FDA Regulatory News and Trends - August 4, 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.

HHS letter to COVID-19 vaccine manufacturers.

• On July 13, 2023, US Department of Health and Human Services (HHS) Secretary Xavier Becerra sent a letter to COVID-19 vaccine manufacturers stating that HHS expects manufacturers to 1) offer updated COVID-19 vaccines and 2) prepare to provide supplies that are sufficient to meet “potential surges in demand and evolving circumstances of COVID-19.”  
• The letter advises manufacturers to “plan the updated COVID-19 vaccine supply and regulatory submissions” so that FDA can “take regulatory action” and CDC can “make recommendations on the vaccination by the latter part of September.”  
• The letter states that “updated COVID-19 vaccines entering the market this fall should be priced at a reasonable rate, reflective of the value that you have obtained through U.S. government investment.”  Secretary Becerra also requested manufacturers to “find sustainable ways to enable continued visibility of the provider network and availability of vaccines,” continuing that the “sharing of information with government partners is fundamental to maintaining our mutual commitment to equity.”
• The letter closes with a plug for HHS’s “Bridge Access Program For COVID-19 Vaccines and Treatments,” under which CDC will purchase vaccines from manufacturers to provide access to vaccines and treatments for adults without other sources of coverage.  The program is also designed to facilitate access to vaccines that manufacturers have previously committed to providing for uninsured or underinsured adults, which will be supported via a partnership between the federal government and pharmacies, rather than with manufacturers.
  
  

Updated guidance on qualification for medical device development tools.

• New guidance sets out FDA’s latest thinking on a voluntary framework for qualification of medical device development tools (MDDTs) for use in evaluating medical devices, replacing previous guidance issued in 2017.
• The reorganized guidance includes new and updated definitions, along with an expanded list of regulatory use cases.
• The updates to the guidance clarify the process for submitting a MDDT proposal for qualification, which consists of two steps: 1) the proposal phase, to determine whether the MDDT is appropriate for qualification; and 2) the qualification phase, which includes assessment of qualification evidence. 
• The regulatory considerations for using MDDTs, and the process by which FDA will communicate about MDDT qualifications, remain unchanged.
  FDA approves the first nonprescription daily oral contraception.
• On July 13, 2023, FDA approved the Opill (norgestrel) tablet for over-the-counter (OTC) use to prevent pregnancy, making it the first nonprescription daily oral contraceptive in the US. Opill will be available at drug stores, convenience stores, grocery stores, and online stores.  
• Opill was originally approved as an oral contraceptive drug for prescription use in 1976. In June 2022, HRA Pharma submitted a supplemental new drug application (sNDA), requesting to switch Opill to an OTC product. The application was significantly amended last year, which extended the goal date by three months.
• To support the switch, the sponsor was required to provide consumer behavior data that demonstrated consumers’ likelihood of using the drug safely and effectively without the intervention of a healthcare provider. HRA Pharma’s evidence showed that the majority of consumers understood “almost all” important label instructions, which supports their ability to use the drug properly.
  
  

Draft guidance on good cause for noncompliance with FDA’s postmarketing studies requirement and clinical trials.

• On July 14, 2023, FDA issued a draft guidance titled, “Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the FDCA.” The draft guidance does not apply to postmarket requirements (PMRs) for pediatric studies, trials required as a condition of accelerated approval, and trials required for drugs approved under the “animal rule.” In addition, the draft guidance does not apply to nonprescription drugs. 
• Under Section 505(o)(3), FDA can require postmarketing studies if “the FDA becomes aware of new safety information” associated with the drug.  The statute requires an applicant to periodically report on the status of each PMR. Noncompliance with the reporting requirement may lead to enforcement actions in the absence of a demonstration of “good cause.”
• FDA considers PMR noncompliance to be reasonable in the following circumstances: 1) The circumstance is directly related to the missed milestone, 2) the circumstance was out of the applicant’s control, and 3) the circumstance could not have been reasonably anticipated and factored in at the time the original PMR timetable was finalized. The draft guidance additionally provides several examples, illustrating situations FDA would or would not consider reasonable under the circumstances.
• Interested parties should submit comments on or before September 12, 2023. 
  
  

Draft guidance for cell and gene therapy products.

• On July 14, 2023, FDA published a new draft guidance titled, “Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products.”  
• The guidance is intended to outline FDA’s current thinking on management and reporting of manufacturing changes for cell and gene therapy products based on a lifecycle approach.  The guidance provides sponsors of Investigational New Drug (IND) Applications and Biologics License Applications (BLA) for cell and gene therapy products with recommendations regarding product comparability.  
• The draft guidance includes recommendations for strong risk management procedures throughout the product lifecycle, as well as recommends basing shelf life on real-time stability data obtained at the long-term storage condition.  The draft guidance also reminds IND and BLA sponsors to notify FDA of manufacturing changes through an IND amendment, BLA supplement, or annual report.  
• The comment period for the guidance closes on September 12, 2023.
  
  

FDA adopts ICH guideline on mutagenic impurities.

• On July 25, 2023, FDA announced that it had adopted the International Council for Harmonization’s (ICH) guideline, “M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk,” including the “M7(R2) Addendum: Application of the Principles of the ICH M7 Guidance to Calculation of Compound-Specific Acceptable Intakes,” and a Q&A document, “M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk: Questions and Answers.”
• ICH initially released the documents for adoption in April 2023, but FDA officially adopted them on July 24, 2023.  
• The M7 guideline was first released in 2014 and was intended to provide a unified approach to address genotoxic impurities, which can cause cancer.  The guideline is intended to provide a practical framework applicable to the identification, categorization, qualification, and control of mutagenic impurities to limit potential carcinogenic risk.  
• The guideline was revised in 2017 to include an addendum.  The final guideline splits the addendum from the guideline itself, and the addendum includes seven new monographs and updates to others.  The addendum additionally lists acceptable intakes or permissible daily exposures for a set of chemicals considered to be mutagens and carcinogens and which are common in pharmaceutical manufacturing.  
• The new Q&A document is intended to provide additional clarification and improve harmonization of the considerations for assessment and control of DNA reactive (mutagenic) impurities and of the information that should be provided during drug development, marketing authorization applications, and/or master files submissions.