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7 February 20237 minute read

FDA Regulatory News and Trends - February 7, 2023

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


DC Court of Appeals opines on scope of NCE exclusivity. The United States Court of Appeals for the District of Columbia Circuit recently issued an opinion regarding the scope of new chemical entity (NCE) exclusivity. The unanimous opinion upheld a district court ruling that affirmed the FDA’s decision to grant Aubagio (teriflunomide) NCE exclusivity. The challenger sought to commence marketing its generic version of teriflunomide sooner by challenging Aubagio’s NCE exclusivity in a series of letters to the FDA. It also sought generic exclusivity for its own product upon market entry. FDA’s decision to grant Aubagio NCE exclusivity was challenged on the grounds that its active ingredient, teriflunomide, had previously been approved as an impurity in Arava (leflunomide). The challengers alternatively argued that teriflunomide was actually approved as an active ingredient in Arava. The FDA approved Arava in 1998 and the drug’s active ingredient, leflunomide, breaks down into teriflunomide. The FDA characterized teriflunomide as an impurity when it approved Arava and the drug was allowed to contain up to 3.5 percent teriflunomide. The challengers argued that teriflunomide contributes to Arava’s activity, and that teriflunomide was “physically present as a bioavailable and physiologically/pharmacologically active component” of Arava. The combination of these factors, the challengers reasoned, meant that FDA approved teriflunomide when it approved Arava. Therefore, the FDA should rescind new chemical entity exclusivity for Aubagio, which used teriflunomide as its active ingredient. The district court rejected the challenger’s argument, and the DC Circuit affirmed this rejection. The Court held that that under the FDCA when the FDA approves a new drug, known impurities in that drug have not “been approved” within the meaning of the statute. Therefore, a new drug that employs a known impurity as its active ingredient is eligible for new chemical entity exclusivity. The Court took care to mention in a footnote that this opinion does not necessarily extend to an applicant seeking approval for a drug with an active ingredient that was approved as an inactive ingredient in another drug. The case is Sandoz Inc. v. Becerra, No. 22-5202 (D.C. Cir. Jan. 10, 2023).

FDA releases draft guidance on the dosage and administration section of prescription drug labeling. FDA has issued draft guidance revising and expanding its 12-year-old recommendations on “Dosage and Administration Section of Labeling for Human Prescription Drug and Biological Products — Content and Format.” In March 2010, FDA issued final guidance on the “dosage and administration section” of drug labeling for drugs and biologics. While this guidance helped to clarify regulatory requirements under 21 CFR 201.57, it still left some questions unanswered due to the peculiarities associated with individual drug labeling. On January 12, FDA released draft guidance revising its earlier suggestions regarding this important section of product labeling, specifically adding recommendations or requirements for making information more accessible to certain patient subpopulations, adding information about switching and substitution, missed doses, vomiting soon after oral administration, and more. Further, the guidance recommends including information about administering other drugs before, during, and after treatment/administration of the subject drug, as well as discontinuation or dosage reduction of a drugs that present withdrawal risks. The draft guidance also provides recommendations related to the use of abbreviations, commonly used symbols, the metric system (for dosage), and US Pharmacopoeia descriptor in order to minimize the potential for medication errors. March 14, 2023 is the last day to submit comments on this significantly expanded guidance which contains approximately three times the amount of material compared to the prior issued document.

FDA announces launch of eSTAR pilot program for medical device submissions with Health Canada. On January 10, 2023, FDA announced that its eSTAR pilot program with Health Canada had officially launched. eSTAR is an interactive PDF template that guides applicants through the process of preparing a comprehensive medical device submission. Currently, use of eSTAR is voluntary, but, starting October 1, 2023, FDA will require most 510(k) submissions to be submitted electronically using eSTAR. The pilot program will allow nine medical device manufacturers to submit their eSTAR premarket review submissions, either a 510(k), de novo, or premarket approval (PMA), to both FDA and Health Canada using a single submission. In vitro diagnostic devices, combination products, CBER-led products, and FDA dual 510(k)/CLIA waiver applications are ineligible for participation in the pilot. As of January 27, 2023, FDA and Health Canada reported that the pilot had reached its maximum capacity of nine participants. Further requests for participation will no longer be accepted.

CDRH calls for ideas on where to invest funding for real-world evidence (RWE). As part of its commitments under the most recent reauthorization of the Medical Device User Fee Amendment (MDUFA V), FDA agreed to investigate and invest in new RWE projects in the premarket space, beyond its existing National Evaluation System for health Technology (NEST) efforts. The agency has now opened a docket to elicit input on how it should utilize user fee funding for RWE projects involving external organizations other than NEST. FDA’s announcement requesting public comments on this issue states that the agency “remains committed to work collaboratively to advance the development of Real-World Data (RWD) and use of RWE to evaluate device performance.” This announcement came hot on the heels of the publication of a FDA Commissioner Robert Califf’s paper titled “Now is the time to fix the evidence generation system” – see the abstract of that paper here. Those interested in submitting funding ideas to the docket should note that the comment period will end March 20, 2023.

FDA issues draft guidance for monkeypox drug development programs. Although new monkeypox cases have declined worldwide since late 2022, there is no authorized or approved monkeypox treatment in the US. To assist monkeypox drug development, FDA has issued a draft guidance, “Mpox: Development of Drugs and Biological Products.” The guidance does not apply to preventative vaccines because vaccine development raises “different and additional considerations, including those pertaining to subject selection, safety monitoring, and effectiveness evaluation.” Notably, the guidance precludes monkeypox drug candidates from seeking approval under the Animal Rule, the regulatory pathway under which smallpox drugs were approved. Consistent with FDA’s past practice, the agency encourages sponsors to engage with the agency during the early phase of the drug development by requesting a pre-IND meeting. This guidance provides nonclinical, virology, and clinical considerations for monkeypox drug development programs, with a focus on recommendations to support initiation of clinical trials. Comments should be submitted on or before March 21, 2023.

FDA issues updates to COVID-19 test guidance documents. On January 12, 2023, FDA released updated versions of two guidance documents related to COVID-19 testing – the Policy for Coronavirus Disease-2019 Tests and the Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests. While the substance of the guidance documents remain largely unchanged, FDA added statements to both guidance documents clarifying that the guidance documents are intended to remain in effect for the duration of the declaration under section 564 of the Federal Food, Drug, and Cosmetic Act issued by the Secretary of Health and Human Services (HHS) on February 4, 2020, declaring that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of the novel coronavirus (the EUA declaration). The previous versions of the documents stated that they were intended to remain in effect for the duration of the public health emergency related to COVID-19 declared by the Secretary of HHS on January 31, 2020 in accordance with section 319(a)(2) of the Public Health Service Act (the Public Health Emergency declaration). While the Public Health Emergency declaration must be renewed every 90 days, the EUA declaration stays in effect until it is terminated by the Secretary of HHS, which typically happens long after the Public Health Emergency declaration is no longer renewed.