Formulation and analytical development of a multi-dose vial presentation of scopolamine hydrobromide trihydrate containing a antimicrobial preservatives (AMP)

The Joint Project Manager for Chemical, Biological, Radiological, and Nuclear Medical is developing scopolamine hydrobromide trihydrate (Scop-HBT) under the Improved Nerve Agent Treatment System - Centrally Acting program. Scop-HBT is an anticholinergic medical countermeasure that temporarily blocks severe or life-threatening muscarinic effects caused by organophosphorus nerve agent (OPNA) poisoning. The single unit dose drug product currently in development represents a significant logistical burden to military first responders that will need to deliver multiple injections of scopolamine during a mass casualty event. A 20 mL multi-dose vial (i.e., 10 to 20 doses) of Scop-HBT for intramuscular injection will significantly decrease the logistical burden associated with having to use multiple vials during mass casualty OPNA exposure incidents, as well as for treating single OPNA exposure casualties over a prolonged period of time. CMC Pharma proposes to complete the chemistry, manufacturing, and controls development (formulation, analytical, process, and stability studies) of a multi-dose presentation of the scopolamine drug product that contains a microbial preservative. CMC intends to leverage its medical countermeasure development experience and its significant specific scopolamine drug product development experience obtained for a unit dose, unpreserved formulation. Preliminary studies have identified baseline formulations and microbial preservatives found in the FDA inactive ingredient database that are compatible with current analytical methods. Specific aims of the proposal include analytical, formulation, and process development of a multi-dose presentation, prototype preparation and subsequent evaluation for stability, antimicrobial effectiveness, forced degradation, and other critical drug product attributes. Appropriate project management will be executed to ensure efficient coordination of efforts between CMC Pharma, subcontractors, and the Government. Analytical, formulation, and process development studies required to identify and manufacture a multi-dose vial presentation of Scop-HBT will be executed and draft drug product specifications and a target product profile will be established. A non-GMP Stability Study of selected prototypes will be conducted to begin to evaluate the shelf life of the formulations. CMC Pharma will complete preservative effectiveness testing of the formulations containing the microbial preservative at subcontractor with the USP test. Studies will be conducted to evaluate the forced degradation of the prototype formulations with acid, base, heat, light and an oxidizing agent to ensure that the methods are appropriate and stability indicating. If funded, this work will provide the foundation for a Scop-HBT multidose vial formulation for further development in a phase II SBIR, leading to FDA approval and commercialization.