FDA’s Final Rule on ACNU and updated postmarking safety reporting requirements for Nonprescription Drugs
Regulatory updates

FDA’s Final Rule on ACNU and updated postmarking safety reporting requirements for Nonprescription Drugs

Regulatory updates

The FDA’s final rule on nonprescription drug products with an Additional Condition for Nonprescription Use (ACNU) introduces significant updates to postmarketing safety and reporting requirements goes into effect on January 27, 2025. These changes aim to enhance clarity, streamline reporting obligations, and ensure the ongoing safety of these drugs in real-world use. 

An ACNU is defined as one or more FDA-approved conditions that an applicant must implement to ensure appropriate self-selection, actual use, or both, of a nonprescription drug product without the supervision of a licensed practitioner if the applicant demonstrates and FDA determines when labelling alone is insufficient to guarantee the product’s safe and effective use. 

The rule is applicable to – 

The new rule is not retroactive and does not affect previously approved nonprescription drug products. In certain situations, if FDA withdraws approval of an application for a nonprescription drug product due to the emergence of a safety issue with regard to appropriate self-selection or actual use of the drug product, the applicant could submit a new application for the product as a nonprescription drug product with an ACNU to ensure appropriate self-selection or actual use, as appropriate.

Example of ACNU: 

Examples of ACNU may include consumer questionnaires on secure platforms to assess eligibility for use or risk assessment tools embedded in purchase systems.

For example, Drug X the proposed ACNU requires consumers to complete an online questionnaire hosted on a website developed by the applicant. This questionnaire is designed to calculate a risk score for a specific serious side effect (side effect E) to determine whether the medication is suitable for the individual. The applicant must justify the self-selection process, including the rationale for the questions and the criteria used to calculate the risk score. This justification might involve explaining the algorithm or program logic that assesses the consumer’s responses. If the consumer achieves an acceptable risk score, they would be permitted to purchase Drug X.

Detailed Overview of Postmarketing Safety and Reporting Changes for ACNU:

  • As per the rule, the applicant must develop written procedures for the surveillance, receipt, evaluation, and reporting of ACNU failures to FDA. 
  • Applicants are required to submit reports of ACNU failures, providing clarity on failure conditions to enhance consistency with other postmarketing obligations. 
  • As per the rule, ICSR report of an ACNU failure must be submitted to FDA when an event occurs that differs from the following, as approved by FDA in the application including: 
    • (1) a failure associated with the implementation of one or more of the key elements of an ACNU or
    • (2) a failure associated with operationalization of the ACNU under.
  • A nonprescription drug product with an ACNU that includes a device constituent part is also subject to combination product reporting requirements, including malfunction reporting for an event involving the device constituent part.
  • To submit a report, the applicant must have; An identifiable reporter, drug product name and  description of the failure in implementation. ICSR report must include information about the drug and reporter, narrative summary of the failure and actions initiated or completed to address the failure.
  • Reports must be submitted to the FDA’s Adverse Event Reporting System (FAERS) within 15 calendar days of acquiring the minimum dataset.
  • If new information about a previously reported failure becomes available, the applicant must investigate and assess the impact. Follow-up reports must be submitted within 15 calendar days of obtaining the new information.
  • Applicants are expected to include summaries of ACNU performance in their annual reports. This includes an analysis of reported failures, patterns, and corrective actions taken.

The FDA will use these reports to monitor real-world use of ACNU-based nonprescription drugs. This data may inform regulatory decisions, including additional labeling requirements or modifications to approved ACNUs. 

ACNU Failure definition and examples:
A failure in the implementation of an ACNU refers to any deviation from the approved ACNU process that may cause or lead to inappropriate medication use or consumer harm. This includes instances where:

  1. The consumer accesses or uses the drug product without fulfilling the ACNU.
  2. The consumer fulfills the ACNU but is unable to access or use the drug product appropriately.
  3. The consumer cannot attempt to fulfill the ACNU due to systematic, technological, or mechanical issues.

Additionally, new MedDRA terms have been added to describe certain ACNU failures, ex. Failure of additional condition for non-prescription use or Issue with additional condition for nonprescription use. 

Examples:

  • For a fictitious drug “Drug X” with an ACNU requiring a consumer to complete an online questionnaire, a report would be necessary if a malfunction prevents eligible consumers from completing the questionnaire or accessing the drug.
  • If a consumer misuses the product due to inaccurate responses in an ACNU questionnaire, the incident must be reported if it leads to an adverse event.
  • If a digital tool integrated into the drug’s dispensing process incorrectly approves ineligible consumers, the failure must be reported and addressed.

The reporting system reflects the FDA’s commitment to safeguarding public health while fostering accountability among applicants to ensure the success of ACNU-based nonprescription drug products.

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