[Federal Register Volume 88, Number 199 (Tuesday, October 17, 2023)]
[Notices]
[Pages 71576-71578]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-22843]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-D-2016]


Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for 
Methanol; 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.'' 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. During the Coronavirus Disease 2019 
(COVID-19) public health emergency (PHE), FDA became aware of reports 
of fatal methanol poisoning of consumers who ingested alcohol-based 
hand sanitizer products that were manufactured with methanol or 
methanol-contaminated ethanol. FDA 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. This 
guidance replaces the guidance for industry entitled ``Policy for 
Testing Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including 
During the Public Health Emergency (COVID-19)'' published in January 
2021.

DATES: The announcement of the guidance is published in the Federal 
Register on October 17, 2023.

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:
    <bullet> 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.
    <bullet> 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:
    <bullet> 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.
    <bullet> 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.'' 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.
    <bullet> 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; or to 
Policy and Regulations Staff, HFV-6, Center for Veterinary Medicine, 
Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855. 
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 Anne Taylor, Center for Biologics Evaluation and Research, 
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 
7301, Silver Spring, MD 20993-0002,

[[Page 71577]]

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 final guidance for industry 
entitled ``Policy for Testing of Alcohol (Ethanol) and Isopropyl 
Alcohol for Methanol.'' This guidance is intended to alert 
pharmaceutical manufacturers 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'') 
contaminated with or substituted with methanol. During the COVID-19 
PHE, FDA became aware of reports of fatal methanol poisoning of 
consumers who ingested alcohol-based hand sanitizer products that were 
manufactured with methanol or methanol-contaminated ethanol. FDA 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.
    This 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.
    This guidance replaces the guidance entitled ``Policy for Testing 
Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including During 
the Public Health Emergency (COVID-19)'' posted in January 2021 and 
announced in the Federal Register on February 23, 2021 (86 FR 10977) 
(hereafter ``2021 COVID-19 Methanol Guidance''). FDA issued the 
guidance to communicate its policy for the duration of the COVID-19 PHE 
declared by the Secretary of Health and Human Services (HHS) on January 
31, 2020, including any renewals made by the HHS Secretary in 
accordance with section 319(a)(2) of the Public Health Service Act (42 
U.S.C. 247d(a)(2)). As stated in the 2021 guidance, at such time when 
the PHE was over, as declared by the HHS Secretary, FDA intended to 
reassess the guidance. Furthermore, in the Federal Register of March 
13, 2023 (88 FR 15417), FDA listed the guidance documents that will no 
longer be effective with the expiration of the PHE declaration, 
guidances that FDA was revising to continue in effect for 180 days 
after the expiration of the PHE declaration to provide a period for 
stakeholder transition and then would no longer be in effect, and 
guidances that FDA was revising to continue in effect for 180 days 
after the expiration of the PHE declaration during which time FDA 
planned to further revise the guidances. The 2021 COVID-19 Methanol 
Guidance is included in the latter category. Although the COVID-19 PHE 
ended May 11, 2023, FDA has determined that the recommendations set 
forth in the 2021 COVID-19 Methanol Guidance are applicable outside the 
context of the COVID-19 PHE. FDA is, therefore, issuing this revised 
final guidance, which will supersede the current guidance. In preparing 
this guidance, FDA considered comments received regarding the 2021 
guidance, as well as the Agency's experience with this matter during 
the PHE. Updates to this guidance include removal of certain language 
regarding the COVID-19 PHE, as well as removal of language related to 
the three hand sanitizer guidance documents that have since been 
withdrawn.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (Sec.  10.115 (21 CFR 10.115)) without initially 
seeking prior comment because the Agency has determined that prior 
public participation is not feasible or appropriate (see Sec.  
10.115(g)(2) and section 701(h)(1)(C)(i) of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 371(h)(1)(C)(i))). Specifically, we are not 
seeking prior comment because, although the COVID-19 PHE has ended, the 
use of hand sanitizers and other drug products containing 
pharmaceutical alcohol remains widespread. Given the serious risks to 
public health, including blindness and death, that can result from 
methanol contamination, it is thus important to public health to 
continue to apply the policy described in the guidance, which 
encourages stringent and continued oversight of such products for the 
possible presence of methanol.
    The guidance represents the current thinking of FDA on ``Policy for 
Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol.'' 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. The 
previously approved collections of information are subject to review by 
the Office of Management and Budget (OMB) under the Paperwork Reduction 
Act of 1995 (PRA) (44 U.S.C. 3501-3521). 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/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.


[[Page 71578]]


    Dated: October 11, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-22843 Filed 10-16-23; 8:45 am]
BILLING CODE 4164-01-P