[Federal Register Volume 88, Number 90 (Wednesday, May 10, 2023)]
[Notices]
[Pages 30139-30141]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-09973]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2023-D-1573]


Testing of Glycerin, Propylene Glycol, Maltitol Solution, 
Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk 
Drug Components for Diethylene Glycol and Ethylene Glycol; Guidance for 
Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
announcing the availability of a final guidance for industry entitled 
``Testing of Glycerin, Propylene Glycol, Maltitol Solution, 
Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk 
Drug Components for Diethylene Glycol and Ethylene Glycol.'' This 
guidance provides updated recommendations on testing and other 
activities that will help pharmaceutical manufacturers, repackers, 
other suppliers, and compounders prevent the use of high-risk drug 
components, including

[[Page 30140]]

glycerin, propylene glycol, maltitol solution, hydrogenated starch 
hydrolysate, and sorbitol solution, that are contaminated with 
diethylene glycol (DEG) and ethylene glycol (EG). These and other 
appropriate measures under current good manufacturing practice (CGMP) 
are vital to prevent incidents of consumer poisoning.

DATES: The announcement of the guidance is published in the Federal 
Register on May 10, 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-2023-D-1573 for ``Testing of Glycerin, Propylene Glycol, Maltitol 
Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other 
High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol.'' 
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 
Office of Compliance, Center for Drug Evaluation and Research, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 4337, 
Silver Spring, MD 20993. Send two self-addressed adhesive labels to 
assist that office in processing your requests. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Tara Gooen Bizjak, Office of 
Manufacturing Quality, Center for Drug Evaluation and Research (HFD-
003), Food and Drug Administration, 10903 New Hampshire Ave., Silver 
Spring, MD 20993, 301-796-3400.

SUPPLEMENTARY INFORMATION:

I. Background

    We are announcing the availability of a guidance for industry 
entitled ``Testing of Glycerin, Propylene Glycol, Maltitol Solution, 
Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk 
Drug Components for Diethylene Glycol and Ethylene Glycol.'' We are 
issuing this guidance consistent with our good guidance practices (GGP) 
regulation (Sec.  10.115 (21 CFR 10.115)). We are implementing this 
guidance without prior public comment because we have determined that 
prior public participation is not feasible or appropriate (Sec.  
10.115(g)(2)). This guidance document is being implemented immediately 
to alert the industry to the potential public health hazard of DEG and 
EG contamination in certain drug components following international 
reports of children's oral liquid drug products with confirmed or 
suspected high levels of DEG or EG contamination. Although this 
guidance document is immediately in effect, it remains subject to 
comment in accordance with FDA's GGP regulation.
    On May 2, 2007, FDA announced the availability of a guidance for 
industry entitled ``Testing of Glycerin for Diethylene Glycol'' 
(hereinafter, 2007 guidance) (72 FR 24316). As explained in detail in 
the 2007 guidance, and described further in this updated guidance, 
there have been repeated instances of DEG poisonings around the world, 
and even in the United States in 1937. Each outbreak resulted in 
numerous fatalities, many of them children. The 2007 guidance 
recommended that certain activities be performed on glycerin, including 
analytical testing, to avoid the use of DEG-contaminated product.
    In 2022 and 2023, numerous countries reported incidents of oral 
liquid drug products, primarily indicated for children, with confirmed 
or suspected contamination with high levels of DEG and EG.\1\ The cases 
of contamination,

[[Page 30141]]

spanning at least seven different countries, were associated with more 
than 300 fatalities--mostly in children under the age of 5.\2\ At this 
time, FDA has no indication that any contaminated products connected to 
these recent international incidents have entered the U.S. drug supply 
chain.
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    \1\ See e.g., WHO urges action to protect children from 
contaminated medicines, World Health Organization, January 23, 2023, 
available at https://www.who.int/news/item/23-01-2023-who-urges-action-to-protect-children-from-contaminated-medicines. The WHO has 
issued global medical alerts addressing these incidents in The 
Gambia (October 5, 2022), Indonesia (November 6, 2022), Uzbekistan 
(January 11, 2023), and the Marshall Islands and Micronesia (Apr 25, 
2023). See Medical Product Alert N[deg]6/2022: Substandard 
(contaminated) paediatric medicines, World Health Organization, 
October 5, 2022, available at https://www.who.int/news/item/05-10-2022-medical-product-alert-n-6-2022-substandard-(contaminated)-
paediatric-medicines; Medical Product Alert N[deg]7/2022: 
Substandard (contaminated) paediatric liquid dosage medicines, World 
Health Organization, November 2, 2022, available at https://www.who.int/news/item/02-11-2022-medical-product-alert-n-7-2022-substandard-(contaminated)-paediatric-liquid-dosage-medicines; 
Medical Product Alert N[deg]1/2023: Substandard (contaminated) 
liquid dosage medicines, World Health Organization, January 11, 
2023, available at https://www.who.int/news/item/11-01-2023-medical-product-alert-n-1-2023-substandard-(contaminated)-liquid-dosage-
medicines; and Medical Product Alert N[deg]4/2023: Substandard 
(contaminated) syrup medicines, World Health Organization, Apr 25, 
2023, available at https://www.who.int/news/item/25-04-2023-medical-
product-alert-n-4-2023--substandard-(contaminated)-syrup-medicines.
    \2\ See WHO urges action to protect children from contaminated 
medicines, World Health Organization, January 23, 2023, available at 
https://www.who.int/news/item/23-01-2023-who-urges-action-to-protect-children-from-contaminated-medicines.
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    This guidance is intended to replace the 2007 guidance and to alert 
the industry that in addition to glycerin, there are other components 
at a high risk of contamination with DEG and EG, including, but not 
limited to, propylene glycol, maltitol solution, hydrogenated starch 
hydrolysate, and sorbitol solution (hereinafter, ``high-risk 
components''). This guidance provides recommendations, including 
analytical testing, to help pharmaceutical manufacturers, repackers, 
other suppliers of high-risk components, and compounders, prevent the 
use of glycerin and other high-risk components that are contaminated 
with DEG or EG.
    The guidance represents the current thinking of FDA on ``Testing of 
Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch 
Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for 
Diethylene Glycol and Ethylene Glycol.'' 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 collection of 
information is subject to review by OMB under the PRA. The collection 
of information for CGMP requirements has 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/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: May 5, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-09973 Filed 5-9-23; 8:45 am]
BILLING CODE 4164-01-P