Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; General Licensing Provisions; Section 351(k) Biosimilar Applications, 31019-31022 [2012-12591]
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31019
Federal Register / Vol. 77, No. 101 / Thursday, May 24, 2012 / Notices
Dated: May 17, 2012.
Elaine L. Baker,
Director, Management Analysis and Services
Office, Centers for Disease Control and
Prevention.
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
[FR Doc. 2012–12675 Filed 5–23–12; 8:45 am]
Proposed Information Collection
Activity; Comment Request
BILLING CODE 4163–18–P
Administration for Children and
Families
Proposed Projects
Title: FPLS Child Support Services
Portal Registration (FCSSP).
OMB No.: 0970–0370.
Description: The purpose of the
Federal Child Support Services Portal
Registration is to collect information
from an authorized individual
registering to use the FPLS Child
Support Services Portal. This
information collection is necessary to
authenticate the individual’s identity
and comply with the statutory
requirement that OCSE establish and
implement safeguards to restrict access
to confidential information in the FPLS
to authorized persons. 42 U.S.C.
653(m)(2).
After identity is authenticated, secure
accounts will be created for authorized
users to view data for their respective
applications.
Respondents: Employers, Financial
Institutions, Insurers, State Agencies,
Local Access and Visitation Providers.
ANNUAL BURDEN ESTIMATES
Number of
respondents
Number of
responses per
respondent
Average
burden hours
per response
Total burden
hours
Registration Screens .......................................................................................
srobinson on DSK4SPTVN1PROD with NOTICES
Instrument
588
1
0.10
58.8
Estimated Total Annual Burden
Hours: 58.8.
In compliance with the requirements
of Section 506(c)(2)(A) of the Paperwork
Reduction Act of 1995, the
Administration for Children and
Families is soliciting public comment
on the specific aspects of the
information collection described above.
Copies of the proposed collection of
information can be obtained and
comments may be forwarded by writing
to the Administration for Children and
Families, Office of Planning, Research
and Evaluation, 370 L’Enfant
Promenade SW., Washington, DC 20447,
Attn: ACF Reports Clearance Officer.
Email address:
infocollection@acf.hhs.gov. All requests
should be identified by the title of the
information collection.
The Department specifically requests
comments on: (a) Whether the proposed
collection of information is necessary
for the proper performance of the
functions of the agency, including
whether the information shall have
practical utility; (b) the accuracy of the
agency’s estimate of the burden of the
proposed collection of information; (c)
the quality, utility, and clarity of the
information to be collected; and (d)
ways to minimize the burden
information to be collected; and (d)
ways to minimize the burden of the
collection of information on
respondents, including through the use
of automated collection techniques or
other forms of information technology.
Consideration will be given to
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comments and suggestions submitted
within 60 days of this publication.
Robert Sargis,
Reports Clearance Officer.
[FR Doc. 2012–12601 Filed 5–23–12; 8:45 am]
BILLING CODE 4184–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2012–N–1029]
Agency Information Collection
Activities; Submission for Office of
Management and Budget Review;
Comment Request; General Licensing
Provisions; Section 351(k) Biosimilar
Applications
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
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: Fax written comments on the
collection of information by June 25,
2012.
SUMMARY:
To ensure that comments on
the information collection are received,
OMB recommends that written
comments be faxed to the Office of
Information and Regulatory Affairs,
OMB, Attn: FDA Desk Officer, Fax: 202–
ADDRESSES:
PO 00000
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395–7285, or emailed to
oira_submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910–New and
title ‘‘General Licensing Provisions;
Section 351(k) Biosimilar
Applications’’. Also include the FDA
docket number found in brackets in the
heading of this document.
FOR FURTHER INFORMATION CONTACT:
Juanmanuel Vilela, Office of
Information Management, Food and
Drug Administration, 1350 Piccard Dr.,
PI50–400B, Rockville, MD 20850,
301–796–7651,
juanmanuel.vilela@fda.hhs.gov.
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.
General Licensing Provisions; Section
351(k) Biosimilar Applications—(OMB
Control Number 0910—New)
On March 23, 2010, the President
signed into law the Patient Protection
and Affordable Care Act (Affordable
Care Act) (Pub. L. 111–148). The
Affordable Care Act contains a subtitle
called the Biologics Price Competition
and Innovation Act of 2009 (BPCI Act)
which amends the Public Health Service
Act (PHS Act) and establishes an
abbreviated licensure pathway for
biological products shown to be
biosimilar to, or interchangeable with,
an FDA-licensed biological reference
product. (See sections 7001 through
7003 of the Affordable Care Act.)
Section 351(k) of the PHS Act (42
U.S.C. 262(k)), added by the BPCI Act,
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Federal Register / Vol. 77, No. 101 / Thursday, May 24, 2012 / Notices
sets forth the requirements for an
application for a proposed biosimilar
product and an application or a
supplement for a proposed
interchangeable product. Section 351(k)
defines biosimilarity to mean ‘‘that the
biological product is highly similar to
the reference product notwithstanding
minor differences in clinically inactive
components’’ and that ‘‘there are no
clinically meaningful differences
between the biological product and the
reference product in terms of the safety,
purity, and potency of the product’’.
(See section 351(i)(2) of the PHS Act.) A
351(k) application must contain, among
other things, information demonstrating
that the biological product is biosimilar
to a reference product based upon data
derived from analytical studies, animal
studies, and clinical studies, unless
FDA determines, in its discretion, that
certain studies are unnecessary in a
351(k) application. (See section
351(k)(2) of the PHS Act.) To
demonstrate interchangeability, an
applicant must provide sufficient
information to demonstrate
biosimilarity and that the biosimilar
biological product can be expected to
produce the same clinical result as the
reference product in any given patient
and, if the biosimilar biological product
is administered more than once to an
individual, the risk in terms of safety or
diminished efficacy of alternating or
switching between the use of the
biosimilar biological product and the
reference product is not greater than the
risk of using the reference product
without such alternation or switch. (See
section 351(k)(4) of the PHS Act.)
Interchangeable products may be
substituted for the reference product
without the intervention of the
prescribing health care provider. (See
section 351(i)(3) of the PHS Act.) This
Federal Register information collection
document begins the process of
requesting public comment and
obtaining OMB approval for the
information collection regarding the
burden on the submission of a 351(k)
application not otherwise covered by
existing OMB approvals.
In estimating the information
collection burden for 351(k)
applications, FDA has reviewed the
collection of information regarding the
general licensing provisions for
biologics license applications under
section 351(a) of the PHS Act to OMB
(approved under OMB control number
0910–0338). For the information
collection burden for 351(a)
applications, FDA described § 601.2(a)
(21 CFR 601.2(a)) as requiring a
manufacturer of a biological product to
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submit an application on forms
prescribed for such purpose with
accompanying data and information
including certain labeling information
to FDA for approval to market a product
in interstate commerce. FDA also added
in the burden estimate the container and
package labeling requirements provided
under §§ 610.60 through 610.65 (21 CFR
610.60 through 610.65). The estimated
hours per response for § 601.2, and
§§ 610.60 through 610.65, were 860
hours.
In addition, in submitting a 351(a)
application, an applicant completes the
Form FDA 356h ‘‘Application to Market
a New Drug, Biologic, or an Antibiotic
Drug for Human Use.’’ The application
form serves primarily as a checklist for
firms to gather and submit certain
information to FDA. The checklist helps
to ensure that the application is
complete and contains all the necessary
information, so that delays due to lack
of information may be eliminated. The
form provides key information to FDA
for efficient handling and distribution to
the appropriate staff for review. The
estimated burden hours for biological
product submissions using FDA Form
356h are included under the applicable
requirements approved under OMB
control number 0910–0338.
FDA intends for an applicant to
submit a 351(k) application following
Form FDA 356h, modifying the
information submitted to support the
information required under section
351(k) of the BPCI Act. To submit an
application seeking licensure of a
proposed biosimilar product under
section 351(k)(2)(A)(i) and (k)(2)(A)(iii),
FDA believes that the estimated burden
hours would be approximately the same
as noted under OMB control number
0910–0338 for a 351(a) application—860
hours. The burden estimates for seeking
licensure of a proposed biosimilar
product that meets the standards for
interchangeability under section
351(k)(2)(B) and (k)(4) would also be
860 hours. Until we gain more
experience with biosimilar applications,
FDA believes this estimate is
appropriate for 351(k) applications
because to determine biosimilarity or
interchangeability of a proposed 351(k)
product, the application and the
information submitted is expected to be
comparably complex and technically
demanding as a proposed 351(a)
application. FDA may determine, in its
discretion, that an element required
under a 351(k) application to be
unnecessary to support licensure of a
biosimilar or interchangeable product.
In those cases, the number of hours per
response may be less than the hours
estimated.
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A summary of the collection of
information requirements in the
submission of a 351(k) application as
described under the BPCI Act follows:
Section 351(k)(2)(A)(i) requires
manufactures of 351(k) products to
submit an application for FDA review
and licensure before marketing a
biosimilar product. An application
submitted under this section shall
include information demonstrating that:
• The biological product is biosimilar
to a reference product based upon data
derived from analytical studies, animal
studies (including toxicity) and a
clinical study or studies (including
immunogenicity and pharmacokinetics
or pharmacodynamics). The Secretary of
Health and Human Services (the
Secretary) may determine that any of
these elements is unnecessary.
• The biological product and
reference product utilize the same
mechanism or mechanisms of action for
the condition or conditions of use
prescribed, recommended, or suggested
in the proposed labeling, but only to the
extent the mechanism or mechanisms of
action are known for the reference
product.
• The condition or conditions of use
prescribed, recommended, or suggested
in the labeling proposed for the
biological product have been previously
approved for the reference product.
• The route of administration, the
dosage form, and the strength of the
biological product are the same as those
of the reference product.
• The facility in which the biological
product is manufactured, processed,
packed, or held meets standards
designed to assure that the biological
product continues to be safe, pure, and
potent.
Section 351(k)(2)(A)(iii) requires the
application to include publiclyavailable information regarding the
Secretary’s previous determination that
the reference product is safe, pure, and
potent. The application may include
any additional information in support of
the application, including publiclyavailable information with respect to the
reference product or another biological
product.
Under section 351(k)(2)(B) and (k)(4),
a manufacturer may include information
demonstrating that the biological
product meets the standards for
interchangeability either in the
application described in this document
to show biosimilarity, or in a
supplement to such an application. The
information submitted to meet the
standard for interchangeability must
show that: (1) The biological product is
biosimilar to the reference product and
can be expected to produce the same
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Federal Register / Vol. 77, No. 101 / Thursday, May 24, 2012 / Notices
clinical result as the reference product
in any given patient and (2) for a
biological product that is administered
more than once to an individual, the
risk in terms of safety or diminished
efficacy of alternating or switching
between use of the biological product
and the reference product is not greater
than the risk of using the reference
product without such alternation or
switch.
In addition to the collection of
information regarding the submission of
a 351(k) application for a proposed
biosimilar or interchangeable biological
product, section 351(l) of the BPCI Act
establishes procedures for identifying
and resolving patent disputes involving
applications submitted under section
351(k) of the PHS Act. The burden
estimates for the patent provisions
under section 351(l)(6)(C) of the BPCI
Act are included in table 1 of this
document and are based on the
estimated number of 351(k) biosimilar
respondents. Based on similar reporting
requirements, FDA estimates this
notification will take 2 hours. A
summary of the collection of
information requirements under
351(l)(6)(C) follows:
Not later than 30 days after a
complaint from the reference product
sponsor is served to a 351(k) applicant
in an action for patent infringement
described under 351(l)(6), section
351(l)(6)(C) requires that the 351(k)
applicant provide the Secretary with
notice and a copy of such complaint.
The Secretary shall publish in the
Federal Register notice any complaint
received under 351(l)(6)(C)(i).
FDA has not received any 351(k)
applications to date. Under table 1 of
this document, the estimated number of
respondents submitting 351(k)
applications is based on the estimated
annual number of manufacturers that
would submit the required information
to FDA and the estimated annual
number of 351(k) submissions FDA
would receive. In making this estimate,
FDA has taken into account, among
other things, the expiration dates of
patents that relate to potential reference
products, and general market interest in
biological products that could be
candidates for 351(k) applications.
On November 2 and 3, 2010, FDA
held a public hearing and established a
public docket to obtain input on specific
issues and challenges associated with
the implementation of the BPCI Act.
(See Docket No. FDA–2010–N–0477.)
Based in part on this input, FDA
announced the availability of three draft
guidances describing FDA’s current
interpretation of certain statutory
requirements added by the BPCI Act as
well as quality and analytical issues,
demonstrating biosimilarity, and
implementation policy issues. These
draft guidances are: ‘‘Biosimilars:
Questions and Answers Regarding
Implementation of the Biologics Price
Competition and Innovation Act of
2009,’’ ‘‘Quality Considerations in
Demonstrating Biosimilarity to a
Reference Protein Product,’’ and
‘‘Scientific Considerations in
Demonstrating Biosimilarity to a
Reference Product.’’ The Federal
Register documents for these guidances
reference this Federal Register
information collection document
regarding the burden on the submission
of a 351(k) application not otherwise
covered by existing OMB approvals. In
addition, we note that the draft
guidance on ‘‘Scientific Considerations
in Demonstrating Biosimilarity to a
Reference Product’’ recommends that
labeling for a product subject to
approval under section 351(k) include
statements that indicate that: (1) The
product is approved as biosimilar to a
reference product for stated
indication(s) and (2) the product (has or
has not) been determined to be
interchangeable with the reference
product. FDA has determined, under 5
CFR 1320.3(c)(2)), that these labeling
recommendations are not ‘‘collections of
information’’ for the purposes of the
PRA because the statements will
comprise solely information that FDA
will supply to the applicant for the
purpose of disclosing it to the public,
i.e., FDA’s determination upon review
of the application submitted under
section 351(k), that the product is
biosimilar and/or interchangeable to its
reference product.
In the Federal Register of February
15, 2012 (77 FR 8880), FDA published
a 60-day notice requesting comments on
the information collection for the
requirements for an application for a
proposed biosimilar product and an
application or a supplement for a
proposed interchangeable product. In
the Federal Register of February 23,
2012 (77 FR 10752), FDA published a
correction to the 60-day notice
providing the correct docket number to
submit comments. FDA received no
comments that pertained to the
information collection analysis.
FDA estimates the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1
351(k) Application for Biosimilars (42 U.S.C. 262(k))
351(k)(2)(A)(i) and (k)(2)(A)(iii) ............................................
351(k)(2)(B) and (k)(4) .........................................................
351(l)(6)(C) ...........................................................................
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1 There
Number of
responses per
respondent
Number of
respondents
2
1
2
Average
burden per
response
Total annual
responses
1
1
1
2
1
2
are no capital costs or operating and maintenance costs associated with this collection of information.
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860
860
2
Total hours
1720
860
4
31022
Federal Register / Vol. 77, No. 101 / Thursday, May 24, 2012 / Notices
Dated: May 17, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012–12591 Filed 5–23–12; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2012–N–0477]
Agency Information Collection
Activities; Proposed Collection;
Comment Request; Investigational
Device Exemptions Reports and
Records
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing an
opportunity for public comment on the
proposed collection of certain
information by the Agency. Under the
Paperwork Reduction Act of 1995 (the
PRA), Federal Agencies are required to
publish notice in the Federal Register
concerning each proposed collection of
information, including each proposed
extension of an existing collection of
information, and to allow 60 days for
public comment in response to the
notice. This notice solicits comments on
investigational device exemptions
reports and records.
DATES: Submit either electronic or
written comments on the collection of
information by July 23, 2012.
ADDRESSES: Submit electronic
comments on the collection of
information to https://
www.regulations.gov. Submit written
comments on the collection of
information to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. All
comments should be identified with the
docket number found in brackets in the
heading of this document.
FOR FURTHER INFORMATION CONTACT:
Daniel Gittleson, Office of Information
Management, Food and Drug
Administration, 1350 Piccard Dr., PI50–
400B, Rockville, MD 20850, 301–796–
5156, daniel.gittleson@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: Under the
PRA (44 U.S.C. 3501–3520), Federal
Agencies must obtain approval from the
Office of Management and Budget
(OMB) for each collection of
information they conduct or sponsor.
‘‘Collection of information’’ is defined
in 44 U.S.C. 3502(3) and 5 CFR
srobinson on DSK4SPTVN1PROD with NOTICES
SUMMARY:
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1320.3(c) and includes Agency requests
or requirements that members of the
public submit reports, keep records, or
provide information to a third party.
Section 3506(c)(2)(A) of the PRA (44
U.S.C. 3506(c)(2)(A)) requires Federal
Agencies to provide a 60-day notice in
the Federal Register concerning each
proposed collection of information,
including each proposed extension of an
existing collection of information,
before submitting the collection to OMB
for approval. To comply with this
requirement, FDA is publishing notice
of the proposed collection of
information set forth in this document.
With respect to the following
collection of information, FDA invites
comments on these topics: (1) Whether
the proposed collection of information
is necessary for the proper performance
of FDA’s functions, including whether
the information will have practical
utility; (2) the accuracy of FDA’s
estimate of the burden of the proposed
collection of information, including the
validity of the methodology and
assumptions used; (3) ways to enhance
the quality, utility, and clarity of the
information to be collected; and (4)
ways to minimize the burden of the
collection of information on
respondents, including through the use
of automated collection techniques,
when appropriate, and other forms of
information technology.
Investigational Device Exemptions
Reports and Records—21 CFR Part 812
(OMB Control Number 0910–0078)—
Extension
Section 520(g) of the Federal Food,
Drug, and Cosmetic Act (the FD&C Act)
(21 U.S.C. 360j(g)) establishes the
statutory authority to collect
information regarding investigational
devices, and establishes rules under
which new medical devices may be
tested using human subjects in a clinical
setting. The Food and Drug
Administration Modernization Act of
1997 (Pub. L. 105–115) added section
520(g)(6) to the FD&C Act and permitted
changes to be made to either the
investigational device or to the clinical
protocol without FDA approval of an
investigational device exemption (IDE)
supplement. An IDE allows a device,
which would otherwise be subject to
provisions of the FD&C Act, such as
premarket notification or premarket
approval, to be used in investigations
involving human subjects in which the
safety and effectiveness of the device is
being studied. The purpose of part 812
(21 CFR part 812) is to encourage, to the
extent consistent with the protection of
public health and safety and with
ethical standards, the discovery and
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development of useful devices intended
for human use. The IDE regulation is
designed to encourage the development
of useful medical devices and allow
investigators the maximum freedom
possible, without jeopardizing the
health and safety of the public or
violating ethical standards. To do this,
the regulation provides for different
levels of regulatory control depending
on the level of potential risk the
investigational device presents to
human subjects. Investigations of
significant risk devices, ones that
present a potential for serious harm to
the rights, safety, or welfare of human
subjects, are subject to the full
requirements of the IDE regulation.
Nonsignificant risk device
investigations, i.e., devices that do not
present a potential for serious harm, are
subject to the reduced burden of the
abbreviated requirements. The
regulation also includes provisions for
treatment IDEs. The purpose of these
provisions is to facilitate the
availability, as early in the device
development process as possible, of
promising new devices to patients with
life-threatening or serious conditions for
which no comparable or satisfactory
alternative therapy is available. Section
812.10 permits the sponsor of the IDE to
request a waiver to all of the
requirements of part 812. This
information is needed for FDA to
determine if waiver of the requirements
of part 812 will impact the public’s
health and safety. Sections 812.20,
812.25, and 812.27 consist of the
information necessary to file an IDE
application with FDA. The submission
of an IDE application to FDA is required
only for significant risk device
investigations.
Section 812.20 lists the data
requirements for the original IDE
application; § 812.25 lists the contents
of the investigational plan; and § 812.27
lists the data relating to previous
investigations or testing. The
information in the original IDE
application is evaluated by the Center
for Devices and Radiological Health to
determine whether the proposed
investigation will reasonably protect the
public health and safety, and for FDA to
make a determination to approve the
IDE.
Upon approval of an IDE application
by FDA, a sponsor must submit certain
requests and reports. Under § 812.35, a
sponsor who wishes to make a change
in the investigation that affects the
scientific soundness of the study or the
rights, safety, or welfare of the subjects,
is required to submit a request for the
change to FDA. Section 812.150 requires
a sponsor to submit reports to FDA.
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]]>Agencies
[Federal Register Volume 77, Number 101 (Thursday, May 24, 2012)]
[Notices]
[Pages 31019-31022]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-12591]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2012-N-1029]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; General Licensing
Provisions; Section 351(k) Biosimilar Applications
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: Fax written comments on the collection of information by June
25, 2012.
ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be faxed to the Office
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer,
Fax: 202-395-7285, or emailed to oira_submission@omb.eop.gov. All
comments should be identified with the OMB control number 0910-New and
title ``General Licensing Provisions; Section 351(k) Biosimilar
Applications''. Also include the FDA docket number found in brackets in
the heading of this document.
FOR FURTHER INFORMATION CONTACT: Juanmanuel Vilela, Office of
Information Management, Food and Drug Administration, 1350 Piccard Dr.,
PI50-400B, Rockville, MD 20850, 301-796-7651,
juanmanuel.vilela@fda.hhs.gov.
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.
General Licensing Provisions; Section 351(k) Biosimilar Applications--
(OMB Control Number 0910--New)
On March 23, 2010, the President signed into law the Patient
Protection and Affordable Care Act (Affordable Care Act) (Pub. L. 111-
148). The Affordable Care Act contains a subtitle called the Biologics
Price Competition and Innovation Act of 2009 (BPCI Act) which amends
the Public Health Service Act (PHS Act) and establishes an abbreviated
licensure pathway for biological products shown to be biosimilar to, or
interchangeable with, an FDA-licensed biological reference product.
(See sections 7001 through 7003 of the Affordable Care Act.)
Section 351(k) of the PHS Act (42 U.S.C. 262(k)), added by the BPCI
Act,
[[Page 31020]]
sets forth the requirements for an application for a proposed
biosimilar product and an application or a supplement for a proposed
interchangeable product. Section 351(k) defines biosimilarity to mean
``that the biological product is highly similar to the reference
product notwithstanding minor differences in clinically inactive
components'' and that ``there are no clinically meaningful differences
between the biological product and the reference product in terms of
the safety, purity, and potency of the product''. (See section
351(i)(2) of the PHS Act.) A 351(k) application must contain, among
other things, information demonstrating that the biological product is
biosimilar to a reference product based upon data derived from
analytical studies, animal studies, and clinical studies, unless FDA
determines, in its discretion, that certain studies are unnecessary in
a 351(k) application. (See section 351(k)(2) of the PHS Act.) To
demonstrate interchangeability, an applicant must provide sufficient
information to demonstrate biosimilarity and that the biosimilar
biological product can be expected to produce the same clinical result
as the reference product in any given patient and, if the biosimilar
biological product is administered more than once to an individual, the
risk in terms of safety or diminished efficacy of alternating or
switching between the use of the biosimilar biological product and the
reference product is not greater than the risk of using the reference
product without such alternation or switch. (See section 351(k)(4) of
the PHS Act.) Interchangeable products may be substituted for the
reference product without the intervention of the prescribing health
care provider. (See section 351(i)(3) of the PHS Act.) This Federal
Register information collection document begins the process of
requesting public comment and obtaining OMB approval for the
information collection regarding the burden on the submission of a
351(k) application not otherwise covered by existing OMB approvals.
In estimating the information collection burden for 351(k)
applications, FDA has reviewed the collection of information regarding
the general licensing provisions for biologics license applications
under section 351(a) of the PHS Act to OMB (approved under OMB control
number 0910-0338). For the information collection burden for 351(a)
applications, FDA described Sec. 601.2(a) (21 CFR 601.2(a)) as
requiring a manufacturer of a biological product to submit an
application on forms prescribed for such purpose with accompanying data
and information including certain labeling information to FDA for
approval to market a product in interstate commerce. FDA also added in
the burden estimate the container and package labeling requirements
provided under Sec. Sec. 610.60 through 610.65 (21 CFR 610.60 through
610.65). The estimated hours per response for Sec. 601.2, and
Sec. Sec. 610.60 through 610.65, were 860 hours.
In addition, in submitting a 351(a) application, an applicant
completes the Form FDA 356h ``Application to Market a New Drug,
Biologic, or an Antibiotic Drug for Human Use.'' The application form
serves primarily as a checklist for firms to gather and submit certain
information to FDA. The checklist helps to ensure that the application
is complete and contains all the necessary information, so that delays
due to lack of information may be eliminated. The form provides key
information to FDA for efficient handling and distribution to the
appropriate staff for review. The estimated burden hours for biological
product submissions using FDA Form 356h are included under the
applicable requirements approved under OMB control number 0910-0338.
FDA intends for an applicant to submit a 351(k) application
following Form FDA 356h, modifying the information submitted to support
the information required under section 351(k) of the BPCI Act. To
submit an application seeking licensure of a proposed biosimilar
product under section 351(k)(2)(A)(i) and (k)(2)(A)(iii), FDA believes
that the estimated burden hours would be approximately the same as
noted under OMB control number 0910-0338 for a 351(a) application--860
hours. The burden estimates for seeking licensure of a proposed
biosimilar product that meets the standards for interchangeability
under section 351(k)(2)(B) and (k)(4) would also be 860 hours. Until we
gain more experience with biosimilar applications, FDA believes this
estimate is appropriate for 351(k) applications because to determine
biosimilarity or interchangeability of a proposed 351(k) product, the
application and the information submitted is expected to be comparably
complex and technically demanding as a proposed 351(a) application. FDA
may determine, in its discretion, that an element required under a
351(k) application to be unnecessary to support licensure of a
biosimilar or interchangeable product. In those cases, the number of
hours per response may be less than the hours estimated.
A summary of the collection of information requirements in the
submission of a 351(k) application as described under the BPCI Act
follows:
Section 351(k)(2)(A)(i) requires manufactures of 351(k) products to
submit an application for FDA review and licensure before marketing a
biosimilar product. An application submitted under this section shall
include information demonstrating that:
The biological product is biosimilar to a reference
product based upon data derived from analytical studies, animal studies
(including toxicity) and a clinical study or studies (including
immunogenicity and pharmacokinetics or pharmacodynamics). The Secretary
of Health and Human Services (the Secretary) may determine that any of
these elements is unnecessary.
The biological product and reference product utilize the
same mechanism or mechanisms of action for the condition or conditions
of use prescribed, recommended, or suggested in the proposed labeling,
but only to the extent the mechanism or mechanisms of action are known
for the reference product.
The condition or conditions of use prescribed,
recommended, or suggested in the labeling proposed for the biological
product have been previously approved for the reference product.
The route of administration, the dosage form, and the
strength of the biological product are the same as those of the
reference product.
The facility in which the biological product is
manufactured, processed, packed, or held meets standards designed to
assure that the biological product continues to be safe, pure, and
potent.
Section 351(k)(2)(A)(iii) requires the application to include
publicly-available information regarding the Secretary's previous
determination that the reference product is safe, pure, and potent. The
application may include any additional information in support of the
application, including publicly-available information with respect to
the reference product or another biological product.
Under section 351(k)(2)(B) and (k)(4), a manufacturer may include
information demonstrating that the biological product meets the
standards for interchangeability either in the application described in
this document to show biosimilarity, or in a supplement to such an
application. The information submitted to meet the standard for
interchangeability must show that: (1) The biological product is
biosimilar to the reference product and can be expected to produce the
same
[[Page 31021]]
clinical result as the reference product in any given patient and (2)
for a biological product that is administered more than once to an
individual, the risk in terms of safety or diminished efficacy of
alternating or switching between use of the biological product and the
reference product is not greater than the risk of using the reference
product without such alternation or switch.
In addition to the collection of information regarding the
submission of a 351(k) application for a proposed biosimilar or
interchangeable biological product, section 351(l) of the BPCI Act
establishes procedures for identifying and resolving patent disputes
involving applications submitted under section 351(k) of the PHS Act.
The burden estimates for the patent provisions under section
351(l)(6)(C) of the BPCI Act are included in table 1 of this document
and are based on the estimated number of 351(k) biosimilar respondents.
Based on similar reporting requirements, FDA estimates this
notification will take 2 hours. A summary of the collection of
information requirements under 351(l)(6)(C) follows:
Not later than 30 days after a complaint from the reference product
sponsor is served to a 351(k) applicant in an action for patent
infringement described under 351(l)(6), section 351(l)(6)(C) requires
that the 351(k) applicant provide the Secretary with notice and a copy
of such complaint. The Secretary shall publish in the Federal Register
notice any complaint received under 351(l)(6)(C)(i).
FDA has not received any 351(k) applications to date. Under table 1
of this document, the estimated number of respondents submitting 351(k)
applications is based on the estimated annual number of manufacturers
that would submit the required information to FDA and the estimated
annual number of 351(k) submissions FDA would receive. In making this
estimate, FDA has taken into account, among other things, the
expiration dates of patents that relate to potential reference
products, and general market interest in biological products that could
be candidates for 351(k) applications.
On November 2 and 3, 2010, FDA held a public hearing and
established a public docket to obtain input on specific issues and
challenges associated with the implementation of the BPCI Act. (See
Docket No. FDA-2010-N-0477.) Based in part on this input, FDA announced
the availability of three draft guidances describing FDA's current
interpretation of certain statutory requirements added by the BPCI Act
as well as quality and analytical issues, demonstrating biosimilarity,
and implementation policy issues. These draft guidances are:
``Biosimilars: Questions and Answers Regarding Implementation of the
Biologics Price Competition and Innovation Act of 2009,'' ``Quality
Considerations in Demonstrating Biosimilarity to a Reference Protein
Product,'' and ``Scientific Considerations in Demonstrating
Biosimilarity to a Reference Product.'' The Federal Register documents
for these guidances reference this Federal Register information
collection document regarding the burden on the submission of a 351(k)
application not otherwise covered by existing OMB approvals. In
addition, we note that the draft guidance on ``Scientific
Considerations in Demonstrating Biosimilarity to a Reference Product''
recommends that labeling for a product subject to approval under
section 351(k) include statements that indicate that: (1) The product
is approved as biosimilar to a reference product for stated
indication(s) and (2) the product (has or has not) been determined to
be interchangeable with the reference product. FDA has determined,
under 5 CFR 1320.3(c)(2)), that these labeling recommendations are not
``collections of information'' for the purposes of the PRA because the
statements will comprise solely information that FDA will supply to the
applicant for the purpose of disclosing it to the public, i.e., FDA's
determination upon review of the application submitted under section
351(k), that the product is biosimilar and/or interchangeable to its
reference product.
In the Federal Register of February 15, 2012 (77 FR 8880), FDA
published a 60-day notice requesting comments on the information
collection for the requirements for an application for a proposed
biosimilar product and an application or a supplement for a proposed
interchangeable product. In the Federal Register of February 23, 2012
(77 FR 10752), FDA published a correction to the 60-day notice
providing the correct docket number to submit comments. FDA received no
comments that pertained to the information collection analysis.
FDA estimates the burden of this collection of information as
follows:
Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of Average
351(k) Application for Number of responses per Total annual burden per Total hours
Biosimilars (42 U.S.C. 262(k)) respondents respondent responses response
----------------------------------------------------------------------------------------------------------------
351(k)(2)(A)(i) and 2 1 2 860 1720
(k)(2)(A)(iii).................
351(k)(2)(B) and (k)(4)......... 1 1 1 860 860
351(l)(6)(C).................... 2 1 2 2 4
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
[[Page 31022]]
Dated: May 17, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-12591 Filed 5-23-12; 8:45 am]
BILLING CODE 4160-01-P
