81 FR 96005 - Compounding and Repackaging of Radiopharmaceuticals by Outsourcing Facilities; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 81, Issue 250 (December 29, 2016)

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Compounding and Repackaging of Radiopharmaceuticals by Outsourcing Facilities.'' Specifically, this guidance sets forth FDA's policy regarding compounding and repackaging of radiopharmaceuticals for human use by entities that are registered with FDA as outsourcing facilities. This guidance describes how FDA intends to apply section 503B of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) to radiopharmaceuticals compounded by outsourcing facilities, and it describes the conditions under which FDA does not intend to take action for violations of certain provisions of the FD&C Act when an outsourcing facility repackages radiopharmaceuticals.

[Federal Register Volume 81, Number 250 (Thursday, December 29, 2016)]
[Notices]
[Pages 96005-96007]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2016-31512]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-D-4317]


Compounding and Repackaging of Radiopharmaceuticals by 
Outsourcing Facilities; Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled 
``Compounding and Repackaging of Radiopharmaceuticals by Outsourcing 
Facilities.'' Specifically, this guidance sets forth FDA's policy 
regarding compounding and repackaging of radiopharmaceuticals for human 
use by entities that are registered with FDA as outsourcing facilities. 
This guidance describes how FDA intends to apply section 503B of the 
Federal Food, Drug, and Cosmetic Act (the FD&C Act) to 
radiopharmaceuticals compounded by outsourcing facilities, and it 
describes the conditions under which FDA does not intend to take action 
for violations of certain provisions of the FD&C Act when an 
outsourcing facility repackages radiopharmaceuticals.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by February 27, 2017. Submit either electronic or written 
comments concerning the collection of information proposed in the draft 
guidance by February 27, 2017.

ADDRESSES: You may submit comments as follows:

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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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-2016-D-4317 for ``Compounding and Repackaging of 
Radiopharmaceuticals by Outsourcing Facilities.'' Received comments 
will be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9 
a.m. and 4 p.m., Monday through Friday.
     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

[[Page 96006]]

redacted/blacked out, will be available for public viewing and posted 
on http://www.regulations.gov. Submit both copies to the Division of 
Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    Submit written requests for single copies of the draft guidance to 
the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10001 New Hampshire Ave., 
Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002. Send one 
self-addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Sara Rothman, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 5197, Silver Spring, MD 20993, 301-796-
3110.

SUPPLEMENTARY INFORMATION: 

I. Background

    In 2013, the Drug Quality and Security Act created a new section 
503B of the FD&C Act (21 U.S.C. 353b), which describes a new category 
of compounders called outsourcing facilities. Section 503B of the FD&C 
Act describes the conditions that must be satisfied for human drug 
products compounded by or under the direct supervision of a licensed 
pharmacist in an outsourcing facility to qualify for exemptions from 
the following three sections of the FD&C Act:
     Section 502(f)(1) (21 U.S.C. 352(f)(1)) (concerning 
labeling with adequate directions for use);
     section 505 (21 U.S.C. 355) (concerning drug approval 
requirements); and
     section 582 (21 U.S.C. 360eee-1 (concerning drug supply 
chain security requirements).
    In contrast to section 503A (21 U.S.C. 353a), section 503B of the 
FD&C Act does not exclude radiopharmaceuticals. In general, FDA's 
policies regarding section 503B of the FD&C Act apply to the 
compounding of radiopharmaceutical drug products. However, the Agency 
has developed specific policies, applicable only to the compounding of 
radiopharmaceuticals by outsourcing facilities, with respect to bulk 
drug substances for use in compounding radiopharmaceuticals and 
compounding radiopharmaceuticals that are essentially copies of 
approved drugs when such compounding is limited to minor deviations, as 
that term is defined in the guidance.
    In addition, because outsourcing facilities may sometimes repackage 
radiopharmaceuticals for patients, but repackaged radiopharmaceuticals 
are not eligible for the exemptions in section 503B of the FD&C Act, 
the draft guidance describes the conditions under which the Agency does 
not 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.
    Elsewhere in this issue of the Federal Register, FDA is announcing 
the availability of a separate draft guidance document concerning 
compounding and repackaging of radiopharmaceuticals by State-licensed 
nuclear pharmacies and Federal facilities that are not registered as 
outsourcing facilities entitled ``Compounding and Repackaging of 
Radiopharmaceuticals by State-Licensed Nuclear Pharmacies and Federal 
Facilities.''
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on ``Compounding 
and Repackaging of Radiopharmaceuticals by Outsourcing Facilities.'' It 
does not establish any rights for any person and is not binding on FDA 
or the public. You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    This draft guidance contains information collection provisions that 
are subject to review by the Office of Management and Budget under the 
Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-3520). The 
title, description, and respondent description of the information 
collection are given under this section with an estimate of the annual 
reporting and recordkeeping burdens. Included in the estimate is the 
time for reviewing instructions, searching existing data sources, 
gathering and maintaining the data needed, and completing and reviewing 
the collection of information.
    We invite comments on the following 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.
    The draft guidance includes the following collections of 
information under the PRA:
    One condition in the draft guidance 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 the following information:
     The statement ``This radiopharmaceutical was repackaged by 
[name of outsourcing facility].'';
     the address and phone number of the outsourcing facility 
that repackaged the radiopharmaceutical;
     the established name of the original, approved 
radiopharmaceutical that was repackaged;
     the lot or batch number of the repackaged 
radiopharmaceutical;
     the dosage form and radioactive dose of the repackaged 
radiopharmaceutical;
     a statement of either the quantity or volume of the 
repackaged radiopharmaceutical, whichever is appropriate;
     the date the radiopharmaceutical was repackaged;
     the beyond-use-date of the repackaged radiopharmaceutical;
     storage and handling instructions for the repackaged 
radiopharmaceutical;
     the National Drug Code (NDC) number of the repackaged 
radiopharmaceutical, if available \1\;
---------------------------------------------------------------------------

    \1\ The NDC number of the original approved drug product should 
not be placed on the repackaged drug product.

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

[[Page 96007]]

     the statement ``Not for resale,'' and, if the repackaged 
radiopharmaceutical is distributed by an outsourcing facility other 
than pursuant to a prescription for an individual identified patient, 
the statement ``Office Use Only''; and
     a list of the active and inactive ingredients, unless such 
information is included on the label for the container from which the 
individual units are removed, as described in this document.
    Another condition in the draft 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 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 the following 
information to facilitate adverse event reporting: http://www.fda.gov/medwatch and 1-800-FDA-1088.
    We estimate that annually a total of approximately 2 outsourcing 
facilities (``No. of Respondents'' in table 1, row 1) will each design, 
test, and produce approximately 5 different labels (``No. of 
Disclosures per Respondent'' in table 1, row 1) for a total of 10 
labels that include the information described previously (including 
directions for use) (``Total Annual Disclosures'' in table 1, row 1). 
We also estimate that designing, testing, and producing each label will 
take approximately 0.5 hours for each repackaged radiopharmaceutical 
(``Average Burden Hours per Disclosure'' in table 1, row 1). The 
provision to add the statement http://www.fda.gov/medwatch and 1-800-
FDA-1088 is not included in this burden estimate because it is not 
considered a collection of information under the PRA because the 
information is ``originally supplied by the Federal Government to the 
recipient for the purpose of disclosure to the public'' (5 CFR 
1320.3(c)(2)).
    The draft guidance also references registration, adverse event 
reporting, product reporting, and current good manufacturing practices 
(CGMP) requirements for outsourcing facilities. The collection of 
information for outsourcing facility registration has been approved by 
the Office of Management and Budget (OMB) under OMB control number 
0910-0777 (79 FR 69859, November 24, 2014). The collection of 
information for adverse event reporting by outsourcing facilities has 
been approved by OMB under OMB control number 0910-0800 (80 FR 60917, 
October 8, 2015). In the Federal Register of August 1, 2016 (81 FR 
50523), FDA estimated the burden resulting from outsourcing facility 
electronic drug product reporting. In the Federal Register of July 2, 
2014 (79 FR 37743), FDA estimated the burden resulting from outsourcing 
facility compliance with CGMP requirements.
    The total estimated third-party disclosure burden resulting from 
the draft guidance is as follows:

                                                 Table 1--Estimated Annual Third-Party Disclosure Burden
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Number of
    Repackaging by outsourcing facilities        Number of     disclosures per    Total annual        Average burden per disclosure        Total hours
                                                respondents       respondent      disclosures
--------------------------------------------------------------------------------------------------------------------------------------------------------
Designing, testing, and producing each label               2                5               10   .5 (30 minutes).......................               5
 on immediate containers, packages and/or
 outer containers.
--------------------------------------------------------------------------------------------------------------------------------------------------------
There are no capital costs or operating and maintenance costs associated with this collection of information.

III. Electronic Access

    Persons with access to the Internet may obtain the draft guidance 
at either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov.

    Dated: December 22, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-31512 Filed 12-28-16; 8:45 am]
 BILLING CODE 4164-01-P