[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]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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.
---------------------------------------------------------------------------
\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).
---------------------------------------------------------------------------
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\
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
[[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