Development of Biosimilar Products: Determinants of Success

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After leaving FDA my focus has been on practicing QbD to deliver, in highly uncertain business environments, complex products and the necessary scientific evidence. This presentation comments on firm's ability to successfully develop and introduce into markets.

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Development of Biosimilar Products: Determinants of Success

  1. 1. BIOSIMILARS: ONTHEREALMOFREALITYDETERMINANTS OF SUCCESSAjaz S. Hussain, Ph.D.Chief Scientific Officer, Wockhardt Ltd.2013 AAPS National Biotechnology ConferenceBIOTEC Open Forum5/20/2013 1Ajaz S. Hussain, Ph.D.
  2. 2. This is my personal point of view5/20/2013 2B.Pharm.CSO VP BiopharmaceuticalsCSODeputy DirectorOffice of Pharmaceutical ScienceAssociate Professorof Pharmaceutics (tenured)Assistant Professorof PharmacyPh.D.InterdisciplinaryAjaz S. Hussain, Ph.D.
  3. 3. This presentation reflects my current interest• After leaving FDA my focus hasbeen on practicing QbD bycontributing to building• effective multidisciplinary teams,• business decision processes andtechnical infrastructure• To deliver, in highly uncertainbusiness environments, complexproducts and the necessaryscientific evidence• Sandoz• Biosimilars and complex generics(e.g., enoxaparin) – within aGerman/Swiss org. environment• Philip Morris International• Plant based vaccines and MRTP’s –QbD systems in a “non-pharma”sector (Swiss org. environment)• Wockhardt• Biosimilars and NCE’s – Indian org.environment5/20/2013 3Ajaz S. Hussain, Ph.D.
  4. 4. An information-theoretic definition: SimilaritySimilarity between Aand B may be measuredby the ratio betweenthe amount ofinformation needed tosate the commonality ofA and B and theinformation needed todescribe what A and BareA way to think about the challenges indeveloping, and communicating about,biosimilarsD. Lin (1998). http://webdocs.cs.ualberta.ca/~lindek/papers/sim.pdf5/20/2013 Ajaz S. Hussain, Ph.D. 4𝑆𝑆𝑆 𝐴, 𝐵 =𝐿𝐿𝐿 𝐼 (𝐶𝐶𝐶𝐶𝐶𝐶 𝐴, 𝐵)𝐿𝐿𝐿 𝐼 (𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝐴, 𝐵)
  5. 5. Success (forthispresentation)A firmsability tosuccessfullydevelopandintroduceintomarketsBiosimilarproductsperEMAregulatoryrequirementsSeveral approvalsand few failures(interferon, insulinand EPO)US FDAregulatoryrequirements351k evolving (note –Omnitrope® , genericenoxaparin & Tevagrastin®)Biosimilarity &Interchangeability5/20/2013 5Ajaz S. Hussain, Ph.D.
  6. 6. Quality of development and regulatorycommunicationDesignProduct &processSpecifications &controlsProduct useinformationUnderstandingAcceptablevariabilityCausal linksFailure modes &likelihoodContinuous –real timePeople,materials,machines andenvironmentMonitoring &control systemProcesscapabilityRecognizeknowledgePrior knowledge– similarproductsLink betweenquality, safety &efficacyIntended useLevel ofunderstandingExperimentalevidence indevelopmentreportsMaterialattributes criticalto qualityFailure modes &likelihoodRisk-basedQMS trackrecordAcceptablevariabilityProcesscapability6IndustryRegulators5/20/2013 Ajaz S. Hussain, Ph.D. 6
  7. 7. Common pitfalls and symptomsInadequate focus on TPP, QTPP (analytics) & market researchFunctional check-boxRush to clinicalCut-paste approach to clinical trials5/20/2013 7Ajaz S. Hussain, Ph.D.
  8. 8. Determinants of successPracticing‘quality bydesign’Design of products, manufacturing processes, clinical trials todeliver a ‘Target Product Profile’ExecutionexcellenceBusiness processes for developing the target products andevidence needed; and effectively communicating thescientific rigor achieved to diverse stakeholdersBreak-awayfrom pastpracticesCertain past business practices and processes often notcompatible with ‘Design Thinking’; unless actively addressedpose a risk to success5/20/2013 8Ajaz S. Hussain, Ph.D.
  9. 9. Practicing ‘quality by design’US FDAChampioned the needfor ‘quality by design’Introduced the notion of ‘designspace’Creatingeffectivebusinessprocessesrequiresovercomingseveral hurdlesInternal hurdles ‘typical generic mind-set’,‘functional divide’, optimisticbusiness projectionsExternal hurdles divergent understanding of‘quality by design’ withinregulatory agencies5/20/2013 9Ajaz S. Hussain, Ph.D.
  10. 10. US FDA QbD Efforts and in the background….5/20/2013 10AAPS Annual Meeting 2003Ajaz S. Hussain, Ph.D.
  11. 11. Closing remarks on Follow-on Proteins5/20/2013 11Ajaz S. Hussain, Ph.D.14-16 Feb 2005
  12. 12. Woodcock: ‘Paradigm Shift’ in Reviews5/20/201312“…companies intending tomarket Biosimilars mustcome to FDA with anextensive characterizationpackage, comparing theirswith the reference product.”“..the amount of clinicalevidence required by FDAwill be related to the amountand the quality of analyticaland functional informationthat is available on anybiosimilar product…”DIA/FDA Biosimilars Conference 12 September 20125/20/2013 Ajaz S. Hussain, Ph.D.
  13. 13. Hurdles in practicing ‘quality by design’RegulatorydifferencesIllustrativeexampleGeneric Vs.BiosimilarenoxaparinRole ofanalytics vs.‘blunt’ clinicalstudies?The ‘generic’way or the wayof newbiologicsFunctionaldivideLacking meansfor effectivereview andchallengePerformanceoften notlinked to KRA’s13• External • Internal5/20/2013 Ajaz S. Hussain, Ph.D. 13
  14. 14. Enoxaparin in EU 2007 and currently5/20/2013 Ajaz S. Hussain, Ph.D. 14Ajaz Hussain: 5th EGA Symposium on Biosimilars, London, 3-4 May 2007
  15. 15. Organizing for success• Inadequate focus onTPP, QTPP (analytics)& market research• Functional check-box• Cut-paste approachto clinical trials• Rush to clinicalCommonpitfallsandsymptomsEarly investment in analytics andunderstanding variability in RLDTPP & QTPP in the context of residualuncertaintyReview/challenge culture and decision‘gates’Design of clinical trials to addressscientific and clinical (market) uncertainty155/20/2013 Ajaz S. Hussain, Ph.D. 15
  16. 16. Often overlooked success factors‘PackageInsert’ &marketingmessages‘Interchange-able’designationAnalytics,mechanismsand clinicalindications ‘Qualityby Design’TargetProductProfileand QTPPAbility tomeasureandexplainMulti-functionalreviewandchallengeNota Thing,But a Way(MIT SloanManagementReview, July 2,2009)16• Transdiciplianry • Design Thinking5/20/2013 Ajaz S. Hussain, Ph.D. 16
  17. 17. Determinants of successPracticing‘quality bydesign’Design of products, manufacturing processes, clinical trials todeliver a ‘Target Product Profile’ExecutionexcellenceBusiness processes for developing the target products andthe evidence needed; and effectively communicating thescientific rigor achieved to diverse stakeholdersBreak-awayfrom pastpracticesCertain past business practices and processes often notcompatible with ‘Design Thinking’; unless actively addressedpose a risk to success5/20/2013 17Ajaz S. Hussain, Ph.D.
  18. 18. Implications for ‘global development’18EU to USor ROWto EU &US• Quality by Design* approach offers asignificant advantage• Minimize additional development costs(e.g., estimated to be additional $ 25-70 million)• Note that in the US; interchangeabilitydesignation expected to weigh heavilyon high (analytical) similarity5/20/2013 Ajaz S. Hussain, Ph.D.*Includes Clinical Quality by Design
  19. 19. Donald R. Stanski, global head of modeling andsimulation at Novartis, identified theopportunity to combine the modeling needs ofthe rich biological development pipelines atNovartis for innovative medicines and at theSandoz generics division for the development offollow-on biological drugs with the academicexpertise at UB.Ajaz Hussain, global head of biopharmaceuticaldevelopment at Sandoz, enthusiasticallysupports this collaboration because it will"greatly contribute to development of novelmethods for understanding mechanisms ofactions and for establishing comparability ofbiosimilar products."http://www.buffalo.edu/ubreporter/archives/vol39/vol39n2/articles/NovartisGift.htmlClinical QbD5/20/2013 19Ajaz S. Hussain, Ph.D.
  20. 20. 5/20/2013 Ajaz S. Hussain, Ph.D. 20http://www.sandoz-biosimilars.com/sandoz_biosimilars/development.shtml (accessed 5 March 2013)Quality by DesignClinical Trial DesignHigh degree of similarity &Commercial viability
  21. 21. ‘Biosimilar rituximab development a rocky road’Roche doesnot see athreat frombiosimilar(rituximab)until 2015Clinical trialdesignopportunityOne reason for the delay –clinical considerations;challenge of extrapolationacross indications“Sandoz and Boehringer are both alreadyrunning Phase III trials, placing themahead of Celltrion in the race, butSamsung and Teva both suspended theirPhase III programmes in October 2012within months of starting them” (FT, April2013)Bayesian hierarchicalmodeling (BHM) approach toclinical trial design. J ClinOncol 29: 2011“With a 35% reduction in sample size, theBHM approach enables borrowing acrossoncology and autoimmune indicationswith equal power and confidence.”http://www.ft.com/cms/s/2/dcad130c-a8fb-11e2-a096-00144feabdc0.html#axzz2TqDBcYlBhttp://www.biosimilarnews.com/roche-doesnt-see-a-threat-from-biosimilars-till-20155/20/2013 21Ajaz S. Hussain, Ph.D.
  22. 22. Next two presentations…..Global BiosimilarDevelopment in a"Shifting" RegulatoryEnvironmentMark McCamish, Ph.D., M.D.Sandoz International GmbHStrategies for GlobalClinical Developmentfor BiosimilarsPartha Roy, Ph.D.Parexel Consulting5/20/2013 Ajaz S. Hussain, Ph.D. 22

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