82 FR 5579 - Considerations in Demonstrating Interchangeability With a Reference Product; Draft Guidance for Industry; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 82, Issue 11 (January 18, 2017)
Food and Drug Administration
Federal Register Volume 82, Issue 11 (January 18, 2017)
| Page Range | 5579-5580 | |
| FR Document | 2017-01042 |
[Federal Register Volume 82, Number 11 (Wednesday, January 18, 2017)] [Notices] [Pages 5579-5580] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2017-01042] [[Page 5579]] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2017-D-0154] Considerations in Demonstrating Interchangeability With a Reference Product; Draft Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice of availability. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Considerations in Demonstrating Interchangeability With a Reference Product.'' This guidance is intended to assist sponsors in demonstrating that a proposed therapeutic protein product (proposed interchangeable product or proposed product) is interchangeable with a reference product for the purposes of submitting a marketing application or supplement under the Public Health Service Act (PHS Act). This guidance is one in a series of guidances that FDA has developed to implement the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). 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comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by March 20, 2017. ADDRESSES: You may submit comments as follows: Electronic Submissions Submit electronic comments in the following way:Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov. If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see ``Written/Paper Submissions'' and ``Instructions''). Written/Paper Submissions Submit written/paper submissions as follows: Mail/Hand delivery/Courier (for written/paper submissions): Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. For written/paper comments submitted to the Division of Dockets Management, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in ``Instructions.'' Instructions: All submissions received must include the Docket No. FDA-2017-D-0154 for ``Considerations in Demonstrating Interchangeability With a Reference Product; Draft Guidance for Industry; Availability.'' Received comments will be placed in the docket and, except for those submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday. Confidential Submissions--To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Division of Dockets Management. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as ``confidential.'' Any information marked as ``confidential'' will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm. Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the ``Search'' box and follow the prompts and/or go to the Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit written requests for single copies of the draft 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 to the Office of Communication, Outreach and Development, Center for Biologics Evaluation and Research, 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 draft guidance document. 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 draft guidance for industry entitled ``Considerations in Demonstrating Interchangeability With a Reference Product.'' This guidance is intended to assist sponsors in demonstrating that a proposed therapeutic protein product (proposed interchangeable product or proposed product) is interchangeable with a reference product for the purposes of submitting a marketing application or supplement under section 351(k) of the PHS Act (42 U.S.C. 262(k)). The BPCI Act amends the PHS Act and other statutes to create an [[Page 5580]] abbreviated licensure pathway in section 351(k) for biological products shown to be biosimilar to or interchangeable with an FDA-licensed biological reference product (see sections 7001 through 7003 of the Patient Protection and Affordable Care Act Of 2010 (Affordable Care Act) (Pub. L. 111-148)). Section 351(k) of the PHS Act sets forth the requirements for an application for a proposed biosimilar product and an application or a supplement for a proposed interchangeable product. Specifically, section 351(k)(4) provides that upon review of an application submitted under section 351(k), or any supplement to such an application, FDA will determine the biological product to be interchangeable with the reference product if FDA determines that the information submitted in the application (or supplement) is sufficient to show that 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 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. Section 351(i) of the PHS Act states that the term interchangeable or interchangeability, in reference to a biological product that is shown to meet the standards described in subsection 351(k)(4), means that the biological product may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product. This guidance gives an overview of important scientific considerations in demonstrating interchangeability, including: The data and information needed to support a demonstration of interchangeability; Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability; Recommendations regarding the use of U.S.-licensed reference products in a switching study or studies; and Considerations for developing presentations, container closure systems, and delivery device constituent parts for proposed interchangeable products. This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the current thinking of FDA on topics sponsors should consider when seeking to demonstrate that a proposed therapeutic protein product is interchangeable with a reference product. It does not establish any rights for any person and is not binding on FDA or the public. II. Topics for Comment In addition to comment on the draft guidance, we also invite general comments on interchangeability, including comments on regulation of an interchangeable product over its lifecycle, as well as comments on the following topics: 1. Since the mid-1990s, FDA has approved manufacturing changes for biological products based on data from comparability assessments comparing the pre-change and post-change product using comparative analytical, and, when necessary, animal and/or clinical (e.g., pharmacokinetic, immunogenicity) studies. A demonstration of comparability between pre- and post-change product supports a determination that the safety and efficacy profile remains the same for the product. With respect to interchangeable products, are there considerations in addition to comparability assessments that FDA should consider in regulating post-approval manufacturing changes of interchangeable products? Your comments should include the scientific rationale and justification for your recommendations, as well as recommendations for processes and systems (including key logistics) to implement your recommendations. 2. As explained in the guidance ``Considerations in Demonstrating Interchangeability With a Reference Product,'' FDA expects that sponsors seeking an interchangeability determination will submit data and information to support a showing that the proposed interchangeable product can be expected to produce the same clinical result as the reference product in all of the reference product's licensed conditions of use. How, if at all, should the Agency consider conditions of use that are licensed for the reference product after an interchangeable product has been licensed? Your comments should include the scientific rationale and justification for your recommendations, as well as recommendations for processes and systems (including key logistics) to implement your recommendations. III. Paperwork Reduction Act of 1995 This draft guidance refers to previously approved collections of information found in FDA regulations. These collections of information are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The collections of information under 21 CFR part 312 have been approved under OMB control number 0910-0014; the collections of information under 21 CFR part 601 have been approved under OMB control number 0910- 0338; and the collections of information under section 351(k) of the PHS Act have been approved under OMB control number 0910-0719. IV. Electronic Access Persons with access to the Internet may obtain the draft guidance at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or https://www.regulations.gov. Dated: January 12, 2017. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2017-01042 Filed 1-17-17; 8:45 am] BILLING CODE 4164-01-P
![Federal Register / Vol. 82, No. 11 / Wednesday, January 18, 2017 / Notices 5579
DEPARTMENT OF HEALTH AND identifies you in the body of your accordance with 21 CFR 10.20 and other
HUMAN SERVICES comments, that information will be applicable disclosure law. For more
posted on https://www.regulations.gov. information about FDA’s posting of
Food and Drug Administration • If you want to submit a comment comments to public dockets, see 80 FR
with confidential information that you 56469, September 18, 2015, or access
[Docket No. FDA–2017–D–0154]
do not wish to be made available to the the information at: http://www.fda.gov/
Considerations in Demonstrating public, submit the comment as a regulatoryinformation/dockets/
Interchangeability With a Reference written/paper submission and in the default.htm.
Product; Draft Guidance for Industry; manner detailed (see ‘‘Written/Paper Docket: For access to the docket to
Availability Submissions’’ and ‘‘Instructions’’). read background documents or the
Written/Paper Submissions electronic and written/paper comments
AGENCY: Food and Drug Administration, received, go to https://
HHS. Submit written/paper submissions as www.regulations.gov and insert the
ACTION: Notice of availability. follows: docket number, found in brackets in the
• Mail/Hand delivery/Courier (for heading of this document, into the
SUMMARY: The Food and Drug written/paper submissions): Division of ‘‘Search’’ box and follow the prompts
Administration (FDA or Agency) is Dockets Management (HFA–305), Food and/or go to the Division of Dockets
announcing the availability of a draft and Drug Administration, 5630 Fishers
Management, 5630 Fishers Lane, Rm.
guidance for industry entitled Lane, Rm. 1061, Rockville, MD 20852.
1061, Rockville, MD 20852.
‘‘Considerations in Demonstrating • For written/paper comments
Submit written requests for single
Interchangeability With a Reference submitted to the Division of Dockets
copies of the draft guidance to the
Product.’’ This guidance is intended to Management, FDA will post your
comment, as well as any attachments, Division of Drug Information, Center for
assist sponsors in demonstrating that a Drug Evaluation and Research, Food
proposed therapeutic protein product except for information submitted,
marked and identified, as confidential, and Drug Administration, 10001 New
(proposed interchangeable product or Hampshire Ave., Hillandale Building,
proposed product) is interchangeable if submitted as detailed in
‘‘Instructions.’’ 4th Floor, Silver Spring, MD 20993–
with a reference product for the 0002; or to the Office of
purposes of submitting a marketing Instructions: All submissions received
must include the Docket No. FDA– Communication, Outreach and
application or supplement under the Development, Center for Biologics
Public Health Service Act (PHS Act). 2017–D–0154 for ‘‘Considerations in
Demonstrating Interchangeability With a Evaluation and Research, Food and
This guidance is one in a series of Drug Administration, 10903 New
guidances that FDA has developed to Reference Product; Draft Guidance for
Industry; Availability.’’ Received Hampshire Ave., Bldg. 71, Rm. 3128,
implement the Biologics Price Silver Spring, MD 20993–0002. Send
Competition and Innovation Act of 2009 comments will be placed in the docket
and, except for those submitted as one self-addressed adhesive label to
(BPCI Act). assist that office in processing your
‘‘Confidential Submissions,’’ publicly
DATES: Although you can comment on requests. See the SUPPLEMENTARY
viewable at https://www.regulations.gov
any guidance at any time (see 21 CFR or at the Division of Dockets INFORMATION section for electronic
10.115(g)(5)), to ensure that the Agency Management between 9 a.m. and 4 p.m., access to the draft guidance document.
considers your comment on this draft Monday through Friday. FOR FURTHER INFORMATION CONTACT:
guidance before it begins work on the • Confidential Submissions—To Sandra Benton, Center for Drug
final version of the guidance, submit submit a comment with confidential Evaluation and Research, Food and
either electronic or written comments information that you do not wish to be Drug Administration, 10903 New
on the draft guidance by March 20, made publicly available, submit your Hampshire Ave., Bldg. 51, Rm. 6340,
2017. comments only as a written/paper Silver Spring, MD 20993–0002, 301–
ADDRESSES: You may submit comments submission. You should submit two 796–1042; or Stephen Ripley, Center for
as follows: copies total. One copy will include the Biologics Evaluation and Research,
information you claim to be confidential Food and Drug Administration, 10903
Electronic Submissions with a heading or cover note that states New Hampshire Ave., Bldg. 71, Rm.
Submit electronic comments in the ‘‘THIS DOCUMENT CONTAINS 7301, Silver Spring, MD 20993–0002,
following way: CONFIDENTIAL INFORMATION.’’ The 240–402–7911.
• Federal eRulemaking Portal: Agency will review this copy, including SUPPLEMENTARY INFORMATION:
https://www.regulations.gov. Follow the the claimed confidential information, in
instructions for submitting comments. its consideration of comments. The I. Background
Comments submitted electronically, second copy, which will have the FDA is announcing the availability of
including attachments, to https:// claimed confidential information a draft guidance for industry entitled
www.regulations.gov will be posted to redacted/blacked out, will be available ‘‘Considerations in Demonstrating
the docket unchanged. Because your for public viewing and posted on Interchangeability With a Reference
comment will be made public, you are https://www.regulations.gov. Submit Product.’’ This guidance is intended to
solely responsible for ensuring that your both copies to the Division of Dockets assist sponsors in demonstrating that a
comment does not include any Management. If you do not wish your proposed therapeutic protein product
confidential information that you or a name and contact information to be (proposed interchangeable product or
mstockstill on DSK3G9T082PROD with NOTICES
third party may not wish to be posted, made publicly available, you can proposed product) is interchangeable
such as medical information, your or provide this information on the cover with a reference product for the
anyone else’s Social Security number, or sheet and not in the body of your purposes of submitting a marketing
confidential business information, such comments and you must identify this application or supplement under
as a manufacturing process. Please note information as ‘‘confidential.’’ Any section 351(k) of the PHS Act (42 U.S.C.
that if you include your name, contact information marked as ‘‘confidential’’ 262(k)). The BPCI Act amends the PHS
information, or other information that will not be disclosed except in Act and other statutes to create an
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![5580 Federal Register / Vol. 82, No. 11 / Wednesday, January 18, 2017 / Notices
abbreviated licensure pathway in The draft guidance, when finalized, will III. Paperwork Reduction Act of 1995
section 351(k) for biological products represent the current thinking of FDA This draft guidance refers to
shown to be biosimilar to or on topics sponsors should consider previously approved collections of
interchangeable with an FDA-licensed when seeking to demonstrate that a information found in FDA regulations.
biological reference product (see proposed therapeutic protein product is These collections of information are
sections 7001 through 7003 of the interchangeable with a reference subject to review by the Office of
Patient Protection and Affordable Care product. It does not establish any rights Management and Budget (OMB) under
Act Of 2010 (Affordable Care Act) (Pub. for any person and is not binding on the Paperwork Reduction Act of 1995
L. 111–148)). FDA or the public. (44 U.S.C. 3501–3520). The collections
Section 351(k) of the PHS Act sets
II. Topics for Comment of information under 21 CFR part 312
forth the requirements for an
application for a proposed biosimilar have been approved under OMB control
product and an application or a In addition to comment on the draft number 0910–0014; the collections of
supplement for a proposed guidance, we also invite general information under 21 CFR part 601 have
interchangeable product. Specifically, comments on interchangeability, been approved under OMB control
section 351(k)(4) provides that upon including comments on regulation of an number 0910–0338; and the collections
review of an application submitted interchangeable product over its of information under section 351(k) of
under section 351(k), or any supplement lifecycle, as well as comments on the the PHS Act have been approved under
to such an application, FDA will following topics: OMB control number 0910–0719.
determine the biological product to be 1. Since the mid-1990s, FDA has IV. Electronic Access
interchangeable with the reference approved manufacturing changes for
product if FDA determines that the Persons with access to the Internet
biological products based on data from may obtain the draft guidance at http://
information submitted in the comparability assessments comparing
application (or supplement) is sufficient www.fda.gov/Drugs/Guidance
the pre-change and post-change product ComplianceRegulatoryInformation/
to show that the biological product is using comparative analytical, and, when
biosimilar to the reference product and Guidances/default.htm, http://
necessary, animal and/or clinical (e.g., www.fda.gov/BiologicsBloodVaccines/
can be expected to produce the same pharmacokinetic, immunogenicity)
clinical result as the reference product GuidanceComplianceRegulatory
studies. A demonstration of Information/Guidances/default.htm, or
in any given patient; and for a biological comparability between pre- and post-
product that is administered more than https://www.regulations.gov.
change product supports a
once to an individual, the risk in terms Dated: January 12, 2017.
determination that the safety and
of safety or diminished efficacy of Leslie Kux,
efficacy profile remains the same for the
alternating or switching between use of Associate Commissioner for Policy.
product. With respect to
the biological product and the reference [FR Doc. 2017–01042 Filed 1–17–17; 8:45 am]
interchangeable products, are there
product is not greater than the risk of BILLING CODE 4164–01–P
using the reference product without considerations in addition to
such alternation or switch. Section comparability assessments that FDA
351(i) of the PHS Act states that the should consider in regulating post-
DEPARTMENT OF HEALTH AND
term interchangeable or approval manufacturing changes of
HUMAN SERVICES
interchangeability, in reference to a interchangeable products? Your
biological product that is shown to meet comments should include the scientific Food and Drug Administration
the standards described in subsection rationale and justification for your
351(k)(4), means that the biological recommendations, as well as
[Docket No. FDA–2016–P–2469]
product may be substituted for the recommendations for processes and
reference product without the systems (including key logistics) to Determination That SYMMETREL
intervention of the health care provider implement your recommendations. (Amantadine Hydrochloride), Syrup, 50
who prescribed the reference product. 2. As explained in the guidance Milligrams/5 Milliliters, Was Not
This guidance gives an overview of ‘‘Considerations in Demonstrating Withdrawn From Sale for Reasons of
important scientific considerations in Interchangeability With a Reference Safety or Effectiveness
demonstrating interchangeability, Product,’’ FDA expects that sponsors
including: AGENCY: Food and Drug Administration,
seeking an interchangeability HHS.
• The data and information needed to determination will submit data and
support a demonstration of information to support a showing that ACTION: Notice.
interchangeability; the proposed interchangeable product
• Considerations for the design and SUMMARY: The Food and Drug
can be expected to produce the same Administration (FDA or Agency) has
analysis of a switching study or studies
clinical result as the reference product determined that SYMMETREL
to support a demonstration of
in all of the reference product’s licensed (amantadine hydrochloride), Syrup, 50
interchangeability;
• Recommendations regarding the use conditions of use. How, if at all, should milligrams/5 milliliters (50 mg/5 mL),
of U.S.-licensed reference products in a the Agency consider conditions of use was not withdrawn from sale for reasons
switching study or studies; and that are licensed for the reference of safety or effectiveness. This
• Considerations for developing product after an interchangeable determination means that FDA will not
mstockstill on DSK3G9T082PROD with NOTICES
presentations, container closure product has been licensed? Your begin procedures to withdraw approval
systems, and delivery device constituent comments should include the scientific of abbreviated new drug applications
parts for proposed interchangeable rationale and justification for your (ANDAs) that refer to SYMMETREL,
products. recommendations, as well as and it will allow FDA to continue to
This draft guidance is being issued recommendations for processes and approve ANDAs that reference
consistent with FDA’s good guidance systems (including key logistics) to SYMMETREL if all other legal and
practices regulation (21 CFR 10.115). implement your recommendations. regulatory requirements are met.
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Document Created: 2018-02-01 15:19:21
Document Modified: 2018-02-01 15:19:21
| 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 of availability. | |
| 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 March 20, 2017. | |
| 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 | 82 FR 5579 |
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