ROCS TEST: Sgt. 1st Class Elijah Williamson, the U.S. Army Medical Test and Evaluation Activity (USAMTEAC) test officer, takes notes as a test player practice administering the Rapid Opioid Countermeasure System autoinjector on a simulated casualty in June 2021 at Camp Bullis Military Training Reservation, Texas. (Photo by Jose Rodriguez, U.S. Army Medical Center of Excellence)
JPEO-CBRND counters high-potency opioid exposure across multiple domains with a unique rapid acquisition approach.
by Erik Heine
Synthetic opioids such as fentanyl are a class of drugs used for pain management. However, the illicit and widespread use of these drugs caused the U.S. to declare opioids a public health emergency in 2017. Because of this opioid crisis, there is a large influx of illicit drugs into the country. This has placed military members—Coast Guard and National Guard for example—at risk of opioid exposure during drug interdictions or site exploitation missions.
One of the most potent opioids military forces may be exposed to is carfentanil, a high-potency opioid that is lethal, even at very low doses, if medical treatment is not provided within minutes of exposure. Carfentanil is about 100 times more potent than fentanyl and about 10,000 times more potent than morphine. For instance, if a Soldier were to breathe it in unwittingly or get it on their skin, even a freckle-size amount could kill them. The Joint Requirements Office (part of the Joint Chiefs of Staff, J8 Directorate) for Chemical, Biological, Radiological and Nuclear Defense (CBRND) identified a critical need to deliver a medical countermeasure that can reverse the effects of accidental or intentional opioid exposure for first responders and military personnel who support civilian law enforcement.
The Joint Project Manager for CBRN Medical’s Rapid Opioid Countermeasure System program team was chartered to develop a medical countermeasure to treat the effects of high-potency opioids via an autoinjector. The aim of the treatment was to prevent fatality and allow military personnel and first responders who have been exposed to remain ambulatory to evacuate to a higher echelon of care. The program team achieved the rapid development and fielding of a 10-milligram naloxone autoinjector using three novel approaches: Public Law 115-92, which “authorize[s] additional emergency uses for medical products to reduce deaths and severity of injuries” resulting from CBRN exposure, the middle-tier of acquisition pathway and other transaction authority agreements. Both of those provide for rapid prototyping.
A FIRST FOR JPEO-CBRND
Industry-average medical development timelines can exceed a decade and cost upwards of a billion dollars to mature a product from discovery through Food and Drug Administration (FDA) approval and commercialization. To combat this, the program team spearheaded a $36 million program to deliver a military medical capability using the middle-tier of acquisition pathway, the first DOD medical program to do so. The middle-tier pathway is used to fill a capability gap with a technology that has a level of maturity that allows for rapid prototyping within five years of program start. Middle-tier acquisition programs are not subject to conventional Federal Acquisition Regulations, instead, the pathway is intended for prototyping and rapid development and fielding.
For developing the autoinjector capability, the middle-tier acquisition pathway was determined to be the most expedient. This allowed the use of a draft capability-development document that served as the requirements document for the program and did not require validation from the Joint Requirements Oversight Council before obtaining approval from the Protection Functional Capability Board. It’s estimated that by using this pathway, the overall acquisition process was accelerated by at least 18 months.
The team used the middle-tier pathway by identifying naloxone as the “gold standard” for treating an opioid overdose. The FDA had approved the use of up to 10 milligrams of naloxone as a safe and effective way to treat opioid overdose. A two-milligram naloxone autoinjector was already commercially available but did not meet military requirements for treatment of highly potent opioids (e.g., carfentanil) and provided electronic voice instructions for civilian patients, unnecessary in a combat situation. In addition, DOD science and technology organizations had determined through animal studies that a single 10-milligram dose would allow rapid treatment of high-potency opioids on the battlefield or in other scenarios requiring rapid countermeasures, while also allowing exposed individuals to retain mobility and survive the initial exposure and evacuate to a higher echelon of medical care.
REGULATIONS, REGULATIONS, REGULATIONS
Next, the program team developed a regulatory strategy to receive FDA approval of the 10-milligram naloxone autoinjector. A regulatory strategy captures the necessary information required to demonstrate safety and efficacy of the product. Using Public Law 115-92, the team met with the FDA to gain feedback. Public Law 115-92 authorizes the FDA to provide DOD assistance to expedite the development and review of products that could diagnose, treat or prevent serious or life-threatening diseases or conditions facing U.S. military personnel. If the FDA recognizes that priority presented by DOD is needed, this can result in critical medical products getting to the warfighter faster. The feedback from the FDA provided validation that the program would be able to meet the five-year timeline for middle-tier acquisition.
LEADING THE WAY
To set the program up for success, the program team conducted market research to identify candidates that could be repurposed for a 10-milligram naloxone autoinjector. The team also needed to know if there were companies that were already producing FDA-approved autoinjectors that met the newly updated and stringent engineering and quality requirements.
Having to seek FDA approval for a new autoinjector would require costly studies, which would dramatically increase the developmental cost and schedule. The program team conducted online research, contacted potential performers using requests for information and canvassed the Medical CBRN Defense Consortium, and other transaction authority agreement consortium.
To further accelerate product development, the program team needed a flexible contracting mechanism that was mutually beneficial to both the government and industry partners. Using other transaction authority promoted increased competition by attracting nontraditional companies that might not ordinarily have the wherewithal to navigate the often difficult Federal Acquisition Regulations. Other transaction authority agreements allow for discussion and collaborations with and between companies during certain parts of the agreement process.
Through source selection, the team selected Kaléo, Inc. as the performer based on their prior success in development of the FDA-approved two-milligram naloxone autoinjector. This allowed the program team to accelerate the development of a 10-milligram naloxone autoinjector. During development, the FDA requested additional studies to demonstrate the safety and efficacy of the 10-milligram dose. Kaléo was able to successfully complete the studies within the contract timeline because of their regulatory experience and expertise. The program team worked with Kaléo to deliver the product under budget, five months ahead of contract schedule, despite numerous challenges presented by the COVID-19 global pandemic and additional FDA requirements.
(See related article in the Fall 2022 issue of Army AL&T, “Not-So-Secret Weapon,” Page 15.)
When the FDA requested more detail on the efficacy of the drug, the program team and Kaléo used that opportunity to make the product even more valuable—using it for prevention, or prophylaxis. The prophylaxis indication would allow the use of the product when entering an area contaminated with high-potency opioids. These studies also support FDA fast track designation. That status enabled priority review of the new drug application.
Typically, review of an application takes 12 months; however, under priority review, the FDA commits to reviewing the application in six months. In February 2022, six months after submission, the FDA approved the 10-milligram naloxone autoinjector new drug application, providing military personnel and chemical-incident first responders with a new capability for both the treatment and prophylaxis protection against high-potency opioids.
Using a streamlined acquisition authority, an innovative contracting vehicle and enhanced engagements with the FDA, the program team decreased cost and schedule for the development and FDA approval of a 10-milligram naloxone autoinjector, and in record time—under four years. The program team delivered more than one capability, treatment and prophylaxis, with a device that can serve both military and first responders around the world.
MEETING THE DEMAND
Even before FDA approval, there was a demand for the 10-milligram naloxone autoinjector from specialized units at high risk for opioid exposure. In early 2022, U.S. Special Operations Command requested expedited use of the 10-milligram naloxone autoinjector in response to a potential threat overseas.
In March 2022, the assistant secretary of defense for health affairs approved the investigational 10-milligram naloxone autoinjector expanded-access protocol, followed shortly by FDA approval. By using already-manufactured product that was excess material from the development effort, the program team quickly supported the request. The delivery of the 10-milligram naloxone autoinjectors closed two capability gaps: DOD’s urgent need to address weaponized opioid exposure risks and provide access to a lifesaving medical countermeasure to combat exposure to high potency opioids.
REAPING THE REWARDS
In recognition of their efforts and building upon previous recognition by the assistant secretary of the Army for acquisition, logistics, and technology and the Edison Awards, the program team received the 2022 Military Health System Research Symposium annual award for outstanding program management (team). This award recognized outstanding medical product program management, highlighting team accomplishments in further maturing medical research and development or commercial efforts. The team was recognized for addressing and minimizing the program’s developmental risks; managing cost, schedule and performance; and adhering to all applicable regulatory requirements.
The award was presented to Saumil Shah, the assistant product manager for the Chemical Defense Pharmaceuticals product office, within the Joint Project Manager for Chemical, Biological, Radiological and Nuclear Medical, in Frederick, Maryland. Upon receiving the award, Shah commended the team, saying “Using innovative strategies, the Rapid Opioid Countermeasure System program team accomplished its goals ahead of schedule and under budget, and satisfied demanding criteria in both the defense department acquisition and FDA regulatory processes.”
“Additionally, the program experienced zero cost overruns during the entire development effort. This could not have happened without an experienced and highly proficient matrixed team, combining functional expertise ranging from acquisition analysts, contracting specialists, financial experts, logisticians, regulatory specialists, legal counsel, technical subject matter experts and program managers.”
The Rapid Opioid Countermeasure System provides a “rescue therapeutic” capability for initial treatment at the point of exposure, as well as a product that can be used as a prophylaxis. It provides an FDA licensed and approved medical product to support the required attributes necessary for treatment of opioid exposure, and to reverse or significantly mitigate the effects and negative impact of opioid exposure.
With the delivery of the 10-milligram naloxone autoinjector, and by promoting research that led to better opioid therapeutics, the program team has increased warfighter readiness, reduced operational risk to potent opioid threat exposure, and taken a major step forward in protecting and maintaining the readiness of the joint force as well as North Atlantic Treaty Organization forces.
For more information, go to https://www.jpeocbrnd.osd.mil.
ERIK HEINE supports the Joint Project Manager for Chemical, Biological, Radiological and Nuclear Medical at Fort Detrick, Maryland. He is a Project Management Professional and holds a B.B.A in computer information systems and decision support systems from James Madison University.