Concentrated Atropine Sulfate Formulations

Organophosphorus nerve agent attacks are an unfortunate reality of modern warfare. Currently, the standard of care is to use up to three sequential doses of the Antidote Treatment Nerve Agent Autoinjector (ATNAA, which contains atropine sulfate, and 2-pyridine aldoxime chloride (2-PAM)) and an anticonvulsant. For severe cases, this is followed by continued dosing of atropine to block muscarinic effects, up to 50-100 mg over 24 hours. However, the maximum concentration of commercially available multi-dose atropine sulfate in the US is 0.4 mg/mL and requires up to 13 vials to treat a single patient. This is logistically demanding to transport and maintain. It would be far better to supply concentrated atropine sulfate, using a single vial to treat the most severely poisoned soldiers. TDA proposes development of a concentrated atropine sulfate formulation of 5-10 mg/mL supplied in a 10-20 mL multi-dose vial with a shelf life of at least 2 years. In Phase I TDA will formulate this drug product, perform quality testing and stability studies, and prepare a pre-submission package for the FDA. This will be in support of product refinement and full testing in Phase II, followed by commercial process development, validation, and FDA registration in Phase III.