FDA Regulatory News and Trends - June 23, 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.

FDA announces additional steps to modernize clinical trials.

• On June 6, 2023, FDA announced the availability of a new draft guidance, “E6(R3) Good clinical Practice (GCP),” adopted from the International Council for Harmonisation (ICH).
  
  
• Once finalized, the new draft guidance will replace the existing version of the guidance, E6(R2).The latest draft guidance includes updated recommendations “aimed at modernizing the design and conduct of clinical trials, making them more agile without compromising data integrity or participant protections. The updates are intended to help pave the way for more efficient clinical trials to facilitate the development of medical products.”


• New recommendations include encouraging the use of innovative digital health technologies (DHTs), such as wearable sensors, to increase efficiency of data collection.Newly added sections also outline that the trial investigator retains ultimate responsibility (and should maintain appropriate supervision over delegated tasks) and emphasize the importance of data governance for both sponsors and investigators.
  
  
• Additionally, the new draft guidance emphasizes the use of proportionate and risk-based and approaches across the lifecycle of a clinical trial and encourages proactive consideration of the trial’s quality so that factors critical to trial quality are considered when designing the trial.
  
  
• The comment period for the new draft guidance closes on September 5, 2023.

FDA to begin inactivating registration of HCT/P manufacturers that have not yet updated their registration.

• On June 1, 2023, FDA announced its intention to begin inactivating the registration of establishments that manufacture human cells, tissues, or other cellular or tissue-based products (HCT/Ps) that have not updated their registration during the annual update period in the human cell and tissue establishment registration system (eHCTERS).
  
  
• Establishments that manufacture HCT/Ps are required to register and list their products with FDA’s Center for Biologics Evaluation and Research (CBER) and update their establishment registration annually each December.
  
  
• Previously, FDA attempted to follow up with establishments that failed to submit their annual registration update; however, FDA will no longer attempt to follow up with such establishments.
  
  
• FDA’s announcement notes that, 90 days after publication of its notice (August 30, 2023) and every January thereafter, FDA will inactivate an HCT/P establishment’s registration when the establishment fails to submit their annual registration update during the previous annual update period between November 15 to December 31.

CDRH seeks comment on at-home medical technology.

• As part of its strategic efforts to advance health equity and to expand access to home-use technologies, CDRH is requesting public comment on several questions related to digital health technologies and their use in non-clinical settings.
  
  
• Among the questions posed, CDRH asks how the FDA can support development of these technologies and facilitate their remote access, as well as which factors should be considered in selecting and designing these products for at-home use, especially where acceptance by diverse patient populations can be improved.
  
  
• Beyond the public comment period, which closes on August 30, 2023, CDRH will continue its mission of developing policies and programs to drive health equity in medical devices, including through the Center’s Patient Engagement Advisory Committee, which is scheduled to convene in early September.

eSTAR beta version for pre-submissions to CDRH.

• With an aim to enhance quality, FDA released a beta version of its electronic Submission Template and Resource (eSTAR) program – a free, interactive PDF form that guides applicants through the process of preparing medical device electronic submissions.
  
  
• Earlier this month, FDA made the eSTAR for Pre-Submissions for non-in vitro and in vitro diagnostic devices available for submissions (PreSTAR). While other eSTARs may also be used for submitting 510(k)s to the Center for Biologics Evaluation and Research, PreSTAR is limited to CDRH submissions.
  
  
• As noted in the final guidance issued in 2022, all 510(k) submissions, unless exempted, must be submitted as electronic submissions using eSTAR starting October 1, 2023.

Guidance document on nonclinical evaluation of the immunotoxic potential of pharmaceuticals.

• FDA’s new guidance document, entitled, “Nonclinical Evaluation of the Immunotoxic Potential of Pharmaceuticals,” is designed to assist sponsors in the nonclinical evaluation of the immunotoxic potential of pharmaceuticals (ie, most small-molecule drugs and select classes of biologics).
  
  
• Immunotoxicity, for the purposes of the guidance, refers to both immunosuppression and stimulation which may lead to hyper-sensitivity and other adverse effects.
  
  
• The now finalized version of a February 2020 draft guidance also continues an Agency trend to harmonize with international standards by citing two ICH guidance documents related to immunotoxicity.

Marketing authorization for the Cue COVID-19 Molecular Test.

• On June 6, 2023, FDA granted marketing authorization for the Cue COVID-19 Molecular Test.
  
  
• The authorization marks the Agency’s first full marketing authorization of an at-home COVID-19 test outside of emergency-use authorities.
  
  
• CDRH Director Jeff Shuren remarked that the Cue marketing authorization is “part of the FDA’s broader effort to advance the development and availability of at-home tests for a variety of medical conditions to expand patient access to testing.”

Final guidance on drug-drug interaction assessment.

• On June 2, 2023, FDA issued a final guidance, titled, “Drug-Drug Interaction Assessment for Therapeutic Proteins.” This guidance replaces a draft guidance that was issued in August 2020 with minor revisions. Notably, the final guidance deleted drug-drug interaction (DDI) studies for antibody drug conjugates (ADC) and added physiologically based PK (PBPK) modeling studies as one of the types of DDI assessment.
  
  
• The guidance aims to help sponsors determine whether DDI studies for therapeutic proteins are necessary. Specifically, DDI studies are warranted when the therapeutic proteins are proinflammatory cytokines, or proinflammatory cytokine modulators. In addition, the guidance provides several examples when the mechanisms are unrelated to proinflammatory cytokines, such as when a therapeutic protein affects human physiological processes agonists.
  
  
• The guidance further discusses the different types of DDI assessments, such as in vitro and animal studies, dedicated clinical studies, population pharmacokinetic (PK) modeling (nested DDI studies), and physiologically based PK (PBPK) modeling studies. Notably, FDA highlighted the importance of PBPK modeling studies in understanding the underlying mechanism of a DDI.

FDA to update AccessGUDID Database and OpenFDA.

• On June 7, 2023, FDA announced that the Agency will update the fields released in the public AccessGUDID Database and the openFDA Unique Device Identifier endpoint to include Global Medical Device Nomenclature (GMDN) Term Codes along with the status of the GMDN Term Code, Active or Obsolete. This update aims to provide end users with enhanced search and retrieval capabilities for GUDID data.
  
  
• The update will be released on August 14, 2023. Labelers are encouraged to review their GUDID records and complete their updates by the end of July 2023.

Revised CDRH pre-submission guidance ahead of upcoming MDUFA V changes.

• On June 2, 2023, CDRH released an update to its guidance, titled, “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program.” These updates are being made in advance of anticipated significant revisions in response to MDUFA V requirements.
  
  
• The current update provides additional guidance in several areas such as potential topics for a pre-submission, timing considerations, process for meeting minutes, and mechanisms to obtain feedback outside of the pre-submission process. In addition, the guidance now encourages pre-submission requests for input on Predetermined Change Control Plans (PCCPs), which are required for devices involving artificial intelligence.
  
  
• While these changes are considered "procedural" as a more significant update is being developed, the information addressed could impact those currently planning a pre-submission request and helps clarify the process and scope of such requests.

Advances in international regulatory recognition.

• On May 26, 2023, the UK Medicines and Healthcare products Regulatory Agency (MHRA) announced the introduction of new international recognition routes for the approval of medicines that are already approved by trusted regulatory partners in Australia, Canada, the EU, Japan, Singapore, Switzerland, and the US. The new framework is projected to be in place by the first quarter of 2024. MHRA is working to establish similar streamlined routes for medical devices and, as part of that work, will launch a targeted consultation on medical devices.
  
  
• FDA and the EU announced an expanded scope of the US-EU Mutual Recognition Agreement Sectoral Annex for Pharmaceutical Good Manufacturing Practices (MRA Annex). The MRA Annex originally only covered pharmaceuticals intended for human use, but now covers veterinary pharmaceuticals as well. This is the first step in reciprocal use of US-EU animal drug inspection expertise and resources to produce greater efficiencies.
  
  
• At present, FDA has confirmed that 16 EU Member States (namely Austria, Belgium, Bulgaria, Denmark, Estonia, Finland, France, Greece, Hungary, Ireland, Luxembourg, Netherlands, Poland, Portugal, Slovenia, and Spain) are capable of carrying out GMP inspections for veterinary products at a US-equivalent level. With this expanded MRA Annex, FDA can rely on GMP inspections of veterinary product facilities from these 16 Member States, and the EU will rely on inspections conducted by the FDA.