`
`
`New and Revised Draft Q&As on
`
`
`Biosimilar Development and the BPCI
`Act (Revision 2)
`
`Guidance for Industry
`
`
`
`
`
`
`
`
`
`
`DRAFT GUIDANCE
`
`
`This guidance document is being distributed for comment purposes only.
`
`
`
`
`Comments and suggestions regarding this draft document should be submitted within 60 days of
`publication in the Federal Register of the notice announcing the availability of the draft
`guidance. Submit electronic comments to https://www.regulations.gov. Submit written
`comments to the Division of Dockets Management (HFA-305), Food and Drug Administration,
`5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with
`
`the docket number listed in the notice of availability that publishes in the Federal Register.
`
`For questions regarding this draft document contact (CDER) Sandra Benton at 301-796-1042 or
`(CBER) Office of Communication, Outreach and Development at 1-800-835-4709 or 240-402-
`8010.
`
`
`
`
`U.S. Department of Health and Human Services
`
`Food and Drug Administration
`
`
`Center for Drug Evaluation and Research (CDER)
`
`Center for Biologics Evaluation and Research (CBER)
`
`
`December 2018
`Biosimilars
`
`
`Revision 2
`
`
`
`
`
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`
`
`
`New and Revised Draft Q&As on
`
`
`Biosimilar Development and the BPCI
`
`Act (Revision 2)
`
`Guidance for Industry
`
`
`
`
`Additional copies are available from:
`
`Office of Communications, Division of Drug Information
`
`
`
`Center for Drug Evaluation and Research
`
`
`Food and Drug Administration
`
`
`
`10001 New Hampshire Ave., Hillandale Bldg., 4th Floor
`
`Silver Spring, MD 20993-0002
`
`
`Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353
`
`
`Email: druginfo@fda.hhs.gov
`
`https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
`
`
`
`and/or
`
`Office of Communication, Outreach and Development
`
`
`Center for Biologics Evaluation and Research
`
`
`
`Food and Drug Administration
`
`
`10903 New Hampshire Ave., Bldg. 71, Room 3128
`
`
`Silver Spring, MD 20993-0002
`
`Phone: 800-835-4709 or 240-402-8010
`
`Email: ocod@fda.hhs.gov
`
`
`
`https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
`
`U.S. Department of Health and Human Services
`
`Food and Drug Administration
`
`Center for Drug Evaluation and Research (CDER)
`
`
`Center for Biologics Evaluation and Research (CBER)
`
`
`December 2018
`
`Biosimilars
`
`
`Revision 2
`
`
`
`
`
`
`
`
`
`
`
`
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`Contains Nonbinding Recommendations
`
`Draft — Not for Implementation
`
`
`
` TABLE OF CONTENTS
`
`
`
`INTRODUCTION......................................................................................................................... 1
`
`BACKGROUND ........................................................................................................................... 3
`
`QUESTIONS AND ANSWERS................................................................................................... 5
`
`I.
`BIOSIMILARITY OR INTERCHANGEABILITY........................................................... 5
`
` 
`II. PROVISIONS RELATED TO REQUIREMENTS TO SUBMIT A BLA FOR A
` 
`“BIOLOGICAL PRODUCT”........................................................................................... 12
`
`
`III. EXCLUSIVITY ................................................................................................................ 14
`
` 
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` 
` 
` 
` 
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`Contains Nonbinding Recommendations
`
`Draft — Not for Implementation
` New and Revised Draft Q&As on Biosimilar Development and the
`BPCI Act (Revision 2)
`
`Guidance for Industry1
`
`
`
`
`
`
`
`1
`2
`3
`4
`5
`6
`
`7
`This draft guidance, when finalized, will represent the current thinking of the Food and Drug
`8 Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not
`9
`binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the
`10
`applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible
`11
`for this guidance as listed on the title page.
`12
`
`13
`
`INTRODUCTION
`14
`15
`
`16
`This draft guidance document provides answers to common questions from prospective
`17
`applicants and other interested parties regarding the Biologics Price Competition and Innovation
`18 Act of 2009 (BPCI Act). The question and answer (Q&A) format is intended to inform
`19
`prospective applicants and facilitate the development of proposed biosimilars and
`interchangeable biosimilars, 2 as well as to describe FDA’s interpretation of certain statutory
`20
`21
`requirements added by the BPCI Act.
`22
`
`23
`The BPCI Act amended the Public Health Service Act (PHS Act) and other statutes to create an
`24
`abbreviated licensure pathway in section 351(k) of the PHS Act for biological products shown to
`25
`be biosimilar to, or interchangeable with, an FDA-licensed biological reference product (see
`26
`sections 7001 through 7003 of the Patient Protection and Affordable Care Act (Pub. L. 111–148)
`27
`(ACA)). FDA believes that guidance for industry that provides answers to commonly asked
`28
`questions regarding FDA’s interpretation of the BPCI Act will enhance transparency and
`29
`facilitate the development and approval of biosimilar and interchangeable products. In addition,
`30
`these Q&As respond to questions the Agency has received from prospective applicants regarding
`
`1 This draft guidance has been prepared by the Center for Drug Evaluation and Research (CDER) and the Center for
`Biologics Evaluation and Research (CBER) at the Food and Drug Administration (FDA or the Agency).
`
`We update guidances periodically. To make sure you have the most recent version of a guidance, check the FDA
`Drugs guidance web page at
`https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
` In this draft guidance, the following terms are used to describe biological products licensed under section 351(k) of
`the PHS Act: (1) biosimilar or biosimilar product refers to a product that FDA has determined to be biosimilar to
`the reference product (see sections 351(i)(2) and 351(k)(2) of the PHS Act) and (2) interchangeable biosimilar or
`interchangeable product refers to a biosimilar product that FDA has also determined to be interchangeable with the
`reference product (see sections 351(i)(3) and 351(k)(4) of the PHS Act). Biosimilarity, interchangeability, and
`related issues are discussed in more detail in the Background section of this draft guidance.
`
`
`
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`Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein
`Product to a Reference Product (April 2015)
`Scientific Considerations in Demonstrating Biosimilarity to a Reference Product
`(April 2015)
`Questions and Answers on Biosimilar Development and the BPCI Act (December
`2018)
`Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a
`Reference Product (December 2016)
`Labeling for Biosimilar Products (July 2018)
`
`Considerations in Demonstrating Interchangeability With a Reference Product
`(January 2017)
`Formal Meetings Between the FDA and Sponsors or Applicants of BsUFA
`Products (June 2018)
`Reference Product Exclusivity for Biological Products Filed Under Section 351(a)
`of the PHS Act (August 2014)
`
`
`
`the appropriate statutory authority under which certain products will be regulated. FDA intends
`31
`to update this draft guidance document to include additional Q&As as appropriate.
`32
`33
`
`This draft guidance document revises the draft guidance document, Biosimilars: Additional
`34
`35 Questions and Answers Regarding Implementation of the Biologics Price Competition and
`36
`Innovation Act of 2009.3 The draft guidance document contains Q&As distributed for comment
`
`purposes only and includes new Q&As, as well as revisions to Q&As that appeared in previous
`37
`38
`versions of the draft or final guidance documents. Additional information about the Q&A format
`39
`for this draft guidance document is provided in the Background section.
`
`40
`FDA is also issuing a final guidance document entitled Questions and Answers on Biosimilar
`41
`42 Development and the BPCI Act. This final guidance document is part of a series of guidance
`43
`documents that FDA has developed to facilitate development of biosimilar and interchangeable
`44
`products. The final guidance documents issued to date address a broad range of issues,
`45
`including:
`46
`
`47
`48
`49
`50
`51
`52
`53
`54
`55
`56
`57
`58
`59
`60
`61
`62
`63
`64
`65
`66
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`
`
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`
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`
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`
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`
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`
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`
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`
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`In addition, FDA has published draft guidance documents related to the BPCI Act, which, when
`finalized, will represent FDA’s current thinking. These draft guidance documents include:
`
`
`
` 3 FDA has adjusted the title of this draft guidance to more clearly communicate that this draft guidance contains
`
`draft questions and answers.
`
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`In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
`67
`Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
`68
`as recommendations, unless specific regulatory or statutory requirements are cited. The use of
`69
`the word should in Agency guidances means that something is suggested or recommended, but
`70
`not required.
`71
`
`72
`73 BACKGROUND
`74
`
`75
`The BPCI Act
`76
`
`77
`The BPCI Act was enacted as part of the ACA on March 23, 2010. The BPCI Act amended the
`78
`PHS Act and other statutes to create an abbreviated licensure pathway for biological products
`79
`shown to be biosimilar to, or interchangeable with, an FDA-licensed biological reference product
`80
`(see sections 7001 through 7003 of the ACA). Section 351(k) of the PHS Act (42 U.S.C.
`81
`262(k)), added by the BPCI Act, sets forth the requirements for an application for a proposed
`82
`biosimilar or interchangeable product.
`83
`
`84
`Section 351(i) defines the term biosimilar or biosimilarity “in reference to a biological product
`85
`that is the subject of an application under [section 351(k)]” to mean “that the biological product
`86
`is highly similar to the reference product4 notwithstanding minor differences in clinically
`87
`inactive components” and that “there are no clinically meaningful differences between the
`88
`biological product and the reference product in terms of the safety, purity, and potency of the
`89
`product” (see section 351(i)(2) of the PHS Act).
`90
`
`91
`Section 351(k)(4) of the PHS Act provides that upon review of an application submitted under
`92
`section 351(k) or any supplement to such application, FDA will determine the biological product
`93
`to be interchangeable with the reference product if FDA determines that the information
`94
`submitted in the application (or a supplement to such application) is sufficient to show that the
`95
`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”5 and that “for a biological
`96
`97
`product that is administered more than once to an individual, the risk in terms of safety or
`98
`diminished efficacy of alternating or switching between use of the biological product and the
`99
`reference product is not greater than the risk of using the reference product without such
`alternation or switch.”6
`100
`101
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`102
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` 4 Reference product means the single biological product licensed under section 351(a) of the PHS Act against which
`
` a biological product is evaluated in a 351(k) application (section 351(i)(4) of the PHS Act).
`
`
`
`
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`5 Section 351(k)(4)(A) of the PHS Act.
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`6 Section 351(k)(4)(B) of the PHS Act.
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`Section 351(i) of the PHS Act states that the term interchangeable or interchangeability, in
`103
`reference to a biological product that is shown to meet the standards described in section
`104
`351(k)(4) of the PHS Act, means that “the biological product may be substituted for the
`105
`reference product without the intervention of the health care provider who prescribed the
`106
`reference product.”
`107
`
`108
`In this draft guidance document, the terms proposed biosimilar product and proposed
`109
`interchangeable product are used to describe products that are under development or are the
`110
`subject of a pending 351(k) biologics license application (BLA).
`111
`
`112
`113 Certain other provisions of the BPCI Act are discussed in the context of the relevant Q&A.
`114
`
`115
`“Question and Answer” Guidance Format
`116
`
`117
`This draft guidance document is a companion to the final guidance document, Questions and
`118
`Answers on Biosimilar Development and the BPCI Act. In this pair of guidance documents,
`119
`FDA issues each Q&A in draft form in this draft guidance document, receives comments on the
`120
`draft Q&A, and, as appropriate, moves the Q&A to the final guidance document, after reviewing
`121
`comments and incorporating suggested changes to the Q&A, when appropriate. A Q&A that
`122 was previously in the final guidance document may be withdrawn and moved to the draft
`123
`guidance document if FDA determines that the Q&A should be revised in some respect and
`124
`reissued in a revised draft Q&A for comment. A Q&A also may be withdrawn and removed
`125
`from the Q&A guidance documents if, for instance, the issue addressed in the Q&A is addressed
`126
`in another FDA guidance document.
`127
`
`128 A reference will follow each question in this draft guidance document describing the publication
`129
`date of the current version of the Q&A, and whether the Q&A has been added to or modified in
`130
`this draft guidance document. FDA has maintained the original numbering of the guidance
`131 Q&As used in the April 2015 final guidance document (Biosimilars: Questions and Answers
`132
`Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009) and
`133 May 2015 draft guidance document (Biosimilars: Additional Questions and Answers Regarding
`134
`Implementation of the Biologics Price Competition and Innovation Act of 2009). For ease of
`135
`reference, a Q&A retains the same number when it moves from the draft guidance document to
`136
`the final guidance document and, where appropriate, when a Q&A is withdrawn from the final
`137
`guidance document and moved to the draft guidance document.
`138
`
`139 Where a Q&A has been withdrawn from the final guidance document, this is marked in the final
`140
`guidance document by several asterisks between nonconsecutively numbered Q&As and, where
`141
`appropriate, explanatory text.
`142
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`143 QUESTIONS AND ANSWERS
`
`
`
`BIOSIMILARITY OR INTERCHANGEABILITY
`
`I.
`
`
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`
`* * * * *
`Q. I.12. How can an applicant demonstrate that its proposed injectable biosimilar
`product or proposed injectable interchangeable product has the same
`“strength” as the reference product?
`[Moved to Draft from Final December 2018]
`
`
`A. I.12. Under section 351(k)(2)(A)(i)(IV) of the PHS Act, an applicant must demonstrate
`that the “strength” of the proposed biosimilar product or proposed interchangeable
`product is the same as that of the reference product. Data and information
`generated as part of the analytical similarity assessment may inform the
`determination that a proposed biosimilar product or proposed interchangeable
`product has the same strength as its reference product. As a scientific matter,
`there may be a need to take into account different factors and approaches in
`determining the “strength” of different biological products. Sponsors should
`discuss their proposed approach with FDA and provide an adequate scientific
`basis for their approach to demonstrating same strength.
`
`
`
`
`
`
`In general, a sponsor of a proposed biosimilar product or proposed
`interchangeable product with an “injection” dosage form (e.g., a solution) can
`demonstrate that its product has the same strength as the reference product by
`demonstrating that both products have the same total content of drug substance (in
`mass or units of activity) and the same concentration of drug substance (in mass
`or units of activity per unit volume). In general, for a proposed biosimilar product
`or proposed interchangeable product that is a dry solid (e.g., a lyophilized
`powder) from which a constituted or reconstituted solution is prepared, a sponsor
`can demonstrate that the product has the same strength as the reference product by
`demonstrating that both products have the same total content of drug substance (in
`mass or units of activity).
`
`Although not a part of demonstrating same “strength,” if the proposed biosimilar
`product or proposed interchangeable product is a dry solid (e.g., a lyophilized
`powder) from which a constituted or reconstituted solution is prepared, the 351(k)
`application generally should contain information that the concentration of the
`proposed biosimilar product or proposed interchangeable product, when
`constituted or reconstituted, is the same as that of the reference product, when
`constituted or reconstituted.
`
`A sponsor should determine the content of drug substance for both the reference
`product and the proposed biosimilar product or proposed interchangeable product
`
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`using the same method. The strength of the proposed product generally should be
`expressed using the same units of measure as the reference product.
`
`
`Q. I.16. How can a proposed biosimilar product applicant fulfill the requirement for
`pediatric assessments or investigations under the Pediatric Research Equity Act
`(PREA)?
`[Updated/Retained in Draft December 2018]
`
`
`A. I.16. Applicants for proposed biosimilar products should address PREA requirements
`based upon the nature and extent of pediatric information in the reference product
`labeling. PREA requirements are applicable to proposed biosimilar products that
`have not been determined to be interchangeable with a reference product only to
`the extent that compliance with PREA would not result in: (1) a condition of use
`that has not been previously approved for the reference product; or (2) a dosage
`form, strength, or route of administration that differs from that of the reference
`
`product.
`
`
`
`As a preliminary matter, we note that there are differences in the use of the term
`
`“extrapolation” in the context of a proposed biosimilar product under the PHS Act
`and in the context of PREA.
`
`
`
` An applicant may provide scientific justification for “extrapolation” to
`support approval of a biosimilar product under section 351(k) of the PHS
`Act for one or more conditions of use. For more information on
`
`
`extrapolation in this context, see FDA’s guidance for industry on Scientific
`Considerations in Demonstrating Biosimilarity to a Reference Product.
`
`
`
`
` “Pediatric extrapolation” refers to establishing the effectiveness of a drug
`in a pediatric population without requiring a separate study in that
`population when the course of the disease and the effects of the drug are
`sufficiently similar in the pediatric population and the adult population (or
`another pediatric population) in which the drug has been studied and
`shown to be effective (see section 505B(a)(2)(B) and (a)(3)(B) of the
`Federal Food Drug and Cosmetic Act (FD&C Act).
`
`
`In the discussion that follows, the term “extrapolation” generally will be used to
`refer to extrapolation to support approval of a biosimilar product under section
`351(k) of the PHS Act for one or more conditions of use, and not to pediatric
`extrapolation.
`
`
`
` Adequate pediatric information in reference product labeling
`
`If the labeling for the reference product contains adequate pediatric
`information (e.g., information reflecting an adequate pediatric assessment)
`
`6
`
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`with respect to an indication for which a biosimilar applicant seeks
`licensure in adults, the biosimilar applicant may fulfill PREA requirements
`for that indication by satisfying the statutory requirements for showing
`biosimilarity and providing an adequate scientific justification under the
`BPCI Act for extrapolating the pediatric information from the reference
`product to the proposed biosimilar product.
`
`If the submitted scientific justification for extrapolation under section
`351(k) of the PHS Act is inadequate, a biosimilar applicant must submit
`appropriate data to fulfill applicable PREA requirements.
`
` Lack of adequate pediatric information in reference product labeling
`
`If the labeling for the reference product does not contain adequate
`pediatric information for one or more pediatric age groups for an
`indication for which a biosimilar applicant seeks licensure in adults, and
`applicable PREA requirements were deferred for the reference product for
`those pediatric age groups, a biosimilar applicant should request a deferral
`of PREA requirements for those pediatric age groups. The biosimilar
`applicant should amend or supplement its 351(k) BLA, as appropriate, to
`seek approval for updated labeling, supported by biosimilar extrapolation
`or appropriate data, that includes relevant pediatric information after the
`reference product labeling is updated with that information.
`
`
`
`
`
`
`
`
`
`If the labeling for the reference product does not contain adequate
`pediatric information for one or more pediatric age groups for an
`indication for which a biosimilar applicant seeks licensure in adults, and
`PREA requirements were waived for, or inapplicable to, the reference
`product for those pediatric age groups, a biosimilar applicant should note
`this information in its initial pediatric study plan (iPSP), if any, but does
`not need to request a waiver of PREA requirements for those age groups.
`For proposed biosimilars, obligations under PREA are circumscribed by
`the BPCI Act to require an assessment only for indications and age groups
`or other conditions of use in which the reference product has been or will
`be assessed. In other words, the Agency has determined that PREA
`requirements are applicable to a proposed biosimilar product that has not
`been determined to be interchangeable with a reference product only to the
`extent that compliance with PREA would not result in: (1) a condition of
`use that has not been previously approved for the reference product, or (2)
`a dosage form, strength, or route of administration that differs from that of
`the reference product.
`
`FDA’s recommendations to biosimilar applicants with respect to the PREA
`requirements reflect a clarification based on the Agency’s interpretation of the
`
`7
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`interaction between section 505B of the FD&C Act (PREA) and section 351(k) of
`the PHS Act. Biosimilar applicants previously requested, and the Agency
`granted, waivers in instances where PREA requirements were waived for or
`determined to be inapplicable to the reference product. However, upon further
`consideration, waivers for biosimilars applicants under those circumstances were
`not necessary, and the practice is more accurately described in terms of the
`Agency’s interpretation of the BPCI Act and PREA. The BPCI Act added section
`351(k) of the PHS Act and amended section 505B of the FD&C Act to specify
`that PREA is applicable to a biosimilar product that has not been determined to be
`interchangeable with a reference product (see section 7002(a), (d)(2) of the BPCI
`Act). FDA reads section 351(k) of the PHS Act and PREA together with respect
`to the need to conduct assessments of and seek licensure for certain pediatric uses
`and pediatric formulations. An application submitted under section 351(k) of the
`PHS Act must include, among other things, information demonstrating that “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” and “the route of administration, the dosage form, and the
`strength of the biological product are the same as those of the reference product”
`(section 351(k)(2)(A)(i)(III)-(IV) of the PHS Act). FDA has determined that,
`when the reference product does not have adequate pediatric use information in its
`labeling or an age-appropriate formulation for a relevant pediatric population, the
`obligations for the biosimilar applicant under PREA are circumscribed by section
`351(k) of the PHS Act insofar as the biosimilar applicant would not be expected
`to obtain licensure for a pediatric use (or describe that use in product labeling)
`that has not been licensed for the reference product and would not be expected to
`obtain licensure of a product that would result in a dosage form, strength, or route
`of administration that differs from that of the reference product.
`
`By establishing an abbreviated licensure pathway for biosimilar and
`interchangeable products, the BPCI Act reflects the strong public health interest in
`the licensure and availability of those products. Such licensure could result in
`increased competition, as well as greater access to biological products. The
`Agency’s interpretation of section 351(k) and PREA assures that biosimilar
`applicants are not subject to greater regulatory burdens than those faced by
`reference product sponsors with respect to the study of pediatric uses.
`
`This approach preserves the intent and availability of an abbreviated licensure
`pathway for biosimilars, while helping to ensure that a biosimilar product is
`labeled and formulated for relevant pediatric conditions of use that have been
`approved for the reference product. FDA also recognizes the important interests
`furthered by PREA and appreciates the need to study pediatric uses of biological
`products and to include pediatric use information in product labeling.
`Consequently, in appropriate cases, FDA may take additional steps within its
`authority to assure that pediatric use information is included in biological product
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`Novo Nordisk A/S Ex. 2021, P. 11
`Mylan Institutional v. Novo Nordisk
`IPR2020-00324
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`Contains Nonbinding Recommendations
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`Draft — Not for Implementation
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`labeling.7 Such actions may include invoking the “marketed drugs” provision
`under PREA, in certain circumstances, to require sponsors to conduct pediatric
`assessments, or take other appropriate steps, to support pediatric labeling for both
`the biosimilar product and the reference product.8
`
`If a biosimilar applicant believes that none of the situations described above
`applies to its proposed product, the applicant should contact FDA for further
`information.
`
`
`Q. I.20. What is the nature and type of information that a sponsor should provide to
`support a post-approval manufacturing change for a licensed biosimilar
`product?
`[New December 2018]
`
`
`A. I.20
`
`In general, a sponsor who intends to make a manufacturing change to a licensed
`biosimilar product should follow the principles outlined in the International
`Council for Harmonisation (ICH) guidance for industry Q5E Comparability of
`Biotechnological/Biological Products Subject to Changes in their Manufacturing
`Process (June 2005). Accordingly, the sponsor should provide sufficient data and
`information to demonstrate the comparability of the biosimilar product before and
`after the manufacturing change. The comparability assessment should include: a)
`side-by-side analytical comparison of a sufficient number of lots of pre-change
`and post-change material, including an assessment of stability; and b) a
`comparison of analytical data from the post-change material to historical
`analytical data from lots used in the analytical similarity assessment, including
`data from lots used in clinical studies that supported licensure of the biosimilar
`product. A well-qualified, in-house reference standard should also be included in
`the comparability exercise. In certain cases, additional reference materials may
`be included in the comparability study. The extent of data and information
`necessary to establish comparability would be commensurate with the type of
`manufacturing change and its potential impact on product quality, safety, and
`efficacy.
`
`In addition, FDA continues to consider the nature and type of information a
`sponsor should provide to support a post-approval manufacturing change to a
`biological product determined by FDA to be interchangeable with the reference
`product under section 351(k)(4) of the PHS Act. FDA intends to provide specific
`recommendations for post-approval manufacturing changes to interchangeable
`biological products in future guidance.
`
`7 For instance, if the Agency determines that the basis for the reference product’s waiver under PREA no longer
`applies to a particular age group (e.g., because it is now feasible to study a younger pediatric age group), FDA may,
`as appropriate, contact the 351(k) biosimilar product sponsor, as well as the reference product sponsor, and require
`further action by both parties to comply with PREA. See § 505B(a)(5) of the FD&C Act.
`8 See § 505B(b) of the FD&C Act.
`
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`Novo Nordisk A/S Ex. 2021, P. 12
`Mylan Institutional v. Novo Nordisk
`IPR2020-00324
`
`

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`Contains Nonbinding Recommendations
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`Draft — Not for Implementation
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`A sponsor may seek approval, in a supplement to an approved 351(k) BLA, of a
`route of administration, a dosage form, or a strength that is the same as that of the
`reference product, but that has not previously been licensed under the 351(k)
`BLA.9 FDA intends to provide specific recommendations on this topic in future
`guidance.
`
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`Q. I.21. May a sponsor seek approval, in a 351(