FDA Regulatory

By now, businesses operating in the over-the-counter (OTC) drug product space should all be familiar with the changes made by Congress to the regulatory system with the final OTC Monograph reform bill, which was included as part of the Coronavirus Aid, Relief, and Economic Security Act that was signed on March 27, 2020 (see our prior posts here and here).

As we’ve reported previously, at the end of 2020, the Office of Non-Prescription Drugs (ONP) of the Food and Drug Administration (FDA), launched a webpage for its brand new user Over-The-Counter Monograph User Fee Program (OMUFA) – available here – published programmatic fee rates for Fiscal 2021 (which ended on September 30, 2021), and subsequently posted a public arrears list of facilities that did not make their FY2021 facility payments as was required to be done by May 10, 2021. Drugs produced by those in-arrears facilities are considered misbranded under the law.

In our last post, we took a brief look back through history at FDA’s approach to regulating medical device software and found that there is little distinction from the agency’s approach to hardware devices. Recently, however, FDA has announced several digital health initiatives aimed at improving the agency’s resources and policies governing software and data systems (including its own internal data systems) and changing the way the agency handles pre-market reviews of and compliance activities for software as a medical device (SaMD) and SaMD manufacturers. In this post, we will review FDA’s digital health improvement highlights from the past few years and take a quick look at the agenda for the transparency of AI/ML-enabled medical devices workshop scheduled for October 14, 2021.

In anticipation of FDA’s virtual public workshop on transparency of artificial intelligence/machine learning (AI/ML)-enabled medical devices scheduled for October 14, 2021, we will be posting a series detailing the history behind FDA’s regulation of software and then reporting our impressions of FDA’s presentations and statements from various attending stakeholders following meeting. In this part, we briefly summarize FDA’s traditional approach to regulating software and how software development quickly revealed the limitations of the original regulatory framework established in the 1976 Medical Device Amendments to the Federal Food, Drug, and Cosmetic Act (FD&C Act).

Agencies of the federal government with a consumer protection mission have always tended to work closely together and to share information, but the COVID-19 pandemic has made those cooperative efforts even more visible to the general public. We blogged in 2020 about the increasing use of warning letters jointly issued by the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC) Division of Advertising Practices in the apparently never-ending fight against fraudulent COVID-19 products (see prior post here). While coordinated FDA and FTC enforcement activities specific to the ongoing public health emergency continue at a brisk pace – as of September 9, 2021, FDA has issued more than 200 warning letters to companies claiming that a product is an effective cure, treatment, or preventative for COVID and the FTC has issued more than 400 pertaining to unsubstantiated health claims for COVID-related products, with many of those being signed by both agencies – these powerhouse regulators also appear to have become more comfortable with announcing joint actions in non-COVID contexts. This trend makes it even more important for manufacturers and marketers of consumer-facing products to be fully aware and compliant with all of their legal and regulatory obligations.

It’s finally here – the Drug Pricing Plan that President Biden ordered the Department of Health and Human Services (HHS) to produce by the end of August (the “Plan”) was released publicly by the Administration on September 9, 2021. The Plan makes it clear that the Biden Administration supports aggressive action to address rising drug prices, including controversial actions such as allowing HHS to negotiate the cost of Medicare Part B and D drugs. The Plan also outlines a set of administrative actions that HHS and its operating agencies can take, without the need for intervention by Congress. A notable gap in the Plan, however, is the Administration’s potential approach to manufacturer rebates and the Rebate Rule.

Has the Food and Drug Administration (FDA) finally ushered in a new era for the U.S. biosimilar marketplace? Many in the industry are hopeful after the Agency approved its first interchangeable biosimilar, Mylan’s Semglee (insulin glargine) on July 28, 2021. Mylan’s Semglee is a long-acting human insulin analog indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. It is both biosimilar to and interchangeable with Lantus (insulin glargine) meaning it can be substituted for Lantus at the pharmacy-level without the need for a prescription from a healthcare professional. This approval is important because it furthers FDA’s commitment to supporting a competitive marketplace for insulin products. The availability of interchangeable biosimilar products can provide more treatment options to patients, lowering the treatment costs and enabling greater access for more patients. One can hope that this approval marks the beginning of a trend in the biosimilar marketplace.

On June 24, 2021, the Food and Drug Administration (FDA) issued the long-awaited Remanufacturing of Medical Devices Draft Guidance, which describes the agency’s current thinking on activities that meet the definition of remanufacturing and a process for determining whether an act done to an original equipment manufacturer’s (OEM’s) legally marketed finished device is considered remanufacturing (the “Draft Remanufacturing Guidance”).

In our most recent year-end blog post on devices and diagnostic products at the Food and Drug Administration (FDA), we summarized the tumultuous events of 2020 with respect to laboratory developed tests (LDTs) and clinical laboratory testing in general during the COVID-19 public health emergency. We highlighted at the time an August 2020 Trump Administration order barring FDA from requiring premarket review for any LDT unless the agency goes through formal rulemaking procedures. We also speculated that although “the regulatory framework and policies surrounding LDTs will be a prominent topic of debate in 2021…there will be no quick resolution of these issues, either at a legislative or agency policy level, in the short term and that LDTs will likely remain in a gray area of FDA regulation and policy for the foreseeable future.”

One of the spillover effects of the COVID-19 pandemic has been the increase in opioid-related deaths. These deaths overwhelmingly affect working-class Americans with limited access and resources to lifesaving drugs such as buprenorphine and naloxone. As a result, the Department of Health and Human Services (HHS) issued the Practice Guidelines for the Administration of Buprenorphine for Treating Opioid Use Disorder (Practice Guidelines) through a waiver of certain certification requirements prescribed by law. The Practice Guidelines remove a longtime prerequisite tied to training and counseling that several practitioners have cited as a barrier to treating patients with Opioid Use Disorder (OUD). The Practice Guidelines could not come soon enough, as a recent study indicates that individuals with OUD experienced decreased access to treatments during the pandemic.

Although we’ve now entered June of 2021 and President Biden has yet to nominate someone to serve as the Commissioner of Food and Drugs, current Acting Commissioner Janet Woodcock and her Senate-confirmed boss, Department of Health and Human Services (HHS) Secretary Xavier Becerra, have wasted no time reviewing and revoking regulatory actions implemented in the waning days of the prior Administration’s tenure in charge of the Executive Branch. As we reported in April, the two leaders co-signed a decision to reverse January 2021 actions by the Trump Administration to exempt a large number of medical device types from Food and Drug Administration (FDA) premarket review, noting in their rationale that not only was FDA not consulted in the prior action but HHS’s original determinations “lacked adequate scientific support, contained multiple errors, and were ultimately flawed.”

On May 27, a similar reversal notice with strikingly similar language about the lack of FDA input or the inclusion of appropriate regulatory expertise in the decision-making process – and once again co-signed by Secretary Becerra and Dr. Woodcock – was published in the Federal Register. The target this time was the prior Administration’s announcement in November 2020 that it was withdrawing all FDA guidance documents prepared and issued as part of the agency’s Unapproved Drugs Initiative (UDI) and terminating the UDI program; that termination notice cited drug costs and competition-related concerns as well as the FDA’s failure to develop and announce the UDI through notice-and-comment rulemaking. We discussed this surprise action by the prior HHS leadership in our 2020 year-in-review blog post and speculated whether a more consumer-protective Department led by Secretary Becerra would be likely to reverse course (see here).

The Food and Drug Administration (FDA) and the National Institutes of Health (NIH) have the authority to regulate clinical trial reporting requirements. Despite this authority, FDA and NIH have scantly enforced this area since the requirements were created by Congress in 2007, hindering the clinical trial transparency promised to the public. However, there may be a shift in the lackadaisical enforcement over such reporting. On April 28, 2021, Acting FDA Commissioner Janet Woodcock, M.D., announced that that the agency had sent more than 40 pre-notices to sponsors of clinical trials for failing to submit required clinical trial results to ClinicalTrials.gov. Notably, a Notice of Noncompliance was issued for the first time.

The U.S. Food and Drug Administration (FDA), industry, policymakers, and consumers share a common goal of ensuring that the foods and beverages Americans eat and drink are safe, and the law has long prohibited the adulteration of a food that “contains any poisonous or deleterious substance which may render it injurious to health.” As science and technology advance, so too does our collective understanding of what that famous statutory phrase from the Food, Drug, and Cosmetic Act should mean. Accordingly, FDA’s mission in overseeing the safety of the food supply is constantly subject to change. One excellent example of that is playing out in real time, because due to enhanced methods of detecting toxic elements in food, consumer interest groups and Congress have raised questions about FDA’s apparent lack of interest in looking for potential contaminants in our foods (even as available data show that the levels of some metals, like lead, have been in a general decline in the food supply as manufacturing also becomes more sophisticated and controlled and industry invests in better detection methods in the advancement of the shared goal of food safety).

On April 16, 2021, Food and Drug Administration (FDA) published twin notices in the Federal Register effectively reversing a move by the Trump administration Department of Health and Human Services (HHS) on January 15, 2021 purporting to exempt 91 medical device types from the premarket notification requirement under Section 510(k) of the Federal Food, Drug, and Cosmetic Act. HHS’s actions on January 15, signed by then-HHS Secretary Alex Azar, sought to make permanent FDA’s grant of temporary enforcement discretion for the 91 device types for the duration of the COVID-19 public health emergency.

In an unexpected twist to a troubling situation that began over two years ago, U.S. Special Counsel Henry Kerner penned a letter to President Biden on March 31, 2021 questioning the Food and Drug Administration’s (FDA’s) handling of a whistleblower case that alleged improprieties surrounding compliance inspections of vaccine manufacturing facilities. Special Counsel Kerner’s letter to the President coincided with his closing of the investigation and his conclusion that the agency’s actions met “all the statutory requirements” but that they nonetheless “do not appear reasonable.” What the new leadership at the FDA’s parent Department of Health and Human Services or within Congress may do with these findings remains to be seen and certainly bears watching in the coming weeks and months. The March 31 letter was also provided to the Democratic Chairs and the ranking Republicans on the Senate Health Committee and the House Energy & Commerce Committee, which oversee FDA operations, increasing the likelihood of additional investigation and potentially public hearings, especially with congressional reauthorization of the various user fee programs looming as a must-pass action for 2022.

The Food and Drug Administration’s (FDA’s) enforcement against cannabidiol (CBD)-containing products continues through the issuance of two new warning letters. On March 22, 2021, FDA published a press release cautioning companies against illegally selling over-the-counter (OTC) CBD products for pain relief. In the warning letters, FDA cited products listing CBD as an inactive ingredient for unapproved drug and misbranding violations.

On March 3, 2021, FDA issued a statement acknowledging that certain entities produce certificates of registration for medical device manufacturers and clarifying that the agency does not issue such certificates. The agency also announced that it sent letters to 25 entities demanding that they stop producing these false and misleading certificates because some device manufacturers and distributors are using them to claim that the devices they produce or sell are cleared, approved, or otherwise authorized by FDA.

In this fireside discussion, Mintz attorney Joanne Hawana and Aaron Josephson and Anthony DeMaio from ML Strategies explored policy activities that will likely have the greatest impact on stakeholders in 2021, and how the new Administration may impact the FDA in the year ahead and beyond.

The Food and Drug Administration (FDA) and the National Telecommunications Information Administration (NTIA) in partnership with three domain name registries disabled nearly 30 websites illegally offering opioids for sale. Working together as part of a pilot program jointly created by the Department of Health and Human Services (HHS) and the Department of Commerce (Commerce), FDA and NTIA aim to reduce the availability of unapproved and misbranded opioids illicitly offered for virtual sale. Based on several joint warning letters and the subsequent shuttering of numerous websites illegally selling opioids, it would appear the partnership is a success. Both agencies and the domain registries have committed to continuing this working relationship beyond the pilot program. Time will tell if the continued joint effort reduces the unlawful sale of opioids online and in turn, minimizes the risks associated with the opioid crisis.

Although the Biden-Harris Administration that assumed control of the Executive Branch on January 20, 2021 immediately ordered a regulatory freeze of new or pending rules while the new administration gets its bearings (as reported by our colleagues in this post), several important changes to the laws enforced by the Food and Drug Administration (FDA) were recently enacted by Congress. As legislative actions, those changes are of course unaffected by President Biden’s regulatory freeze and so we thought worth a summary to ensure our readers are up to speed on the large amount of activity that occurred in the final weeks of the 116th Congress and the Trump Administration.

Please join Mintz’s Employment, Labor & Benefits and Health Law attorneys and noted immunologist Dr. Darryl Carter for a webinar to discuss key takeaways from the EEOC’s recently updated vaccination guidance and other COVID-19–related workplace question.