Notice2023-09973
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
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Published
May 10, 2023
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
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 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.
Full Text
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<title>Federal Register, Volume 88 Issue 90 (Wednesday, May 10, 2023)</title>
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[Federal Register Volume 88, Number 90 (Wednesday, May 10, 2023)]
[Notices]
[Pages 30139-30141]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[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:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<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-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 <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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,
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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 <a href="https://www.who.int/news/item/23-01-2023-who-urges-action-to-protect-children-from-contaminated-medicines">https://www.who.int/news/item/23-01-2023-who-urges-action-to-protect-children-from-contaminated-medicines</a>. 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 <a href="https://www.who.int/news/item/05-10-2022-medical-product-alert-n-6-2022-substandard-">https://www.who.int/news/item/05-10-2022-medical-product-alert-n-6-2022-substandard-</a>(contaminated)-
paediatric-medicines; Medical Product Alert N[deg]7/2022:
Substandard (contaminated) paediatric liquid dosage medicines, World
Health Organization, November 2, 2022, available at <a href="https://www.who.int/news/item/02-11-2022-medical-product-alert-n-7-2022-substandard-">https://www.who.int/news/item/02-11-2022-medical-product-alert-n-7-2022-substandard-</a>(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 <a href="https://www.who.int/news/item/11-01-2023-medical-product-alert-n-1-2023-substandard-">https://www.who.int/news/item/11-01-2023-medical-product-alert-n-1-2023-substandard-</a>(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
<a href="https://www.who.int/news/item/23-01-2023-who-urges-action-to-protect-children-from-contaminated-medicines">https://www.who.int/news/item/23-01-2023-who-urges-action-to-protect-children-from-contaminated-medicines</a>.
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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
<a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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
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