[Federal Register Volume 85, Number 217 (Monday, November 9, 2020)]
[Notices]
[Pages 71348-71350]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-24807]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-D-2268]


Insanitary Conditions at Compounding Facilities; 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 or Agency) is announcing 
the availability of a final guidance for industry entitled ``Insanitary 
Conditions at Compounding Facilities.'' Drug products compounded under 
insanitary conditions could become contaminated and cause serious 
adverse events, including death, in patients. FDA is issuing this 
guidance to help compounding facilities and State regulatory agencies 
understand some examples of what FDA considers to be insanitary 
conditions that could cause a drug to become contaminated or rendered 
injurious to health. These examples are intended to help compounding 
facilities take action to prevent the occurrence of these and other 
insanitary conditions, as well as to implement appropriate corrective 
actions when such conditions already exist.

DATES: The announcement of the guidance is published in the Federal 
Register on November 9, 2020.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances on any guidance 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

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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-2016-D-2268 for ``Insanitary Conditions at Compounding 
Facilities.'' 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.
     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.
    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. Send one self-
addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the final guidance document.

FOR FURTHER INFORMATION CONTACT: Jinhee Lee, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 51, Rm. 5225, Silver Spring, MD 20993, 301-796-6770.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Insanitary Conditions at Compounding Facilities.'' \1\ Under 
section 501(a)(2)(A) of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) (21 U.S.C. 351(a)(2)(A)), a drug is adulterated if it has been 
prepared, packed, or held under insanitary conditions whereby it may 
have been contaminated with filth or rendered injurious to health. Drug 
products compounded under insanitary conditions could become 
contaminated and cause serious adverse events, including death, in 
patients. Although sections 503A and 503B of the FD&C Act (21 U.S.C. 
353a and 353b) provide exemptions for compounded drugs from specified 
provisions of the FD&C Act if certain conditions are met, neither 
section provides an exemption from section 501(a)(2)(A) of the FD&C 
Act. Any drug that is prepared, packed, or held under insanitary 
conditions is deemed to be adulterated under the FD&C Act, including 
drugs produced by a compounding facility.
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    \1\ For the purpose of this guidance, FDA regards compounding 
facilities as pharmacies, Federal facilities, and outsourcing 
facilities that compound or repackage drugs, or that mix, dilute, or 
repackage biological products.
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    Since the 2012 fungal meningitis outbreak associated with 
injectable drug products that a pharmacy compounded and shipped to 
patients and healthcare providers across the country, the Agency has 
identified insanitary conditions at many of the compounding facilities 
that it has inspected, and numerous compounders have voluntarily 
recalled drug products intended to be sterile and also temporarily or 
permanently ceased sterile operations because of these findings. 
Generally, State licensed pharmacies do not register with FDA unless 
they are outsourcing facilities. As a result, the Agency is often not 
aware of these pharmacies, their conditions and practices, and 
potential problems with the quality of their drug products. Although 
FDA does conduct some surveillance inspections, FDA does not inspect 
the vast majority of State licensed pharmacies in the United States 
unless, for example, FDA receives a complaint, such as a report of a 
serious adverse event or product quality issue. FDA does, however, 
routinely inspect outsourcing facilities registered with FDA.\2\ 
Regardless of whether a facility is routinely inspected by FDA, it is 
critical that both State licensed pharmacies and outsourcing facilities 
identify and remediate, as well as work to prevent, the occurrence of 
insanitary conditions within their facilities. Because insanitary 
conditions can result in drug contamination and patient injury, 
corrective action should be implemented expeditiously in order to 
prevent the recurrence of such conditions.
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    \2\ See section 503B(b)(4) of the FD&C Act.
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    In the Federal Register of September 26, 2018 (83 FR 48631), FDA 
announced the availability of a revised draft guidance for industry 
entitled ``Insanitary Conditions at Compounding Facilities.'' The 
revised draft guidance provided examples of conditions that the Agency 
has observed at compounding facilities it has inspected and considers 
to be insanitary conditions. The revised draft guidance also described 
corrective actions that compounding facilities should take when they 
identify such conditions and the regulatory actions FDA may take in 
response to identified insanitary conditions.
    FDA received comments on the revised draft guidance from various

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stakeholders (e.g., physicians, pharmacies, outsourcing facilities). 
Several comments were submitted concerning the implications of the 
policies described in the revised draft guidance for physicians who 
compound or repackage drug products or mix, dilute, or repackage FDA-
licensed biological products in their offices. In response to these 
comments, FDA made changes, where appropriate, in the final guidance. 
The changes include adding a footnote to state that ``processing of 
beta-lactams'' does not refer to mixing, reconstituting, or other such 
acts that are performed in accordance with the directions contained in 
FDA-approved labeling; adding a footnote to reflect that the FDA does 
not generally object to rapid movement temporary blocking or disruption 
of first air in the ISO 5 area when necessary for the safe handling of 
radiopharmaceuticals to minimize radiation exposure, and revising the 
language in a footnote concerning the scope of physician compounding or 
repackaging activities to state that FDA generally does not intend to 
take action under section 501(a)(2)(A) of the FD&C Act against a 
physician who is compounding a drug product, repackaging an FDA-
approved drug product, or who is mixing, diluting, or repackaging an 
FDA-licensed biological product, provided that it occurs in the 
physician's office for in-office administration to the physician's 
patients; and adding recommendations encouraging compounders to use 
risk evaluation strategies and risk management tools to develop 
appropriate controls necessary to prevent the occurrence of insanitary 
conditions at their facilities. In addition, editorial changes were 
made to the guidance for clarity.
    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 ``Insanitary Conditions at Compounding 
Facilities.'' The examples described in the final guidance do not 
constitute an exhaustive list of conditions FDA considers to be 
insanitary conditions. 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

    This guidance contains no collection 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.
    However, this guidance refers to a previously approved FDA 
collection of information. This collection of information is subject to 
review by OMB under the PRA. The collections of information in 21 CFR 
part 7 pertaining to FDA's recall regulations have been approved under 
OMB control number 0910-0249.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov.

    Dated: November 3, 2020.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2020-24807 Filed 11-6-20; 8:45 am]
BILLING CODE 4164-01-P