PfSPZ Vaccines: Quality Systems, Manufacturing, Regulatory, and Clinical Quality and Data Management Support for Product Commercialization

摘要

ABSTRACT Sanaria’s Plasmodium falciparum (Pf) sporozoite (SPZ) vaccines development program is receiving overwhelming global support. Eleven trials of Sanaria’s two primary PfSPZ vaccines which include ~1,500 subjects, were initiated in late 2015 (Tanzania, U.S.) or will start in early 2016 (Kenya, Ghana, Equatorial Guinea (EG), Burkina Faso, Germany, and the U.S.). These trials will assess 1 to 3 dose regimens based on a trial in Germany showing 100% protective efficacy against controlled human malaria infection (CHMI) 9 weeks after the last dose of a 3-dose, 8-week regimen. Protective efficacy is durable against CHMI for at least a year, and against intense natural transmission in Mali for at least 6 months. This success has led to the development, in collaboration with the International PfSPZ Consortium, of a 4-stage clinical development plan. The completed trials (stage 1) and above-mentioned new trials (stage 2) are intended to optimize immunization regimens in preparation for pivotal phase 3 clinical trials (stage 3) to support a Biologics License Application (BLA) to the FDA and commercialization (launch). Stage 4 (post licensure) includes a mass vaccine administration (MVA) campaign to halt transmission of Pf and eliminate the parasite from the >250,000 population of Bioko Island, EG. Through SBIR grants and U.S. military contracts, Sanaria is scaling up manufacturing and improving its vaccine manufacturing facility to meet phase 3 and launch compliance. However there are critically important, unfunded components of our quality assurance (QA), quality control (QC), manufacturing, regulatory, and clinical quality and data management programs, which must be upgraded and finalized. This CRPP project will address several of these key components. The overarching goal is to augment Sanaria’s current efforts to achieve commercialization readiness and optimize chances of a successful phase 3 program, BLA, product launch, and post launch phase 4 testing and maintenance. We will, 1) Establish and implement a QA and QC program that meets harmonized regulatory standards with appropriate organizational and systems infrastructure; 2) Formally assess manufacturing processes, including Failure Modes and Effects Analysis (FMEA) risk assessment and validation of the aseptic manufacturing processes; 3) Transition to regulatory submissions in electronic common technical document (eCTD) format, establish a platform for hosted regulatory document management, develop a strategic framework for FDA submissions and interactions, and develop and implement plans for BLA submission and regulatory SOP completion; and 4) Develop phase 3 compliant clinical quality systems, including clinical SOPs, establish a CDISC compliant clinical data management platform, import data from clinical trials, generate Clinical Study Reports (CSRs) for all clinical trials lacking CSRs, and conduct a quality review audit of trial master files. Funding of this proposal will significantly shorten the time until product licensure and launch, which will lead to sales and income at least a year earlier than otherwise possible, and will save many lives.