80 FR 24258 - Scientific Considerations in Demonstrating Biosimilarity to a Reference Product; Guidance for Industry; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 80, Issue 83 (April 30, 2015)
Food and Drug Administration
Federal Register Volume 80, Issue 83 (April 30, 2015)
| Page Range | 24258-24259 | |
| FR Document | 2015-10062 |
[Federal Register Volume 80, Number 83 (Thursday, April 30, 2015)] [Notices] [Pages 24258-24259] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2015-10062] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0605] Scientific Considerations in Demonstrating Biosimilarity to a Reference Product; Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled ``Scientific Considerations in Demonstrating Biosimilarity to a Reference Product.'' This guidance is intended to assist sponsors in demonstrating that a proposed therapeutic protein product is biosimilar to a reference product for the purpose of submitting a marketing application through an abbreviated licensure pathway. This guidance gives an overview of FDA's approach to determining biosimilarity. DATES: Submit either electronic or written comments on Agency guidances at any time. ADDRESSES: Submit written requests for single copies of the guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002, or Office of Communication, Outreach, and Development, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document. Submit electronic comments on the guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: Sandra Benton, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6340, Silver Spring, MD 20993-0002, 301- 796-1042, or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 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 guidance for industry entitled ``Scientific Considerations in Demonstrating Biosimilarity to a Reference Product.'' This guidance is intended to assist sponsors in demonstrating that a proposed therapeutic protein product is ``biosimilar'' \1\ to a reference product for the purpose of submitting a marketing application through the abbreviated licensure pathway under section 351(k) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(k)). --------------------------------------------------------------------------- \1\ In section 7002(b)(3) of the Patient Protection and Affordable Care Act (Affordable Care Act), Pub. L. 111-148, ``biosimilar'' or ``biosimilarity'' means ``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.'' --------------------------------------------------------------------------- The Biologics Price Competition and Innovation Act of 2009 (BPCI Act), enacted as part of the Affordable Care Act (Pub. L. 111-148) on March 23, 2010, created an abbreviated licensure pathway under section 351(k) of the PHS Act for biological products demonstrated to be biosimilar to, or interchangeable with, a reference product. Under this abbreviated licensure pathway, FDA will license a proposed biological product submitted under section 351(k) of the PHS Act if FDA ``determines that the information submitted in the application . . . is sufficient to show that the biological product is biosimilar to the reference product. . . .'' and the 351(k) applicant (or other appropriate person) consents to an inspection of the facility that is the subject of the application (i.e., a facility in which the proposed biological product is manufactured, processed, packed, or held).\2\ The guidance gives an overview of FDA's approach to determining biosimilarity. FDA intends to consider the totality of the evidence submitted in a 351(k) application and is recommending that sponsors use a stepwise approach in their development of biosimilar products. The guidance discusses important scientific considerations in demonstrating biosimilarity, including: --------------------------------------------------------------------------- \2\ Section 7002(a)(2) of the Affordable Care Act, adding section 351(k)(3) of the PHS Act (citing section 351(a)(2)(C) of the PHS Act). ---------------------------------------------------------------------------A stepwise approach to demonstrating biosimilarity, which can include a comparison of the proposed product and the reference product with [[Page 24259]] respect to structure, function, animal toxicity, human pharmacokinetics (PK) and pharmacodynamics (PD), clinical immunogenicity, and clinical safety and effectiveness; The totality-of-the-evidence approach that FDA will use to review applications for biosimilar products, consistent with a longstanding Agency approach to evaluation of scientific evidence; and General scientific principles in conducting comparative structural analyses, functional assays, animal testing, human PK and PD studies, clinical immunogenicity assessment, and comparative clinical trials (including clinical study design issues). In the Federal Register of February 15, 2012 (77 FR 8883), FDA announced the availability of the draft guidance of the same title dated February 2012. FDA received a number of comments on the draft guidance. In response to these comments, FDA provides further clarification of the scientific considerations applicable to the conduct of comparative structural analysis, functional assays, animal studies, and clinical testing. The final guidance also provides additional information on clinical trial design and selection of study endpoint and population. It also explains FDA's current thinking on when a comparative clinical trial may not be needed. In addition, editorial changes were made to improve clarity. The guidance announced in this notice finalizes and replaces the draft guidance dated February 2012. This guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidance represents the Agency's current thinking on scientific considerations in demonstrating biosimilarity to a reference product. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations. II. Comments Interested persons may submit either electronic comments regarding this document to http://www.regulations.gov or written comments to the Division of Dockets Management (see ADDRESSES). It is only necessary to send one set of comments. Identify comments with the docket number found in brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov. III. The Paperwork Reduction Act of 1995 This guidance describes information collection provisions that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-3520). This guidance references information collections that are already approved by OMB and are not expected to change as a result of the guidance. This includes information collections related to the submission of: (1) An investigational new drug application, which is covered under 21 CFR part 312 and approved under OMB Control No. 0910- 0014; (2) a new drug application, which is covered under 21 CFR 314.50 and approved under OMB control number 0910-0001; (3) a biologics license application under section 351(a) of the PHS Act, which is covered under 21 CFR part 601 and approved under OMB control number 0910-0338; and (4) a biologics license application under section 351(k) of the PHS Act, which is covered under 21 CFR part 601 and approved under OMB control number 0910-0719. IV. Electronic Access Persons with access to the Internet may obtain the document at either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm, or http://www.regulations.gov. Dated: April 24, 2015. Peter Lurie, Associate Commissioner for Public Health Strategy and Analysis. [FR Doc. 2015-10062 Filed 4-29-15; 8:45 am] BILLING CODE 4164-01-P
![24258 Federal Register / Vol. 80, No. 83 / Thursday, April 30, 2015 / Notices
is only necessary to send one set of DEPARTMENT OF HEALTH AND 7301, Silver Spring, MD 20993–0002,
comments. Identify comments with the HUMAN SERVICES 240–402–7911.
docket number found in brackets in the SUPPLEMENTARY INFORMATION:
heading of this document. Received Food and Drug Administration
I. Background
comments may be seen in the Division [Docket No. FDA–2011–D–0605]
of Dockets Management between 9 a.m. FDA is announcing the availability of
and 4 p.m., Monday through Friday, and Scientific Considerations in a guidance for industry entitled
will be posted to the docket at http:// Demonstrating Biosimilarity to a ‘‘Scientific Considerations in
www.regulations.gov. Reference Product; Guidance for Demonstrating Biosimilarity to a
Industry; Availability Reference Product.’’ This guidance is
III. The Paperwork Reduction Act of intended to assist sponsors in
1995 AGENCY: Food and Drug Administration, demonstrating that a proposed
HHS. therapeutic protein product is
This guidance refers to previously ACTION: Notice. ‘‘biosimilar’’ 1 to a reference product for
approved collections of information the purpose of submitting a marketing
found in FDA regulations, which are not SUMMARY: The Food and Drug application through the abbreviated
expected to change as a result of the Administration (FDA) is announcing the licensure pathway under section 351(k)
guidance. These collections of availability of a guidance for industry of the Public Health Service Act (PHS
information are subject to review by the entitled ‘‘Scientific Considerations in Act) (42 U.S.C. 262(k)).
Office of Management and Budget Demonstrating Biosimilarity to a The Biologics Price Competition and
(OMB) under the Paperwork Reduction Reference Product.’’ This guidance is Innovation Act of 2009 (BPCI Act),
Act of 1995 (44 U.S.C. 3501–3520). The intended to assist sponsors in enacted as part of the Affordable Care
collections of information related to the demonstrating that a proposed Act (Pub. L. 111–148) on March 23,
submission of: (1) An investigational therapeutic protein product is 2010, created an abbreviated licensure
biosimilar to a reference product for the pathway under section 351(k) of the
new drug application, which is covered
purpose of submitting a marketing PHS Act for biological products
under 21 CFR part 312 and approved
application through an abbreviated demonstrated to be biosimilar to, or
under OMB control number 0910–0014; licensure pathway. This guidance gives interchangeable with, a reference
(2) a new drug application, which is an overview of FDA’s approach to product. Under this abbreviated
covered under 21 CFR 314.50 and determining biosimilarity. licensure pathway, FDA will license a
approved under OMB control number proposed biological product submitted
DATES: Submit either electronic or
0910–0001; (3) a biologics license under section 351(k) of the PHS Act if
written comments on Agency guidances
application (BLA) under section 351(a) at any time. FDA ‘‘determines that the information
of the PHS Act, which is covered under submitted in the application . . . is
ADDRESSES: Submit written requests for
part 601 (21 CFR part 601) and sufficient to show that the biological
single copies of the guidance to the
approved under OMB control number product is biosimilar to the reference
Division of Drug Information, Center for
0910–0338; and (4) a BLA under section product. . . .’’ and the 351(k) applicant
Drug Evaluation and Research, Food
351(k), which is covered under part 601 and Drug Administration, 10001 New (or other appropriate person) consents
and approved under OMB control Hampshire Ave., Hillandale Building, to an inspection of the facility that is the
number 0910–0719. 4th Floor, Silver Spring, MD 20993– subject of the application (i.e., a facility
0002, or Office of Communication, in which the proposed biological
IV. Electronic Access product is manufactured, processed,
Outreach, and Development, Center for
Persons with access to the Internet Biologics Evaluation and Research packed, or held).2 The guidance gives an
may obtain the document at either (CBER), Food and Drug Administration, overview of FDA’s approach to
http://www.fda.gov/Drugs/Guidance 10903 New Hampshire Ave., Bldg. 71, determining biosimilarity. FDA intends
Rm. 3128, Silver Spring, MD 20993– to consider the totality of the evidence
ComplianceRegulatoryInformation/
0002. Send one self-addressed adhesive submitted in a 351(k) application and is
Guidances/default.htm, http://www.fda.
label to assist that office in processing recommending that sponsors use a
gov/BiologicsBloodVaccines/Guidance
your requests. See the SUPPLEMENTARY stepwise approach in their development
ComplianceRegulatoryInformation/ of biosimilar products. The guidance
default.htm, or http:// INFORMATION section for electronic
access to the guidance document. discusses important scientific
www.regulations.gov. considerations in demonstrating
Submit electronic comments on the
Dated: April 24, 2015. guidance to http://www.regulations.gov. biosimilarity, including:
Peter Lurie, • A stepwise approach to
Submit written comments to the
demonstrating biosimilarity, which can
Associate Commissioner for Public Health Division of Dockets Management (HFA–
include a comparison of the proposed
Strategy and Analysis. 305), Food and Drug Administration,
product and the reference product with
[FR Doc. 2015–10063 Filed 4–29–15; 8:45 am] 5630 Fishers Lane, Rm. 1061, Rockville,
BILLING CODE 4164–01–P MD 20852. 1 In section 7002(b)(3) of the Patient Protection
FOR FURTHER INFORMATION CONTACT: and Affordable Care Act (Affordable Care Act), Pub.
Sandra Benton, Center for Drug L. 111–148, ‘‘biosimilar’’ or ‘‘biosimilarity’’ means
‘‘that the biological product is highly similar to the
mstockstill on DSK4VPTVN1PROD with NOTICES
Evaluation and Research, Food and
reference product notwithstanding minor
Drug Administration, 10903 New differences in clinically inactive components,’’ and
Hampshire Ave., Bldg. 51, Rm. 6340, that ‘‘there are no clinically meaningful differences
Silver Spring, MD 20993–0002, 301– between the biological product and the reference
796–1042, or Stephen Ripley, Center for product in terms of the safety, purity, and potency
of the product.’’
Biologics Evaluation and Research, 2 Section 7002(a)(2) of the Affordable Care Act,
Food and Drug Administration, 10903 adding section 351(k)(3) of the PHS Act (citing
New Hampshire Ave., Bldg. 71, Rm. section 351(a)(2)(C) of the PHS Act).
VerDate Sep<11>2014 17:01 Apr 29, 2015 Jkt 235001 PO 00000 Frm 00029 Fmt 4703 Sfmt 4703 E:\FR\FM\30APN1.SGM 30APN1](https://thefederalregister.org/doc/80_FR_24341/page/1.svg)
![Federal Register / Vol. 80, No. 83 / Thursday, April 30, 2015 / Notices 24259
respect to structure, function, animal will be posted to the docket at http:// availability of a guidance for industry
toxicity, human pharmacokinetics (PK) www.regulations.gov. entitled ‘‘Biosimilars: Questions and
and pharmacodynamics (PD), clinical Answers Regarding Implementation of
III. The Paperwork Reduction Act of
immunogenicity, and clinical safety and the Biologics Price Competition and
1995
effectiveness; Innovation Act of 2009.’’ This guidance
• The totality-of-the-evidence This guidance describes information is intended to provide answers to
approach that FDA will use to review collection provisions that are subject to common questions from sponsors
applications for biosimilar products, review by the Office of Management and interested in developing proposed
consistent with a longstanding Agency Budget (OMB) under the Paperwork biosimilar products, biologics license
approach to evaluation of scientific Reduction Act of 1995 (the PRA) (44 application (BLA) holders, and other
evidence; and U.S.C. 3501–3520). This guidance interested parties regarding FDA’s
• General scientific principles in references information collections that interpretation of the Biologics Price
conducting comparative structural are already approved by OMB and are Competition and Innovation Act of 2009
analyses, functional assays, animal not expected to change as a result of the (BPCI Act). This guidance finalizes
testing, human PK and PD studies, guidance. This includes information several questions and answers (Q&As)
clinical immunogenicity assessment, collections related to the submission of: from the draft guidance entitled
and comparative clinical trials (1) An investigational new drug ‘‘Biosimilars: Questions and Answers
(including clinical study design issues). application, which is covered under 21 Regarding Implementation of the
In the Federal Register of February CFR part 312 and approved under OMB Biologics Price Competition and
15, 2012 (77 FR 8883), FDA announced Control No. 0910–0014; (2) a new drug Innovation Act of 2009’’ issued
the availability of the draft guidance of application, which is covered under 21 February 15, 2012.
the same title dated February 2012. FDA CFR 314.50 and approved under OMB DATES: Submit either electronic or
received a number of comments on the control number 0910–0001; (3) a written comments on Agency guidances
draft guidance. In response to these biologics license application under at any time.
comments, FDA provides further section 351(a) of the PHS Act, which is ADDRESSES: Submit written requests for
clarification of the scientific covered under 21 CFR part 601 and single copies of this guidance to the
considerations applicable to the conduct approved under OMB control number Division of Drug Information, Center for
of comparative structural analysis, 0910–0338; and (4) a biologics license Drug Evaluation and Research, Food
functional assays, animal studies, and application under section 351(k) of the and Drug Administration, 10001 New
clinical testing. The final guidance also PHS Act, which is covered under 21 Hampshire Ave., Hillandale Building,
provides additional information on CFR part 601 and approved under OMB 4th Floor, Silver Spring, MD 20993; or
clinical trial design and selection of control number 0910–0719. Office of Communication, Outreach and
study endpoint and population. It also IV. Electronic Access Development (HFM–40), Center for
explains FDA’s current thinking on Persons with access to the Internet Biologics Evaluation and Research
when a comparative clinical trial may may obtain the document at either (CBER), Food and Drug Administration,
not be needed. In addition, editorial http://www.fda.gov/Drugs/Guidance 1401 Rockville Pike, Suite 200N,
changes were made to improve clarity. ComplianceRegulatoryInformation/ Rockville, MD 20852–1448. Send one
The guidance announced in this notice Guidances/default.htm, http:// self-addressed adhesive label to assist
finalizes and replaces the draft guidance www.fda.gov/BiologicsBloodVaccines/ that office in processing your requests.
dated February 2012. GuidanceComplianceRegulatory See the SUPPLEMENTARY INFORMATION
This guidance is being issued Information/default.htm, or http:// section for electronic access to the
consistent with FDA’s good guidance www.regulations.gov. guidance document.
practices regulation (21 CFR 10.115). Submit electronic comments on the
The guidance represents the Agency’s Dated: April 24, 2015. guidance to http://www.regulations.gov.
current thinking on scientific Peter Lurie, Submit written comments to the
considerations in demonstrating Associate Commissioner for Public Health Division of Dockets Management (HFA–
biosimilarity to a reference product. It Strategy and Analysis. 305), Food and Drug Administration,
does not create or confer any rights for [FR Doc. 2015–10062 Filed 4–29–15; 8:45 am] 5630 Fishers Lane, Rm. 1061, Rockville,
or on any person and does not operate BILLING CODE 4164–01–P MD 20852.
to bind FDA or the public. An FOR FURTHER INFORMATION CONTACT:
alternative approach may be used if Sandra Benton, Center for Drug
such approach satisfies the DEPARTMENT OF HEALTH AND Evaluation and Research, Food and
requirements of the applicable statutes HUMAN SERVICES Drug Administration, 10903 New
and regulations. Hampshire Ave., Bldg. 51, Rm. 6340,
Food and Drug Administration
Silver Spring, MD 20993–0002, 301–
II. Comments [Docket No. FDA–2011–D–0611] 796–1042; or Stephen Ripley, Center for
Interested persons may submit either Biologics Evaluation and Research,
electronic comments regarding this Biosimilars: Questions and Answers Food and Drug Administration, 10903
document to http://www.regulations.gov Regarding Implementation of the New Hampshire Ave., Bldg. 71, Rm.
or written comments to the Division of Biologics Price Competition and 7301, Silver Spring, MD 20993–0002,
Innovation Act of 2009; Guidance for
mstockstill on DSK4VPTVN1PROD with NOTICES
Dockets Management (see ADDRESSES). It 240–402–7911.
is only necessary to send one set of Industry; Availability
SUPPLEMENTARY INFORMATION:
comments. Identify comments with the AGENCY: Food and Drug Administration,
docket number found in brackets in the I. Background
HHS.
heading of this document. Received ACTION: Notice. FDA is announcing the availability of
comments may be seen in the Division a guidance for industry entitled
of Dockets Management between 9 a.m. SUMMARY: The Food and Drug ‘‘Biosimilars: Questions and Answers
and 4 p.m., Monday through Friday, and Administration (FDA) is announcing the Regarding Implementation of the
VerDate Sep<11>2014 17:01 Apr 29, 2015 Jkt 235001 PO 00000 Frm 00030 Fmt 4703 Sfmt 4703 E:\FR\FM\30APN1.SGM 30APN1](https://thefederalregister.org/doc/80_FR_24341/page/2.svg)
Document Created: 2018-02-21 10:15:00
Document Modified: 2018-02-21 10:15:00
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice. | |
| Dates | Submit either electronic or written comments on Agency guidances at any time. | |
| Contact | Sandra Benton, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6340, Silver Spring, MD 20993-0002, 301- 796-1042, or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911. | |
| FR Citation | 80 FR 24258 |
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