Before the COVID-19 Pandemic, there were other smaller scale outbreaks such as SARS as well as the H1N1 pandemic flu scare in the early 2000s that triggered changes in public health approaches. One such change was the establishment of the Department of Defense Advanced Development and Manufacturing (DoD-ADM) Facility in Alachua, Florida.
A Defense Advanced Research Projects Agency (DARPA)-sponsored evaluation of the U.S. Government’s biological medical countermeasure (MCM) response capacity conducted in 2009 following the H1N1 influenza spread, identified an unmet need to rapidly develop, license, and manufacture biological MCMs required to protect military and civilian populations during time of CBRN crisis, which includes naturally occurring Pandemics as well as deliberate attacks. From that report, a memorandum was created in 2010, by John O. Brennan, Assistant to the President for Homeland Security and Counterterrorism, to Robert M. Gates, Secretary of Defense, to “Establish agile and flexible advanced development and manufacturing capabilities to support the development, licensure, and production of medical countermeasures that address the needs of our military and the nation.”
In 2009, the DoD was facing a bit of a Goldilocks issue. The quantities of medical countermeasures that they needed to produce were too small to attract interest from large and robust commercial pharmaceutical companies like Pfizer and Merck, yet they were too large and had regulatory challenges for small start-up biotech companies that often lacked experience with the FDA’s Animal Rule. The lack of an “in-between” manufacturer and an inability to have access to a production schedule when it was needed presented a gap in meeting the warfighters’ needs.
In response to the memorandum, the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) spearheaded an effort to establish a public/private partnership to address the military’s unmet needs, giving the Government priority access for manufacturing of MCM’s in the event of a national emergency.
Nanotherapeutics, Inc. (later rebranded as Ology Bioservices, Inc.) was awarded the contract to establish the DoD-ADM in 2013. Located in Alachua, Florida, the DoD-ADM is a biologics manufacturing facility capable of producing MCMs that protect the warfighter against chemical/biological warfare agents and emerging infectious diseases.
In 2017, Ology Bioservices officially opened the DoD-ADM, a 183,000 sq. ft. biological multi-product development and drug substance manufacturing facility. At that time, the DoD-ADM facility included four independent processing suites, which are compliant with current Good Manufacturing Practices (cGMP) and International Standards Organization (ISO) 8 standards. In addition, these suites operate using biosafety practices up to and including BSL-3 , inclusive of all necessary safety and decontamination infrastructure measures.
In April 2021, National Resilience (Resilience) acquired Ology Bioservices and continued supporting the DoD needs. Consistent with the public/private partnership, Resilience and the JPEO-CBRND through a cost share agreement expanded the manufacturing capability as a result to the global COVID pandemic needs with the addition of four more drug substance (BSL-2) process suites and supporting infrastructure, more than doubling the manufacturing capacity. In addition, the expansion included establishing a new automated drug product filling and packaging capability. The drug substance manufacturing capability became operational in the summer of 2022. The drug product filling and packaging capability is currently undergoing qualification and is set to be fully operational by the end of calendar year 2023.
“We started with just one building in Alachua,” said Mr. Tim Schiavoni, Director of the Advanced Development Manufacturing Capability (ADMC) Program Office within JPEO-CBRND. “But now there is an entire campus that includes a separate building just for process development and two buildings for manufacturing drug substance, which more than doubles the previous capacity. Additionally, we are establishing an automated filling and packaging capability. This campus can now provide end-to-end production of medical countermeasures for the warfighter.”
As a result of the DoD investments, the DOD-ADM Facility offers priority access to all infrastructure and manufacturing capabilities, which is unique in the commercial space; it is US-based manufacturing, when many products are now made OCONUS; and it possesses both cGMP compliant and BSL-3 (but not BSAT) capable operations, which is a rare combination of requirements.
The DoD-ADM also provides access to FDA known manufacturing modalities and technologies that improve cost and accelerates production and regulatory approval. These technologies include monoclonal antibodies (mAbs), nucleic acid plasmids/DNA vaccines, and inactivated viral vaccines (using a proprietary Vero Cell line as the vector).
Features of the DoD-ADM Facility include single-use/disposable technologies that allow for maximum flexibility through rapid changeover and reconfiguration; open “ballroom” room design and portable process equipment allowing for easy reconfiguration of work areas for multiple process operations; and utility segregation and uni-directional flow eliminating cross contamination while supporting multiple distinct products at once. The DoD-ADM Facility serves as an example of careful management of a public/private partnership delivering value for DoD.
“This is a one stop shop for developing, scaling up, manufacturing, filling, and shipping products out, we can get everything done and into the hands of warfighters quickly,” Schiavoni said.
Figure 1 - Manufacturing equipment within the ADM facility in Alachua, FL where the JPEO-CBRND has a public-private partnership for defense MCM manufacturing needs.
Over the past ten plus years, the public/private partnership with the DoD has resulted in a fully functional facility that has produced multiple commercial and government funded biological MCMs, including monoclonal antibodies (mAb) to support Phase 1 clinical trials against Botulism Neurotoxin (BoNT) and COVID-19. Specifically, for BoNT JPEO-CBRND and the Defense Threat Reduction Agency (DTRA) Joint Science and Technology Office (JSTO) utilized the DoD-ADM to complete the development, manufacture, and regulatory advancement of a BoNT mAb. The BoNT mAb Investigational New Drug (IND) application was submitted to the FDA 26 Nov 2019, allowing for subsequent Phase 1 and Phase 2 Clinical Trials. This program is now earmarked to be placed in the JPL CBRND EB’s Rapid Access to Products in Development (RAPID) Program.
At its inception, the DoD-ADM operated under a unique paradigm of a traditional Contractor Owned, Contractor Operated (COCO) facility, in which the contractor owned the land and exterior building shell, but all the facility’s interior infrastructure needed for the development and manufacturing of MCMs were funded and owned by the DoD and subsequently sustained by DoD funds. This arrangement of both public (DoD) funds and private (contractor) funds allowed the DoD to have priority access to the MCM manufacturing capability when needed while simultaneously allowing the contractor to seek out commercial work.
However, in FY22, this arrangement entered a new chapter when the JPEO-CBRND transferred ownership and sustainment of the USG-funded portion of the capability over to the contractor in exchange for continued priority access along with no sustainment costs being funded by the DoD. The result was that the government still has priority access to the entire facility, but now without the financial and logistical burden of owning and maintaining the equipment. This transition demonstrates the new agile and entrepreneurial environment of the government post COVID-19.
The transition also shows how a public/private partnership can make iterative improvements by implementing feedback, lessons learned, and being flexible as needs arise to meet the needs of the joint force.
The way that the JPEO-CBRND maintained and implemented changes to the DoD-ADM facility to ensure it could remain an asset and have all the pieces needed to rapidly respond, demonstrates how lessons learned were implemented to evolve and keep the DoD-ADM as a state-of-the-art facility.
“Through this transition, we were able to evolve the public/private relationship and pivot to maintaining priority access without incurring continued maintenance costs,” Schiavoni said. Funds that were previously earmarked to sustain the capability are now being used to not only establish new manufacturing technologies such as inactivated viral vaccines and cell-free protein synthesis, but also optimize existing operations like media/buffer preparation and quality control analysis of products to ensure the facility continues to be a rapid response center of excellence for the warfighter.
Standing up a facility and working with the public to ensure it has the credentials, equipment and specialties needed for government use, without fully owning it, is a model that JPEO-CBRND may follow again in the future.
“As the government we have the need, the requirements, and the specializations needed to create facilities that can ensure our warfighters have products they need to be protected quickly,” said Bruce Goodwin, Joint Project Lead for CBRND Enabling Biotechnologies.
“In the government, we usually hold onto and use our own facilities behind our gates, but this is a new way of doing things. We can work with public companies to set these facilities up, get them running and be able to have access to them when needs arise, but otherwise the facilities can be supported by non-government commercial entities. By setting things up but not owning and maintaining it forever, it allows us to save time and money in the long run while still supporting our defense needs,” said Goodwin.
JPEO-CBRND is proud of the work it accomplished in standing up the DoD-ADM and looks forward to building additional partnerships to support rapid response and maintain readiness while building the Army of 2030 and beyond.