FDA Regulatory News and Trends - August 18, 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.

QTc information in human prescription drug and biological product labeling.

• On August 8, 2023, FDA issued a draft guidance advising manufacturers of non-antiarrhythmic human prescription drug and biological products to incorporate corrected QT (QTc) interval prolongation related information into the labeling. 
  
  
• The draft guidance recommends a boxed warning for QTc interval prolongation when there is reasonable evidence of a causal association between the drug and any of the following conditions: cardiac death with QTc interval prolongation, torsade de pointes (TdP), polymorphic ventricular tachycardia, signs or symptoms of serious or life-threatening arrythmias, or other life-threatening cardiac adverse reactions with QTc interval prolongation. 
  
  
• Using a fictitious drug, FDA provided examples of recommended statement to describe the effect of a drug on the QTc Interval and recommended dosage modification for QTc prolongation. 
  
  
• Interested parties should submit comments on or before October 10, 2023. 
  
  

Draft guidance on clinical considerations for studies of devices intended to treat opioid use disorder.

• On July 27, 2023, FDA issued new draft guidance setting out its current thinking on the design and development of opioid use disorder (OUD) device studies, including key definitions, clinical outcomes, and considerations for the patient population.
  
  
• The draft guidance aligns with FDA’s current final guidance on the same subject for drug sponsors and aims to provide consistency across OUD treatment trials.
  
  
• The draft guidance acknowledges the complexities and operational challenges with studying OUD treatments, including subjective outcomes, placebo effects, concomitant treatments, and potential bias, and encourages sponsors to develop alternative methodologies to overcome these challenges. 
  
  
• The guidance is open for comment through October 26, 2023.

CDRH releases guidance for hydrogen peroxide-based contact lens care products.

• On July 27, 2023, the Center for Devices and Radiological Health (CDRH) published a new guidance document titled, “Hydrogen Peroxide-Based Contact Lens Care Products: Consumer Labeling Recommendations - Premarket Notification (510(k)) Submissions.”
  
  
• The guidance provides industry with recommendations on the content of labeling for hydrogen peroxide-based contact lens care products. CDRH notes that this information is important because serious eye injuries have occurred due to misuse of these products.
  
  
• Companies manufacturing these products should update labeling (including carton, package insert, and bottle labeling) to provide additional and clearer information to consumers on proper use and risks as detailed in the guidance.

 
CDER releases guidance on acceptable intake limits for nitrosamine drug substance-related impurities.

• On August 4, 2023, the Center for Drug Evaluation and Research (CDER) published a new guidance document titled, “Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities.”
  
  
• Nitrosamine drug substance-related impurities (NDSRIs) have been identified in many drug products. The latest guidance provides industry with a framework for predicting the mutagenic and carcinogenic potential of NDSRIs and recommends acceptable intake limits.
  
  
• CDER explains that APIs that contain secondary amine or dimethyl tertiary amine centers are at risk of forming NDSRIs by nitrosation of the amine center. Due to the complex nature of this area, CDER has also published an accompanying website to further aid companies who may be impacted by these new recommendations.

Two draft guidance documents on the development of PEPFAR products.

• On August 3, 2023, FDA released two new draft guidance documents: “PDUFA Waivers, Reductions, and Refunds for Fixed-Combinations and Single-Entity Versions of Previously Approved Antiretrovirals under PEPFAR” (PDUFA draft guidance) and “Fixed-Combinations and Single-Entity Versions of Previously Approved Antiretrovirals for the Treatment or Prevention of HIV-1 Under PEPFAR” (Previously Approved Antiretrovirals draft guidance).
  
  
• The PDUFA draft guidance describes circumstances under which an applicant may be eligible for a barrier-to-innovation waiver under PDUFA for certain new drug applications for single-entity and fixed-combination antiretroviral drug products for the treatment or prevention of HIV-1.  This is an updated version of a previous guidance finalized by FDA in February 2007 and then updated in draft form in June 2018.  
  
  
• The Previously Approved Antiretrovirals draft guidance provides recommendations for applications for single-entity and fixed-combination antiretroviral drug products for the treatment or prevention of HIV-1 infection that are intended for procurement under the President’s Emergency Plan for AIDS Relief (PEPFAR).  When finalized, this guidance will replace the previous final guidance for industry, “Fixed Dose Combinations, Co-Packaged Drug Products, and Single-Entity Versions of Previously Approved Antiretrovirals for the Treatment of HIV,” issued in October 2006.
  
  
• Comments on the PDUFA draft guidance are due on October 2, 2023, and comments on the Previously Approved Antiretrovirals draft guidance are due on November 1, 2023. 
  
  

Final guidance on waivers, exceptions, and exemptions from Section 582 requirements.

• On August 4, 2023, FDA released a Guidance for Industry addressing waivers, exceptions, and exemptions from the requirements of the Drug Supply Chain Security Act (DSCSA). The DSCSA outlines requirements for manufacturers, repackagers, wholesale distributors, dispensers, and third-party logistics providers (trading partners) to facilitate the efficient distribution and availability of drug products in the US.
  
  
• There are three pathways to obtain a waiver, exception, or exemption from the DSCSA: (1) authorized manufacturers, wholesale distributors, or dispensers (under section 582(a)(3)(A)(i) of the FD&C Act); (2) manufacturers or repackagers (under section 582(a)(3)(A)(ii); and (3) any interested stakeholder (under section 582(a)(3)(A)(iii)).
  
  
• In addition to providing recommendations related to the form of a request, the guidance states that the primary factors governing the approval of a request include (1) undue economic hardship, (2) emergency medical reasons, (3) the container of the product package proving too small to accommodate a label containing the required information, and (4) that approval is otherwise appropriate to maintain public health.  FDA will also consider the potential risks that a proposed waiver, exception, or exemption may pose to the security of the supply chain; if the submission seeks a waiver, exception, or exemption that could affect a broad segment of industry and/or multiple trading partners, FDA may deny or defer the request if it determines that an FDA-initiated exception, exemption, or other regulatory action would be more appropriate.
  
  
• If FDA denies a request, FDA will accept a request for reconsideration, provided the request explains the nature of the issue and identifies any new information that would justify a change in FDA’s prior conclusions.  FDA recommends a reconsideration request be submitted no later than 12 business days after the denial.

Draft guidance on cosmetic facility registration and product listing.

• On August 7, 2023, FDA issued a draft guidance on cosmetic facility registrations and product listings, pursuant to its new authorities under the Modernization of Cosmetics Regulation Act of 2022 (MoCRA).  The draft guidance, once finalized, will provide specific procedures and the timeline for facility registration and product listing requirements. 
  
  
• Certain small businesses and drug/device facilities are exempt from the section 607 requirement. In addition, certain types of facilities that are not included under MoCRA, such as beauty shops and salons, cosmetic product retailers, and trade shows where free cosmetic samples are provided, among others. 
  
  
• All covered facilities and products are expected to submit the required information on or before December 29, 2023.  A new electronic submission portal will be available for submitting registration and product listing information in October 2023, and FDA will also provide a paper form as an alternative submission tool, although electronic submission is strongly preferred.  
  
  
• Interested parties should submit the comments on or before September 7, 2023.

Final guidance on assessing user fees under BsUFA reauthorization.

• Following the recent passing of the Biosimilar User Fee Act III, which covers fiscal years 2023-2027, the final guidance elaborates on approved user fees, FDA's criteria for determining which products are subject to those fees, and the Agency's guidelines concerning exceptions and waivers. 
  
  
• The guidance also outlines the procedure for making payments to FDA and the possible consequences for failing to remit required BsUFA fees, as well as the process for requesting reconsideration if the FDA denies a waiver or refund of user fees.
  
  
• Biosimilar program fees decreased substantially for the second year in a row based on the Agency’s expected biosimilar application volume. FDA estimated that a total of 120 biosimilar programs would be active in fiscal year 2024 and projected that it would receive 14 biosimilar applications for approval, representing an increase that will help drive down annual costs for each individual user.

Guidance on CDER’s Quality Standards Program.

• On July 27, 2023, CDER finalized its 2019 draft guidance establishing its Program for the Recognition of Voluntary Consensus Standards Related to Pharmaceutical Quality. The program includes a comprehensive listing of recognized voluntary consensus standards related to pharmaceutical quality that apply to all drugs, from branded to OTC products, as well as drug constituent parts of combination products.  FDA has used such standards to develop and/or evaluate performance characteristics of dosage forms, testing methodologies, manufacturing practices, product standards, scientific protocols, ingredient specifications, labeling of drug products, and other technical or policy criteria.
  
  
• Currently, when a standard is referenced in an application, CDER must determine whether it is acceptable, scientifically sound, and aligned with FDA policies. CDER’s Quality Standards Program streamlines application assessment by recognizing voluntary consensus standards and partially removing this burden from the assessor so that they will only need to consider whether the applicant has used a recognized standard appropriately. 
  
  
• More specifically, the guidance adds FAQs and clarifies CDER’s process of recognizing a new standard while confirming that FDA can still request additional information even if a standard is recognized for a particular use. The document also explains the CDER’s practice of recognizing parts of standards when a standard as a whole conflicts with an existing regulation or published guidance.