33. Biosimilar.ppt

Biosimilars and regulations

1. © Ramaiah University of Applied Sciences
1
Faculty of Pharmacy
Course Code: MPL104T
Lecture No. 33
Biosimilar

2. © Ramaiah University of Applied Sciences
2
Faculty of Pharmacy
Content
•Biosimilars
•Regulatoryconcernsregardingbiosimilardevelopment

3. © Ramaiah University of Applied Sciences
3
Faculty of Pharmacy
Lecture objectives
Bytheendofthislecture,studentswillbeableto:
•Describewhatisbiosimilars
•Discusssomeregulatoryconcernsregardingbiosimilar
development
•Somebiosimilarscurrentlyonthemarket

4. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Biologics Are Complex
•Biologicsareinnovativemedicationsthataren’tmade,theyaregrownin
livingcells
•Biologicsarecomplexmolecules–upto1,000timeslargerthan
conventionalmedicine
•Manufacturingabiologicisacomplexprocessthattakesseveralmonths
fromstarttofinish
•It’simportanttorememberthatbiologicmedicinescanneverbeexactly
duplicatedbytwodifferentmanufacturersinthewaythatsimpler
medicationscan

5. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Biologics Have Revolutionized Healthcare
•Althoughrelativelynew,biologicsarealreadyusedbymorethan350
millionpatientsworldwide
•Biologicmedicinesrevolutionizedhowdiseasesandconditionssuch
asrheumatoidarthritis,Crohn’sdisease,hemophilia,multiple
sclerosis,andmanyotherdisordersaretreated
•Patternedafterproteinsthebodyitselfproduces,biologicscantreat
manyseriousdiseasesinwaysconventionalmedicinescannot

6. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Biosimilars
•Biosimilarsareproductsthatare“highlysimilar”to(butnotexactcopiesof)
thereferencebiologicproduct
•AsapartoftheAffordableCareAct(ACA),CongressprovidedtheFood&
DrugAdministration(FDA)authoritytoreviewandapprovebiosimilar
versionsofFDAapprovedbiologicmedicines.TheFDAisintheprocessof
developingguidelinestoapprovebiosimilars
•Whilethereareasmallnumberofbiosimilarsapprovedinseveralother
countries,therearecurrentlynoneapprovedforuseintheUnitedStates
•TheFDAreceiveditsfirstapplicationforapprovalofabiosimilarinJuly2014

7. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
What Biosimilars Are…And Are Not
•Asthenamesuggests,biosimilarsaresimilartoaparticularbiologic,
theyarenotthesame
•Allbiosimilarsdifferfromtheinnovativeproductandfromeach
other
•Theyarenotgenericbiologics

8. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Why There Can Be No “Generic Biologics”
•Theactiveingredientofabiosimilarcan,atbest,onlyresemblethat
oftheoriginalbiologic
•Howaninnovatorcompanymakesitsbiologiccanneverbe
duplicateddowntothelastdetail;abiosimilarismadeusingdifferent
cellsanddifferentprocesses

9. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Ensuring Safety And Effectiveness
•Thevariationsbetweenaninnovatorbiologicandabiosimilarcould
potentiallytriggeranattackagainstabiosimilarbythebody’s
defenses
–Thiscouldcauseunwantedand/orunsafesymptomsorrenderthe
biosimilar,andpossiblytheoriginalbiologic,lesseffective
•Toensurecomparablesafetyandeffectiveness,biosimilarsrequire
morethoroughtestingthangenericmedicines

10. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Access to Biologics and Patient Welfare
•Itisimportanttoprovideaccesstobiologictreatmentsforpatients
whoneedthem,andbiosimilarsplayapartinmeetingthisgoal
•Anequallyandperhapsmoreimportantconsiderationistoensure
patientsafetyandwelfareinallstagesofdevelopment,approval,and
monitoringofbiologics,includingbiosimilars

11. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Important Issues for Patients
Asfederalagenciesandthestatesimplementthenewbiosimilarslaw,
theyaremakingimportantdecisionsabouttheregulationofbiosimilars
thatarecrucialtoassuringpatientsafety.
•Interchangeability:Thisyear,theFDAwillbedecidewhatstandards
mustbemetforabiosimilarmedicinetobejudged
“interchangeable”withtheoriginalbiologicmedicine.Strict
standardsareneededtoensurepatientsafety

12. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Important Issues for Patients
•RigorousTestingForEachCondition:TheFDAwillbedeterminingwhetherdrug
companiesmustconductrigorousclinicaltestingtoprovethatabiosimilarworks
safelyineachdistinctgroupofpatientswiththatdisease.Failuretoperform
adequatetestingineachgroupofpatientsanddiseasetypemayputpatientsat
risk
•Naming:Usingadistinguishablebutrelatednon-proprietarynameforbiosimilar
medications(i.e.,distinguishablefromtheoriginalbiologic)wouldenablemedical
professionalsandtheFDAtobettertracktheseproductsandmoreeasilyaccess
anyadversereactionsthatmayoccurinpatientswhousebiologics,including
biosimilars

13. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Important Issues for Patients, (Continued)
Asfederalagenciesandthestatesimplementthenewbiosimilarslaw,theyaremaking
importantdecisionsabouttheregulationofbiosimilarsthatarecrucialtoassuring
patientsafety.
•FDATransparency:Improvedtransparencythroughouttheapplicationand
approvalprocessofbiosimilarsisimportanttoassureappropriateoversightandto
ensurethatallvoices,particularlythoseofpatients,areheard.
•Substitution/Notification:Becauseevenaninterchangeablebiosimilarwillnotbe
identicaltotheoriginalbiologicmedicine,mostdoctorandpatientgroupsfeelitis
importantforaprescribingdoctortobenotifiedafterapharmacistsubstitutesa
biosimilarforaprescribedbiologicmedicine.Abiosimilarthatisnot
interchangeableshouldonlybeusedifprescribedbyanappropriatehealth
professional.
•Recordkeeping:Ensuringpharmacistsmaintainrecordsofsubstitutionsfor
significantperiodsoftimewouldallowthemedicalcommunitytotracklong-term
treatmentoutcomesofbiosimilars.

14. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
What United Spinal Association Has Said About
Biosimilars
•“TheFDAisexpectedtopublishproposedguidanceforpubliccommentthisyear
relatedtokeyaspectsofimplementationofthebiosimilarslaw.WeneedCongress
toholdoversighthearingsonthisimportantprocessandweurgetheFDAto
releaseguidanceassoonaspossiblethatensurepatientsafety,patientaccessto
therightbiologicmedicines,patientchoiceandfulltransparency”
•“Choiceshouldbeatthecenterofanydecisiontosubstituteorswitchtherapies
andshouldonlybedecidedbythepatientandprovider.Patientchoiceneedstobe
preservedandregulatorydecisionsmustbebasedonsoundscience”
•“Biosimilarregulationsmustputpatientsafetyfirst.Policymakersandregulators
mustaddressappropriatepatientsafetyandefficacyconcernsastheyrelateto
decisionsaroundinterchangeability,clinicalindications,labeling,namingand
substitution”
–Particularattentionmustbegiventoassurethatrigorousclinicaltestingproves
thatabiosimilarworkssafelyineachandeveryconditionordiseaseforwhich
itisapprovedtobeprescribed,aswellasineachdistinctgroupofpatientswith
thatdisease

15. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Biosmilars
•AreBiosimilarsGenericVersionsOfBiologicMedications?
•WhatIsABiologicMedication?
•“Anyvirus,therapeuticserum,toxin,antitoxin,oranalogousproduct
applicabletotheprevention,treatment,orcureofdiseasesor
injuries”
•Hormones(insulin,growthhormone)
•BloodandBloodProducts
•Vaccines
•Interleukins
•Antibodies(bevacizumab,trastuzumab)

16. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
WhatisABiosimilar?
•Abiologicproductthatis“highlysimilar”orinterchangeablewithabiologic
product
•EstablishedinUSbytheBiologicsPriceCompetitionandInnovationActof
2009
•Noclinicallymeaningfuldifferencesintermsofsafety,purityandpotency
•Availableinsamedosagestrengthandform
•ManufacturedaccordingtocurrentGoodManufacturingPractice(cGMP)
regulations,
•Synonyms:follow-onbiologic,follow-onprotein,generic
biopharmaceutical,biogeneric,comparablebiologic,subsequent-entry
biologic

17. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
WhyDoWeCareAboutBiosimilars?
•Biologicmedications:
-Verycommonlyused
-Veryexpensive
-Useisrapidlyincreasing:Nearly200biologicandrecombinant
biotechnologymedicineshelping800millionpatientsworldwide-
Patentsareexpiring
•Pharmacistswillplayakeyroleinfutureutilization

18. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
WhatBiosimilarsAreAlreadyOnTheMarket?
•USA:Filgrastim-sdz(Zarxio)
Recentlyrejectedseveralproducts
•EU:InsulinGlargine(Abasaglar)-Epoetinalfa(Abseamed,Binocrit,
EpoetinalfaHexal)-EpoetinZeta(Retacrit,Silapo)-Etanercept
(Benepali)-Filgrastim(Accofil,Biofrastim,FilgrastimHexal,Filgrastim
Ratiopharm,Grastofil,Nivestim,Ratiograstim,Tevagrastim,Zarzio)-
Follitropinalfa(Bemfola,Ovaleap)-Infliximab(Inflectra,Remsima)-
Somatotropin(Omnitrope,Valtropin)

19. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
•Biologicalmedicinesaremedicinesthataremadebyor
derivedfromabiologicalsource,suchasabacterium,yeastor
blood.Theycanconsistofrelativelysimplemolecules,suchas
humaninsulinorerythropoietin,orcomplexmoleculessuch
asmonoclonalantibodies

20. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
•Abiosimilarmedicineisabiologicalmedicinethatissimilarto
anotherbiologicalmedicinewhichhasalreadybeengranted
marketingauthorisation.Thestandardapproachtolicensingofa
genericmedicine,wherethemedicinemustdemonstrate
bioequivalence(thatisthebioavailabilityofthegenericmedicine
mustnotdiffersignificantlywhengivenatthesamedosageunder
similarconditions),isnotsufficientforbiosimilarmedicines.For
licensingintheEuropeanUnion,themanufacturerofthebiosimilar
medicinemustdemonstratethatthemedicineis:
•similartotheoriginalreferenceproductanddoesnothaveany
meaningfuldifferencesfromtheoriginalreferenceproductinterms
ofquality,safetyorefficacy

21. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
This contains prescribing principles to:
–promote the safe introduction of biosimilar medicines
–promote prescriber confidence
–encourage a consistent approach across NHSScotland
–support National Procurement
–support the review of the Scottish Medicines
Consortium policy on biosimilar medicines, and
–recognise the potential savings that can be achievable
within NHSScotland by the use of biosimilar
medicines.

22. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
•Theprescribingframeworkispresentedintheformatofaseriesof
frequentlyaskedquestions,withadditionalsupportivedetail
•TheseFAQsaresummarisedinthenextfewslides
•Forfullinformationpleaserefertotheprescribingframework
document
•HealthcareImprovementScotlandfacilitatedcollaborationbetween
ADTCsandanexpertadvisorygrouptodeveloptheframework.
–A series of meetings were held and consultation with ADTCs
–Advisory group members were drawn from relevant specialist
clinical areas across NHS Scotland

23. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Q:Shouldbiosimilarmedicinesbeused?
A:Useofbiosimilarmedicinesagrees,theyshouldbeconsideredasa
treatmentoptionforappropriatepatientsforwhomabiological
medicineisbeingconsideredaspartoftheirtreatmentpathway

24. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Q:Canpatientsestablishedonabiologicalmedicinebe
switchedtoanotherbiologicalmedicine,forexamplea
biosimilar?
A:Individualpatientsmaybeswitchedtoanotherbiological
medicine,includingabiosimilarmedicine,aspartofaclinician-
ledmanagementprogrammewhichhasappropriatemonitoring
inplace

25. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Q:Aredifferentapproachestotheuseofbiosimilarmedicines
requiredindifferentclinicalspecialties?
A:Therearedifferingclinicalcharacteristicswithinspecialties
whichmaybeimportanttoconsiderwhenusingbiosimilar
medicines
Whilepracticeisevolving,somespecialtiesmayconsiderthat
itismostappropriatetousebiosimilarmedicinesinnew
patients

26. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Q:Arethereanyspecificefficacyorsafetyconcernsassociatedwith
theuseofbiosimilarmedicines?
A:Therearenospecificefficacyorsafetyconcernsidentifiedfor
biosimilarmedicinesbut,asforallbiologicalmedicines,clinical
experiencewithbiosimilarmedicinesisstillemergingtoguidetheir
use
Asforallnewmedicines,adversedrugreactionstobiosimilar
medicinesshouldbereportedthroughtheYellowCardScheme

27. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Q:Howshouldbiologicalmedicines,includingbiosimilar
medicines,bemonitored?
A:Clinicaloutcomesforindividualpatientsonanybiological
medicineshouldbemeasuredusingestablishedrecognised
systemsformonitoringdiseaseactivityandresponseto
treatment
Clinicalregistriesarebeingestablishedforanumberof
biologicalmedicines.Itwouldbeappropriatetoexplorethe
expansionofthesedatabasestocapturedetailsofbiosimilar
medicines

28. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Q:Howshouldbiologicalandbiosimilarmedicinesbe
prescribedandproductdetailsrecorded?
A:Biologicalmedicines,includingbiosimilarmedicines,should
beprescribedbybothgenericandbrandnameandthe
brandnameandbatchnumbershouldberecordedonthe
patient’sprescription,caserecordorotherappropriate
clinicalsystem

29. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Q:Whatinformationshouldbeprovidedtopatients?
A:Themanufacturer’spatientinformationleafletshouldbe
suppliedtoallpatientsreceivinganymedicine,includinga
biosimilarmedicine

30. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Areas of Concern
•PrescriberConfidence
•Interchangability/Substitution
•Immunogenicity
•Pharmacovigilence
•Naming
•Education

31. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Prescriber Confidence
•Aswithanythingnew,muchwestilldonotknow
-Provider’sultimatelywanttoDoNoHarm
-WhatMedicationisptactuallyreceiving?
-Ifasubstitutionoccurs,when,bywhom,towhat,
consistentlyorinconsistently?
-Aretheyreallythesame?
-Whoisgoingtohaveoversightandmonitorforissues?

32. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Interchangability/Substitution
•Donotrushbiosimilars,don’tundermineacceptance-
“DispenseAsWritten”-Moredataandslowintroductioninto
clinicalpracticewillallowmonitoring
•Aboveall:GOODCOMMUNICATIONbetweenProvider,
Patient,andPharmacy

33. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Immunogenicity
•Allbiologicshavepotentialtocontributetoanimmune
response
-Variousproductandpatientrelatedfactors
-Product:structural,processing,formulation,storage,
handling,presenceofimpurities
-Patient:geneticbackground,immunestatus,routeof
administration
•Adverseeventsuniquetobiosimilarsmaybefounddueto
slightdifferences-Reactionscantakeuptoseveralmonthsto
manifest

34. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Pharmacovigilence
•Potentialforimmunogenicitywhenswitchingbetween
innovatorandbiosimilarproducts
•Dataonswitchingisimportant
•Post-marketingpharmacovigilienceisneededtodetectand
assess
•Rarebutseriouseventsunlikelytobedetectedpriorto
marketing

35. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Naming
•ImportanceofsortingoutNaming:
•>30biosimilarstostimulateredbloodcellproduction
stimulatingagentsonmarketinThailand
•One(ormore)causedadeadlyconditionknownasPureRed
CellAplasia(PRCA)
•SinceallsharethesameINN,difficulttodeterminewhich
productscontributedtothisissue

36. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Education For Pharmacists
•Substitutingproductsatthedispensinglevel
•DevelopingP&Tpoliciesregardinguse
•Understandingcost/coverage
•Inputonlawsandregulationsregardinguse
•Educatingotherhealthcareproviders
•Educatingpatients
•Ongoingsurveillance/pharmacovigilance

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Faculty of Pharmacy
•What are biosimilar drugs?

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Faculty of Pharmacy
Biologics vs. Small Molecule Drugs
Mellstedt H. EJC Supplements2013;11:1-11.

39. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Small Molecule Synthesis: Aspirin

40. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Manufacturing of Small Molecules
1.Chemical process based on a series of
controlled and predictable chemical
reactions
2.Process is standardized between
manufacturers
3.Final structure easily verified
4.Contaminants are quantifiable

41. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Biologic Categories
•Monoclonal antibodies
•Complex sugars
•Blood derivatives
•Vaccines
•Recombinant or purified proteins
–Cytokines
–Thrombolytic agents
–Enzymes

42. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Biosimilar Manufacturing
•Several major steps included in development
–Modifying the selected gene of interest
–Inserting the desired gene into a specific host cell
–Replicating cell line and increased protein
expression
–Harvesting protein products from the cell
–Purifying the selected protein
•More patents on the process than on the drug

43. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Biosimilar Manufacturing
http://www.pharmqd.comAccessed 2014 Oct 16.

44. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Similarities and Differences
“Similar” vs. Reference Product
BIOSIMILARSpecification Comparisonwith REFERENCE
Formulation May be different
Delivery device/container May be different
Routes of administration Licensure depends on application
Conditionsof use Licensure includes all indications for
reference product (recent precedent)
Strength Must be the same
Specific potentialmoleculardifferencesAmino acid substitution
N-and C-terminal modifications
Mismatched disulfide bonds
Post-translation modifications folding
Carboxylation
Formylation
Glycosylation
Methylation
Phosphorylation
PEGylation
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm259809.htm

45. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Are biosimilar drug issues new ?
Which, if any, are relevant to current discussion?
•Human Growth Hormone
–First to be substituted
•Human Insulin
–Many choices, little hesitation to interchange
•Interferon Alpha 2a, 2b, Beta, Gamma
–Payer directed formulary equivalence / interchange
•Influenza Vaccine
–Multiple manufacturers; you provide what you can get
•Heparin
–Harvested, purified, equivalence by batch
•Low molecular weight heparin (LMWH)
–Significant dosing issues when interchanged
•Anti-infectives
–Therapeutic Class representative for sensitivity tests
•CMS considered erythropoietin and darbepoetin “Functional Equivalents”

46. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
FDA Approval Pathways
†
FDCA = Federal Food Drug and Cosmetic Act
¥
PHSA = Public Health Service Act
Drugs
•Small-molecules
•Approved via FDCA
Biologics
•Approved via PHSA
¥
New Drug
Application
(NDA)
505(b)(1)
Safety and Efficacy
must be
demonstrated
Abbreviated New
Drug Application
(ANDA)
505(b)(2)
Bioequivalence
must be
demonstrated
Biologics License
Application
(BLA)
351(a)
Safety and Efficacy
must be
demonstrated
Biosimilar Biologics
License Application
351(k)
Must demonstrate
that it is highly similar
to 351(a) reference
Interchangeable
biosimilars require
more data

47. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Many types of biologic products
Referenceor
Originator
Biosimilar Interchangeable
Biosimilar
New biologic
approved via
BLA
Depthof data
submitted to the
FDA
“Standard” data
package
Abbreviateddata
package
Abbreviated data
package, more
information on
efficacy and safety
“Standard” data
package; efficacy
and safety on its
own merit
Compared to
reference?
N/A Yes Yes NotRequired
Current example
in USA
Filgrastim
Neupogen®
Filgrastim-sndz
Zarxio®
Not Yet Tbo-filgrastim
Granix®

48. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Guideline on Similar Biological Medicinal Products (Oct 05)
Guideline on Similar Biological Medicinal Products
Containing Biotechnology-Derived Proteins as Active
Substance: Quality Issues (June 06)
Overarching
Quality
Annexes
Epoetin
July 2006
G-CSF
June 2006
Insulin
June 2006
HGH
June 2006
General
Applicable
to all
Biosimilars
Specific:
Product data
requirements
Guideline on Similar Biological Medicinal Products
Containing Biotechnology-Derived Proteins as Active
Substance: Nonclinical & Clinical Issues (June 06)
Nonclinical
& Clinical
Heparin LMWH &
Others Draft
13 biosimilar marketing authorizations have been granted
EMA Model: Biosimilars Regulations
www.ema.europa.eu
EMA=European Medicines Agency

49. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Biosimilar Pharmacovigilance:
Role of the Pharmacist
•Monitor and report
–Adverse events: FDA MedWatch
–Medication errors
•Correct assessment of safety event
–What was ordered vs. what patient received ?
•Maintenance of EMR
•Bar code administration
•Medication reconciliation for all providers
•Consider transitions of care

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Faculty of Pharmacy
Does coding help differentiate ?
•NDC and HCPCS codes can support differentiation
•Billing claims data can be a useful in pharmacovigilance
–Outcomes
–Adverse Events
•Problems with using billing data
–NDA: Leuprolide Acetate (depot formulations)
•Lupron Depot: intramuscular injection
•Eligard: subcutaneous injection
•2013 HCPCS code:
•J1950: Injection, leuprolide acetate (for depot suspension), per 3.75 mg
–BLA: Epoetin alfa
•Procrit® and Epogen®
•2013 HCPCS codes:
•J0885: Injection, epoetin alfa, (for non-ESRD use), 1000 units
•J0886: Injection, epoetin alfa, 1000 units (for ESRD on dialysis)

51. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Biosimilar Pharmacovigilance
ZuñigaL, CalvoB. PharmacoepidemiolDrug Saf. 2010 Jul;19:661-9.
Felix T, et al. Nat Biotechnol. 2014 ;32:128-30.
CasadevallN, et al. Expert Opin Biol Ther. 2013;13:1039-47.
Pharmacovigilance
•Define monitoring parameters
•Easy reporting methods
•Real-time data
•Ensure traceability
Risk minimization
•Healthcare provider feedback and
communication
•Recalls and alerts
•REMS?
Constant Monitoring to Identify and Characterize Safety
Risk
•Naming standards
•Integration into electronic medical
record (EMR)
•Drug codes: HCPCS, NDC, etc.
•Prospective registries

52. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
AGENDA
•What are biosimilar drugs?
•Regulatory issues
•Safety concerns and Pharmacovigilence
•Indications for use
•Financial implications
•Summary / Key Points

53. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Interchangeability Definition
•Interchangeability definition
–“Biosimilar to the U.S.-licensed reference biological product …
expected to produce the same clinical resultas the reference
product in any given patient.”
–“For a biological product that is administered more than once to an
individual, the risk in terms of safetyor diminished efficacy of
alternating or switching between use of the biological product and
the reference product will not be greater than the risk of using the
reference product without such alternation or switch”
PHS Act, section 351(k)(4). http://www.fda.gov/downloads/drugs/
guidancecomplianceregulatoryinformation/ucm216146.pdf. Accessed 2014 Nov 13.

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Faculty of Pharmacy
•Biological products approved by FDA and dates of
approval
•Approval pathway: e.g., 351(a), 351(k)
•Lists if a biosimilar is interchangeable
•Defines exclusivity period
FDA “Purple Book”
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalAppl
ications/TherapeuticBiologicApplications/Biosimilars/ucm411418.htm. Accessed 2014 Oct 16.

55. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
“Documented” Practice Standards
Decision Domains Supporting Use
Restricted Formularies
and Clinical Pathways
Evidence
Rated
Compendia
Reference
biologic
labeled
indication
Biosimilar
labeled
indications

56. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Are Indications Interchangeable ?
•Provider Formulary and P&T committee
–Is the “risk” of unknown worth the “benefit”
–Ability to monitor and report (pharmacovigilance)
–Multiple providers (especially oral chemo)
–What evidence will they require to support interchange
•Payers
–How will payers make their coverage determinations?
–Compendia therapeutic class representatives

57. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Generics vs Biosimilars

58. © Ramaiah University of Applied Sciences
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Faculty of Pharmacy
Summary
•Biologicsareinnovativemedicationsthataren’tmade,theyare
growninlivingcells
•Biosimilarisabiologicproductthatis“highlysimilar”or
interchangeablewithabiologicproduct
•Allbiologicshavepotentialtocontributetoanimmuneresponse
•Potentialforimmunogenicitywhenswitchingbetweeninnovator
andbiosimilarproducts