Welcome to 2023: What you missed during the Holiday break


Jan. 03, 2023

As you start this new year, you’re probably spending quite a bit of time catching up on regulatory news you would have missed if you (like us) took some time off for the holiday. AgencyIQ has you covered with this concise recap of the biggest FDA-related news that happened during Christmas and New Year’s.

A quick note before we begin:

Congressional review of FDA’s accelerated approval of Biogen’s Aduhelm faults regulator for “atypical” review, lack of process controls and inadequate record-keeping.

  • A new report ( backup link) released in the waning days of the last Congress took issue with the manner in which the FDA granted accelerated approval to Biogen’s Alzheimer’s disease drug Aduhelm (aducanumab), calling the agency’s interactions with Biogen “atypical” and not in keeping with established protocols. The report was the conclusion of an 18-month investigation by the House Energy & Commerce Committee.
  • Among the more noteworthy findings of the 46-page report:
    • There were “at least” 40 FDA-Biogen “working group” meetings – and likely more, since the agency lacked a “clear record” of informal meetings and other interactions. The FDA, according to the report, “found that the extent of collaboration between FDA and Biogen was atypical and ‘exceeded the norm in some respects.’”
    • FDA and Biogen worked together to write a “Joint Briefing Document” for a crucial external advisory committee meeting – a level of collaboration that wasn’t unprecedented, but still had never been done outside of an oncology setting. The report took issue with the joint document, noting that it “afforded Biogen advance insight into FDA’s responses and direct guidance from the agency in drafting the company’s own sections,” and “did not adequately represent differing views within FDA.” The FDA’s own internal review concluded that the joint briefing document was “not an appropriate approach in this instance.”
    • Following a decisive advisory committee hearing in which the committee voted against traditional approval for Aduhelm, the FDA had “abruptly changed course” and “pivoted” to consideration of accelerated approval for Aduhelm despite not having done so in the previous nine months. Notably, advisory committee members were never asked about accelerated approval considerations, which include whether beta amyloid plaque is a suitable surrogate endpoint for use.
    • FDA accepted an unusually broad indication for use for Aduhelm despite a “lack of clinical data on all Alzheimer’s disease stages and Biogen’s reservations.” The report notes that Biogen had only studied Aduhelm in specific subsets of patients with Alzheimer’s disease – not in all “people with Alzheimer’s disease,” as the FDA-approved label states as the indication for use.
  • The E&C Committee report offers three recommendations for the FDA for future interactions with companies. First, to “ensure that all substantive FDA interactions with drug sponsors are properly memorialized.” Second, to “establish a protocol for joint FDA-Drug Sponsor Briefing Documents for Advisory Committees,” including standards for appropriate use and development. And third, to update its guidance on the development and review of new Alzheimer’s disease drugs “in order to provide industry and the public with a complete understanding of the agency’s current view on how these drugs should be evaluated.”

FDA rejects PhRMA petitions on drug importation plans as moot, sidestepping arguments

  • On December 30, 2022 the FDA responded ( 1, 2) to a pair of citizen petitions ( 1, 2) that had been submitted in December 2020 by the law firm Covington & Burling LLP on behalf of the pharmaceutical trade group PhRMA, which had petitioned regulators to “discontinue” efforts to implement prescription drug importation plans through various means. Chief among the stated concerns of the petitions was that there was no way for the FDA to ensure the safety of products imported through the proposed plans, and that FDA was therefore unable to satisfy one of the essential statutory conditions on which the plans were based.
  • FDA’s responses to both petitions were relatively brief, in part owing to the agency’s own actions long before. During the waning months of the Trump administration, the FDA had issued two drug importation “requests for proposals” (RFPs) which sought to eventually permit personal drug importation by entities on behalf of individuals (instead of by states), as well as the importation of insulin products. However, both proposals were subsequently withdrawn on July 9, 2021 without explanation.
  • The withdrawals made FDA’s responses rather straightforward. “In light of the Withdrawal Notice, we are dismissing as moot your request,” FDA wrote in both notices. However, both petitions also included other matters which FDA largely rejected, rather than ignored. For example, PhRMA had petitioned FDA to “adopt or follow certain processes or procedures for the Agency’s review of applications for drug reimportation” for insulin, which FDA rejected as out of scope for a Citizen Petition, which must only request that FDA “take or refrain from taking” an administrative action. Similarly, the other petition make “requests that FDA abide by legal requirements,” which FDA said were “not requests to ‘take or refrain from taking’ an administrative action, and so are not the appropriate subject of a citizen petition.”
  • It’s worth noting that PhRMA is engaged in other efforts to stymie FDA’s drug importation program, including ongoing legal action and additional Citizen Petitions (1, 2) to which FDA has not yet provided a substantial response.

Medical device updates: Classifications and TAP website updates.

  • The FDA finalized seven formal classification orders for a variety of medical devices. The devices run the gamut of therapeutic areas – from gastroenterology-urology, neurological, cardiovascular (three products), orthopedic, immunology and microbiology. Notably, all seven devices were formally categorized as Class II with special controls (see below for a full list), following the granting of De Novo market access requests for the associated products over the last three years. The spate of device classifications indicate a return to normal work for CDRH, as these actions were generally de-prioritized during the height of the Covid-19 pandemic due to capacity constraints. Notably, the categorization is technically effective as of the granting of a De Novo in a particular product class, but the formal final orders establish the specific regulatory citations for device types within the FDA’s legal framework.
  • A full list of the newly codified-as-Class-II-products: On January 1st, CDRH issued the order to establish gastrointestinal lesion software detection systems as Class II – a categorization that has been in effect since the granting of the De Novo request for the FDA Cosmo Artificial Intelligence-AI’s GI Genus system in 2021. On December 30th, the agency issued an order to classify pediatric Autism Spectrum Disorder (ASD) diagnosis aids as a Class II, following the 2021 granting of the De Novo request for Cognoa’s ASD Diagnosis Aid. On the 29th, there were two orders issued, both to codify Class II categorizations for extracorporeal systems for carbon dioxide removal (De Novo granted in 2021) and resorbable implants for anterior cruciate ligament (ACL) repair (De Novo granted in 2020). On the 28th, the published order codified the Class II categorization for interventional cardiovascular implant simulation software devices, which were also first granted a De Novo in 2021. Finally, there were two classification orders on the 27th: one for Human Leukocyte Antigen (HLA) typing companion tests and adjunctive hemodynamic indicators with decision points – also following the granting of De Novo requests in recent years.
  • The Total product lifecycle advisory program (TAP) pilot is now live. Per a December 29th update to the TAP website (and flagged in a communication from CDRH), “The Soft Launch phase of the TAP Pilot will begin on January 1, 2023. During the TAP Pilot Soft Launch phase, the FDA intends to enroll up to 15 devices in the Office of Health Technology 2 (OHT2): Office of Cardiovascular devices.” However, that update does not provide additional information on the enrollment process or procedures – AgencyIQ recently discussed the parameters and operation of the pilot’s “soft launch.”

Emergency diagnostics updates.

  • Mpox updates: There are now five EUA authorized mpox tests. The most recent authorization is for the Bectron, Dickinson & Company (BD) VIASURE RT-PCR reagents for the BD MAX system, which lists an EUA issued date of December 23rd. Notably, the most recent Federal Register notice announcing an EUA was formally published on December 30th, for Roche, although the EUA is effective as of November 15. With the total number of EUAs for mpox diagnostics now at five – and, notably, all from “experienced developers” – the question remains as to how many EUAs the agency will be granting for mpox. As AgencyIQ has discussed, in order to be considered a “priority” for EUA review, sponsors needed to meet a series of criteria and submit a notice of intent by October 13. CDRH never formally acknowledged how many notices of intent it received for mpox, but given the overall prevalence of mpox in the U.S. it does seem likely that the FDA would align the total number of authorizations with the relative risk.
  • Covid-19 updates: The FDA has added the first test to its list of tests that could be “expected to have reduced performance” in the omicron variant (or subvariants): The DxTerity SARS-CoV-2 RT PCR CE Test. The new addition comes after CDRH has raised concerns about test performance in the newer variants, even updating the way that serial testing strategies should be designed for authorized antigen tests. While the agency had previously determined that three specific products would actually “fail to detect” (note: not have reduced performance) the omicron variant (or subvariants), those products have now been modified to address the issue.
  • The first virtual town hall of the new year will be held on January 11th, 2023. This town hall will focus on both Covid-19 and mpox.

Plan B One-Step updates

  • Plan B One-Step (PBOS) is an emergency contraceptive measure. Plan B was first approved as a two-pill course in 1999. In 2009, the one-course pill (PBOS) was approved, and the two-course pill subsequently ceased manufacturing and marketing. Over the last 15 years, PBOS has been available without a prescription (i.e., over-the-counter) for an increasing number of women. While OTC availability was initially limited to women 18 and older (July 2009), the age restrictions were gradually loosened before full removal in June 2013, allowing it to be used without age restrictions.
  • But there has long been controversy about a specific statement on the drug’s label – a controversy the FDA has sought to quell. On December 23, 2022 the FDA approved a supplemental application for PBOS (levonorgestrel) to update the drug’s labeling to remove some information related to the drug’s mechanism of action from the Drug Facts Label (DFL) and Consumer Information Leaflet for Plan B One-Step.
  • According to FDA’s FAQ page on Plan B, the updated information is now “consistent with the best available scientific evidence.” Specifically, FDA’s review found that Plan B One-Step works by inhibiting or delaying ovulation and the midcycle hormonal changes without a direct effect on fertilization or implantation. As POLITICO Pro summarized: “In addition to emphasizing that the pill works before ovulation, it also states that it will not work if a person is already pregnant.” As the change makes clear, the drug does not cause the abortion of an embryo or fetus.
  • The updates come as FDA considers shifting more drugs in the reproductive health space to OTC status. While FDA announced the scheduling of a joint meeting between its Nonprescription Drugs Advisory Committee and Obstetrics, Reproductive and Urologic Drugs Advisory Committee to consider a proposal for the first oral contraceptive (Opill) to become available over-the-counter in the U.S. [ Read AgencyIQ analysis here], the meeting was subsequently postponed indefinitely after FDA told Perrigo it needed an additional 90 days “to review additional information requested related to the Opill Rx-to-OTC switch.” AgencyIQ expects the meeting may be rescheduled this year, and likely in late February 2023.
  • As AgencyIQ has previously discussed, the Supreme Court’s decision in June 2022 to overturn decades of legal precedent in Dobbs v. Jackson Women’s Health Organization has undoubtedly placed the FDA in a tenuous position. In the new Congress, lawmakers in both parties are likely to focus heavily on any FDA action (or inaction) to make contraceptive health products more widely available, such as approving over-the-counter birth control bills, relaxing restrictions on mifepristone, or fighting in court against any states which seek to restrict access to emergency contraceptives of mifepristone.

To contact the author of this item, please email Laura DiAngelo ( [email protected]), Amanda Conti ( [email protected]) or Alexander Gaffney ( [email protected])
To contact the editor of this item, please email Alexander Gaffney

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