OVERDOSE AVERTED: ORA staff are working with private sector pharmaceutical companies to develop a naloxone auto-injector—similar to the materiel pictured here—to reverse the effects of an opioid overdose on the battlefield. (Photo by Mark Herlihy, U.S. Air Force)
USAMRDC’s Office of Regulatory Affairs facilitates the development of future medical materiel by making sure that all of the eyes are dotted and the tees are crossed.
by Ramin A. Khalili
You don’t need a crystal ball to get a peek at the future of warfighter medical solutions. Instead, just talk with Cyndi Donovan of the U.S. Army Medical Research and Development Command’s (USAMRDC) Office of Regulatory Affairs (ORA). Donovan is a clinical research associate in the office, and watches from the ground-level as command industry partners develop and test new medical devices, drugs and biologics—all potential solutions for the modern Soldier. She and the rest of the ORA team are tasked with guiding those solutions from infancy to, ultimately, a mature, fully realized product for use in the battlefield. For that reason—and so many others—ORA has become an increasingly important player in the USAMRDC operation.
Currently, as part of a collaboration with USAMRDC’s U.S. Army Medical Materiel Development Activity’s Force Health Protection division, Donovan is working with Kaléo. A Virginia-based pharmaceutical company contracted by DOD to develop a high-dose auto-injector for naloxone, which is an opioid agonist. That means that it stops or prevents the effects of opioid drugs. In a combat situation, powerful opioids could be aerosolized and deployed as a chemical weapon. A naloxone delivery system like Kaléo’s auto-injector could be used on the battlefield to help mitigate opioid exposure and save warfighter lives. The product is already being used by special forces units and is pre-positioned at various U.S. military installations across the globe for expedited distribution in case an imminent threat presents itself.
Donovan, who has been with ORA since 2009, is a former pediatric oncology nurse. She previously worked at high-profile universities such as Georgetown in Washington, D.C., and Johns Hopkins in Maryland. However, there’s something her current role offers that, as she puts it, those other places just can’t match. While Donovan said she can’t know the person who is receiving the drug, or the product, or the tool individually as she used to in nursing, she said “I do feel like I am part of a bigger piece of the puzzle that’s saving someone’s life,” noting that Kaléo’s auto-injector is scheduled to be commercially available by July.
REGULAR REGULATION
Saving lives is, indeed, one of ORA’s broader goals—one that feeds into the command’s overall mission and vision. As its name suggests, the Office of Regulatory Affairs is chiefly tasked with monitoring all regulatory affairs of USAMRDC and is responsible for all clinical, quality and internal regulatory efforts within the command to help advance promising military products to the warfighter. If that sounds like a lot of weight to carry, that’s because it is. Their work is front and center and provides more value and impact than most people realize. ORA is known for maintaining a sprawling infrastructure that touches just about every corner of the command and, sometimes, beyond.
“A lot of business at MRDC—things like getting regulated products out to the warfighter, for example—wouldn’t happen if ORA wasn’t here,” said ORA director Lisa Borek as she described a sort of brass-tacks breakdown of the organization’s impact. “A lot of people don’t fully understand what we do and how we function as the centralized regulatory capability available to both USAMRDC and the DOD; and that’s a shame because we’re a pretty big group.” That work, which boils down to providing the knowledge and regulatory guidance required to navigate the occasionally tricky regulatory affairs pathway, is critical to the mission of both USAMRDC and, to a larger extent, the DOD as well.
The process of helping usher a product down, an oftentimes complex regulatory pathway, makes the organization an integral part of the overall research, development and acquisition effort. Normally, the development of medical products regulated by the U.S. Food and Drug Administration (FDA) follows rigorous approval paths to ensure safety and effectiveness. ORA’s main function is to act as the facilitator between military medical research and the FDA. By acting as a navigator of sorts, ORA helps to develop regulatory strategies through those pathways, applying and interpreting FDA regulations and guidance for partner organizations.
RELEVANT CARE: A Soldier supplies medical care during the USAMRDC Soldier and Noncommissioned Officer of the Year competition, held in March in San Antonio. ORA’s goal is to advance military-relevant products, including those used in battlefield medical care, to the warfighter through flexible and innovative regulatory pathways. (Photo by Dr. Steven Galvan, U.S. Army Institute of Surgical Research)
MAKE IT HAPPEN
“We are everywhere,” said ORA deputy director Maj. Victor Zottig. He described the organization’s role as that of a facilitator between product developers and the FDA. “We deal with a very interesting and innovative space, and we have to come up with creative solutions to make sure those products pass FDA muster—but then also get to the warfighter as soon as possible.”
ORA’s portfolio includes more than 100 different and varied products across all stages of research and development (as the saying goes around the office, you never see the same thing twice, and it never gets boring). Currently, ORA is partnering with U.S. Army Medical Materiel Development Activity (USAMMDA)’s Warfighter Brain Health Project Management Office on proper protocols for a pair of adaptive clinical trials, along with a slew of vaccines and therapeutics to help combat everything from infectious diseases to traumatic brain injury and post-traumatic stress disorder. Since compliance efforts usually last the entire life cycle of a given product, it’s common for ORA to provide oversight and regulatory consultation for anywhere from a couple years to the better part of decade, if need be.
The benefits of connecting with ORA early in the product development process include, perhaps most importantly, opportunities for industry partners to plan for a more efficient allocation of financial resources. For example, knowing whether a product may require a specific study to gain FDA approval will likely help a team use money and time more effectively and efficiently. Indeed, even if an industry partner is unsure whether the product they’re developing needs to meet any FDA requirements at all—products like software or certain types of diagnostics, for instance—ORA can answer those questions before the work even begins.
“By interacting with us early, we hopefully can avoid some of the shortcomings of the product development process,” Zottig said. “A lot of pre-clinical trial research doesn’t necessarily require extensive FDA oversight, but by the time you need FDA guidance when entering early product development—by then it’s almost too late.”
TEAMWORK: Cyndi Donovan, center, poses with USAMMDA staffers during a site visit to Germany in 2020. (Photo courtesy of Cyndi Donovan)
KNOWLEDGE BAKED IN
Because that process needs to be as streamlined as possible, working with ORA is simple. For example, when an industry partner contracts with USAMRDC with the goal of developing a certain product, ORA joins the project management team almost immediately to begin providing advice and guidance on how to ultimately obtain FDA approval. Then, project team members review the proposed testing efforts for the product (clinical trials, toxicity studies, etc.) and discuss the creation of a unique strategy to ensure the product being developed clears all regulatory milestones as required by the FDA. In this way, ORA operates as the “translators” of the regulatory world ensuring that both the FDA and the product developers are speaking the same language in their pursuit of a common goal: FDA approval.
Any product that receives an FDA approval is, of course, the ultimate goal for all involved. Zottig calls ORA the command’s “connective tissue” because the office works with so many people and programs within USAMRDC.
This enormous infrastructure allowed ORA to help facilitate portions of the command’s response to the coronavirus pandemic. During that time, while USAMRDC was helping secure personal protective equipment like face shields, face masks and specimen collection devices—products it helped physically create via on-site 3D printing technology—ORA teamed with the U.S. Army Medical Materiel Development Activity’s Additive Manufacturing Working Group to ensure said products were approved in a compliant manner. While such an effort would’ve taken years under normal circumstances, ORA was able to process the necessary regulatory requirements for those new products in just weeks due, in large part, to their knowledge and familiarity of the FDA process.
CONCLUSION
For Donovan and the team at ORA, this kind of work is what makes the end-result so rewarding. “What I really take pride in is being part of a team that knows exactly what to do to get something started, do it quickly, and, in essence, get the right product out at the right time for the right needs,” Donovan said. “I feel my presence here and my contribution here is really needed, after all, what more could you hope for when you know your work is meaningful?”
For more information about USAMRDC, go to https://mrdc.amedd.army.mil. For more information about ORA, go to https://mrdc.amedd.army.mil/index.cfm/resources/researcher_resources/regulated_activities_overview.
RAMIN KHALILI is a writer with USAMRDC’s Public Affairs Office. Before assuming his current role, he spent five years as the knowledge manager for USAMRDC’s Combat Casualty Care Research Program. During his previous work as a broadcast journalist, he earned an Associated Press Award for his work in Phoenix, Arizona, before serving as Chief NASA Correspondent for CBS in Orlando, Florida. He holds a B.A. in communications from Penn State University.
