[Federal Register Volume 89, Number 114 (Wednesday, June 12, 2024)]
[Notices]
[Pages 49880-49884]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-12783]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2024-N-2583]
Agency Information Collection Activities; Proposed Collection;
Comment Request; Human Drug Compounding, Repackaging, and Related
Activities Regarding Sections 503A and 503B of the Federal Food, Drug,
and Cosmetic Act
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is
announcing an opportunity for public comment on the proposed collection
of certain information by the Agency. Under the Paperwork Reduction Act
of 1995 (PRA), Federal Agencies are required to publish notice in the
Federal Register concerning each proposed collection of information,
including each proposed extension of an existing collection of
information, and to allow 60 days for public comment in response to the
notice. This notice solicits comments on information collection
associated with Agency guidance documents pertaining to pharmacies,
outsourcing facilities, and other entities with regard to human drug
compounding, repackaging, and related activities.
DATES: Either electronic or written comments on the collection of
information must be submitted by August 12, 2024.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of August 12, 2024. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are received on or before that date.
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 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-2024-N-2583 for ``Human Drug Compounding, Repackaging, and Related
Activities Regarding Sections 503A and 503B of the Federal Food, Drug,
and Cosmetic Act.'' Received comments, those filed in a timely manner
(see ADDRESSES), 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, 240-402-7500.
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
[[Page 49881]]
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, 240-402-7500.
FOR FURTHER INFORMATION CONTACT: Rachel Showalter, Office of
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 240-994-7399,
[email protected].
SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3521), Federal
Agencies must obtain approval from the Office of Management and Budget
(OMB) for each collection of information they conduct or sponsor.
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR
1320.3(c) and includes Agency requests or requirements that members of
the public submit reports, keep records, or provide information to a
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A))
requires Federal Agencies to provide a 60-day notice in the Federal
Register concerning each proposed collection of information, including
each proposed extension of an existing collection of information,
before submitting the collection to OMB for approval. To comply with
this requirement, FDA is publishing notice of the proposed collection
of information set forth in this document.
With respect to the following collection of information, FDA
invites comments on these topics: (1) whether the proposed collection
of information is necessary for the proper performance of FDA's
functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
Human Drug Compounding, Repackaging, and Related Activities Regarding
Sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act
OMB Control Number 0910-0858--Extension
I. Background
This information collection helps support implementation of
sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act
(FD&C Act) (21 U.S.C. 353a and 21 U.S.C. 353b), which govern
compounding by pharmacies, outsourcing facilities, and other entities.
Compounding is generally a practice in which a licensed pharmacist, a
licensed physician, or, in the case of an outsourcing facility, a
person under the supervision of a licensed pharmacist, combines, mixes,
or alters ingredients of a drug to create a medication tailored to the
needs of an individual patient. Although compounded drugs can serve an
important medical need for certain patients, they also present risks to
patients. FDA's compounding program aims to protect patients from
unsafe, ineffective, and poor-quality compounded drugs, while
preserving access to lawfully marketed compounded drugs for patients
who have a medical need for them. Respondents to the information
collection are pharmacies, outsourcing facilities, and other entities.
II. Guidances
To assist respondents in complying with statutory requirements, we
have issued the following topic-specific guidance documents:
Table 1--Published Guidance Documents Regarding Sections 503A and 503B
of the FD&C Act
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Notice of availability
Title publication date
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Compounding and Repackaging of September 26, 2018 (83
Radiopharmaceuticals by State-Licensed Nuclear FR 48633).
Pharmacies, Federal Facilities, and Certain
Other Entities (Radiopharmaceutical Compounding
and Repackaging Guidance) (available at https://www.fda.gov/media/102615/download).
Compounding and Repackaging of September 26, 2018 (83
Radiopharmaceuticals by Outsourcing Facilities FR 48630).
(Radiopharmaceutical Compounding and
Repackaging by Outsourcing Facilities Guidance)
(available at https://www.fda.gov/media/102637/download download).
Repackaging of Certain Human Drug Products by January 13, 2017 (82
Pharmacies and Outsourcing Facilities FR 4343).
(Repackaging Guidance) (available at https://www.fda.gov/media/90978/download).
Mixing, Diluting, or Repackaging Biological January 19, 2018 (83
Products Outside the Scope of an Approved FR 2787).
Biologics License Application (Biological
Products Guidance) (available at https://www.fda.gov/media/90986/download).
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These guidance documents were issued consistent with FDA's good
guidance practice regulations in 21 CFR 10.115, which provide for
public comment at any time. The guidance documents communicate FDA's
current thinking on the respective topics and include information
collection that may result in expenditures of time and effort by
respondents. In FDA's notices of availability for the guidance
documents, we also solicited public comment under the PRA on the
information collection provisions. FDA has developed and maintains a
searchable guidance database available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. Guidance
documents covered by this information collection may be found by
choosing ``Center for Drug Evaluation and Research'' from among the FDA
Organizations, and by selecting the term
[[Page 49882]]
``Compounding'' from among the possible Filters.\1\
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\1\ Guidance documents applicable to animal drug compounding
regulated by the Center for Veterinary Medicine would also be
returned if no FDA Organization is selected; this information
collection covers only those compounding guidance documents issued
by the Center for Drug Evaluation and Research and Center for
Biologics Evaluation and Research.
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A. Radiopharmaceutical Compounding and Repackaging Guidance
Because Congress explicitly excluded radiopharmaceuticals from
section 503A of the FD&C Act (see section 503A(d)(2)), compounded
radiopharmaceuticals are not eligible for the exemptions under section
503A from section 505 of the FD&C Act (21 U.S.C. 355) (concerning new
drug approval requirements), section 502(f)(1) of the FD&C Act (21
U.S.C. 352(f)(1)) (concerning labeling with adequate directions for
use), and section 501(a)(2)(B) of the FD&C Act (21 U.S.C. 351(a)(2)B))
(concerning current good manufacturing practice (CGMP) requirements).
In addition, the FD&C Act does not provide an exemption for repackaged
radiopharmaceuticals. The guidance describes the conditions under which
FDA does not intend to take action for violations of sections 505,
502(f)(1), and 501(a)(2)(B) of the FD&C Act when a State-licensed
nuclear pharmacy, Federal facility, or other facility that is not an
outsourcing facility and that holds a radioactive materials license for
medical use issued by the Nuclear Regulatory Commission or by an
Agreement State compounds or repackages radiopharmaceuticals for human
use. The guidance explains that one condition is that the compounded
radiopharmaceutical is not essentially a copy of an approved
radiopharmaceutical. As described in the guidance, FDA does not intend
to consider a compounded radiopharmaceutical to be essentially a copy
if, among other reasons, there is a change between the compounded
radiopharmaceutical and the approved radiopharmaceutical that produces
a clinical difference for an identified individual patient, as
determined by the prescribing practitioner and documented in writing on
the prescription or order. In addition, FDA does not intend to consider
a compounded radiopharmaceutical to be essentially a copy if the FDA-
approved radiopharmaceutical is on FDA's drug shortage list (see
section 506E of the FD&C Act (21 U.S.C. 356e)) at the time of
compounding and distribution. If the facility compounded a drug that is
identical or nearly identical to an approved drug product that appeared
on FDA's drug shortage list, the facility should maintain documentation
(e.g., a notation on the order for the compounded drug) regarding the
status of the drug on FDA's drug shortage list at the time of
compounding, distribution, and dispensing.
B. Radiopharmaceutical Compounding and Repackaging by Outsourcing
Facilities Guidance
In contrast to section 503A, section 503B of the FD&C Act does not
exclude radiopharmaceuticals. Therefore, FDA's overall policies
regarding section 503B of the FD&C Act apply to the compounding of
radiopharmaceuticals. However, we have developed specific policies that
apply only to the compounding of radiopharmaceuticals by outsourcing
facilities using bulk drug substances and to the compounding of
radiopharmaceuticals by outsourcing facilities that are essentially
copies of approved drugs when such compounding is limited to minor
deviations, as that term is defined in the guidance. FDA issued this
guidance in part to describe the conditions under which the Agency does
not generally intend to take action for violations of sections 505 and
502(f)(1) of the FD&C Act when an outsourcing facility repackages
radiopharmaceuticals for human use.
As discussed in the guidance, one condition is that if a
radiopharmaceutical is repackaged by an outsourcing facility, the label
on the immediate container (primary packaging, e.g., the syringe) of
the repackaged product includes certain information.
C. Repackaging Guidance
The guidance describes the conditions under which FDA does not
intend to take action for violations of sections 505 (concerning new
drug applications), 502(f)(1) (concerning labeling with adequate
directions for use), 582 ((21 U.S.C. 360eee-1) concerning drug supply
chain security requirements), and (where specified in the guidance)
501(a)(2)(B) of the FD&C Act (concerning CGMPs), when a State-licensed
pharmacy, Federal facility, or outsourcing facility repackages certain
prescription drugs. One condition discussed in the guidance is that if
a drug is repackaged by an outsourcing facility, the label on the
immediate container (primary packaging, e.g., the syringe) of the
repackaged product includes certain information described in the
guidance.
Conditions discussed in the guidance include that if a drug is
repackaged by an outsourcing facility, the label on the immediate
container (primary packaging, e.g., the syringe) and on the container
from which the individual units are removed for administration
(secondary packaging, e.g., the bag, box, or other package in which the
repackaged products are distributed) of the repackaged product include
certain information described in the guidance.
D. Biological Products Guidance
Certain licensed biological products may sometimes be mixed,
diluted, or repackaged in a way not described in the approved labeling
for the product to meet the needs of a specific patient. As described
in the guidance, biological products subject to licensure under section
351 of the Public Health Service (PHS) Act (42 U.S.C. 262) are not
eligible for the statutory exemptions available to certain compounded
drugs under sections 503A and 503B of the FD&C Act. In addition, a
biological product that is mixed, diluted, or repackaged outside the
scope of an approved biologics license application (BLA) is considered
an unlicensed biological product under section 351 of the PHS Act.
This guidance document describes several conditions under which FDA
does not intend to take action for violations of section 351 of the PHS
Act and sections 502(f)(1), 582, and (where specified) 501(a)(2)(B) of
the FD&C Act, when a State-licensed pharmacy, a Federal facility, or an
outsourcing facility dilutes, mixes, or repackages certain biological
products outside the scope of an approved BLA.
One condition discussed in the guidance is that if the labeling for
the licensed biological product includes storage instructions, handling
instructions, or both (e.g., protect from light, do not freeze, keep at
specified storage temperature), the labeling for the biological product
that is mixed, diluted, or repackaged specifies the same storage
conditions. Another condition described in the guidance is that, if the
biological product is mixed, diluted, or repackaged by an outsourcing
facility, the label on the immediate container (primary packaging,
e.g., the syringe) of the mixed, diluted, or repackaged product
includes certain information described in the guidance. In addition,
the guidance communicates that as a condition for biological products
mixed, diluted, or repackaged by an outsourcing facility that, if the
immediate product label is too small to bear the active and inactive
ingredients, such information is included on the label of the container
from which the
[[Page 49883]]
individual units are removed for administration (secondary packaging,
e.g., the bag, box, or other package in which the mixed, diluted, or
repackaged biological products are distributed).
The guidance also communicates FDA's thinking about the condition
for biological products mixed, diluted, or repackaged by an outsourcing
facility that the label on the container from which the individual
units are removed for administration include directions for use. These
directions include, as appropriate, the dosage and administration and
the following information to facilitate adverse event reporting:
https://www.fda.gov/medwatch and 1-800-FDA-1088.
Finally, another condition described in the guidance is that
outsourcing facilities maintain records of the testing performed in
accordance with ``Appendix A--Assigning a BUD for Repackaged Biological
Products Based on Stability Testing'' of the guidance for biological
products repackaged by outsourcing facilities for which the beyond use
date (BUD) is established based on a stability program conducted in
accordance with Appendix A.
Section III.C of the guidance, ``Licensed Allergenic Extracts for
Subcutaneous Immunotherapy,'' discusses the preparation of prescription
sets (i.e., licensed allergenic extracts that are mixed and diluted to
provide subcutaneous immunotherapy to an individual patient) by a
physician, a State-licensed pharmacy, a Federal facility, or an
outsourcing facility. Another condition described in the guidance is
that if the prescription set is prepared by an outsourcing facility,
the label of the container from which the individual units of the
prescription set are removed for administration (secondary packaging)
includes the following information to facilitate adverse event
reporting: https://www.fda.gov/medwatch and 1-800-FDA-1088. Each
prescription set prepared by an outsourcing facility is also
accompanied by instructions for use.
III. Electronic Product Reporting to FDA
Outsourcing facilities submit their initial and biannual product
reports identifying drug products repackaged during the previous 6-
month period to FDA via the Agency's electronic Drug Registration and
Listing System (eDRLS) as explained in the Radiopharmaceutical
Compounding and Repackaging Guidance by Outsourcing Facilities and the
Repackaging Guidance. Also, we expect to receive no waiver requests
from the electronic submission process for initial product reports and
semiannual reports.
We estimate the burden of this information collection as follows:
Table 2--Estimated Annual Recordkeeping Burden \1\
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Number of
Recommended activity; Number of records per Total annual Average burden per Total hours
guidance section recordkeepers recordkeeper records recordkeeping
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Radiopharmaceutical Compounding and Repackaging Guidance
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Consultation between the 10 25 250 .05 (3 minutes)..... 12.5
compounder and prescriber
and the notation on the
prescription or order
documenting the
prescriber's determination
of clinical difference
(section III.A of the
Radiopharmaceutical
Compounding and Repackaging
Guidance).
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Biological Products Guidance
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Maintaining records of 5 30 150 0.083 (5 minutes)... 12.5
testing performed in
accordance with Appendix A
of the Biological Products
Guidance (section III.B of
the Biological Products
Guidance).
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Total................... 15 ............... 400 .................... 25
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Table 3--Estimated Annual Third-Party Disclosure 1 2
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Number of
Recommended activity; Number of disclosures per Total annual Average burden per Total hours
guidance section respondents respondent disclosures disclosure
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Radiopharmaceutical Compounding and Repackaging by Outsourcing Facilities Guidance
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Designing, testing, and 2 5 10 0.5 (30 minutes).... 5
producing each label on
immediate containers,
packages, and/or outer
containers (section III.B
of the Radiopharmaceutical
Compounding and Repackaging
Guidance by Outsourcing
Facilities).
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Repackaging Guidance
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Designing, testing, and 6 36 216 1................... 216
producing each label on
immediate containers,
packages, and/or outer
containers (section III.A
of the Repackaging
Guidance).
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Biological Products Guidance
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Designing, testing, and 15 5 75 0.5 (30 minutes).... 37.5
producing the label,
container, packages, and/or
outer containers for each
mixed, diluted, or
repackaged biological
product (section III.B of
the Biological Products
Guidance).
Designing, testing, and 5 300 1,500 0.5 (30 minutes).... 750
producing each label on
immediate containers,
packages, and/or outer
containers for each
licensed allergenic extract
(section III.C of the
Biological Products
Guidance).
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Total................... 28 ............... 1,801 .................... 1,009
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Totals may not sum due to rounding.
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Table 4--Estimated Annual Reporting Burden \1\
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Number of
Recommended activity; guidance Number of disclosures per Total annual Average burden Total hours
section respondents respondent disclosures per disclosure
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Radiopharmaceutical Compounding and Repackaging by Outsourcing Facilities Guidance
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Biannual product reports 2 2 4 3 12
identifying drug products
repackaged by the outsourcing
facility during the previous 6-
month period (section III.B of
the Radiopharmaceutical
Compounding and Repackaging
Guidance by Outsourcing
Facilities).....................
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Repackaging Guidance
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Biannual product reports 6 2 12 3 36
identifying drug products
repackaged by the outsourcing
facility during the previous 6-
month period (section III.A of
the Repackaging Guidance).......
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Total........................ 8 ............... 16 ............... 48
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
For purposes of our analysis, we characterize the burden associated
with the time and effort expended on the information collection
recommendations discussed in the respective guidance documents as
either recordkeeping, reporting, or third-party disclosure activities.
We reconfigured the original table by splitting it into three tables to
better differentiate between the estimated annual recordkeeping burden,
the estimated annual reporting burden, and the estimated annual third-
party disclosure burden. At the same time, our findings show that
compliance with recordkeeping requirements applicable to compounded and
repackaged drug products is standard practice in the compounding and
selling of these drug products under States' pharmacy laws and other
State laws governing recordkeeping by healthcare professionals and
healthcare facilities. Therefore, we excluded from our estimate
recordkeeping practices discussed in the respective guidance documents
we consider usual and customary. We invite comment on this assumption.
For the Repackaging Guidance, to correct a clerical error, we have
adjusted the number of disclosures per respondent from 21 to 36 because
each respondent is estimated to average 6 different products and
average 6 different strengths, which requires 36 (6 x 6) unique labels
per respondent. The initial narrative reflected that each product would
come in 6 different strengths and thus require 6 unique labels, but due
to a clerical error, this information was not correctly included in the
table. We also adjusted the number of respondents to 6 to match the
number of respondents designing, testing, and producing labels. In
addition, we adjusted the total number of disclosures per respondent to
2 given the biannual reporting requirement.
For the Radiopharmaceutical Compounding and Repackaging by
Outsourcing Facilities Guidance, a row for biannual product reporting
was added to capture product reporting that was inadvertently omitted.
Our estimated burden for the information collection reflects
constant respondent numbers. The original numbers were based on the
information the program received from product reporting data. We do not
have a mechanism in place to determine whether or not these numbers
have fluctuated upward or downward; however, based on analogous
observations of industry through program experience (some product
reports), we believe these numbers are constant. Repackagers who are
also registered as outsourcing facilities (OF) are not entity types
that are individually regulated as repackagers. They are subsumed in
the OF entity type and not easily distinguishable. They may or may not
report their repackaging operations.
We are updating the information collection to include burden
attendant to reporting and disclosure recommendations found in the
Agency guidance documents that was inadvertently omitted in the
original information collection due to clerical errors. The burden
estimate is adjusted to reflect a resulting increase of 114 hours and
94 responses annually.
Dated: June 6, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-12783 Filed 6-11-24; 8:45 am]
BILLING CODE 4164-01-P