be included in late-phase studies. Trials of all stages will have to include pregnant women and women who are not actively avoiding pregnancy, along with several other sub-groups, including racial and ethnic minorities and elderly patients. Randomized, controlled trials will have to enroll evenly between placebo and the candidate vaccine, and the FDA said an approved vaccine can be used as a control for subsequent vaccine studies.

In the discussion of statistical considerations, the guidance calls for a 50% efficacy endpoint both at the completion of the study and at any interim analysis, a superior metric to 11 out of 15 of the vaccines listed at the CDC website. The most recent influenza vaccine to exceed that mark is the 2013-14 vaccine for the H1N1 virus, which provided an effectiveness rate of 52%.

The FDA said the terms of the guidance will continue to apply after the public health emergency has been withdrawn, and that any revisions will be made within 60 days of the termination of the emergency. The guidance makes some concessions on manufacturing considerations, including the use of a virtual site inspection, depending on that manufacturing site’s compliance history.

High-throughput Testing Emphasized

The FDA’s EUA program for testing and diagnostics is still a key component in the U.S. federal government’s efforts to rein in the COVID-19 pandemic, and the agency is now focused on bringing high-throughput testing into the picture. Timothy Stenzel, director of the FDA’s Office of In Vitro Diagnostics and Radiology said on a June 24 town hall that the FDA is also working on an EUA template for molecular testing for the pandemic, which would also help to enable the volume of testing needed to reopen the economy.

According to the FDA’s transcript of the town hall, the agency has received a number of questions about the distinction between testing for diagnosis, screening and surveillance. Stenzel asked that test developers comb through existing guidance and templates for answers to their questions prior to contacting the agency, and said the emphasis is on point-of-care and high-throughput testing systems. The agency’s review of such systems is contingent on receipt of an EUA filing that contains sufficient data for review, including separate reporting for the various antibody isotypes stimulated by the virus.

The FDA made good on Stenzel’s promise, adding two templates for molecular testing at the template webpage. The July 2 update provides one template each for commercial manufacturers and labs, and there are provisions in the documents for asymptomatic testing for screening purposes and for testing of specimen pools.