Welcome to FDA Regulatory News and Trends, designed to help you identify significant legal developments and navigate the evolving business, legal and regulatory world.

FDA focuses on key areas of science in annual regulatory planning document. On September 6, the Food and Drug Administration (FDA) issued the 2022 edition of its publication, “Advancing Regulatory Science at FDA: Focus Areas of Regulatory Science.” This document is an annual summary of the broad areas of the FDA’s scientific work. It points out that the range of products that the agency regulates, “from food to cosmetics, supplements, drugs, devices, biologics (in people and animals) and tobacco makes the case that multiple areas of science must be brought together in order to derive optimal regulatory decisions.” In defining the FDA’s priorities, the publication asserts that “we aim to advance regulatory science in several cross-cutting areas. In the 2021 report, we identified priorities in women’s health, minority health, health equity across diverse groups, and the One Health initiative. In 2022, we bolstered our cross-cutting topics to include pediatric health, rare diseases, and oncology.”

FDA updates its guidance on use of monkeypox drug. On September 15, the FDA updated its guidance for the use of TPOXX® (tecovirimat) for the treatment of monkeypox. The safety and efficacy of TPOXX® to treat monkeypox in humans has not been established. The FDA warned against overuse of the drug, saying that even a small mutation in the virus that causes monkeypox could make the medication ineffective. The agency cautioned that a single molecular change to monkeypox “could have a large impact on the antiviral activity of TPOXX®.” It said that scientists at the Centers for Disease Control are activelymonitoring for changes in the monkeypox virus that could make the virus less susceptible to TPOXX®. Because of the potential for the virus to become resistant to the drug, the FDA said, it is important for patients to use it in a judicious manner, ideally within the randomized clinical study sponsored by the National Institutes of Allergy and Infectious Diseases (NIAID) and also through the CDC under an FDA authority called Expanded Access.

FDA will consider first US over-the-counter birth control pill. On September 12, the FDA announced that it has scheduled a joint meeting to consider a pharmaceutical company application for what could be the first over-the-counter daily birth control pill available in the US. The joint meeting will be held on November 18 with the FDA’s Nonprescription Drugs Advisory Committee and the Obstetrics, Reproductive, and Urologic Drugs Advisory Committee, according to the company. If approved by the FDA, which may not occur until 2023, the company’s progestin-only daily pill would be the first non-prescription birth control pill sold in the US. The company filed its application to move its birth control pill from prescription to over the counter in July. Many countries in Asia, Africa and Latin America already permit birth control pills to be sold over the counter.

FDA draft guidance on software is designed to promote innovative technologies. On September 13, the FDA issued a draft guidance titled “Computer Software Assurance for Production and Quality System Software.” This draft guidance provides recommendations on risk-based computer software assurance activities for computers and automated data processing systems that are used as part of medical device production or the quality system. The draft guidance is intended to describe "computer software assurance" as a risk-based approach to establish confidence in the automation used for production or quality systems, identify where additional rigor may be appropriate, and describe various methods and testing activities that may be applied to establish computer software assurance and provide objective evidence to fulfill regulatory requirements. The agency said it believes that these recommendations will help foster the adoption and use of innovative technologies that promote patient access to high-quality medical devices and help manufacturers to keep pace with the dynamic, rapidly changing technology landscape, while promoting compliance with laws and regulations implemented by the FDA.

FDA issues guidance about labeling of sodium, potassium and phosphorus in drugs. On September 8, the FDA issued a draft guidance concerning the quantitative labeling of sodium, potassium and phosphorus in over-the-counter and prescription drugs for humans. It points out that people with several common medical conditions may need to restrict their intake of these elements and that such elements may be present in drug products as constituents of active or inactive ingredients; thus, it is important for the consumer to know how much of them is present in a given medicine. The draft guidance therefore provides information and recommendations concerning the quantification of sodium, potassium and phosphorus in drug product labeling because these substances are common constituents of ingredients that are sometimes present in drug products in amounts that may represent a significant portion of an individual’s total daily intake.

FDA and NIH launch new partnership to advance understanding of ALS. On September 14, the FDA and the National Institutes of Health (NIH) announced the launch of the Critical Path for Rare Neurodegenerative Diseases (CP-RND) – a public-private partnership aimed at advancing the understanding of neurodegenerative diseases and fostering the development of treatments for amyotrophic lateral sclerosis (ALS) and other rare neurodegenerative diseases. The FDA and NIH have selected the Critical Path Institute External Link Disclaimer (C-Path) as the convener of this partnership. “There is a crucial need to develop new treatments that can improve and extend the lives of people diagnosed with rare neurodegenerative diseases, including ALS. Collaboration across public and private sectors can accelerate the progress to address this urgent need,” said FDA Chief Medical Officer Hilary Marston. The Accelerating Access to Critical Therapies for Amyotrophic Lateral Sclerosis Act was signed into law last December by President Joe Biden. It requires the FDA and NIH to establish and implement a public-private partnership on ALS no later than one year after enactment.

Novartis Pharmaceuticals (Novartis) files a citizen petition addressing “skinny label” issue. A September 12, 2022 petition urges the FDA to deny the approval of any generic versions of Entresto® (sacubitril/valsartan) until the expiration of its exclusivity in February 2024, even if the generic drugmakers seek to carve out the patent- and exclusivity-protected use. This is the second citizen petition Novartis filed over the same issue. Earlier this year, the FDA denied Novartis’s initial petition without commenting on the approvability of generic drugs referencing Entresto®. Entresto®, Novartis’s blockbuster heart drug, was first approved in July 2015 for patients with Heart Failure With Reduced Ejection Fraction (HFrEF). In February 2021, the FDA expanded Entresto’s indication to include patients with Heart Failure with Preserved Ejection Fraction (HFpEF). Novartis quickly listed the relevant patents in the Orange Book. The approval of the February 2021 supplement not only significantly revised Entresto’s label but also gave Entresto® a three-year exclusivity, both of which form the bases of Novartis’s argument in its citizen petition. Specifically, Novartis argued that, if generic drugmakers carve out Entresto’s exclusivity-protected use in its labeling, the FDA would have to make changes to the current labeling of Entresto®, which exceeds the FDA’s statutory and regulatory authority and is inconsistent with FDA precedent and longstanding agency interpretations of the ANDA “same labeling” regulations. Novartis additionally argued that an ANDA with a section VIII statement, or a skinny label, would require generic drugmakers to rely on the discontinued labeling by omitting the patent-protected use in HFpEF patients. However, such practice is “inconsisten[t] with statute” according to Novartis. Finally, Novartis argued that a skinny label omitting a patent-protected dosing regimen would render a generic drug less safe and effective than Entresto®.

FDA will convene meeting on pulse oximeters in November. On September 15, the FDA announced a virtual meeting of the CDRH Anesthesiology and Respiratory Devices Panel of the Medical Devices Advisory Committee to be held on November 1, 2022, from 9 am to 6 pm EDT. The committee will discuss ongoing concerns that pulse oximeters may be less accurate in individuals with darker skin pigmentations. The committee will also discuss factors that may affect pulse oximeter accuracy and performance, the available evidence about the accuracy of pulse oximeters, recommendations for patients and healthcare providers, and the amount and type of data that should be provided by manufacturers to assess pulse oximeter accuracy and to guide other regulatory actions as needed. On June 21, the FDA had issued an update to its current safety advice about pulse oximeters and indicated that such a meeting was forthcoming.

FDA is sued over its alleged double standard for blood medications. On September 14, Octapharma, the maker of Fibryga® (fibrinogen), a blood medication, sued the FDA in the US District Court for the District of Columbia over what the company says are the FDA’s “sharply uneven” standards for different blood medications. The company argued that it was subjected to multimillion-dollar clinical trials while competitors in the blood medication field were allowed to skip that step. The suit says that the FDA wrongly classified the fibrinogen products of three blood centers as “blood components” exempt from clinical trials while classifying Fibryga® as a “blood derivative” that is subject to clinical trials. Fibryga® is a human fibrinogen concentrate indicated for the treatment of acute bleeding episodes in adults and children with congenital fibrinogen deficiency.

Federal appeals court rules that private lawsuit is preempted by FDA’s enforcement power. A three-judge panel of the US Court of Appeals for the 9th Circuit on September 13 affirmed a California judge's decision to dismiss a pharmaceutical manufacturer's claims that a compounding pharmacy unlawfully produced copies of its FDA-approved blood pressure medication. The court ruled that the claims were preempted by the FDA's exclusive enforcement power. It held that Nexus Pharmaceuticals Inc. could not privately sue Central Admixture Pharmacy Services Inc. (CAPS) over claims that it was manufacturing and selling a generic version of Nexus' drug Emerphed® without FDA approval. Nexus had argued it was allowed to sue CAPS for damages under state statutes prohibiting the sale of non-FDA-approved drugs. CAPS compounds the drug under the Food, Drug, and Cosmetics Act. The Ninth Circuit held the state statutes are rooted in the FDCA and are therefore preempted by the act's provision giving the FDA sole enforcement authority. “Proceedings to enforce or restrain violations of the FDCA, including the compounding statute, must be by and in the name of the United States, not a private party,” Judge Andrew Kleinfeld wrote for the court. Nexus’s claim is such a proceeding, so it is barred by the exclusive enforcement statute.”

FDA releases guidance for use of real-world data in applications. On September 8, the FDA released a guidance document titled “Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drug and Biological Products.” The FDA said in the document that, in order to facilitate the agency’s internal tracking of submissions that include real-world data (RWD) and real-world evidence (RWE), it wishes to encourage sponsors and applicants to identify in their submission cover letters certain uses of RWD/RWE. This guidance applies, the agency said, to submissions for investigational new drug applications (INDs), new drug applications (NDAs) and biologics license applications (BLAs) that contain RWD or RWE intended to support a regulatory decision regarding product safety and effectiveness. The agency said that RWD are data relating to patient health status and the delivery of healthcare that are routinely collected from a variety of sources. That can include electronic health record data, medical claims data, product or disease registry data, data obtained from digital health technologies and data gathered from other sources that can inform on health status, such as questionnaires. RWE is the clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of RWD.

FDA finalizes 510(k) Electronic Submission Requirement. The FDA issued the final guidance, Electronic Submission Template for Medical Device 510(k) Submissions, on September 22, 2022, providing details of the 510(k) electronic submission requirements and the corresponding timetables for implementation. In sum, effective October 2023, the FDA expects all 510(k) submissions to comply with the new electronic submission requirement, with the FDA being clear it has no intention to grant waivers. The use of electronic Submission Template And Resource (eSTAR) system is voluntary for the next year and, even after October 2023, will be available for voluntary use for de novo submissions, in addition to being required for 510(k) submissions.