The global death toll from Malaria is estimated to be upwards of 600,000 people each year, with more than 1,000 children succumbing every day. Plasmodium falciparum (Pf) Sporozoite (SPZ)-based vaccines are the only intervention in humans, proven to induce robust, high-level (>90%) and long-lasting (at least 14 months) protective efficacy against malaria, forming the basis of Sanaria's unique technology platform of aseptic, purified, cryopreserved live Plasmodium falciparum Sporozoites (PfSPZ). Among its products, PfSPZ Vaccine contains live PfSPZ attenuated by radiation, PfSPZ-GA1 is attenuated genetically, and PfSPZ-CVac comprises of infectious parasites that are arrested at the blood stage by co-administration of chemoprophylactic drugs like chloroquine. To date, 100% protective efficacy against controlled human malaria infection (CHMI) has been achieved in five clinical trials in the United States, Tanzania, Mali, and Germany in individuals vaccinated with PfSPZ Vaccine or PfSPZ-CVac, and efficacy against intense natural transmission of malaria has been established in Mali. Driven by the stellar clinical safety and efficacy results, and backed by an uncommon consortium of international investigators from >35 research groups in 18 countries, Sanaria plans to receive approval for a Biologics License Application (BLA) by the beginning of 2019 for travelers and by 2020 for all age groups and for mass vaccination programs intended to eliminate Pf malaria from geographically defined regions. Sanaria received Fast Track Designation in 2016 from the FDA for PfSPZ Vaccine, in recognition of its progress. In keeping with the aggressive clinical timeline, and scaling-up manufacturing operations, our 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 biological, physical, chemical and engineering principles. Significant technological advancements included the first-ever development of prototypes for batch-processing mosquitoes in two steps of decapitation and gland extrusion and collection, resulting in at least a 3-fold higher throughput with reduced operator fatigue, a 10-15 fold reduction in operator training time, and significantly improved product purity. In Phase II we propose to implement the semi-automated mosquito microdissection system (sAMMS) in cGMP manufacturing, and incorporate further automation by combining novel fluidic, sensing, and vision-guided robotic strategies. Fully automated mosquito microdissection systems (fAMMS) that are compatible with downstream processing will be tested iteratively to meet efficiency and consistency standards for robust operations in compliance with current Good Manufacturing Practices (cGMP). By moving iteratively towards greater operator productivity, and eventually elimination of almost all operators, in a more economically efficient production process, automation of mosquito discussion will accelerate Sanaria's march to licensure, and greatly facilitate the increased production volumes required for post-licensure deployment to benefit enormous numbers of individuals world-wide in need of this vaccine.
Public Health Relevance Statement: Malaria claims upwards of 600,000 human lives each year, with more than 1,000 children succumbing every day. Sanaria's Plasmodium falciparum (Pf) sporozoite (SPZ)-based vaccines against malaria have demonstrated outstanding safety and efficacy in numerous clinical trials. The manufacturing procedure for PfSPZ-based involves the extraction of salivary glands of mosquitoes by dissection. Our aim in this proposal is to first implement an interim semi- automated prototype for mosquito microdissection (sAMMS) in this key production step during pharmaceutical manufacturing. In parallel we will investigate and develop a fully automated system (fAMMS) for commercial-scale production to facilitate greater efficiencies, reduced timeframes, greatly reduced training periods, increased product purity, and mitigation of human error and operator fatigue. Such an outcome will accelerate Sanaria's march to licensure and greatly facilitate the increased production volumes required to meet the demand for post- licensure distribution to populations with greatest need, world-wide.
Project Terms: Automation; Dorsum; Back; Biologic Assays; Bioassay; Assay; Biological Assay; Blood Reticuloendothelial System; Blood; Chemical Engineering; youngster; childrens'; children; Children (0-21); Child Youth; 0-11 years old; Child; Khingamin; Chlorochin; Chloroquine; Clinical Trials; Death; Cessation of life; Dissection; drug/agent; Pharmaceutic Preparations; Medication; Drugs; Pharmaceutical Preparations; Engineering; Equipment; Equipment Design; Exercise; Lack of Energy; Fatigue; Geography; Germany; Goals; Modern Man; Human; Laboratories; Licensure; Malaria; Plasmodium Infections; Paludism; Falciparum Malaria; Plasmodium falciparum Malaria; Mali; Manuals; Methods; microwave electromagnetic radiation; microwave radiation; Microwaves; Microwave Electromagnetic; Culicidae; Mosquitoes; Parasites; Plasmodium falciparum; P.falciparum; P. falciparum; P falciparum; Plasmodium yoelii; Production; Productivity; Research; Research Personnel; Researchers; Investigators; Robotics; Safety; Salivary Glands; Salivary Glands Head and Neck; Tanzania; Technology; Testing; Time; United States; Vaccines; visual function; Sight; Vision; TimeLine; Decapitation; base; improved; Procedures; Area; Clinical; Phase; Biological; Ensure; Training; Individual; Licensing; Liquid substance; liquid; fluid; Attenuated; Staging; Robot; programs; Stream; System; Country; Sporozoites; age group; Performance; success; Microdissection; novel; Positioning Attribute; Position; Radiation; Intervention; interventional strategy; Intervention Strategies; Mass Vaccinations; Pharmacologic Substance; Pharmacological Substance; Pharmaceuticals; Pharmaceutical Agent; Gland; International; in vivo; Collection; Vaccinated; Validation; Process; developmental; Development; Output; cost; designing; design; Sporozoite vaccine; Outcome; manufacturing process; scale up; Population; mouse model; murine model; prototype; protective efficacy; manufacturing scale-up; operation; malaria transmission; malaria infection; malaria-infected
