Nonprescription Drug Product With an Additional Condition for Nonprescription Use

<RULE> DEPARTMENT OF HEALTH AND HUMAN SERVICES <SUBAGY>Food and Drug Administration</SUBAGY> <CFR>21 CFR Parts 201 and 314</CFR> <DEPDOC>[Docket No. FDA-2021-N-0862]</DEPDOC> <RIN>RIN 0910-AH62</RIN> <SUBJECT>Nonprescription Drug Product With an Additional Condition for Nonprescription Use</SUBJECT> <HD SOURCE="HED">AGENCY:</HD> Food and Drug Administration, Department of Health and Human Services (HHS). <HD SOURCE="HED">ACTION:</HD> Final rule. <SUM> <HD SOURCE="HED">SUMMARY:</HD> The Food and Drug Administration (FDA, the Agency, or we) is issuing a final rule to establish requirements for a nonprescription drug product with an additional condition for nonprescription use (ACNU). A nonprescription drug product with an ACNU is a drug product that could be marketed without a prescription if an applicant implements an additional condition to ensure appropriate self-selection or appropriate actual use, or both, by consumers without the supervision of a practitioner licensed by law to administer such drug. The final rule is intended to increase options for applicants to develop and market safe and effective nonprescription drug products and increase consumer access to appropriate, safe, and effective drug products, which could improve public health. </SUM> <EFFDATE> <HD SOURCE="HED">DATES:</HD> This rule is effective January 27, 2025. </EFFDATE> <HD SOURCE="HED">ADDRESSES:</HD> For access to the docket to read background documents or comments received, go to <E T="03">https://www.regulations.gov</E> and insert the docket number found in brackets in the heading of this final rule into the “Search” box and follow the prompts, and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500. <FURINF> <HD SOURCE="HED">FOR FURTHER INFORMATION CONTACT:</HD> <E T="03">With regard to the final rule:</E> Myla Dellupac, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Silver Spring, MD 20993-0002, 301-837-7461. <E T="03">With regard to the information collection:</E> Amber Sanford, Office of Operations, Food and Drug Administration, Three White Flint North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-8867, <E T="03">PRAStaff@fda.hhs.gov.</E> </FURINF> <SUPLINF> <HD SOURCE="HED">SUPPLEMENTARY INFORMATION:</HD> <HD SOURCE="HD1">Table of Contents</HD> <EXTRACT> <FP SOURCE="FP-1">I. Executive Summary</FP> <FP SOURCE="FP1-2">A. Purpose of the Final Rule</FP> <FP SOURCE="FP1-2">B. Summary of the Major Provisions of the Final Rule</FP> <FP SOURCE="FP1-2">C. Legal Authority</FP> <FP SOURCE="FP1-2">D. Benefits, Costs, and Transfers</FP> <FP SOURCE="FP-1">II. Table of Abbreviations/Commonly Used Acronyms in This Document</FP> <FP SOURCE="FP-1">III. Background</FP> <FP SOURCE="FP1-2">A. Need for the Regulation</FP> <FP SOURCE="FP1-2">B. FDA's Regulatory Framework</FP> <FP SOURCE="FP1-2">C. History of the Rulemaking</FP> <FP SOURCE="FP1-2">D. Summary of Comments to the Proposed Rule</FP> <FP SOURCE="FP1-2">E. General Overview of the Final Rule</FP> <FP SOURCE="FP-1">IV. Legal Authority</FP> <FP SOURCE="FP-1">V. Comments on the Proposed Rule and FDA Response</FP> <FP SOURCE="FP1-2">A. Introduction</FP> <FP SOURCE="FP1-2">B. Description of General Comments and FDA Responses</FP> <FP SOURCE="FP1-2">C. Comments on Applicability and FDA Responses</FP> <FP SOURCE="FP1-2">D. Comments on Definition and FDA Responses</FP> <FP SOURCE="FP1-2">E. Comments on Separate Application Required for a Nonprescription Drug Product With an ACNU and FDA Responses</FP> <FP SOURCE="FP1-2">F. Comments on Specific Requirements for an Application for a Nonprescription Drug Product With an ACNU and FDA Responses</FP> <FP SOURCE="FP1-2">G. Comments on Nonprescription and Prescription Approval and Simultaneous Marketing and FDA Responses</FP> <FP SOURCE="FP1-2">H. Comments on Refusal To Approve an Application With an ACNU and FDA Response</FP> <FP SOURCE="FP1-2">I. Comments on Other Postmarketing Reports and FDA Responses</FP> <FP SOURCE="FP1-2">J. Comments on General Labeling Requirements and FDA Responses</FP> <FP SOURCE="FP1-2">K. Comments on Format Requirements for Required ACNU Statement and FDA Responses</FP> <FP SOURCE="FP1-2">L. Comments on Exemption From Adequate Directions for Use and FDA Responses</FP> <FP SOURCE="FP1-2">M. Comment on Misbranding and FDA Response</FP> <FP SOURCE="FP1-2">N. Miscellaneous Comments and FDA Responses</FP> <FP SOURCE="FP-1">VI. Effective Date</FP> <FP SOURCE="FP-1">VII. Economic Analysis of Impacts</FP> <FP SOURCE="FP1-2">A. Introduction</FP> <FP SOURCE="FP1-2">B. Summary of Benefits, Costs, and Transfers</FP> <FP SOURCE="FP-1">VIII. Analysis of Environmental Impact</FP> <FP SOURCE="FP-1">IX. Paperwork Reduction Act of 1995</FP> <FP SOURCE="FP-1">X. Federalism</FP> <FP SOURCE="FP-1">XI. Consultation and Coordination With Indian Tribal Governments</FP> <FP SOURCE="FP-1">XII. References</FP> </EXTRACT> <HD SOURCE="HD1">I. Executive Summary</HD> <HD SOURCE="HD2">A. Purpose of the Final Rule</HD> FDA is finalizing this rule to establish requirements for a nonprescription drug product with an ACNU. A nonprescription drug product with an ACNU is a drug product that could be legally marketed without a prescription if an applicant implements an additional condition to ensure appropriate self-selection or appropriate actual use, or both, by consumers without the supervision of a practitioner licensed by law to administer such drug. Without this rule, nonprescription drug products are limited to drug products that can be labeled with sufficient information for consumers to appropriately self-select and use the drug product without the supervision of a practitioner licensed by law to administer such drug. For certain drug products, labeling alone cannot adequately communicate the information needed for consumers to appropriately self-select or use the drug product without the supervision of a practitioner licensed by law to administer such drug. The final rule is intended to increase options for applicants  <SU>1</SU> <FTREF/> to develop and market safe and effective nonprescription drug products and increase consumer access to appropriate, safe, and effective drug products, which could improve public health. <FTNT> <SU>1</SU>  While we recognize that in certain circumstances “sponsor” is the correct term for the person who would be developing a nonprescription drug product with an ACNU, we used the term “applicant” throughout the final rule for consistency (see the definition for applicant in 21 CFR 314.3(b) and for sponsor in 21 CFR 312.3(b)). </FTNT> <HD SOURCE="HD2">B. Summary of the Major Provisions of the Final Rule</HD> This final rule establishes requirements for a nonprescription drug product with an ACNU, including application, labeling, and postmarketing reporting requirements. In addition to applicable existing application requirements, the final rule establishes the specific requirements for a new drug application (NDA) or abbreviated new drug application (ANDA) for a nonprescription drug product with an ACNU. In circumstances where a prescription drug product is already approved, the rule requires an applicant to submit a separate application for the approval of a nonprescription drug product with an ACNU, rather than a supplement to the existing application for the approved prescription drug product. The final rule establishes specific labeling requirements, including the content and format of specific labeling statements. Additionally, the rule requires that an applicant submit a postmarketing report of an ACNU failure. The final rule clarifies that an ACNU constitutes a meaningful difference  <FTREF/> <SU>2</SU> between a prescription drug product and a nonprescription drug product that makes the nonprescription drug product safe and effective for use without the supervision of a practitioner licensed by law to administer such drug; therefore, a prescription drug product and a nonprescription drug product with an ACNU with the same active ingredient may be simultaneously marketed even if they do not have meaningful differences other than the ACNU, such as different indications or strengths. <FTNT> <SU>2</SU>  FDA has used the terms “meaningful difference” and “clinically meaningful difference” interchangeably. Both refer to the same scientific determination. See, <E T="03">e.g.,</E> 83 FR 13994 (April 2, 2018) and 87 FR 68702 (November 16, 2022). </FTNT> The final rule specifies that FDA will refuse to approve an application for a nonprescription drug product with an ACNU if the application fails to meet applicable requirements. The final rule exempts a nonprescription drug product with an ACNU from the requirement to be labeled with adequate directions for use, provided that certain labeling conditions are met and the ACNU is implemented by the applicant as approved by FDA. Finally, the final rule explains certain circumstances in which a nonprescription drug product with an ACNU would be misbranded. FDA received many comments supporting the proposed rule's intent to increase options for applicants to develop and market safe and effective nonprescription drug products and increase consumer access to appropriate, safe, and effective drug products. Additionally, we received comments expressing concerns about certain proposed requirements and the burden of those requirements for applicants. In response to several comments expressing concerns about the proposed postmarketing reporting requirements for nonprescription drug products with an ACNU, we are revising the proposed requirements to provide greater clarity for when a postmarketing report of ACNU failure must be submitted to FDA and to reduce the burden on applicants by decreasing any po ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Preview showing 10k of 322k characters. Full document text is stored and available for version comparison. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━