71576 Federal Register / Vol. 88, No. 199 / Tuesday, October 17, 2023 / Notices 

Mary B. Jones, 

ACF/OPRE Certifying Officer. 

[FR Doc. 2023–22809 Filed 10–16–23; 8:45 am] 

BILLING CODE 4184–41–P 

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: 

• 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.’’ 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; 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, 


lotter on DSK11XQN23PROD with NOTICES1
Federal Register / Vol. 88, No. 199 / Tuesday, October 17, 2023 / Notices 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 Statelicensed 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 finishedproduct 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 (§ 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 § 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/guidancecompliance-regulatory-information/ 

guidances-drugs, https://www.fda.gov/ 

vaccines-blood-biologics/guidancecompliance-regulatory-informationbiologics, https://www.fda.gov/ 

regulatory-information/search-fdaguidance-documents, or https://

www.regulations.gov. 


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71578 Federal Register / Vol. 88, No. 199 / Tuesday, October 17, 2023 / Notices 

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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2023–P–3682] 

Determination That ZOFRAN ODT 

(Ondansetron) Orally Disintegrating 

Tablets, 4 Milligrams and 8 Milligrams, 

Were Not Withdrawn From Sale for 

Reasons of Safety or Effectiveness 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or the Agency) has 

determined that ZOFRAN ODT 

(ondansetron) orally disintegrating 

tablets, 4 milligrams (mg) and 8 mg, 

were not withdrawn from sale for 

reasons of safety or effectiveness. This 

determination means that FDA will not 

begin procedures to withdraw approval 

of abbreviated new drug applications 

(ANDAs) that refer to these drug 

products, and it will allow FDA to 

continue to approve ANDAs that refer to 

the products as long as they meet 

relevant legal and regulatory 

requirements. 

FOR FURTHER INFORMATION CONTACT: 

Veniqua Stewart, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 6219, 

Silver Spring, MD 20993–0002, 301– 

796–3267, Veniqua.stewart@

fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: Section 

505(j) of the Federal Food, Drug, and 

Cosmetic Act (FD&C Act) (21 U.S.C. 

355(j)) allows the submission of an 

ANDA to market a generic version of a 

previously approved drug product. To 

obtain approval, the ANDA applicant 

must show, among other things, that the 

generic drug product: (1) has the same 

active ingredient(s), dosage form, route 

of administration, strength, conditions 

of use, and (with certain exceptions) 

labeling as the listed drug, which is a 

version of the drug that was previously 

approved, and (2) is bioequivalent to the 

listed drug. ANDA applicants do not 

have to repeat the extensive clinical 

testing otherwise necessary to gain 

approval of a new drug application 

(NDA). 

Section 505(j)(7) of the FD&C Act 

requires FDA to publish a list of all 

approved drugs. FDA publishes this list 

as part of the ‘‘Approved Drug Products 

With Therapeutic Equivalence 

Evaluations,’’ which is known generally 

as the ‘‘Orange Book.’’ Under FDA 

regulations, drugs are removed from the 

list if the Agency withdraws or 

suspends approval of the drug’s NDA or 

ANDA for reasons of safety or 

effectiveness or if FDA determines that 

the listed drug was withdrawn from sale 

for reasons of safety or effectiveness (21 

CFR 314.162). 

A person may petition the Agency to 

determine, or the Agency may 

determine on its own initiative, whether 

a listed drug was withdrawn from sale 

for reasons of safety or effectiveness. 

This determination may be made at any 

time after the drug has been withdrawn 

from sale, but must be made prior to 

approving an ANDA that refers to the 

listed drug (§ 314.161 (21 CFR 314.161)). 

FDA may not approve an ANDA that 

does not refer to a listed drug. 

ZOFRAN ODT (ondansetron) orally 

disintegrating tablets, 4 mg and 8 mg, 

are the subject of NDA 020781, held by 

Sandoz Inc., and initially approved on 

January 27, 1999. ZOFRAN ODT is 

indicated for the prevention of nausea 

and vomiting associated with: highly 

emetogenic cancer chemotherapy, 

including cisplatin greater than or equal 

to 50 mg/m2; initial and repeat courses 

of moderately emetogenic cancer 

chemotherapy; and radiotherapy in 

patients receiving either total body 

irradiation, single high-dose fraction to 

the abdomen, or daily fractions to the 

abdomen. ZOFRAN ODT is also 

indicated for the prevention of 

postoperative nausea and/or vomiting. 

ZOFRAN ODT (ondansetron) orally 

disintegrating tablets, 4 mg and 8 mg, 

are currently listed in the ‘‘Discontinued 

Drug Product List’’ section of the Orange 

Book. 

Sun Pharmaceutical Industries 

Limited submitted a citizen petition 

dated August 24, 2023 (Docket No. 

FDA–2023–P–3682), under 21 CFR 

10.30, requesting that the Agency 

determine whether ZOFRAN ODT 

(ondansetron) orally disintegrating 

tablets, 4 mg and 8 mg, were withdrawn 

from sale for reasons of safety or 

effectiveness. 

After considering the citizen petition 

and reviewing Agency records and 

based on the information we have at this 

time, FDA has determined under 

§ 314.161 that ZOFRAN ODT 

(ondansetron) orally disintegrating 

tablets, 4 mg and 8 mg, were not 

withdrawn from sale for reasons of 

safety or effectiveness. The petitioner 

has identified no data or other 

information suggesting that ZOFRAN 

ODT (ondansetron) orally disintegrating 

tablets, 4 mg and 8 mg, were withdrawn 

for reasons of safety or effectiveness. We 

have carefully reviewed our files for 

records concerning the withdrawal of 

ZOFRAN ODT (ondansetron) orally 

disintegrating tablets, 4 mg and 8 mg, 

from sale. We have also independently 

evaluated relevant literature and data 

for possible postmarketing adverse 

events. We have reviewed the available 

evidence and determined that these 

drug products were not withdrawn from 

sale for reasons of safety or 

effectiveness. 

Accordingly, the Agency will 

continue to list ZOFRAN ODT 

(ondansetron) orally disintegrating 

tablets, 4 mg and 8 mg, in the 

‘‘Discontinued Drug Product List’’ 

section of the Orange Book. The 

‘‘Discontinued Drug Product List’’ 

delineates, among other items, drug 

products that have been discontinued 

from marketing for reasons other than 

safety or effectiveness. FDA will not 

begin procedures to withdraw approval 

of approved ANDAs that refer to these 

drug products. Additional ANDAs for 

these drug products may also be 

approved by the Agency as long as they 

meet all other legal and regulatory 

requirements for the approval of 

ANDAs. If FDA determines that labeling 

for these drug products should be 

revised to meet current standards, the 

Agency will advise ANDA applicants to 

submit such labeling. 

Dated: October 10, 2023. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2023–22844 Filed 10–16–23; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2023–D–4067] 

Diabetic Foot Infections: Developing 

Drugs for Treatment; Draft 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 draft 

guidance for industry entitled ‘‘Diabetic 

Foot Infections: Developing Drugs for 

Treatment.’’ The purpose of this draft 

guidance is to assist sponsors in the 


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