2021-03548. Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including During the Public Health Emergency (COVID-19); Guidance for Industry; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice of availability.

SUMMARY:

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including During the Public Health Emergency (COVID-19).” This guidance is intended to alert pharmaceutical manufacturers and pharmacists in State-licensed pharmacies or Federal facilities who engage in drug compounding 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 and is concerned that other drug products containing ethanol or isopropyl alcohol (pharmaceutical alcohol), which are widely used active ingredients in a variety of drug products, could be similarly vulnerable to methanol contamination. 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. The guidance outlines a policy intended to help pharmaceutical manufacturers and pharmacists in State-licensed pharmacies or Federal facilities who engage in drug compounding avoid the use of pharmaceutical alcohol that is contaminated with or substituted with methanol in drug products. Given the public health emergency presented by coronavirus disease 2019 (COVID-19), this guidance document is being implemented without prior public comment because FDA has determined that prior public participation is not feasible or appropriate, but it remains subject to comment in accordance with the Agency's good guidance practices.

DATES:

The announcement of the guidance is published in the Federal Register on February 23, 2021. The guidance document is immediately in effect, but it remains subject to comment in accordance with the Agency's good guidance practices.

ADDRESSES:

You may submit either electronic or written comments on Agency guidances at any time as follows:

Electronic Submissions

Submit electronic comments in the following way:

• Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov.
• If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Written/Paper Submissions

Submit written/paper submissions as follows:

• Mail/Hand Delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”

Instructions: All submissions received must include the Docket No. FDA-2020-D-2016 for “Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including During the Public Health Emergency (COVID-19).” Received comments will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.

• Confidential Submissions—To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.govinfo.gov/​content/​pkg/​FR-2015-09-18/​pdf/​2015-23389.pdf.

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, 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.

You may submit comments on any guidance at any time (see 21 CFR 10.115(g)(5)).

Submit written requests for single copies of the guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002; or to the Office of Communication, Outreach and Development, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT:

Francis Godwin, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 4342, Silver Spring, MD 20993-0002, 301-796-5362; or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911; or Julie Bailey, Center for Veterinary Medicine (HFV-140), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 240-402-0700.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry entitled “Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including During the Public Health Emergency (COVID-19).” This guidance is intended to alert pharmaceutical manufacturers ^[1] and pharmacists in State-licensed pharmacies or Federal facilities who engage in compounding to the potential public health hazard of alcohol (ethyl alcohol or ethanol) or isopropyl alcohol (collectively “pharmaceutical alcohol” ^[2] ) 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 and is concerned that other drug products containing pharmaceutical alcohol, which are widely used active ingredients in a variety of drug products, could be similarly vulnerable to methanol contamination. 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.

The guidance outlines a policy intended to help pharmaceutical manufacturers and pharmacists in State-licensed pharmacies or Federal facilities who engage in compounding avoid the use of pharmaceutical alcohol that is contaminated with or substituted with methanol in drug products. The policy outlined in the guidance includes, but is not limited to: (1) Performing a specific identity test that includes a limit test for methanol on each container within each shipment of each lot of pharmaceutical alcohol before the component is used in the manufacture or preparation of drug products; (2) knowing the entities in pharmaceutical manufacturers' supply chain for pharmaceutical alcohol (i.e., knowing the identities and appropriately qualifying the manufacturer of the pharmaceutical alcohol and any subsequent distributor(s)); (3) ensuring that all personnel in pharmaceutical manufacturing facilities (especially personnel directly responsible for receipt, testing, and release of pharmaceutical alcohol) are made aware of the importance of proper testing and the potential hazards if the testing is not done; and (4) establishing finished product test methods to ensure that when testing for ethanol or isopropyl alcohol content (assay), the method also distinguishes between the active ingredient and methanol. The policy outlined in this guidance applies to pharmaceutical alcohols used as an active or inactive ingredient in a drug.

In light of the public health emergency related to COVID-19 declared by the Secretary of the Department of Health and Human Services (HHS), FDA has determined that prior public participation for this guidance is not feasible or appropriate and is issuing this guidance without prior public comment (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. FDA will review comments, and the guidance will be updated accordingly.

This guidance is intended to remain in effect for the duration of the public health emergency related to COVID-19 declared by HHS, including any renewals made by the Secretary in accordance with section 319(a)(2) of the Public Health Service Act (42 U.S.C. 247d(a)(2)). However, the recommendations and processes described in the guidance are expected to assist the Agency more broadly in its efforts to ensure that pharmaceutical alcohol that is contaminated with or substituted with methanol is not used in drug products beyond the termination of the COVID-19 public health emergency and reflect the Agency's current thinking on this issue. 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.

This guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidance represents the current thinking of FDA on “Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including During the Public Health Emergency (COVID-19).” 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.

II. Paperwork Reduction Act of 1995

While this guidance contains no collection of information, it does refer to previously approved FDA collections of information. Therefore, clearance by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not required for this guidance. The previously approved collections of information are subject to review by OMB under the PRA. The collections of information in 21 CFR part 314 have been approved under OMB control number 0910-0001; the collections of information in 21 CFR part 312 have been approved under OMB control number 0910-0014; the collections of information in 21 CFR part 601 have been approved under OMB control number 0910-0338; and the collections of information in 21 CFR parts 210 and 211 have been approved under OMB control number 0910-0139.

III. Electronic Access

Persons with access to the internet may obtain the guidance at https://www.fda.gov/​drugs/​guidance-compliance-regulatory-information/​guidances-drugs,, https://www.fda.gov/​vaccines-blood-biologics/​guidance-compliance-regulatory-information-biologics,, https://www.fda.gov/​emergency-preparedness-and-response/​coronavirus-disease-2019-covid-19/​covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders,, or https://www.regulations.gov.

Dated: February 16, 2021.

Lauren K. Roth,

Acting Principal Associate Commissioner for Policy.

Footnotes

1.  References to “manufacturers” includes registered outsourcing facilities, repackers, relabellers, and suppliers of alcohol.

2.  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.