[Federal Register Volume 80, Number 33 (Thursday, February 19, 2015)]
[Notices]
[Pages 8881-8884]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-03418]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2014-D-1525]
Mixing, Diluting, or Repackaging Biological Products Outside the
Scope of an Approved Biologics License Application; Draft Guidance for
Industry; Availability
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or the Agency) is
announcing the availability of a draft guidance for industry entitled
``Mixing, Diluting, or Repackaging Biological Products Outside the
Scope of an Approved Biologics License Application.'' This draft
guidance describes the conditions under which FDA does not intend to
take action against a state-licensed pharmacy, a Federal facility, or
outsourcing facility that mixes, dilutes, or repackages certain
biological products without obtaining an approved biologics license
application (BLA).
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draft guidance before it begins work on the final version of the
guidance, submit either electronic or written comments on the draft
guidance by May 20, 2015.
ADDRESSES: Submit written requests for single copies of this guidance
to the Division of Drug Information, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 2201, Silver Spring, MD 20993-0002; or the Office of
Communication, Outreach and Development, Center for Biologics
Evaluation and Research (CBER), Food and Drug Administration, 10903 New
Hampshire Avenue, Bldg. 71, Rm. 3128, 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 guidance document.
Submit electronic comments on the guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Leah Christl, Center for Drugs
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 6426, Silver Spring, MD 20903, 301-796-
0869; or Stephen Ripley, Center for Biologics Evaluation and Research,
Food and Drug Administration, 10903
[[Page 8882]]
New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002,
240-402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Mixing, Diluting, or Repackaging of Biological Products
Outside the Scope of an Approved Biologics License Application.''
Certain licensed biological products may need to 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. For example, for some
biological products there is no licensed pediatric strength and/or
dosage form. In addition, there may be certain circumstances when a
person would remove a licensed biological product from its original
container and place it into a different container(s) (repackage it), in
a manner that is not within the scope of the approved labeling for the
product. As described in the draft guidance, mixed, diluted, or
repackaged biological products are not eligible for the statutory
exemptions available to certain compounded drugs under sections 503A
and 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21
U.S.C. 353A and 353B). In addition, a biological product that is mixed,
diluted, or repackaged outside the scope of an approved BLA is
considered an unlicensed biological product under section 351 of the
Public Health Service (PHS) Act (21 U.S.C. 262).
This draft guidance describes the conditions under which FDA does
not intend to take action for violations of section 351 of the PHS Act
and section 502(f)(1) (21 U.S.C. 352(f)(1) and where specified, section
501(a)(2)(B) (21 U.S.C. 351(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 without
obtaining an approved BLA.
Elsewhere in this issue of the Federal Register, the Agency is
making available for comment a draft guidance entitled ``Repackaging of
Certain Human Drug Products by Pharmacies and Outsourcing Facilities.''
When these two guidances become final, they will address and clarify
the Agency's policy regarding hospital pharmacies repackaging and
safely transferring repackaged drug, including biological products, to
other hospitals within the same health system during a drug shortage.
Therefore, under section 506F(d) of the FD&C Act (21 U.S.C. 356f(d),
when FDA issues these as final guidances, section 506F will no longer
apply.
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). This guidance, when
finalized, will represent FDA's current thinking on mixing, diluting,
and repackaging of biological products not within the scope of the
product's approved BLA as described in the approved labeling for the
product. It does not create or confer any rights for or on any person
and does not operate to bind FDA or the public. An alternative approach
may be used if such approach satisfies the requirements of the
applicable statutes and regulations.
II. Comments
Interested persons may submit either electronic comments regarding
this document to http://www.regulations.gov or written comments to the
Division of Dockets Management (see ADDRESSES). It is only necessary to
send one set of comments. Identify comments with the docket number
found in brackets in the heading of this document. Received comments
may be seen in the Division of Dockets Management between 9 a.m. and 4
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.
III. Paperwork Reduction Act of 1995
This draft guidance contains information collection provisions that
are subject to review by OMB under the Paperwork Reduction Act of 1995
(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 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.
Title: Draft Guidance for Industry: Mixing, Diluting, or
Repackaging of Biological Products Outside the Scope of an Approved
Biologics License Application.
Description: The draft guidance describes FDA's policy with respect
to the mixing, diluting, and repackaging of certain types of biological
products that have been licensed under section 351 of the PHS Act when
such activities are not within the scope of the product's approved BLA
as described in the approved labeling for the product. The draft
guidance describes the conditions under which FDA does not intend to
take action for violations of section 351 of the PHS Act and section
502(f)(1) and where specified, section 501(a)(2)(B) of the FD&C Act,
when a state-licensed pharmacy, a Federal facility, or an outsourcing
facility mixes, dilutes, or repackages certain biological products
without obtaining an approved BLA.
The draft guidance includes the following collection of information
under the PRA.
One condition described in the draft 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 the following information:
The statement ``This product was mixed or diluted by [name
of outsourcing facility],'' or ``This product was repackaged by [name
of outsourcing facility]'' whichever statement is appropriate;
the address and phone number of the outsourcing facility
that mixed, diluted, or repackaged the biological product;
the proper name of the original biological product that
was mixed, diluted, or repackaged;
the lot or batch number of the mixed, diluted, or
repackaged biological product;
the dosage form and strength;
a statement of either the quantity or the volume of the
mixed, diluted, or repackaged biological product, whichever is
appropriate;
the date the biological product was mixed, diluted, or
repackaged;
the beyond-use-date (BUD) of the mixed, diluted, or
repackaged biological product;
storage and handling instructions for the mixed, diluted,
or repackaged biological product;
the National Drug Code (NDC) number of the mixed, diluted,
or
[[Page 8883]]
repackaged biological product, if available; \1\
---------------------------------------------------------------------------
\1\ The NDC number of the original licensed biological product
should not be placed on the mixed, diluted, or repackaged biological
product.
---------------------------------------------------------------------------
The statement ``Not for resale,'' and, if the biological
product is distributed by an outsourcing facility other than pursuant
to a prescription for an individual identified patient, the statement
``Office Use Only''; and
If included on the label of the FDA-licensed product from
which the biological product is being mixed, diluted, or repackaged, a
list of the active and inactive ingredients; and if the ingredients are
listed because they were listed on the original product, the label of
the mixed, diluted, or repackaged product should include any additional
ingredients that appear in the mixed, diluted, or repackaged product.
Another condition in the draft guidance is that, if the immediate
product label is too small or the mixed, diluted, or repackaged product
is otherwise unable to accommodate a label with sufficient space to
bear the active and inactive ingredients, such information should be
included on the label of the container from which the 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).
In addition, the draft guidance describes the conditions that the
container label include 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. Another condition in the draft guidance is that each mixed,
diluted, or repackaged biological product is also accompanied by a copy
of the prescribing information that accompanied the original licensed
biological product that was mixed, diluted, or repackaged.
We estimate that annually a total of approximately five registered
outsourcing facilities that mix, dilute, or repackage biological
products (``Number of Respondents'' in table 1, row 1) will each
design, test, and produce approximately five different labels
(``Frequency per Disclosure'' in table 1, row 1), for a total of 25
labels that include the information set forth in section III.B of the
draft guidance (including directions for use) (``Total Disclosures'' in
table 1, row 1). We also estimate that designing, testing, and
producing each label will take approximately 0.5 hours (``Hours per
Disclosure'' in table 1, row 1). The provision to add 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)).
Section III.C of the draft guidance discusses the preparation of
prescription sets (i.e., licensed allergenic extracts that are combined
to provide subcutaneous immunotherapy to an individual patient) by a
physician, state-licensed pharmacy, a Federal facility, or outsourcing
facility. Under the draft guidance, if the prescription set is mixed or
diluted by an outsourcing facility, the label on the immediate
container of the prescription set (primary packaging) includes:
The patient's name as identified on the prescription;
the statement ``This prescription set was prepared by
[name of outsourcing facility]'';
the address and phone number of the outsourcing facility
that prepared the prescription set;
the identity of each allergenic extract in the
prescription set and the quantity of each;
the dilution of each dilution vial;
the lot or batch number of the prescription set;
the date the prescription set was prepared;
the BUD of the prescription set;
storage and handling instructions for the prescription
set; and
the statement ``Not for resale''.
In addition, under the draft guidance, 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: http://www.fda.gov/medwatch and
1-800-FDA-1088. Each prescription set prepared is also accompanied by
instructions for use and the FDA approved package insert for each
allergenic extract.
We estimate that annually a total of approximately five outsourcing
facilities that prepare prescription sets (``Number of Respondents'' in
table 2, row 1) will each include the information set forth in section
III.C of the draft guidance (including directions for use) on the
labels, packages, and/or containers of approximately 300 prescription
sets (``Frequency per Disclosure'' in table 2, row 1) for a total of
1500 disclosures (``Total Disclosures'' in table 2, row 1). We also
estimate that the initial process of designing, testing, and producing,
and attaching each label, package, and/or container to each
prescription set will take approximately 0.5 hours (``Hours per
Disclosure'' in table 2, 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)).
We also estimate that a total of approximately five outsourcing
facilities (``Number of Respondents'' in table 2, row 2) will each
design, test, and produce the instructions for use and a copy of
prescribing information, as set forth in section III.C of the draft
guidance, for approximately 300 prescription sets (``Frequency per
Disclosure'' in table 2, row 2) for a total of 1500 disclosures (total
disclosures'' in table 2, row 2), which we estimate will take
approximately 1 hour for each prescription set (``Hours per
Disclosure'' in table 2, row 2). The provision to include http://www.fda.gov/medwatch and 1-800-FDA-1088 is not included in this burden
estimate because they are 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 total estimated third-party disclosure burden resulting from
the draft guidance is as follows:
[[Page 8884]]
Table 1--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
Biological product mixing, Number of Frequency per Total Hours per
diluting, and repackaging respondents disclosure disclosures disclosure Total hours
----------------------------------------------------------------------------------------------------------------
Designing, testing, and 5 5 25 0.5 12.5
producing the label,
container, packages, and/or
outer containers for each
mixed, diluted, or repackaged
biological product............
Prescribing information 5 5 25 1 25
labeling accompanying each
mixed, diluted, or repackaged
drug product..................
--------------------------------------------------------------------------------
Total...................... .............. .............. .............. .............. 37.5
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
*(30 minutes)
Table 2--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
Preparation of prescription Number of Frequency per Total Hours per
sets respondents disclosure disclosures disclosure Total hours
----------------------------------------------------------------------------------------------------------------
Designing, testing, and 5 300 1500 0.5 750
producing each label on
immediate containers,
packages, and/or outer
containers....................
Including instructions for use 5 300 1500 1 1500
labeling and the original
package insert(s) for each
prescription set..............
--------------------------------------------------------------------------------
Total...................... .............. .............. .............. .............. 2250
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
*(30 minutes)
The draft guidance also references registration, product reporting,
current good manufacturing practice (CGMP) requirements, and the
payment of certain fees by human drug compounding outsourcing
facilities. In the Federal Register of December 4, 2013 (78 FR 72899),
FDA estimated the burden resulting from outsourcing facility
registration. In the Federal Register of December 4, 2013 (78 FR
72897), FDA estimated the burden resulting from outsourcing facility
interim product reporting. In the Federal Register of April 1, 2014 (79
FR 18297), FDA estimated the burden resulting from the payment of
certain fees by outsourcing facilities. In the Federal Register of July
2, 2014 (79 FR 37743), FDA estimated the burden resulting from
outsourcing facility compliance with CGMP requirements.
IV. Electronic Access
Persons with access to the Internet can obtain the document at
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm or http://www.regulations.gov.
Dated: February 11, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-03418 Filed 2-18-15; 8:45 am]
BILLING CODE 4164-01-P