CNPR,NAPSR EXAM QUESTIONS AND ANS
b b b bb
WERS A+ GRADED
b b
DrugbDiscoveryb-
bANSWERb•bUnlikebsmallbmoleculebdrugsb(pharmaceuticals),blargebmolecule bdrugsb(bioph
armaceuticals)barebmainlybprotein-based
o Thesebprotein-
basedbdrugsbarebsimilarbtobnaturalbbiologicalbcompoundsbfoundbinbhumanbbodyborbt
hey'rebfragmentsbthatbmimicbactivebpartbofbnaturalbcompounds
DiscoverybofbPharmaceuticalsb-
bANSWER bstartsbw/bscanningbhundredsbofbcompounds,bwhetherbw/bactual bmaterialsb(irrati
onalbapproach)borbvirtualbsimulationsb(rationalbapproach)
• PharmaceuticalsbarebnewbchemicalbentitiesbNCEsbandbarebproducedbsynthesizedbin
manufacturingbplantsbusingbtechniquesbbasedbuponbchemicalbreactionsbofbreactants
DiscoverybofbBiopharmaceuticalsb-
bANSWERbresearchersbmustbstudybcompoundsbw/inbhumans
o Ex.bHormonesborbotherbbiologicalbresponsebmodifiersbandbtheirbeffectsbonbbiologicalb
processes
o Inbsomebinstances,binvestigatebpathogensbsuchbasbthebinfluenzabvirusborbbacteriabtob
obtainbvaccines
o Inbotherbcases,bresearchersbcopybthesebbiologicalbresponsebmodifiersbandbusebthembasb
replacementbtherapy
o Protein-
basedbdrugsbarebmanufacturedbinbbiologicalbsystems,bsuchbasblivingbcells,bproducingb
desiredbproteinbmoleculesbinblargebreactionbvesselsborbbybextractionbfrombanimalbser
um
o Becomingbincreasinglybimportant
• Morebpotentbandbspecific—
morebsimilarbtobproteinsbw/inbbodybthereforebmorebeffectivebinbtreatingbourbdiseases
AreasbofbBiopharmaceuticalsb-bANSWERb•bProphylactic→bpreventivebasbinbvaccines
,• Therapeutic→bantibodies
• Replacementbtherapy→bhormones,bgrowthbfactors
Biologicsb -b ANSWERb FDAb definitionb is:
o BiologicbproductbsubjectbtoblicensurebunderbPublicbHealthbServicebActbisbanybvirus,bt
herapeuticbserum,btoxin,bantitoxin,bvaccine,bblood,babbloodbcomponentborbderivative,ba
llergenicbproduce,borbanalogousbproduct,bapplicablebtobprevention,btreatmentborbcurebofb
diseasesborbinjuriesbtobhumans.bThesebinclude,bbutbarebnotblimitedbto,bbacterialbandbvir
albvaccines,bhumanbbloodbandbplasmabandbtheirbderivatives,bandbcertainbbiotechnolog
ybproductsbsuchbasbinterferonsbandberythropoietins.bManybbiologicsbarebprotein-
basedbmedicines,bandbtherebarebbloodbproductsbthatbmaybbebpreparedbfrombblood,bsu
chbasbclottingbfactors.
Vaccination-
bANSWERb•bThebprinciplebofbvaccinationbisbthatbthebadministrationbofbabsmallbamountbofbabv
accine,bthatbisbanbantigenbthatbhasbbeenbtreated,bstimulatesbourbimmunebsystembandbcau
sesbantibodiesbtobbebproducedbtobreactbagainstbthebforeignbantigen.b•bLaterbinblife,bifbwebar
ebexposedbagainbtobthebsamebantigen,bthenbourbimmunebsystembwillbelicitbabmemorybresp
onsebandballowbthebdefensebmechanismsbtobbebturnedbonbandbantibodiesbdevelopedbtobfi
ghtbthebinvadingbantigen.
• Containsbantigenicbcomponentsbthatbarebobtainedbfromborbderivedbfrombpathogen
o Includebmainlybviruses,bbacteria,bparasitesbandbfungi
o Researchbhasbshownbthatbpartbofbpathogenbthatbcausesbdiseaseb(virulence)bcanbbeb
decoupledbfrombprotectivebpartb(immunity)
• Developmentbfocusesbonbmeansbtobreducebvirulencebfactorbwhilebretainingbimmunity
stimulation
• Oralborbparenteral
VaccinebPreparationsb-
ANSWERbAttenuatedbVaccinesbKilledborbInactivatedb
b
Vaccines
Toxoids
AttenuatedbVaccinesb-
bANSWERb•bThebvirulence bofbthebpathogenbcanbbebreducedbinbseveralbways,bsuchbasb•bByb
chemicalbtreatment,bbybtemperaturebadaptationborbby
,growingbthebpathogenbinbabspecifiedbotherbthanbnaturalbhostb(passaging),badvantagesbare
• Lowbcostbpreparation,belicitbdesiredbimmunologicalbresponsebandbnormallybsinglebdoseb
isbsufficient.b•bDisadvantagesbareb•bAbpotentialbtobrevertbtobvirulencebandb•bLimitedbshelfbli
fe
KilledborbInactivatedbVaccinesb-
bANSWERb•bKillingborbinactivationbofbthebpathogenbisbusuallybdonebbybchemicalbandbtemp
eraturebtreatment.b•bTreatmentbwithbformaldehydebisbmostbcommon.b•bOtherbchemicalsbu
sedbarebphenolbandbacetone.b•bIrradiationbofbthebpathogenbisbanotherbmethodbtobrenderbit
binactive.b•bAdvantagesbarebthatbitbisbnonreversiblebintobvirulencebandbhavebrelativelybsta
blebshelfblife.
• Morebexpensivebtobproduce,bgreaterbcontrolbrequiredbinbproductionbtobassurebreliableb
processesbforbcompletebinactivation,bmaybneedbmultiplebboosterbvaccinationsbsincebtr
eatmentbprocessesbmaybresultbinbreducedbimmunologicalbresponse
Toxoidsb -b ANSWERb •b resultb fromb toxinsb producedb byb theb pathogen
• Advantagesbandbdisadvantagesbarebsimilarbtobkilled/inactivatedbvaccines.bAdvantagesb
ofbnon-
reversalbtobvirulencebandbrelativelybstable,bdisadvantagesbincludebhigherbcostbofbproduct
ionbandbmorebcontrolbisbrequiredbforbproductionbtobensurebprocessesbreliablebtobensureb
completebinactivation.bReducedbimmunologicalbresponsebpossiblebasbabresultbofbtreatm
entbprocessesbhencebmultiplebboosterbvaccinationsbmaybbebrequired.
NewbVaccinesb-
bANSWER b•bAdvancesbinbgenomics,bmolecularbbiologybandbrecombinantbtechnologybhasb
providedbnewbdirectionsbforbdiscovery,bdevelopmentbandbmanufacturebofbvaccines
• Currentbapproachbisbminimalistbstrategybtobdecouplebvirulencebandbimmunitybfunctions
• Aimbisbtobusebonlybimmunitybpartbtobconferbprotection,bsobvaccinebisbsafebtobbe
administered
• Approachbcanbbebdividedbintobsubunit,bvector-based,bDNAbandbpeptidebvaccines
SubunitbVaccinesb-
bANSWERb•bUsebonlybpartbofbbacteriaborbvirusbinsteadbofbentirebpathogenbPartbisbderivedbf
romboutsidebenvelopebproteinbofbpathogenbRequiresbknowledgebofbgenomebsequencebofb
pathogenbbybidentifyingbopenbreadingbframesb(ORF)bthatbpotentiallybencodebnovelbantige
nicbsurfacebproteinsbknownbasbepitopes,bwhichbbindbtobantibodiesbWhenbidentified,bORFsb
clonedbtobexpressbproteinbepitopesbusing
self-replicatingb plasmids
, ItbisbpossiblebtobstudybthebbindingbpropertiesbofbthebepitopebusingbtechniquesbsuchbasbEL
ISAborbFACS.bThebmostbpromisingbepitopebcandidatesbarebinjectedbintobanimalsbtobtestbforb
antibodybresponses.bobThosebthatbworkbarebaffinitybmaturedbandboptimizedbintobvaccine
bcandidates, bwithbthebpossibilitybofbfurtherbtestsbbeforebhumanbclinicalbtrials.bobAlsobwork
ingbonbmultiplebepitopebsubunitbvaccinesbtobprovidebdifferentbantigenicbbindingbsites
Vector-basedbVaccinesb-
bANSWER b•bThebvirusesbandbbacteriabarebdetoxifiedbtobbebusedbasbvehiclesbcarryingbvacci
nesb•bSubunitbvaccinesbarebsuppliedbbybcarrierbvehicle,bwhichbactsbtobinducebimmunebres
ponseb•bMorebthanbonebtypebofbenvelopebproteinsbcanbbebsuppliedbwithbthisbtechniqueb•bT
hisbtypebofbvector-basedbvaccinebisbbeingbstudiedbinbclinicalbtrials
DNAbVaccinesb-bANSWERb•bAlsobknownbasbnucleicbvaccinesborbgeneticbimmunization
• Hostbisbdirectlybinjectedbw/bselectedbviralbgenesbthatbarebengineeredbtobcontainbDNAbse
quencesbencodingbforbantigensb•bHostsbcellsbtakebupbthesebgenes,bexpressbantigensbpres
entedbtobimmunebcells,bandbstimulatebimmunebresponsebPeptidebVaccinesb-
bANSWERb•bChemicallybsynthesized.bTypicallyb8-
24baminobacidsbinblengthb•bGenerallybsmallb•bAlsobreferredbtobasbpeptidomimeticbvaccinesb
duebtobtheirbabilitybtobmimicbepitopes
• Thebpeptidebchainbcanbbebbuiltbintobcyclicbcomponents,bbranchedbchain,borbotherbconfi
gurationsbofbcomplexbstructures.b•bTheybhavebconformationbsimilarbtobepitopesbandbthusb
canbbebrecognizedbbybimmunebcells.b•bPotentialbepitopesbwerebsearchedbusingbinbsilicob
vaccinebdesignbapproach.b•b3Dbstructuresbsimilarbtobnativebepitopesbofbthebpathogenbisb
thebmostbcrucialbaspectbtobbebproducedbinbpeptidebvaccines.
Adjuvantb-bANSWERb•bVaccinesbformulatedbw/bcertainbsubstancesbtobenhancebimmune
response
• Latinbadjuvare→btobhelp
• Mostb commonb adjuvants b forb humansb areb aluminum b hydroxide, b aluminum b phosphateb and
calciumbphosphate
• Othersbincludebbacteriabandbcholesterol
• Mineralboilbemulsionsbnormallybadjuvantsbusedbinbanimalbstudies
• AdjuvantbknownbasbFreund'sbCompletebAdjuvantbconsistsbofbkilledbtuberclebbacillibin
water-in-mineralboilbemulsion
• Freund'sbIncompletebAdjuvantbisbwater-in-oilbemulsion
b b b bb
WERS A+ GRADED
b b
DrugbDiscoveryb-
bANSWERb•bUnlikebsmallbmoleculebdrugsb(pharmaceuticals),blargebmolecule bdrugsb(bioph
armaceuticals)barebmainlybprotein-based
o Thesebprotein-
basedbdrugsbarebsimilarbtobnaturalbbiologicalbcompoundsbfoundbinbhumanbbodyborbt
hey'rebfragmentsbthatbmimicbactivebpartbofbnaturalbcompounds
DiscoverybofbPharmaceuticalsb-
bANSWER bstartsbw/bscanningbhundredsbofbcompounds,bwhetherbw/bactual bmaterialsb(irrati
onalbapproach)borbvirtualbsimulationsb(rationalbapproach)
• PharmaceuticalsbarebnewbchemicalbentitiesbNCEsbandbarebproducedbsynthesizedbin
manufacturingbplantsbusingbtechniquesbbasedbuponbchemicalbreactionsbofbreactants
DiscoverybofbBiopharmaceuticalsb-
bANSWERbresearchersbmustbstudybcompoundsbw/inbhumans
o Ex.bHormonesborbotherbbiologicalbresponsebmodifiersbandbtheirbeffectsbonbbiologicalb
processes
o Inbsomebinstances,binvestigatebpathogensbsuchbasbthebinfluenzabvirusborbbacteriabtob
obtainbvaccines
o Inbotherbcases,bresearchersbcopybthesebbiologicalbresponsebmodifiersbandbusebthembasb
replacementbtherapy
o Protein-
basedbdrugsbarebmanufacturedbinbbiologicalbsystems,bsuchbasblivingbcells,bproducingb
desiredbproteinbmoleculesbinblargebreactionbvesselsborbbybextractionbfrombanimalbser
um
o Becomingbincreasinglybimportant
• Morebpotentbandbspecific—
morebsimilarbtobproteinsbw/inbbodybthereforebmorebeffectivebinbtreatingbourbdiseases
AreasbofbBiopharmaceuticalsb-bANSWERb•bProphylactic→bpreventivebasbinbvaccines
,• Therapeutic→bantibodies
• Replacementbtherapy→bhormones,bgrowthbfactors
Biologicsb -b ANSWERb FDAb definitionb is:
o BiologicbproductbsubjectbtoblicensurebunderbPublicbHealthbServicebActbisbanybvirus,bt
herapeuticbserum,btoxin,bantitoxin,bvaccine,bblood,babbloodbcomponentborbderivative,ba
llergenicbproduce,borbanalogousbproduct,bapplicablebtobprevention,btreatmentborbcurebofb
diseasesborbinjuriesbtobhumans.bThesebinclude,bbutbarebnotblimitedbto,bbacterialbandbvir
albvaccines,bhumanbbloodbandbplasmabandbtheirbderivatives,bandbcertainbbiotechnolog
ybproductsbsuchbasbinterferonsbandberythropoietins.bManybbiologicsbarebprotein-
basedbmedicines,bandbtherebarebbloodbproductsbthatbmaybbebpreparedbfrombblood,bsu
chbasbclottingbfactors.
Vaccination-
bANSWERb•bThebprinciplebofbvaccinationbisbthatbthebadministrationbofbabsmallbamountbofbabv
accine,bthatbisbanbantigenbthatbhasbbeenbtreated,bstimulatesbourbimmunebsystembandbcau
sesbantibodiesbtobbebproducedbtobreactbagainstbthebforeignbantigen.b•bLaterbinblife,bifbwebar
ebexposedbagainbtobthebsamebantigen,bthenbourbimmunebsystembwillbelicitbabmemorybresp
onsebandballowbthebdefensebmechanismsbtobbebturnedbonbandbantibodiesbdevelopedbtobfi
ghtbthebinvadingbantigen.
• Containsbantigenicbcomponentsbthatbarebobtainedbfromborbderivedbfrombpathogen
o Includebmainlybviruses,bbacteria,bparasitesbandbfungi
o Researchbhasbshownbthatbpartbofbpathogenbthatbcausesbdiseaseb(virulence)bcanbbeb
decoupledbfrombprotectivebpartb(immunity)
• Developmentbfocusesbonbmeansbtobreducebvirulencebfactorbwhilebretainingbimmunity
stimulation
• Oralborbparenteral
VaccinebPreparationsb-
ANSWERbAttenuatedbVaccinesbKilledborbInactivatedb
b
Vaccines
Toxoids
AttenuatedbVaccinesb-
bANSWERb•bThebvirulence bofbthebpathogenbcanbbebreducedbinbseveralbways,bsuchbasb•bByb
chemicalbtreatment,bbybtemperaturebadaptationborbby
,growingbthebpathogenbinbabspecifiedbotherbthanbnaturalbhostb(passaging),badvantagesbare
• Lowbcostbpreparation,belicitbdesiredbimmunologicalbresponsebandbnormallybsinglebdoseb
isbsufficient.b•bDisadvantagesbareb•bAbpotentialbtobrevertbtobvirulencebandb•bLimitedbshelfbli
fe
KilledborbInactivatedbVaccinesb-
bANSWERb•bKillingborbinactivationbofbthebpathogenbisbusuallybdonebbybchemicalbandbtemp
eraturebtreatment.b•bTreatmentbwithbformaldehydebisbmostbcommon.b•bOtherbchemicalsbu
sedbarebphenolbandbacetone.b•bIrradiationbofbthebpathogenbisbanotherbmethodbtobrenderbit
binactive.b•bAdvantagesbarebthatbitbisbnonreversiblebintobvirulencebandbhavebrelativelybsta
blebshelfblife.
• Morebexpensivebtobproduce,bgreaterbcontrolbrequiredbinbproductionbtobassurebreliableb
processesbforbcompletebinactivation,bmaybneedbmultiplebboosterbvaccinationsbsincebtr
eatmentbprocessesbmaybresultbinbreducedbimmunologicalbresponse
Toxoidsb -b ANSWERb •b resultb fromb toxinsb producedb byb theb pathogen
• Advantagesbandbdisadvantagesbarebsimilarbtobkilled/inactivatedbvaccines.bAdvantagesb
ofbnon-
reversalbtobvirulencebandbrelativelybstable,bdisadvantagesbincludebhigherbcostbofbproduct
ionbandbmorebcontrolbisbrequiredbforbproductionbtobensurebprocessesbreliablebtobensureb
completebinactivation.bReducedbimmunologicalbresponsebpossiblebasbabresultbofbtreatm
entbprocessesbhencebmultiplebboosterbvaccinationsbmaybbebrequired.
NewbVaccinesb-
bANSWER b•bAdvancesbinbgenomics,bmolecularbbiologybandbrecombinantbtechnologybhasb
providedbnewbdirectionsbforbdiscovery,bdevelopmentbandbmanufacturebofbvaccines
• Currentbapproachbisbminimalistbstrategybtobdecouplebvirulencebandbimmunitybfunctions
• Aimbisbtobusebonlybimmunitybpartbtobconferbprotection,bsobvaccinebisbsafebtobbe
administered
• Approachbcanbbebdividedbintobsubunit,bvector-based,bDNAbandbpeptidebvaccines
SubunitbVaccinesb-
bANSWERb•bUsebonlybpartbofbbacteriaborbvirusbinsteadbofbentirebpathogenbPartbisbderivedbf
romboutsidebenvelopebproteinbofbpathogenbRequiresbknowledgebofbgenomebsequencebofb
pathogenbbybidentifyingbopenbreadingbframesb(ORF)bthatbpotentiallybencodebnovelbantige
nicbsurfacebproteinsbknownbasbepitopes,bwhichbbindbtobantibodiesbWhenbidentified,bORFsb
clonedbtobexpressbproteinbepitopesbusing
self-replicatingb plasmids
, ItbisbpossiblebtobstudybthebbindingbpropertiesbofbthebepitopebusingbtechniquesbsuchbasbEL
ISAborbFACS.bThebmostbpromisingbepitopebcandidatesbarebinjectedbintobanimalsbtobtestbforb
antibodybresponses.bobThosebthatbworkbarebaffinitybmaturedbandboptimizedbintobvaccine
bcandidates, bwithbthebpossibilitybofbfurtherbtestsbbeforebhumanbclinicalbtrials.bobAlsobwork
ingbonbmultiplebepitopebsubunitbvaccinesbtobprovidebdifferentbantigenicbbindingbsites
Vector-basedbVaccinesb-
bANSWER b•bThebvirusesbandbbacteriabarebdetoxifiedbtobbebusedbasbvehiclesbcarryingbvacci
nesb•bSubunitbvaccinesbarebsuppliedbbybcarrierbvehicle,bwhichbactsbtobinducebimmunebres
ponseb•bMorebthanbonebtypebofbenvelopebproteinsbcanbbebsuppliedbwithbthisbtechniqueb•bT
hisbtypebofbvector-basedbvaccinebisbbeingbstudiedbinbclinicalbtrials
DNAbVaccinesb-bANSWERb•bAlsobknownbasbnucleicbvaccinesborbgeneticbimmunization
• Hostbisbdirectlybinjectedbw/bselectedbviralbgenesbthatbarebengineeredbtobcontainbDNAbse
quencesbencodingbforbantigensb•bHostsbcellsbtakebupbthesebgenes,bexpressbantigensbpres
entedbtobimmunebcells,bandbstimulatebimmunebresponsebPeptidebVaccinesb-
bANSWERb•bChemicallybsynthesized.bTypicallyb8-
24baminobacidsbinblengthb•bGenerallybsmallb•bAlsobreferredbtobasbpeptidomimeticbvaccinesb
duebtobtheirbabilitybtobmimicbepitopes
• Thebpeptidebchainbcanbbebbuiltbintobcyclicbcomponents,bbranchedbchain,borbotherbconfi
gurationsbofbcomplexbstructures.b•bTheybhavebconformationbsimilarbtobepitopesbandbthusb
canbbebrecognizedbbybimmunebcells.b•bPotentialbepitopesbwerebsearchedbusingbinbsilicob
vaccinebdesignbapproach.b•b3Dbstructuresbsimilarbtobnativebepitopesbofbthebpathogenbisb
thebmostbcrucialbaspectbtobbebproducedbinbpeptidebvaccines.
Adjuvantb-bANSWERb•bVaccinesbformulatedbw/bcertainbsubstancesbtobenhancebimmune
response
• Latinbadjuvare→btobhelp
• Mostb commonb adjuvants b forb humansb areb aluminum b hydroxide, b aluminum b phosphateb and
calciumbphosphate
• Othersbincludebbacteriabandbcholesterol
• Mineralboilbemulsionsbnormallybadjuvantsbusedbinbanimalbstudies
• AdjuvantbknownbasbFreund'sbCompletebAdjuvantbconsistsbofbkilledbtuberclebbacillibin
water-in-mineralboilbemulsion
• Freund'sbIncompletebAdjuvantbisbwater-in-oilbemulsion
