[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]
BILLING CODE 4164-01-P