FDA Regulatory News and Trends

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

New draft guidance on expanded access. On November 1, 2022, FDA released a new draft guidance titled Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers. When finalized, this guidance will replace a previous guidance issued in June 2016 and updated in October 2017. The new draft guidance includes updates related to Institutional Review Board (IRB) review, informed consent, and requirements established by the 21^st Century Cures Act (Cures Act) and the FDA Reauthorization Act of 2017 (FDARA). In an updated answer related to IRB review, the guidance states that for individual patient expanded access INDs, FDA may allow waivers from the requirement for review and approval at a convened IRB meeting under certain conditions. Updates related to informed consent include additional detail on the requirements for informed consent and the inclusion of a template informed consent form as an appendix. Another question on informed consent clarifies that to meet regulatory requirements, sponsors may either include a statement that the study involves research, or alternatively, that the drug is investigational, and FDA has not determined that the drug is safe or effective. The guidance also includes an update noting that sponsors may meet the Cures Act requirements for making expanded access policies publicly available by posting on the manufacturer’s website or on the Reagan-Udall Foundation Expanded Access Navigator, and that FDA does not intend to consider posting the policy to be promotion of an investigational drug. Additionally, the new draft guidance clarifies that, under FDARA, sponsors should post their expanded access policies by the earlier of (1) the first initiation of a phase 2 or phase 3 study or (2) 15 days after the drug receives a fast track, breakthrough, or regenerative advanced therapy designation. Comments on the draft guidance are due January 3, 2023.

Update to EUA labeling requirements for SARS-CoV-2 antigen tests. The FDA has updated Emergency Use Authorization labeling requirements for all currently authorized SARS-CoV-2 antigen tests that offer repeat or serial testing. The revision requires test developers to submit a supplemental EUA request to the FDA with updated labeling to reflect the revised authorized uses. For a test that was previously authorized for testing of symptomatic individuals, the test is now authorized for use at least twice over three days with at least 48 hours between tests; for a test that was previously authorized for testing of asymptomatic individuals, the test is now authorized for use at least three times over five days with at least 48 hours between tests.

FDA publishes Notice that the agency will launch the CMC Development and Readiness Pilot program. The Notice, published on October 31, 2022, provides eligibility criteria, the content of the application, and selection criteria. Starting April 1, 2023, FDA will accept requests to participate in the CDRP program. Products with accelerated clinical development timelines, such as products with Breakthrough Therapy (BT), Fast Track (FT), and Regenerative Medicine Advance Therapy (RMAT) designations, are eligible to apply. No more than nine proposals will be selected, with approximately six CBER-regulated products and three CDER-regulated products. Interested applicants should provide a detailed CMC development plan and proposed timing for meetings with FDA. The pilot features increased communication between FDA and sponsors and explores the use of science- and risk-based regulatory approaches. Specifically, two dedicated CMC meetings will be granted, and sponsors will have an opportunity for follow-up discussions to address questions arising from the meeting or meeting minutes, or if additional clarifications are needed. Sponsors interested in the program should be aware that certain information relevant to the CDRP may be publicly disclosed.

FDA issues final guidance on cell and gene therapy umbrella clinical trials. FDA’s recently published final guidance provides recommendations to sponsors studying multiple versions of a cellular or gene therapy product in an early phase clinical trial for a single disease. Even though multiple versions of a product may be studied simultaneously in a single clinical trial, each version is generally submitted to the FDA in its own investigational new drug application (IND), since the variances between the product versions are intended to yield differences in safety or activity. Because these studies are not intended to provide primary evidence of effectiveness to support a marketing application and generally are not adequately powered to demonstrate a statistically significant difference in efficacy between the study arms, sponsors have expressed interest in gathering preliminary safety and activity evidence using multiple versions of a therapy product in a single clinical trial, which could help sponsors conduct these types of umbrella trials more efficiently and thus bring therapies to market sooner. In addition to providing examples of the types of changes to a product design that constitute distinct versions, this guidance provides recommendations for how to organize and structure the INDs, submit new information, and report adverse events.

FDA issues a clarification regarding face-to-face formal meetings– video conferences count, and virtual-only at this time. FDA has expanded the definition of “face-to-face” meeting to include virtual conferences with the camera on (eg, “a face-to-face meeting ‘includes in-person meetings and virtual meetings on IT platforms that allow for both audio and visual communication.’”) Consistent with the Agency’s position since the onset of the COVID-19 pandemic, FDA is only conducting virtual meetings for face-to-face meetings at this time. FDA has also clarified that it is still possible to request a teleconference, but a meeting that is audio only is not considered to be face-to-face.

US Patent and Trademark Office announces a public “listening session.” On November 7, the USPTO announced it will hold a listening session of January 19, 2023, in order to collect public comment on proposed initiatives between the agencies that are the result of President Biden’s Executive Order “Promoting Competition in the American Economy.” Some of the topics the USPTO listed include enhancing collaboration between the FDA and the USPTO regarding Orange Book and Purple Book listed patents that are subject to USPTO proceedings under the American Invents Act (AIA) and ensuring that applicants provide consistent information between USPTO and FDA filings. Furthermore, the listening sessions are designed to gather comment on how the two agencies can work together to address areas where their responsibilities overlap, such as skinny labeling, patents on risk evaluation and mitigation strategies (REMS), and Orange Book use codes for method of use patents. The notice mentions more areas where the USPTO is seeking public input, including how parties must navigate AIA proceedings and Hatch-Waxman litigation. Interested speakers must register by January 5 and registration to attend in-person or virtually ends January 17. Speaking slots are limited.

FDA Medical Device Advisory Committee acknowledges inequities in pulse oximeter accuracy and makes recommendations. On November 1, FDA’s Anesthesiology and Respiratory Therapy Devices Panel of the Medical Device Advisory Committee met to discuss ongoing concerns that pulse oximeters may be less accurate in individuals with darker skin pigmentations. The panel received written comments on the topic and listened to presentations from FDA, clinicians, researchers, professional societies, patients and industry. The panel agreed that clinical evidence demonstrates that pulse oximeter devices are less accurate when used on individuals with darker skin, which may result in increased health risks for this patient group. The panel discussed tools for the assessment of skin pigmentation and recommended that future studies should evaluate the full spectrum of skin pigmentation with an adequate sample size to ensure sufficient accuracy for all patients. The panel also indicated the need for additional studies to better reflect real-world performance of these devices, as additional factors like device fit and location may also have meaningful impact on accuracy. The panel’s labeling discussion yielded some of the most specific recommendations of the meeting. For prescription pulse oximeter devices, the panel recommended that specific information regarding the accuracy of devices across various levels of skin pigmentation be included, while over-the-counter (OTC) pulse oximeter device packaging should plainly indicate that the product is not intended for medical use or clinical decision making. FDA is reviewing the panel’s recommendations and will consider additional actions.

FDA clears first at-home test to predict lung and liver disease. The FDA has granted the first-ever clearance of a direct-to-consumer saliva collection test to screen for a protein deficiency associated with an elevated risk of developing either lung and/or liver disease. The AlphaID test, manufactured by Barcelona-based diagnostic firm Grifols, works by having the consumer use an at-home collection kit and sending the sample to a certified lab for processing. Results are available via an online portal within a few weeks. The new at-home test looks for genetic markers to detect alpha1-antitrypsin (alpha-1) deficiency, the most common risk factor for liver and lung diseases including COPD – a group of respiratory diseases that includes emphysema and chronic bronchitis and affects an estimated 16 million Americans, according to the Centers for Disease Control. The AlphaID test relies on the same Grifols alpha-1 diagnostic that has been available to physicians since 2018. Grifols advises that patients discuss their test results with their physicians because only a healthcare professional can make an alpha-1 diagnosis.

Updates to Least Burdensome Guidance. In late October 2022, FDA issued a guidance titled “Developing and Responding to Deficiencies in Accordance with the Least Burdensome Provisions.” This guidance applies to instances where the FDA issues requests for additional information or deficiency letters to sponsors during review of marketing applications (ie, premarket approval (PMA), humanitarian device exemption (HDE), 510(k), or de novo submissions). The guidance provides principles that FDA reviewers should follow when developing deficiency letters and suggests content and format. The guidance also provides recommendations on how sponsors should provide responses to deficiency letters. The appendix to the guidance provides examples of deficiencies and sponsor responses for various types of marketing applications.