[Federal Register Volume 86, Number 160 (Monday, August 23, 2021)]
[Notices]
[Pages 47113-47117]
[FR Doc No: 2021-17996]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-N-0359]

Agency Information Collection Activities; Submission for Office
of Management and Budget Review; 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.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing that a
proposed collection of information has been submitted to the Office of
Management and Budget (OMB) for review and clearance under the
Paperwork Reduction Act of 1995.

DATES: Submit written comments (including recommendations) on the
collection of information by September 22, 2021.

ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be submitted to https://www.reginfo.gov/public/do/PRAMain. Find this particular information
collection by selecting ``Currently under Review--Open for Public
Comments'' or by using the search function. The OMB control number for
this information collection is 0910-0858. Also include the FDA docket
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Domini Bean, Office of Operations,
Food and Drug Administration, Three White Flint North, 10A-12M, 11601
Landsdown St., North Bethesda, MD 20852,<PHONE_NUMBER>,
<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.

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--Revision

    This information collection supports 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. Our 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.
    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
------------------------------------------------------------------------
                                                  Notice of availability
                      Title                          publication date
------------------------------------------------------------------------
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'').
Compounding and Repackaging of                    September 26, 2018 (83
 Radiopharmaceuticals by Outsourcing Facilities    FR 48630).
 (``Radiopharmaceutical Outsourcing Repackaging
 Guidance'').
Repackaging of Certain Human Drug Products by     January 13, 2017 (82
 Pharmacies and Outsourcing Facilities             FR 4343).
 (``Repackaging Guidance'').
Mixing, Diluting, or Repackaging Biological       January 19, 2018 (83
 Products Outside the Scope of an Approved         FR 2787).
 Biologics License Application (``Biologics
 Guidance'').
------------------------------------------------------------------------

    These guidance documents were issued consistent with our Good
Guidance Practice regulations in 21 CFR part 10.115 which provide for
public comment at any time. The guidance documents communicate our
current thinking on the respective topics and include information
collection that may result in expenditures of time and effort by
respondents. In our notices of availability 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
``Compounding'' from among the possible ``Topic'' filters.\1\ For
efficiency of operations we are consolidating the related information
collections.
---------------------------------------------------------------------------

    \1\ Guidance documents applicable to animal drug compounding
regulated by our Center for Veterinary Medicine would also be
returned if no FDA Organization is selected; this information
collection covers only those Compounding documents issued by the
Center for Drug Evaluation and Research.
---------------------------------------------------------------------------

Compounding and Repackaging of Radiopharmaceuticals by State-Licensed
Nuclear Pharmacies, Federal Facilities, and Certain Other Entities

    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. This guidance document 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.

Radiopharmaceutical Outsourcing Repackaging 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 apply to the compounding of radiopharmaceutical
drug products. 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. The guidance also
provides that the label 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) includes: (1) The active and inactive ingredients, if the
immediate product label is too small to include this information, and
directions for use, including (as appropriate) dosage and
administration and (2) the following information to facilitate adverse
event reporting: and 1-800-FDA-1088.

Repackaging Guidance

    This 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)
section 501(a)(2)(B) of the FD&C Act (concerning CGMPs), when a state-
licensed pharmacy, Federal facility, or outsourcing facility repackages
certain prescription drug products. 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.
    Another condition discussed in the guidance is that the label 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) includes: (1)
The active and inactive ingredients, if the immediate product label is
too small to include this information, and directions for use,
including (as appropriate) dosage and administration, (2) directions
for use, including, as appropriate, dosage and administration, and (3)
the following information to facilitate adverse event reporting:
https://www.fda.gov/medwatch and 1-800-FDA-1088.

Biologics 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 (for example, 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, for example, 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 individual units are removed for
administration (secondary packaging, for example, the bag, box, or
other package in which the mixed, diluted, or repackaged biological
products are distributed).
    The guidance also communicates our 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 (that is, 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.
    In the Federal Register of April 29, 2021 (86 FR 22674), we
published a 60-day notice requesting public comment on the proposed
collection of information. No comments were received.
    We estimate the burden of the information collection as follows:

                                                    Table 2--Estimated Annual Recordkeeping Burden 1
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                             Number of
                        Activity                             Number of      disclosures    Total annual    Average burden per disclosure    Total hours
                                                            respondents   per respondent    disclosures
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                              Radiopharmaceutical Guidance
--------------------------------------------------------------------------------------------------------------------------------------------------------
Consultation between the compounder and prescriber and                10              25             250  .05 (3 minutes)...............            12.5
 the notation on the prescription or order documenting
 the prescriber's determination of clinical difference.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                Radiopharmaceutical Outsourcing And Repackaging Guidance
--------------------------------------------------------------------------------------------------------------------------------------------------------
Designing, testing, and producing each label on                        2               5              10  0.5 (30 minutes)..............               5
 immediate containers, packages and/or outer containers.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Repackaging Guidance
--------------------------------------------------------------------------------------------------------------------------------------------------------
Designing, testing, and producing each label on                        6              21             126  1.............................             126
 immediate containers, packages, and/or outer containers.
Biannual product reports identifying drug products                     3               4              12  3.............................              24
 repackaged by the outsourcing facility during the
 previous 6-month period (Guidance Section III.A.).
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                   Biologics Guidance
--------------------------------------------------------------------------------------------------------------------------------------------------------
Designing, testing, and producing the label, container,               15               5              75  0.5 (30 minutes)..............            37.5
 packages, and/or outer containers for each mixed,
 diluted, or repackaged biological product.
Designing, testing, and producing each label on                        5             300           1,500  0.5 (30 minutes)..............             750
 immediate containers, packages and/or outer containers
 for each licensed allergenic extract.
Maintaining records of testing performed in accordance                 5              30             150  0.083 (5 minutes).............            12.5
 with Biologics Guidance Appendix A.
                                                         -----------------------------------------------------------------------------------------------
    Total...............................................  ..............  ..............           2,123  ..............................           967.5
--------------------------------------------------------------------------------------------------------------------------------------------------------
1 There are no capital costs or operating and maintenance costs associated with this collection of information.

    As defined in 44 U.S.C. 3502(13), the term ``recordkeeping
requirement'' means a requirement imposed on respondents to maintain
specified records, as well as a requirement to ``retain such records;
notify third parties, the Federal Government, or the public of the
existence of such records; disclose such records to third parties, the
Federal Government, or the public; or report to third parties, the
Federal Government, or the public regarding such records.'' For
purposes of our analysis, therefore, we have characterized the burden
associated with the time and effort expended on the information
collection recommendations discussed in the respective guidance
documents as recordkeeping activities. 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. We have therefore excluded
from our estimate recordkeeping practices discussed in the respective
guidance documents we consider usual and customary. We invite comment
on this assumption.

Radiopharmaceutical Compounding and Repackaging Guidance

    We estimate 10 compounders annually will consult a prescriber to
determine whether a compounded radiopharmaceutical has a change that
produces a clinical difference for an identified individual patient as
compared to the comparable approved radiopharmaceutical. We estimate
that those compounders will document this determination on 250
prescriptions or orders for compounded radiopharmaceuticals. We assume
consultation between the compounder and the prescriber and noting this
determination on each prescription or order that does not already
document this determination will take 3 minutes (0.05 hours) per
prescription or order, for a total of approximately 12.5 hours.

Radiopharmaceutical Outsourcing and Repackaging Guidance

    We estimate a total of 2 outsourcing facilities annually will each
design, test, and produce an average of 5 different labels for a total
of 10 labels, as described in the guidance (including directions for
use). We assume that designing, testing, and producing each label will
take 30 minutes (0.5 hours) for each repackaged radiopharmaceutical,
for a total of 5 hours. We consider that the provision to include
``https://www.fda.gov/medwatch'' and ``1-800-FDA-1088'' is not a
collection of information as defined in 5 CFR 1320.3(c)(2) and is
therefore exempt from OMB review and approval under the PRA.

Repackaging Guidance

    Based on current data for outsourcing facilities, we estimate 6
outsourcing facilities annually will submit an initial report
identifying all drugs repackaged in the facility in the previous year.
For the purposes of this estimate, each product's structured product
labeling (SPL) submission is considered a separate response and
therefore each facility's product report will include multiple
responses. Taking into account that a particular product that is
repackaged may come in different strengths and can be reported in a
single

SPL response, we estimate that each facility will average approximately
6 products.
    Similarly, we estimate that 6 outsourcing facilities will submit an
initial report identifying all drugs repackaged in the facility in the
past year. Taking into account that a particular product that is
repackaged may come in different strengths and can be reported in a
single SPL response, we assume that each facility will average 6
products. Our estimate is based on current product reporting data. We
expect that each product report will consist of multiple SPL responses
per facility and assume preparing and electronically submitting this
information will take up to 2 hours for each initial SPL response.
    We also estimate 3 registered outsourcing facilities will submit a
report twice each year (June and December) that identifies all drugs
repackaged at the facility in the previous 6 months. We also estimate
that an average of 3 facilities will prepare and submit 3 SPL responses
and assume that preparing and submitting this information
electronically could also take up to 2 hours per response. If a product
was not repackaged during a particular reporting period, outsourcing
facilities do not need to send an SPL response for that product during
that reporting period. Our figures reflect what we believe to be the
average burden among respondents. We expect to receive no waiver
requests from the electronic submission process for initial product
reports and semiannual reports.

Biologics Guidance

    We estimate 15 outsourcing facilities annually who mix, dilute, or
repackage biological products will each design, test, and produce 5
different labels, for a total of 75 labels that include the information
set forth in section III.B--``Mixing, Diluting, or Repackaging Licensed
Biological Products'' of the guidance (including directions for use) as
well as inclusion of storage instructions, handling instructions, or
both. We assume that designing, testing, and producing each label will
take 30 minutes (0.5 hours). We consider that the provision to include
``https://www.fda.gov/medwatch'' and ``1-800-FDA-1088'' is not a
collection of information as defined in 5 CFR 1320.3(c)(2) and is
therefore exempt from OMB review and approval under the PRA.
    We estimate that annually a total of 5 outsourcing facilities that
prepare prescription sets will each include on the labels, packages,
and/or containers of approximately 300 prescription sets the
information set forth in section III.C ``Licensed Allergenic Extracts
for Subcutaneous Immunotherapy'' of the draft guidance (including
directions for use), for a total of 1,500 disclosures. We assume the
initial process of designing, testing, and producing labeling and
attaching to each prescription set each label, package, and/or
container will take approximately 30 minutes (0.5 hours), for a total
of approximately 750 hours.
    Finally, we estimate that annually five outsourcing facilities who
repackage biological products and establish a BUD in accordance with
Appendix A--``Assigning a BUD for Repackaged Biological Products Based
On Stability Testing'' will maintain 150 records of the testing, as
described in Appendix A of the guidance. We assume maintaining the
records will take 5 minutes per record, for a total of 12.5 hours.
    Our estimated burden for the information collection reflects
program changes and adjustments. We are changing the scope of the
information collection to include burden attendant to provisions found
in the Agency guidance documents discussed in this notice and have
adjusted our estimate to reflect a resulting increase of 955 hours and
1,873 responses annually.

    Dated: August 5, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-17996 Filed 8-20-21; 8:45 am]
BILLING CODE 4164-01-P


[Federal Register Volume 82, Number 130 (Monday, July 10, 2017)]
[Notices]
[Page 31768]
[FR Doc No: 2017-14336]

-----------------------------------------------------------------------

DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Project No. 14698-001]

Shenango Dam Hydroelectric Company, LLC; Notice of Surrender of
Preliminary Permit

    Take notice that Shenango Dam Hydroelectric Company, LLC, permittee
for the proposed Shenango Hydroelectric Project, has requested that its
preliminary permit be terminated. The permit was issued on December 2,
2015, and would have expired on November 30, 2018.\1\ The project would
have been located at the U.S. Army Corps of Engineers' Shenango dam on
the Shenango River, near the Borough of Sharpsburg, Mercer County,
Pennsylvania.
---------------------------------------------------------------------------

    \1\ 153 FERC ] 62,155 (2015).
---------------------------------------------------------------------------

    The preliminary permit for Project No. 14698 will remain in effect
until the close of business, July 30, 2017. But, if the Commission is
closed on this day, then the permit remains in effect until the close
of business on the next day in which the Commission is open.\2\ New
applications for this site may not be submitted until after the permit
surrender is effective.
---------------------------------------------------------------------------

    \2\ 18 CFR 385.2007(a)(2) (2016).

    Dated: June 30, 2017.
Kimberly D. Bose,
Secretary.
[FR Doc. 2017-14336 Filed 7-7-17; 8:45 am]
 BILLING CODE 6717-01-P