Automating mosquito microdissection for a malaria PfSPZ vaccine

ABSTRACTThe global death toll from Malaria is estimated to be upwards ofpeople each yearwith more thanchildren succumbing every dayPlasmodium falciparumPfSporozoiteSPZbased vaccines are the only intervention in humansproven to induce robusthigh levelandgtand long lastingat leastmonthsprotective efficacy against malariaforming the basis of Sanaria s unique technology platform of asepticpurifiedcryopreserved live Plasmodium falciparum SporozoitesPfSPZAmong its productsPfSPZ Vaccine contains live PfSPZ attenuated by radiationPfSPZ GAis attenuated geneticallyand PfSPZ CVac comprises of infectious parasites that are arrested at the blood stage by co administration of chemoprophylactic drugs like chloroquineTo dateprotective efficacy against controlled human malaria infectionCHMIhas been achieved in five clinical trials in the United StatesTanzaniaMaliand Germany in individuals vaccinated with PfSPZ Vaccine or PfSPZ CVacand efficacy against intense natural transmission of malaria has been established in MaliDriven by the stellar clinical safety and efficacy resultsand backed by an uncommon consortium of international investigators from andgtresearch groups incountriesSanaria plans to receive approval for a Biologics License ApplicationBLAby the beginning offor travelers and byfor all age groups and for mass vaccination programs intended to eliminate Pf malaria from geographically defined regionsSanaria received Fast Track Designation infrom the FDA for PfSPZ Vaccinein recognition of its progressIn keeping with the aggressive clinical timelineand scaling up manufacturing operationsour goal in Phase I was to automate a key step of isolating SPZ from the salivary glands of mosquitoes based on amalgamating and integrating various biologicalphysicalchemical and engineering principlesSignificant technological advancements included the first ever development of prototypes for batch processing mosquitoes in two steps of decapitation and gland extrusion and collectionresulting in at least afold higher throughput with reduced operator fatigueafold reduction in operator training timeand significantly improved product purityIn Phase II we propose to implement the semi automated mosquito microdissection systemsAMMSin cGMP manufacturingand incorporate further automation by combining novel fluidicsensingand vision guided robotic strategiesFully automated mosquito microdissection systemsfAMMSthat are compatible with downstream processing will be tested iteratively to meet efficiency and consistency standards for robust operations in compliance with current Good Manufacturing PracticescGMPBy moving iteratively towards greater operator productivityand eventually elimination of almost all operatorsin a more economically efficient production processautomation of mosquito discussion will accelerate Sanaria s march to licensureand greatly facilitate the increased production volumes required for post licensure deployment to benefit enormous numbers of individuals world wide in need of this vaccine Malaria claims upwards ofhuman lives each yearwith more thanchildren succumbing every daySanaria s Plasmodium falciparumPfsporozoiteSPZbased vaccines against malaria have demonstrated outstanding safety and efficacy in numerous clinical trialsThe manufacturing procedure for PfSPZ based involves the extraction of salivary glands of mosquitoes by dissectionOur aim in this proposal is to first implement an interim semiautomated prototype for mosquito microdissectionsAMMSin this key production step during pharmaceutical manufacturingIn parallel we will investigate and develop a fully automated systemfAMMSfor commercial scale production to facilitate greater efficienciesreduced timeframesgreatly reduced training periodsincreased product purityand mitigation of human error and operator fatigueSuch an outcome will accelerate Sanaria s march to licensure and greatly facilitate the increased production volumes required to meet the demand for postlicensure distribution to populations with greatest needworld wide