Principles of a Science-BasedPrinciples of a Science-BasedRegulatory Pathway for BiosimilarRegulatory Pathway for Biosimil...
Overview• Biosimilars• Biologics Price Competition and InnovationAct of 2009 (BPCIA)• FDA Draft Guidances Relating to Impl...
• However, both generics and biosimilars have the same dosage form,strength, and route of administration as their respecti...
Biologics Price Competition andInnovation Act of 2009 (BPCIA)• Created an abbreviated licensure pathway for biological pro...
5BPCIA Established a Regulatory Pathway forTwo Types of Biosimilar Products• BPCIA created an approval pathway for biosimi...
FDA Draft Guidance to IndustryRelating to Implementation of BPCIA• In February 2012, FDA issued three draft guidance docum...
FDA Draft Guidance: Quality Considerationsin Demonstrating Biosimilarity• Provides FDA’s views on comparative analytical s...
FDA Draft Guidance: Scientific Considerationsin Demonstrating Biosimilarity• Overview of FDA’s current thinking on demonst...
Draft Guidance: Biosimilars: Q&AsRegarding Implementation of the BPCIA• Provides answers to three categories of common que...
FDA’s Stepwise Approach toDemonstrate Biosimilarity• FDA proposes to use risk-based, totality-of-the-evidence approach toe...
PhRMA’s Comments on FDA’sProposed “Stepwise” Approach• Evaluation of biosimilars to demonstrate the absence of clinicallym...
• Applicants should minimize controllable process anddesign differences and provide scientific justification forchanges to...
PhRMA’s Comments onAnalytical Testing• Multiple analytical procedures thatare sufficiently sensitive should beperformed to...
PhRMA’s Comments onPreclinical Testing• In vitro functional assays are important tothe evaluation of biologic activity and...
PhRMA’s Comments onClinical TestingFDA guidance should recognize that:•Clinical testing is essential to determinethat ther...
• Each indication for which a biosimilar applicant is seeking approval will needto be supported with clinical data, unless...
PhRMA’s Comments onImmunogenicity Testing• Biologics have the potential to evoke an immuneresponse; even seemingly small c...
PhRMA’s Comments onProduct Labeling• Product labeling should include a clear statement to indicate whetherthe product is a...
PhRMA’s Comments onPharmacovigilance• The pharmacovigilance plan for each approvedbiosimilar should be tailored to the ben...
Naming of Biosimilar Products• Unique non-proprietary names are an essential feature of a robustsystem for adequately trac...
Summary• A biosimilar is highly similar to, but not the same as, anFDA-licensed reference biologic product• A rigorous, sc...
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13. Dr. Kristin Van Goor - PhRMA

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“Principles of a Science-Based Regulatory Pathway for Biosimilar Products”

Provides an overview of the guiding principles for a science-based regulatory pathway for biosimilar products

Published in: Health & Medicine, Business
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13. Dr. Kristin Van Goor - PhRMA

  1. 1. Principles of a Science-BasedPrinciples of a Science-BasedRegulatory Pathway for BiosimilarRegulatory Pathway for BiosimilarProductsProductsKristin Van Goor
  2. 2. Overview• Biosimilars• Biologics Price Competition and InnovationAct of 2009 (BPCIA)• FDA Draft Guidances Relating to Implementationof BPCIA• PhRMA’s Comments on the FDA’s Draft Guidances• Summary2
  3. 3. • However, both generics and biosimilars have the same dosage form,strength, and route of administration as their respective parentproducts for approved conditions of useBiosimilars Are Not Generics3= ≠ ≠
  4. 4. Biologics Price Competition andInnovation Act of 2009 (BPCIA)• Created an abbreviated licensure pathway for biological productsshown to be biosimilar to or interchangeable with an FDA-licensedreference product• Sponsor must show that the proposed product• Is highly similar to a single, FDA-licensed biological referenceproduct• Utilizes the same mechanism(s) of action (to the extent known forthe reference product) for the proposed condition(s) of use of thebiosimilar that have been previously approved for the referenceproduct• Has the same route of administration, dosage form, and strengthas the reference product4
  5. 5. 5BPCIA Established a Regulatory Pathway forTwo Types of Biosimilar Products• BPCIA created an approval pathway for biosimilar products andinterchangeable biological products• Both biosimilar and interchangeable biological products must bedemonstrated to be highly similar to an innovative biological product• BPCIA establishes a higher standard for interchangeable products1. Biosimilar to the reference product2. Expected to produce the same clinical result asthe reference product in any given patient3. No increased risk associated with alternating orswitching between the interchangeable product andthe reference product compared with using only thereference productMust Meet3 CriteriaMust Meet3 Criteria
  6. 6. FDA Draft Guidance to IndustryRelating to Implementation of BPCIA• In February 2012, FDA issued three draft guidance documentson biosimilar product development to assist industry in developingthese products• When finalized, these guidances will represent the FDA’s currentthinking on these topics6
  7. 7. FDA Draft Guidance: Quality Considerationsin Demonstrating Biosimilarity• Provides FDA’s views on comparative analytical studies that make up onecomponent of the demonstration of biosimilarity to a reference product• Analytical similarities – amino acid sequence, molecularweight, complexity, degree of heterogeneity, functional properties,impurity profiles, etc• Extensive, robust comparative physiochemical andfunctional studies – biological assays, binding assays,enzyme kinetics, etc• Comparative stability studies – multiple stress conditions,eg, high temperature, freeze/thaw, light exposure, etc• Describes considerations for additional chemistry,manufacturing, and controls (CMC) information thatmay be relevant to the assessment of biosimilarity• In addition to comparative analytical studies, an assessment of biosimilaritywill generally include animal studies and clinical trials7
  8. 8. FDA Draft Guidance: Scientific Considerationsin Demonstrating Biosimilarity• Overview of FDA’s current thinking on demonstrating biosimilarity by using atotality-of-the-evidence approach to evaluation of scientific data• Discusses FDA’s view on important scientific considerations including• Stepwise approach to demonstrating biosimilarity• Considerations of the complexities of therapeuticprotein products• General scientific principles in conducting structuraland functional analyses and assays• Animals studies, including toxicity, PK/PD, andimmunogenicity studies• Clinical studies, including pharmacology andimmunogenicity studies, and general considerationsfor clinical safety and efficacy data• Extrapolation of clinical data across indications• Postmarketing safety monitoring considerations8
  9. 9. Draft Guidance: Biosimilars: Q&AsRegarding Implementation of the BPCIA• Provides answers to three categories of common questionsfrom sponsors interested in developing biosimilar products• Biosimilarity or interchangeability• Provisions related to a requirement tosubmit a Biologic License Application (BLA)for a “biological product”• Reference product exclusivity• Intended to promote transparency and facilitate developmentprograms for proposed biosimilar products by addressingquestions that may arise in the early stages of developmentQQAA9
  10. 10. FDA’s Stepwise Approach toDemonstrate Biosimilarity• FDA proposes to use risk-based, totality-of-the-evidence approach toevaluate all available data and information• However, FDA has the discretion to determine that an element above isunnecessary for approval10
  11. 11. PhRMA’s Comments on FDA’sProposed “Stepwise” Approach• Evaluation of biosimilars to demonstrate the absence of clinicallymeaningful differences should include comparative molecularevaluations, preclinical studies and clinical testing• Seemingly small changes to a product’s structure or means ofproduction may have unintended clinical consequences• Such consequences may be very difficult to predict, particularly forproducts for which the sponsor lacks extensive manufacturingexperience• A science-based approach should include at least one comparativeclinical trial of adequate size and design to establish that theproposed biosimilar product does not possess clinically meaningfuldifferences in safety and efficacy from its reference product11
  12. 12. • Applicants should minimize controllable process anddesign differences and provide scientific justification forchanges to controllable elements of the proposedbiosimilar product• Intentionally introduced changes may lead to unintendedor unanticipated differences between a biosimilar and itsreference product, and diminish the feasibility of anabbreviated development program• Additional analytical, preclinical, and clinical studies maybe necessary to demonstrate that a proposed biosimilarproduct is highly similar to its reference productPhRMA’s Comments on MinimizingControllable Differences12
  13. 13. PhRMA’s Comments onAnalytical Testing• Multiple analytical procedures thatare sufficiently sensitive should beperformed to detect differencesbetween a proposed biosimilar andreference product• Even state-of-the-art technologymay not identify all differences• Understanding the limitations of theanalytical program will be essentialto design appropriate preclinical andclinical testing to evaluate remaininguncertainties 13
  14. 14. PhRMA’s Comments onPreclinical Testing• In vitro functional assays are important tothe evaluation of biologic activity and thedemonstration of biosimilarity• In vitro studies alone are insufficient toestablish that a proposed biosimilar doesnot possess clinically meaningful differencescompared to a reference product• Preclinical animal testing, based on soundscience and performed according to ICHguidelines, also plays an important role inbiosimilarity assessment14
  15. 15. PhRMA’s Comments onClinical TestingFDA guidance should recognize that:•Clinical testing is essential to determinethat there are no clinically meaningfuldifferences between a proposedbiosimilar product and its referenceproduct•Patient wellbeing should be ensured withimmunogenicity testing and at least onecomparative clinical trial to detect safetyor efficacy differences15
  16. 16. • Each indication for which a biosimilar applicant is seeking approval will needto be supported with clinical data, unless strong scientific justification forextrapolation is provided• Should be sufficiently rigorous to ensure that safety andefficacy can be predicted in an unstudied indication• Applicants seeking to extrapolate data acrosspopulations within an indication should study thepopulation(s) most sensitive to differences in safety,efficacy, and immune response• Important to demonstrate that there are no significantdifferences in PK and bio-distribution• Restricting extrapolation to indications that share the same, well-definedmechanism of action will help to ensure that the disease states are similarand well understoodPhRMA’s Comments onExtrapolation of Clinical DataApproval AApproval A Approval BApproval BIndication AIndication A Indication BIndication BClinical DataClinical Data16
  17. 17. PhRMA’s Comments onImmunogenicity Testing• Biologics have the potential to evoke an immuneresponse; even seemingly small changes to a referencebiologic may significantly alter immunogenicity• FDA should require that pre- and postmarket testing beperformed, including preclinical, clinical, andpostmarketing pharmacovigilance• Increased or decreased immunogenicity relative to areference product may have potentially severe clinicalconsequences• Extrapolation of data to support another indication shouldinclude immunogenicity assessments in the patientpopulation most sensitive to immune responses17
  18. 18. PhRMA’s Comments onProduct Labeling• Product labeling should include a clear statement to indicate whetherthe product is a biosimilar or if it is an interchangeable product• The labels of biosimilars that are not interchangeable should clearlyindicate that the products are not interchangeable with the referenceproduct• However, PhRMA believes that additional labelingis necessary for health professionals to makeinformed prescribing decisions, including:• A description of clinical data (type and quantity) thatsupports the biosimilars indications18
  19. 19. PhRMA’s Comments onPharmacovigilance• The pharmacovigilance plan for each approvedbiosimilar should be tailored to the benefit-risk profileof the biosimilar and the reference product• Postmarket studies and risk evaluation andmitigation strategy (REMS) programs may berequired as part of broader postmarket safetymonitoring• Undetected differences may emerge in thepostmarket period due to the abbreviated premarketprogram, data extrapolation, or product drift19
  20. 20. Naming of Biosimilar Products• Unique non-proprietary names are an essential feature of a robustsystem for adequately tracking adverse events• Biosimilars and their reference products should have unique namesregardless of possible later approval as an “interchangeable” product• Necessary to prevent inappropriate substitution of a non-interchangeableproduct if there are both biosimilar and interchangeable productsavailable for the same reference product20
  21. 21. Summary• A biosimilar is highly similar to, but not the same as, anFDA-licensed reference biologic product• A rigorous, science-based process for evaluating proposedbiosimilars and their reference products – which includes analytical,preclinical, and clinical testing – is essential to ensure the quality,safety, and efficacy of biosimilars• Unique non-proprietary names for biosimilar and interchangeablebiological products are essential to a robust pharmacovigilancesystem that adequately protects patient safety• The decision to take a particular biological medicine should be madewith the oversight and guidance of a physician• Patient well-being is the paramount concern• Incentive for continued innovation of biologics is critical to ensurepatient access to new medicines21

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