Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application; Draft Guidance for Industry; Availability, 8881-8884 [2015-03418]
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Federal Register / Vol. 80, No. 33 / Thursday, February 19, 2015 / Notices
TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
Number of
records per
recordkeeper
Number of
recordkeepers
Compounding MOU between FDA and States
Average burden per recordkeeping
(in Hours)
Total annual
records
Total Hours
State recordkeeping for 3 years of compounding complaints .............................................................................
25
15
375
1
375
Total ............................................................................
25
15
375
1
375
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
TABLE 3—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1
Number of
disclosures
per
respondent
Number of
respondents
Compounding MOU between FDA and States
Average burden per disclosure
(in Hours)
Total annual
disclosures
Total hours
State notification to pharmacists, pharmacies, and physicians that its participation in the MOU has been terminated by FDA ...................................................................
1
1
1
1
1
Total ..............................................................................
1
1
1
1
1
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
emcdonald on DSK67QTVN1PROD with NOTICES
VII. Request for Comments
VIII. Electronic Access
FDA invites comments from
interested persons on the new draft
standard MOU that would establish an
agreement between the signatory States
and FDA regarding the appropriate
investigation by such States of
complaints relating to compounded
human drug products distributed
outside the State, and the distribution of
inordinate amounts of compounded
human drug products interstate. The
Agency is providing a 120-day comment
period.
After considering any comments on
the new draft standard MOU submitted
to this docket, FDA intends to finalize
the standard MOU and make it available
for signature by individual States. FDA
will determine at the time of publication
of the final MOU how long it will allow
States to consider whether to sign the
MOU before FDA begins to enforce the
5 percent limit in those States that have
not signed an MOU.
Interested persons may submit either
electronic comments regarding this
document to https://www.regulations.gov
or written comments to the Division of
Dockets Management (see ADDRESSES). It
is only necessary to send one set
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 https://
www.regulations.gov.
Persons with access to the Internet
may obtain the draft standard MOU at
https://www.regulations.gov.
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Dated: February 12, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015–03420 Filed 2–18–15; 8:45 am]
BILLING CODE 4164–01–P
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.
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).
SUMMARY:
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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 https://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
DATES:
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emcdonald on DSK67QTVN1PROD with NOTICES
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
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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 https://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 https://
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.
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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
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Federal Register / Vol. 80, No. 33 / Thursday, February 19, 2015 / Notices
repackaged biological product, if
available; 1
• 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 FDAlicensed 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: https://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,
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1 The NDC number of the original licensed
biological product should not be placed on the
mixed, diluted, or repackaged biological product.
VerDate Sep<11>2014
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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 https://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: https://
www.fda.gov/medwatch and 1–800–
FDA–1088. Each prescription set
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8883
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 https://
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 https://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:
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Federal Register / Vol. 80, No. 33 / Thursday, February 19, 2015 / Notices
TABLE 1—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1
Number of
respondents
Biological product mixing, diluting, and repackaging
Frequency per
disclosure
Total
disclosures
Hours per
disclosure
Total hours
Designing, testing, and producing the label, container,
packages, and/or outer containers for each mixed, diluted, or repackaged biological product .........................
Prescribing information labeling accompanying each
mixed, diluted, or repackaged drug product ..................
5
5
25
0.5
5
5
25
1
Total ............................................................................
........................
........................
........................
........................
12.5
25
37.5
1 There
*(30
are no capital costs or operating and maintenance costs associated with this collection of information.
minutes)
TABLE 2—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1
Number of
respondents
Preparation of prescription sets
Frequency per
disclosure
Total
disclosures
Hours per
disclosure
Total hours
Designing, testing, and producing each label on immediate containers, packages, and/or outer containers .....
Including instructions for use labeling and the original
package insert(s) for each prescription set ....................
5
300
1500
0.5
750
5
300
1500
1
1500
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.
emcdonald on DSK67QTVN1PROD with NOTICES
IV. Electronic Access
Persons with access to the Internet
can obtain the document at either
https://www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm, https://
www.fda.gov/BiologicsBloodVaccines/
GuidanceComplianceRegulatory
Information/default.htm or https://
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
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2014–D–1524]
Repackaging of Certain Human Drug
Products by Pharmacies and
Outsourcing Facilities; Draft Guidance
for Industry; Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of availability.
The Food and Drug
Administration (FDA or the Agency) is
announcing the availability of a draft
guidance for industry entitled
‘‘Repackaging of Certain Human Drug
Products by Pharmacies and
Outsourcing Facilities.’’ This guidance
describes the conditions under which
FDA does not intend to take action for
violations of the Federal Food, Drug,
and Cosmetic Act (the FD&C Act), when
a state-licensed pharmacy, a Federal
facility, or an outsourcing facility
repackages human drug products.
When this guidance becomes final,
the Agency may also consider
withdrawing or revising other guidance
documents that address human drug
repackaging, including section 446.100
of the Compliance Program Guidance
(CPG) Manual, entitled ‘‘Regulatory
Action Regarding Approved New Drugs
and Antibiotic Drug Products Subjected
to Additional Processing or other
Manipulations,’’ which was issued in
January 1991, and section 460.100 of the
SUMMARY:
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CPG Manual, entitled ‘‘Hospital
Pharmacies—Status as Drug
Manufacturer,’’ which was issued in
October 1980.
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. 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 https://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: Gail
Bormel, Food and Drug Administration,
10001 New Hampshire Ave., Silver
Spring, MD 20903, 301–796–3110.
SUPPLEMENTARY INFORMATION:
I. Announcement of Draft Guidance
FDA is announcing the availability of
a draft guidance for industry entitled
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]]>Agencies
[Federal Register Volume 80, Number 33 (Thursday, February 19, 2015)]
[Notices]
[Pages 8881-8884]
From the Federal Register Online via the Government Printing 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 https://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 https://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 https://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: https://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 https://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: https://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
https://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 https://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 https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm or https://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
