Document ID: FDA-2012-N-0129-0006
Agency: fda
Document Type: Notice
Title: Agency Information Collection Activities; Proposed Collection;
Comment Request; General Licensing Provisions; Section 351(k) Biosimilar Applications
Posted Date: 2015-02-03T05:00Z

[Federal Register Volume 80, Number 22 (Tuesday, February 3, 2015)]
[Notices]
[Pages 5761-5763]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2015-02025]

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-N-0129]

Agency Information Collection Activities; Proposed Collection; 
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 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 the information collection in 
an application for a proposed biosimilar product and an application for 
a supplement for a proposed interchangeable product.

DATES: Submit either electronic or written comments on the collection 
of information by April 6, 2015.

ADDRESSES: Submit electronic comments on the collection of information 
to http://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: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver 
Spring, MD 20993-0002, PRAStaff@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 
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.

General Licensing Provisions; Section 351(k) Biosimilar Applications 
(OMB Control Number 0910-0719)--Extension

    The Patient Protection and Affordable Care Act (Affordable Care 
Act) (Pub. L. 111-148) 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

[[Page 5762]]

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, 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.)
    In estimating the information collection burden for 351(k) 
applications, we reviewed the number of 351(k) applications FDA has 
received through fiscal year (FY) 2014, as well as the collection of 
information regarding the general licensing provisions for biologics 
license applications under section 351(a) of the PHS Act submitted 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, are 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.
    To submit an application seeking licensure of a proposed biosimilar 
product under section 351(k)(2)(A)(i) and (k)(2)(A)(iii) of the PHS 
Act, 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, 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 information collection 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 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 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

[[Page 5763]]

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 section 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 section 351(l)(6)(C)(i).
    Based on the number of 351(k) applications FDA received through FY 
2014, we estimate that we will receive approximately five 351(k) 
applications annually. The number of respondents submitting 351(k) 
applications is based on the number of sponsors submitting 351(k) 
applications through FY 2014. In making these estimates, 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.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of
 351(k) Applications (42 U.S.C.      Number of     responses per   Total annual   Average burden    Total hours
             262(k))                respondents     respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
351(k)(2)(A)(i) and                            5               1               5             860           4,300
 351(k)(2)(A)(iii) Biosimilar
 Product Applications...........
351(k)(2)(B) and (k)(4)                        2               1               2             860           1,720
 Interchangeable Product
 Applications or Supplements....
351(l)(6)(C) Patent Infringement               5               1               5               2              10
 Notifications..................
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............           6,030
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    Dated: January 28, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-02025 Filed 2-2-15; 8:45 am]
BILLING CODE 4164-01-P