Agriculture Reference
In-Depth Information
The. binding. capacity. of. this. membrane. is. much. higher. than. that. of. the. equivalent.
anion-exchange.resins..One.of.the.attractive.features.of.membranes.is.that.they.espe-
cially.have.higher.binding.capacity.for.large-size.impurities,.which.are.abundant.in.
feed.streams.and.a.major.cause.for.column.clotting.
225
.Since.plant.feed.streams.have.
unusually. abundant. high-molecular-weight. impurities,. membrane. separation. may.
provide. a. promising. noncolumn. chromatographic. solution. for. problems. associated.
with.large.chromatographic.columns,.such.as.low.low.rate.and.expensive.operations.
in. column. packing,. cleaning,.and.validation..In.fact,.preliminary.tests. have. shown.
that. this. technique. can. be. successfully. applied. in. purifying. PMPs.. For. example,.
separations. with.a.combination.of.cation-exchange.and.protein.A.membranes.have.
successfully.puriied.a.tobacco-derived.antipseudomonas.human.mAb.(06ad).
226
.The.
high. binding. capacity. and. scalability. of. this. technique. make. it. highly. suitable. for.
very.large-scale.manufacturing.operations..Many.speculated.that.membrane.separa-
tion. is. likely. to. be. the. irst. nonchromatographic. method. used. in. production-scale.
processing.of.biopharmaceuticals.
164
Regardless.of.the.puriication.method.used.or.the.nature.of.a.speciic.target.pro-
tein,.the.overall.extraction.and.puriication.design.has.to.be.robust,.scalable,.cost-
effective,.and.compliant.to.cGMP.regulations..An.ideal.puriication.scheme.should.
have.no.more.than.three.processing.steps.in.order.to.achieve.high.product.purify.while.
maintaining.a.practical.recovery.rate..In.addition,.the.PMP.puriication.and.manu-
facturing.process.must.be.governed.by.an.independent.quality.management.system.
(QMS). similar. to. regulations. used. by. other. expression. systems.
227,228
. Accordingly,.
materials.and.processes.widely.accepted.by.the.pharmaceutical.industry.should.be.
considered.irst.during.process-development.to.minimize.future.regulatory.expendi-
ture..Furthermore,.in.spite.of.the.lack.of.animal.viruses.and.other.infectious.agents.
in.plants,.it.must.be.validated.that.the.puriication.process.is.adequate.in.removing.
endotoxin,. phenolics,. and. alkaloids. as. well. as. potential. herbicide. and. insecticide.
contaminations.from.the.inal.product.
PLANT SPECIES USED FOR PMP PRODUCTION
A.diversity.of.plant.species.and.expression.systems.has.been.used.to.express.phar-
maceutical.proteins..The.choice.of.a.system.for.a.particular.transgenic.protein.pro-
duction.depends.not.only.on.speciic.biological.properties.of.the.target.protein/host.
plant. species. but. also. on. economical,. regulatory,. and. social. factors.. The. optimal.
plant.expression.system.for.a.target.pharmaceutical.protein.must.have.(1).one.or.more.
expression.cassettes.with.genetic.elements.that.can.drive.the.high-level.expression.of.
the.transgene,. (2).the.ability.to.target.the. transgenic.protein.to.a.cellular.compart-
ment.where.it.is.stable,.and.(3).technologies.to.isolate.and.purify.the.target.protein.
from.host.plants..The.optimal.plant.species.coupled.to.the.optimal.expression.system.
must.also.(1).produce.high-yield.biomass,.(2).have.facile.scalability,.(3).have.sufi-
cient.biomass.stability.during.the.required.storage.period,.and.(4).have.a.reasonable.
land. and. labor. requirement. for. plant. growth. and. harvesting.. Other. economic. fac-
tors.may.include,.for.example,.the.value.of.the.protein.product,.which. will.dictate.
the. affordability. of. investment. in. new. equipment. and. labor. as. well. as. in. convert-
ing. existing. farming. and. food. processing. infrastructure. for. molecular. pharming..
Search WWH ::
Custom Search