CURRENT GOOD MANUFACTURING PROCESS (CGMP) MANUFACTURING OF 100,000 DOSES OF ALFQ FOR PHASE 2B/3 CLINICAL TRIALS AND THE CAPABILITY TO MANUFACTURE FOR A COMMERCIALLY LICENSED VACCINE

WRAIR has a requirement to manufacture 100,000 doses (minimum of 20,000 doses/lot) of ALFQ under cGMP conditions as part of COVID-19 vaccine development program. The Government's Operation Warp Speed (OWS) aims to deliver millions of doses of safe and effective vaccines. In response to OWS, the Government requires partners that can cGMP manufacture and release thousands of doses of ALFQ and have capabilities to scale up the manufacturing to millions of doses. The Government requires partners to cGMP manufacture 100,000 doses (minimum of 20,000 doses/lot) of ALFQ in compliance with 21 CFR Part 210 and 211. Studies Chemistry, Manufacturing, and Controls Information. In addition, the manufacturing of ALFQ preferably should be compliant with relevant MHRA and EMA regulations and guidance. ALFQ is an adjuvant formulation composed of ALF55 drug substance (DS), QS-21, and Sorensen's Phosphate Buffer for which the Army owns a patent (US Patent: US10434167B2). GMP-grade lipid components and QS-21, and USP-grade excipients can be procured commercially. ALFQ has a molar ratio of approximately DMPC: cholesterol: DPMG:3D-PHAD: QS-21 at 9:12.2:1:0.11:0.05. The ALF55 DS is an Army Liposome Formulation (ALF) with monophosphoryl lipid A and 55% cholesterol. The lipid assembly contains DMPC, cholesterol, DMPG, and 3D-PHAD in a molar ratio of 9:12.2:1:0.11 (DMPC: cholesterol: DMPG:3D-PHAD). The ALF55 DS has a particle size distribution of 30'150 nm while the ALFQ drug product (DP) has a polydisperse size distribution ranging from nm to ?m. The previous lot of ALF55 DS was manufactured by lipid deposition method. Other scalable processes for the manufacturing of ALF55 DS can be proposed.