Document ID: FDA-2021-N-1043-0003
Agency: fda
Document Type: Notice
Title: Exemption of Certain Categories of Biological Products From Certain Reporting Requirements Under the Federal Food, Drug, and Cosmetic Act
Posted Date: 2023-04-13T04:00Z

[Federal Register Volume 88, Number 71 (Thursday, April 13, 2023)]
[Notices]
[Pages 22454-22456]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-07772]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-N-1043]

Exemption of Certain Categories of Biological Products From 
Certain Reporting Requirements Under the Federal Food, Drug, and 
Cosmetic Act

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
issuing a final order to exempt certain categories of biological 
products from certain reporting requirements under the Federal Food, 
Drug, and Cosmetic Act (FD&C Act) as amended by the Coronavirus Aid, 
Relief, and Economic Security Act (CARES Act). Specifically, each 
person who registers with FDA with regard to a drug is required to 
report annually to FDA on the amount of each listed drug that was 
manufactured, prepared, propagated, compounded, or processed by such 
person for commercial distribution; however, certain biological 
products or categories of biological products may be exempted by order 
from these reporting requirements if FDA determines that applying such 
reporting requirements is not necessary to protect the public health. 
This final order exempts two categories of biological products from 
these reporting requirements because the Agency has determined that 
applying such requirements is not necessary to protect the public 
health.

DATES: This order is effective May 15, 2023.

ADDRESSES: For access to the docket to read background documents or 
comments received, go to https://www.regulations.gov and insert the 
docket number found in brackets in the heading of this final rule 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.

FOR FURTHER INFORMATION CONTACT: Jessica Gillum, 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--Reporting Requirements Under Section 510(j)(3) of the 
FD&C Act

    On March 27, 2020, the CARES Act (Pub. L. 116-136) was enacted to 
aid response efforts and ease the economic impact of the Coronavirus 
Disease 2019. In addition, the CARES Act included authorities to 
enhance FDA's ability to identify, prevent, and mitigate possible drug 
shortages by, among other things, enhancing FDA's visibility into drug 
supply chains.
    Section 3112(e) of the CARES Act added new paragraph (3) to section 
510(j) of the FD&C Act (21 U.S.C. 360(j)(3)), which requires that each 
person who registers with FDA under section 510 of the FD&C Act with 
regard to a drug must report annually to FDA on the amount of each 
listed drug that was manufactured, prepared, propagated, compounded, or 
processed by such person for commercial distribution. These reporting 
requirements in section 510(j)(3)(A) of the FD&C Act enhance FDA's 
ability to address drug shortages by enabling the Agency to identify 
manufacturing sites impacted and develop potential options to remediate 
shortage risks to the product supply chain.
    Under section 510(j)(3)(B) of the FD&C Act, FDA may exempt certain

[[Page 22455]]

biological products or categories of biological products regulated 
under section 351 of the Public Health Service Act (42 U.S.C. 262) from 
some or all of the reporting requirements under section 510(j)(3)(A) of 
the FD&C Act, if FDA determines that applying such reporting 
requirements is not necessary to protect the public health.
    In the Federal Register of October 27, 2021 (86 FR 59395), FDA 
published a proposed order entitled ``Exemption of Certain Categories 
of Biological Products from Certain Reporting Requirements Under the 
Federal Food, Drug, and Cosmetic Act'' in which FDA proposed to exempt 
certain categories of biological products from certain reporting 
requirements under FD&C Act as amended by the CARES Act. Specifically, 
FDA proposed to exempt the following two categories of biological 
products from all of the reporting requirements under section 
510(j)(3)(A) of the FD&C Act pursuant to section 510(j)(3)(B) of the 
FD&C Act because the Agency determined that applying such requirements 
is not necessary to protect the public health: (1) Blood and blood 
components for transfusion and (2) cell and gene therapy products, 
where one lot treats a single patient.

II. Comments on the Proposed Order and FDA Response

    In response to the October 27, 2021, proposed order, FDA received 
one comment by the close of the comment period. We describe and respond 
to the comment in this section of the document.
    (Comment 1) One comment recommends that FDA expand the proposed 
order to also exempt ``made-to-stock'' cell and gene therapy products. 
The comment asserts that the supply chains for such products are 
``well-established and well-understood'' from information in the 
biologics license applications (BLAs), and generally do not involve 
wholesale distributors, brokers, or other intermediaries.
    (Response) We decline to expand the order to exempt ``made to 
stock'' cell and gene therapy products. ``Made-to-stock'' cell and gene 
therapy products are generally manufactured in lots or batches for 
commercial distribution, based on projected product demand, and they 
are not typically for use where one lot treats a single patient. We 
disagree that the supply chains for ``made-to-stock'' cell and gene 
therapy products are well-established and well-understood. Even though 
they may not involve wholesale distributors, brokers, or other 
intermediaries, FDA has limited visibility into the supply chains for 
such products. We reiterate that the CARES Act included authorities to 
enhance FDA's ability to identify, prevent, and mitigate possible drug 
shortages by, among other things, improving FDA's visibility into drug 
supply chains. When FDA is notified of an impending manufacturing 
problem that could lead to a supply interruption,\1\ having information 
about the amount of each listed drug that was manufactured, prepared, 
propagated, compounded, or processed for commercial distribution, as 
reported under section 510(j)(3)(A) of the FD&C Act, can provide 
insight into how much manufacturing typically occurs at the affected 
facility and whether the problem may lead to a drug shortage. 
Furthermore, these data can help the Agency to identify and measure 
supply chain vulnerabilities that could be longer term risk factors for 
drug shortages. We anticipate that requiring registrants to report 
annually under section 510(j)(3)(A) of the FD&C Act on the amount of 
``made-to-stock'' cell and gene therapy products manufactured, 
prepared, propagated, compounded, or processed for commercial 
distribution will improve FDA's visibility into the supply chains for 
these products and enhance the Agency's ability to identify, prevent, 
and mitigate possible shortages. There is not an adequate basis at this 
time for FDA to determine that applying such reporting requirements to 
this category of biological products is not necessary to protect the 
public health. Thus, there is not an adequate basis to exempt ``made-
to-stock'' cell and gene therapy products from the reporting 
requirements under section 510(j)(3)(A) of the FD&C Act pursuant to 
section 510(j)(3)(B) of the FD&C Act.
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    \1\ See, e.g., section 506C(a) of the FD&C Act (21 U.S.C. 355d) 
(notifications of discontinuance or interruption in the production 
of life-saving drugs).
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III. Exempted Categories of Biological Products

    FDA is finalizing the order to exempt the following two categories 
of biological products from all of the reporting requirements under 
section 510(j)(3)(A) of the FD&C Act pursuant to section 510(j)(3)(B) 
of the FD&C Act because FDA has determined that applying such reporting 
requirements is not necessary to protect the public health:
     Blood and blood components for transfusion; and
     Cell and gene therapy products, where one lot treats a 
single patient.

A. Blood and Blood Components for Transfusion

    In accordance with section 510(j)(3)(B) of the FD&C Act, this order 
exempts blood and blood components for transfusion from the reporting 
requirements under section 510(j)(3)(A) of the FD&C Act. In light of 
FDA's existing visibility into the supply chain for this category of 
products, requiring registrants to report annually under section 
510(j)(3)(A) of the FD&C Act on the amount of such products 
manufactured, prepared, propagated, compounded, or processed for 
commercial distribution is not needed to enhance the Agency's ability 
to identify, prevent, and mitigate possible shortages. As such, FDA has 
determined that applying the reporting requirements under section 
510(j)(3)(A) of the FD&C Act to this category of biological products is 
not necessary to protect the public health.
    Generally, registered blood establishments are inspected on a 
biennial basis by the Agency. There are approximately 1,900 registered 
blood establishments that manufacture blood and blood components for 
transfusion, all located in the United States, as well as a small 
number of United States military blood establishments that are located 
internationally in order to provide blood and blood components to 
United States military personnel onsite when needed. The supply chains 
for blood and blood components for transfusion are well-established and 
well-understood based on the nature of the products; namely, blood is 
collected from human donors via venipuncture, separated into components 
(if applicable), and stored at specified temperatures and under the 
complete control of each blood establishment. Additionally, supply 
chains for blood and blood components for transfusion are controlled 
and secure from initial donation to final product delivery to the 
transfusion site and, generally, do not involve wholesale distributors, 
brokers, or other intermediaries. Further, many registered blood 
establishments voluntarily submit the amount of blood and blood 
components for transfusion manufactured as part of the Health and Human 
Services National Blood Collection and Utilization Survey (NBCUS), 
which, historically, has a high response rate.\2\
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    \2\ See https://doi.org/10.1111/trf.16449. The response rate for 
the 2019 NBCUS was 94 percent for community-based blood collection 
facilities and 84 percent for hospital-based blood collection 
facilities.

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[[Page 22456]]

B. Cell and Gene Therapy Products, Where One Lot Treats a Single 
Patient

    In accordance with section 510(j)(3)(B) of the FD&C Act, this order 
exempts cell and gene therapy products, where one lot treats a single 
patient, from the reporting requirements under section 510(j)(3)(A) of 
the FD&C Act. In light of FDA's existing visibility into the supply 
chain for this category of products, requiring registrants to report 
annually under section 510(j)(3)(A) of the FD&C Act on the amount of 
such products manufactured, prepared, propagated, compounded, or 
processed for commercial distribution, is not needed to enhance the 
Agency's ability to identify, prevent, and mitigate possible shortages. 
As such, FDA has determined that applying the reporting requirements 
under section 510(j)(3)(A) of the FD&C Act to this category of 
biological products is not necessary to protect the public health.
    Manufacturers of cell and gene therapy products, where one lot 
treats a single patient, maintain a highly controlled and secure supply 
chain from initial request for treatment of a patient to final product 
delivery to the site where the treatment occurs. This is because, due 
to the nature of these products, manufacturers implement strict chain 
of identity procedures to track products through the manufacturing 
process, to make sure the correct product gets to the correct patient. 
Additionally, the supply chains for these products are well-established 
and well-understood from information described in the BLA, and 
generally do not involve wholesale distributors, brokers, or other 
intermediaries.
    Additionally, pursuant to Sec.  600.81 (21 CFR 600.81), the Agency 
generally receives lot distribution reports every 6 months from BLA 
holders. Specifically, reports submitted to the Agency under Sec.  
600.81 include, among other information, the fill lot numbers for the 
total number of dosage units of each strength or potency distributed, 
the label lot number (if different from fill lot number), the number of 
doses in fill lot/label lot, and the date of release of fill lot/label 
lot for distribution. For this category of biological products, because 
one lot treats a single patient, the lot distribution reports submitted 
to the Agency under Sec.  600.81 represent the amount of product 
manufactured for commercial distribution, and additional reporting of 
such information under section 510(j)(3)(A) of the FD&C Act would be 
redundant.

IV. Paperwork Reduction Act of 1995

    This final order contains information collection provisions that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). The 
information collection provisions of this final order are approved 
under 0910-0045.

V. Effective Date

    This final order is effective 30 days after its date of publication 
in the Federal Register.

    Dated: April 7, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-07772 Filed 4-12-23; 8:45 am]
BILLING CODE 4164-01-P