Pharmaceutical Development, Planning, and CMO Identification for the Expedited Advancement of a Scopolamine Multi-Dose-Vial Drug Product

CMC Pharma is proposing this Phase II SBIR to continue the development and testing of a multi-dose vial of a scopolamine hydrobromide trihydrate (Scop-HBT) ready-to-use intramuscular solution formulation. The Joint Project Manager for Chemical, Biological, Radiological, and Nuclear Medical (JPM CBRN Medical) is developing Scop-HBT under the Improved Nerve Agent Treatment System - Centrally Acting (INATS CA) program. Scop-HBT has established anticholinergic properties and a multi-dose presentation could improve outcomes for OPNA poisoning and reduce the logistical burden of single-dose auto injectors or vials. A multi-dose 20-mL presentation could provide 10-20 doses, thus reducing the vial requirements of a unit dose by 10- to 20-fold. Reducing the logistical burden by 10- to 20-fold would streamline supplying, storing, carrying, using, and disposing of vials needed to treat numerous subjects during a mass casualty OPNA exposure incident. Scop-HBT was selected as a candidate addition to the OPNA treatment regimen because it has established anticholinergic activity, crosses the blood brain barrier, is anticipated to be compatible with the standard nerve agent emergency treatment regimen and has complementary pharmacological profiles to atropine. In addition, Scop-HBT is approved by the FDA for a different indication; thus an active pharmaceutical ingredient (API) supply chain already exists that meets U.S. Pharmacopeia (USP) standards and cGMPs. CMC Pharma has completed significant previous work under a Phase I SBIR and additional research programs funded by the DoD. During these previous efforts, CMC Pharma identified a lead and several backup formulations for further development and intends to leverage the learnings from all previous efforts to execute the current proposal. CMC Pharma has the personnel, facilities and long standing professional relationships with subcontractors that are ideally suited for this effort. The personnel engaged in the proposed effort have decades of experience moving products into development and through FDA approval. The purpose of the project described herein is to expedite the development of a preserved, multi-dose vial presentation of a ready-to-use Scop-HBT formulation for IM injection. To that end, CMC Pharma proposes to prepare and evaluate prototype lead and backup formulations; continue to develop, enhance, and qualify the analytical methods utilized for those evaluations; develop an integrated product development plan; and to identify, recommend, and qualify a cGMP manufacturing site for the drug product. CMC Pharma intends to utilize funding from this and future efforts to move the multi-dose Scop-HBT drug product through development and FDA approval for both civilian and military use.