Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Chemical Defense Acquisition Programsment stage, allowing MITS to engage with the scienceand technology base early in the process. If multiplecandidates are pursued, down-selection criteria areevaluated during technology development and adown-selection recommendation is typically made atmilestone B.Between milestones A and B, the MITS JPMO pursuesprocess development and pilots lot production ofcandidate drugs under current good manufacturingpractices (cGMPs). Required work includes clinicaland analytical assay development, dose range andsafety studies in animals in accordance with goodlaboratory practices, investigational new drug (IND)submission to the FDA, and Phase 1 human clinicalsafety studies compliant with good clinical practices.Emergency use authorization may be prepared andsubmitted to the FDA for review with, or shortly after,IND submission.Intellectual property rights are addressed as part ofthe product transition package (ie, licensure purchase,the need to trace origin to ascertain if it was governmentfunded and, if so, claim government purposelicense rights, etc). Intellectual property rights may bea concern for future products, and the MITS JPMO willexamine all available options to ensure that productsare developed and produced in a manner equitable tothe government. Final decision on this approach willbe determined by the MITS JPMO.System Development and DemonstrationDuring the system development and demonstrationphase, the systems integrator, in conjunction withcommercial partners, develops validated processesand produces consistency lots and conducts Phase 2(expanded safety) human studies, definitive animalefficacy studies, and complete toxicology studies.During this phase, the systems integrator files thenew drug application or other necessary regulatorydocumentation and requests FDA submission review.Items carried by service members undergo developmentaland initial operational tests and evaluationsduring this phase. The system development anddemonstration phase concludes with FDA approvalof the pharmaceutical.Production and DeploymentAs the production and deployment phase begins,products are stockpiled, and post-marketing surveillanceis conducted. The MITS JPMO begins investigatingpost-production support plans and shelf lifeextension program efforts while monitoring productstability. Initial operating capability for drug developmentis achieved when the FDA approves the productand the contractor can ensure adequate and efficientmanufacturing capability. The initial operating capabilityis calculated as 1/x of the troop equivalentdoses required for full operating capability, with xbeing the threshold shelf life. Full operating capabilityis achieved when the required FDA-approvedtroop equivalent doses have been produced for thestockpile.Operations and Support PhaseThe MITS JPMO remains responsible for lifecyclemanagement of the approved pharmaceuticals throughthe operations and support phase of acquisition sustainment,maintaining and safeguarding the industrialcapacity to support full production, and addressingregulatory issues such as long-term human safetystudies, shelf life extension, and post-marketing surveillance(ie, Phase 4 clinical trials). MITS transfersprocurement and logistical management to medicallogistics organizations, such as the Defense SupplyCenter Philadelphia or the US Army Medical MaterielAgency, once initial stockpile quantities are in place.Funding for maintaining the stockpile in the operationsand support phase is the responsibility of theindividual services.Acquisition Manufacturing StrategyThe technology base develops a laboratory-scalemanufacturing process that is capable of producingonly small quantities of drug product. This processmust be transferred to a manufacturing facility thatadheres to cGMPs and development efforts initiated toensure technology can be duplicated or new processespursued. One or more small cGMP pilot lots are manufacturedfor use in the Phase 1 and 2 clinical trials andanimal toxicity studies. Scaling up the manufacturingprocess, rather than producing additional lots at thesmaller scale, can result in significant cost and schedulesavings. The manufacturing process is validated andconsistency lots are manufactured concurrent withPhase 2 trials. After FDA approval, replenishment lotsare produced to meet requirements, depending on theshelf life approved by the FDA for each product.Acquisition Test and Evaluation StrategyThe acquisition of medical CBRN defense productsfor the DoD is tailored to comply with the requirementsof both the DoD and the FDA. In a memorandum datedNovember 21, 2003, the deputy under secretary of theArmy required every chemical or biological defense649