[Federal Register Volume 88, Number 105 (Thursday, June 1, 2023)]
[Notices]
[Pages 35885-35886]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-11570]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2023-N-0742]
Human Cells, Tissues, and Cellular and Tissue-Based Product
Establishments That Are Improperly Registered in the Electronic Human
Cell and Tissue Establishment Registration System Due to Lack of Annual
Registration Update; Action Dates
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of intent.
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SUMMARY: The Food and Drug Administration (FDA) is announcing its
intention to begin inactivating the registration of establishments that
manufacture human cells, tissues, or cellular or tissue-based products
(HCT/Ps) that have not updated their registration during the annual
update period, in accordance with FDA regulations, in the electronic
human cell and tissue establishment registration system (eHCTERS). FDA
regulations require establishments that manufacture certain HCT/Ps to
update their establishment registration annually. These regulations
also require establishments to amend their registration within 30
calendar days of certain changes.
DATES: This notice is applicable August 30, 2023.
FOR FURTHER INFORMATION CONTACT: Andrew C. Harvan, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
HCT/Ps are defined in Sec. 1271.3(d) (21 CFR 1271.3(d)) as
articles containing or consisting of human cells or tissues that are
intended for implantation, transplantation, infusion, or transfer into
a human recipient. FDA has a tiered, risk-based approach to the
regulation of HCT/Ps. If all of the criteria in 21 CFR 1271.10(a) are
met, and none of the exceptions in Sec. 1271.15 (21 CFR 1271.15)
apply, then the HCT/P is regulated solely under section 361 of the PHS
Act (42 U.S.C. 264) and the regulations in part 1271 (21 CFR part 1271)
(361 HCT/P), and FDA's premarket review and approval are not required.
Establishments that manufacture 361 HCT/Ps are required to register
and list their HCT/Ps with FDA's Center for Biologics Evaluation and
Research (CBER) using the electronic registration and listing system
(Sec. Sec. 1271.1(b), 1271.21, and 1271.22 (21 CFR 1271.1(b), 1271.21,
and 1271.22)).1 2 Under Sec. 1271.3(b), establishment
``means a place of business under one management, at one general
physical location, that engages in the manufacture of [HCT/Ps].'' This
includes ``any individual, partnership, corporation, association, or
other legal entity engaged in the manufacture of [HCT/Ps] . . . [and
includes] [f]acilities that engage in contract manufacturing services .
. . .'' Under Sec. 1271.3(e), ``manufacture means, but is not limited
to, any or all steps in the recovery, processing, storage, labeling,
packaging, or distribution of any human cell or tissue, and the
screening or testing of the cell or tissue donor.''
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\1\ An establishment that meets any of the exceptions in Sec.
1271.15 is not required to register or comply with other
requirements in part 1271.
\2\ Manufacturers of HCT/Ps that are regulated as drugs,
devices, and/or biological products under section 351 of the PHS Act
(42 U.S.C. 262) and/or the Federal Food, Drug, and Cosmetic Act and
applicable regulations, must register and list their products in
accordance with part 207 or part 807 (21 CFR part 207 or part 807),
as applicable (Sec. 1271.1(b)(2)). FDA does not require
establishments that manufacture HCT/Ps regulated as drugs, devices,
and/or biological products that are only for use in research under
an investigational new drug application (IND) (21 CFR part 312) or
an investigational device exemption (IDE) (21 CFR part 812) to
register and list those HCT/Ps in accordance with part 207 or part
807 if they do not engage in other activities that would require
them to register (21 CFR 207.13(e), 807.65(f), and 812.1).
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Pursuant to Sec. 1271.21, establishments that manufacture 361 HCT/
Ps must register with FDA and submit a list of every HCT/P that they
manufacture within 5 days after beginning operations. Establishments
are required to update their registration annually each December.
Establishments are also required to update their HCT/P list when
changes occur. Such new information must be submitted at the time of
change, or each June or December, whichever month occurs first. An
establishment may accomplish its required annual registration update in
conjunction with updating its HCT/P list.
In addition, under 21 CFR 1271.26, if the ownership or location of
the
[[Page 35886]]
establishment changes or if there is a change in the establishment's
U.S. agent's name, address, telephone number, or email address, then
establishments must also amend their registration within 30 calendar
days. Of note, the regulations make clear that FDA's ``acceptance of an
establishment registration and HCT/P listing form does not constitute a
determination that an establishment is in compliance with applicable
rules and regulations or that the HCT/P is licensed or approved by
FDA'' (21 CFR 1271.27(b)).
Registration is performed using CBER's eHCTERS. Establishments
electronically submit required registration and HCT/P listing
information, as well as updates to such information, through their
eHCTERS account.\3\ The public can access eHCTERS to search and review
tissue establishment registration information (registered, inactive,
and pre-registered establishments) through the eHCTERS Public Query
Application.
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\3\ Electronic submission of HCT/P establishment and product
listing information may be waived in certain circumstances as
described in 21 CFR 1271.23. Submission of a request for a waiver
does not excuse timely compliance with registration and listing
requirements.
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Complete, accurate, and up-to-date establishment registration and
HCT/P listing information is essential to FDA's mission. If
registration and listing information is outdated or otherwise
unreliable, the integrity of the HCT/P registration and listing
database is compromised. Registration information assists FDA in
identifying industry participants and the scope of HCT/Ps manufactured.
This assists FDA in more efficiently monitoring industry and providing
new information including guidances, policies, and requirements.
Establishment registration information also assists FDA in reacting
swiftly to newly discovered or understood risks by enabling FDA to
quickly alert industry of our concerns and, when appropriate, to
conduct establishment inspections. Without this information, FDA would
not be able to effectively monitor compliance under FDA's risk-based
surveillance inspection program.
Establishment registration and HCT/P listing information is also
widely used outside of FDA for various purposes. The public uses the
Public Query Application of eHCTERS to search for and locate HCT/P
establishments. For example, certain voluntary healthcare accreditation
organizations require hospitals or surgical centers to annually confirm
that their tissue suppliers are registered with FDA. Therefore,
inclusion of inaccurate or outdated information in eHCTERS can
negatively affect public health.
II. Circumstances Under Which HCT/P Registration and Listing
Information Becomes Inaccurate or Outdated
Establishments that manufacture HCT/Ps are required to update their
registration annually in December, even if there are no changes or
updates to their information (Sec. 1271.21). Every year, many HCT/P
establishments fail to update their registration information during the
annual update period. In recent years, 390 of 2671, 379 of 2361, and
319 of 2431 registered domestic and foreign establishments failed to
submit their annual registration for 2019, 2020, and 2021,
respectively. Some of the establishments have not submitted their
annual update for more than 2 years.
After the annual registration period ends, CBER generates a list of
establishments that have failed to submit their annual registration
update. From this list, FDA attempts to follow up with each of these
establishments to rectify their registration status. However, for a
variety of reasons, such as outdated contact information, FDA is not
able to contact some of these establishments. The follow-up process,
including sending a reminder email and contact by phone, requires
considerable additional time and FDA staff resources.
When establishments fail to update their registration information
in eHCTERS, they are improperly registered in eHCTERS and improperly
displayed in the Public Query Application as ``Registered''. Not only
does this inaccurate and outdated information compromise the integrity
of eHCTERS, it also hinders the public's ability to rely on
establishment registration information.
III. FDA's Intended Response
To address the above registration and listing problems, FDA is
encouraging establishments that are required to register under part
1271 to review their current registration to ensure its accuracy. Any
registrations that are outdated should be updated as soon as possible.
Establishments are required to annually update their registration
pursuant to FDA regulations. Establishments who do not submit their
annual registration are in violation of the regulations at part 1271.
Ninety days after publication of this notice, and every January
thereafter, FDA will inactivate an HCT/P establishment's registration
when the establishment fails to submit their annual registration update
during the previous annual update period between November 15 to
December 31. FDA will no longer attempt to follow up with
establishments to rectify their registration status. The eHCTERS Public
Query Application will display the establishment registration status as
``inactive'' and include the last annual registration year. Email
notification of the inactivation will be sent to the reporting official
of the establishment, and the reporting official may access the
establishment's account in eHCTERS to change or update its
registration. If the email notifying the establishment of the change in
registration status to ``inactive'' is undeliverable, FDA will call the
phone number of the establishment to provide notification.
If an establishment changes or updates its registration in eHCTERS
after its registration has been inactivated due to failure to annually
update registration information, the eHCTERS Public Query Application
will display the establishment's status as ``Registered'' and the last
annual registration year will be updated to the current year.
IV. Resources Available To Assist With Updating Registration and HCT/P
Listings
Access to part 1271 is available at: https://www.ecfr.gov/current/title-21/chapter-I/subchapter-L/part-1271?toc=1. The instructions for
using eHCTERS to complete HCT/P establishment registration and HCT/P
listing and submitting the annual registration updates, as well as
information on the eHCTERS Public Query Application, are available at:
https://www.fda.gov/vaccines-blood-biologics/biologics-establishment-registration/tissue-establishment-registration. Questions concerning
registration can be emailed to [email protected].
Dated: May 18, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-11570 Filed 5-31-23; 8:45 am]
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