Contains Nonbinding Recommendations Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including During the Public Health Emergency (COVID-19) Guidance for Industry January 2021 U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) Center for Veterinary Medicine (CVM) Current Good Manufacturing Practice (CGMP) Contains Nonbinding Recommendations Preface Public Comment This guidance is being issued to address the Coronavirus Disease 2019 (COVID-19) public health emergency. This guidance is being implemented without prior public comment because the Food and Drug Administration (FDA or the Agency) has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency’s good guidance practices. Comments may be submitted at any time for Agency consideration. Submit written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to https://www.regulations.gov. All comments should be identified with the docket number FDA-2020-D-2016 and complete title of the guidance in the request. Additional Copies Additional copies are available from the FDA webpage titled “COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders,” available at https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/covid-19-related- guidance-documents-industry-fda-staff-and-other-stakeholders, and the FDA Webpage titled “Hand Sanitizers | COVID-19” available at: https://www.fda.gov/drugs/coronavirus-covid- 19-drugs/hand-sanitizers-covid-19, and the FDA webpage titled “Search for FDA Guidance Documents,” available at https://www.fda.gov/regulatory-information/search-fda-guidance- documents. You may also send an e-mail request to [email protected] to receive an additional copy of the guidance. Please include the document number FDA-2020-D-2016 and complete title of the guidance in the request. Questions For questions regarding ethanol or isopropyl alcohol for use in hand sanitizer products, contact FDA at [email protected]. For other questions regarding this document contact the applicable Center at: CDER (Email: [email protected]), CBER (Email: [email protected]), or CVM (Email: [email protected]). Contains Nonbinding Recommendations TABLE OF CONTENTS I. INTRODUCTION .......................................................................................................... 1 II. BACKGROUND ............................................................................................................. 3 III. POLICY ON TESTING FOR METHANOL …………………………………………...6 Contains Nonbinding Recommendations Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including During the Public Health Emergency (COVID-19) Guidance for Industry1 This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the title page. I. INTRODUCTION The Food and Drug Administration (FDA or Agency) plays a critical role in protecting the United States from emerging infectious diseases, such as the Coronavirus Disease 2019 (COVID-19) pandemic. FDA is committed to providing timely guidance to support continuity and response efforts to this pandemic. This guidance is intended to alert pharmaceutical manufacturers2 and pharmacists in State- licensed pharmacies or Federal facilities who engage in drug compounding3 to the potential public health hazard of alcohol (ethyl alcohol or ethanol) or isopropyl alcohol contaminated with or substituted with methanol. FDA is aware of reports of fatal methanol poisoning of consumers who ingested alcohol-based hand sanitizers that were manufactured with methanol or methanol-contaminated ethanol.4 FDA has also received numerous reports of dermal toxicity associated with such products. 1 This guidance was developed by the Center for Drug Evaluation and Research (CDER), Food and Drug Administration, in cooperation with the Center for Biologics Evaluation and Research and the Center for Veterinary Medicine. 2 For the purposes of this guidance, references to “manufacturers” include registered outsourcing facilities because outsourcing facilities are subject to current good manufacturing practice (CGMP) requirements. See section 503B(a) of the Federal, Food, Drug, and Cosmetic Act (FD&C Act); see also draft guidance for industry Current Good Manufacturing Practice—Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act. When finalized, this guidance will represent the FDA’s current thinking on this topic. For the most recent version of a guidance, check the FDA guidance web page at https://www.fda.gov/regulatory- information/search-fda-guidance-documents. References to “manufacturers” also include repackers, relabellers, and suppliers of alcohol. 3 See section 503A of the FD&C Act. 4 Yip L, Bixler D, Brooks DE, et al. Serious Adverse Health Events, Including Death, Associated with Ingesting Alcohol-Based Hand Sanitizers Containing Methanol — Arizona and New Mexico, May–June 2020. MMWR Morb Mortal Wkly Rep 2020;69:1070–1073. DOI: http://dx.doi.org/10.15585/mmwr.mm6932e1external icon. 1 Contains Nonbinding Recommendations FDA also is concerned that other drug products containing ethanol or isopropyl alcohol (pharmaceutical alcohol5), which are widely used active ingredients in a variety of drug products, could be similarly vulnerable to methanol contamination. For example, certain inhalation products, mouthwashes, cough and cold products, and many topical drug products include pharmaceutical alcohol. As the COVID-19 pandemic has increased the demand for hand sanitizer products, the demand for pharmaceutical alcohol as the active ingredient of those products has also increased. In the past, increased stress on supply chains has made ingredients more vulnerable to economically motivated adulteration. For these reasons, the policy outlined in this guidance applies to pharmaceutical alcohol used as an active or inactive ingredient in a drug regardless of whether the drug product is a hand sanitizer. This policy will help pharmaceutical manufacturers and pharmacists who engage in drug compounding avoid using pharmaceutical alcohol contaminated with or substituted with methanol in drug products.6 The Agency is issuing this guidance to communicate its policy for the duration of the public health emergency declared by the Secretary of Health and Human Services (HHS) on January 4 31, 2020, including any renewals made by the HHS Secretary in accordance with section 319(a)(2) of the Public Health Service Act (PHS Act) (42 U.S.C. 247d(a)(2)). At such time when the public health emergency is over, as declared by the Secretary, FDA intends to reassess this guidance. FDA is continually assessing the needs and circumstances related to this policy, and as relevant needs and circumstances evolve, FDA intends to update or modify this policy as appropriate. Therefore, within 60 days following the termination of the public health emergency, FDA intends to revise and replace this guidance with any appropriate changes based on comments received on this guidance and the Agency’s experience with implementation. Given this public health emergency, and as discussed in the Notice in the Federal Register of March 25, 2020 (85 FR 16949), titled “Process for Making Available Guidance Documents Related to Coronavirus Disease 2019,” available at https://www.govinfo.gov/content/pkg/FR- 2020-03-25/pdf/2020-06222.pdf, this guidance is being implemented without prior public comment because the FDA has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C)(i) of the FD&C Act (21 U.S.C. 371(h)(1)(C)(i)) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency’s good guidance practices. The contents of this document do not have the force and effect of law and are not meant to bind the public in any way, unless specifically incorporated into a contract. This document is intended only to provide clarity to the public regarding existing requirements under the law. FDA guidance documents, including this guidance, should be viewed only as recommendations, unless 5 For the purposes of this guidance, we use the term pharmaceutical alcohol to mean either ethanol (ethyl alcohol) or isopropyl alcohol (2-propanol). Both are used as an active ingredient in alcohol-based hand sanitizers and may be used in other drug products as an active or inactive ingredient. 6 In this guidance, “drug” and “drug product” include both human and animal drugs and biological products. 2 Contains Nonbinding Recommendations specific regulatory or statutory requirements are cited. The use of the word should in FDA guidances