Pilot Bioproduction Facility (PBF)

Dr. Kenneth H. Eckels, is chief of the PBF, a pilot-scale production facility for vaccines that are needed for Phase I clinical trials in humans. The PBF follows strict FDA guidelines called Good Manufacturing Practices (GMP) that are required for this kind of production. The PBF manufactures vaccine lots for both government (Army, Navy, NIH, and USAID) as well as private companies. “Before the Technology Transfer Act of 1986, you couldn’t partner with outside entities to bring resources back to WRAIR – everything was in one direction,” he explained. “We did vaccine research and development paid for by the Army and had some partnerships with industry, including a big one with SmithKline Beecham – now [GSK]. They tapped into the research we were doing on hepatitis A and were able to license and market the first hepatitis A vaccine. Now we have CRADAs that enable us to partner with private businesses and universities and have the partner pay for the vaccine production. We in the PBF don’t really consider ourselves R&D – we’re way at the end of ‘D.’ We exist for the mission. The Army has a list of vaccines they need and they always have first priority, with malaria right at the top, which we have been working on since the early ’90s. At that time, USAID came to us with money and resources for malaria vaccines, supplementing what the Army was putting into it.”

Nearly from its inception, the PBF has been able to bring in various products not on the list of Army requirements and threats.

“We knew we would have no core funding and would have to do everything on a fee-for-service basis, which is still how we do it. Companies come to us with leading-edge technologies, for the most part proprietary, so we make sure what we do for them stays in a file exclusive to them that we can’t use with someone else. These partnerships broaden our knowledge base and keep us funded as an Army resource,” Eckels said.

“We knew we would have no core funding and would have to do everything on a fee-for-service basis, which is still how we do it. Companies come to us with leading-edge technologies, for the most part proprietary, so we make sure what we do for them stays in a file exclusive to them that we can’t use with someone else. These partnerships broaden our knowledge base and keep us funded as an Army resource,” Eckels said.

“We knew right from the get-go that to be able to perform GMP production we would need to bring money in from outside; the Army was not going to pay for the operation totally. We have companies come to us with limited budgets that are funded by investor money and often NIH grants. Which means they may only be here for a short time, then go away to do clinical testing.  If the vaccine is successful in Phase I testing they often come back to us for more production.”

Unlike most government research facilities, the majority of those working at the PBF do not have Ph.Ds. and are heavily reliant on job skills that come from on-the-job training.

“We no longer do research, only development and manufacturing. At last count, we had 31 contract personnel, with only me and my deputy chief being government employees. We also have two soldiers in the labs who are very eager to learn new skills and eventually take what they learn elsewhere when they leave the Army,” he said.

“WRAIR has world-class vaccine research groups that are very product oriented. I sit on many of the coordinating vaccine working groups [project teams] so I often know what will be coming to the PBF. And we are heavily dependent on these groups to keep us busy and move the products to clinical testing. Clinical testing results often bring interest from private companies looking for promising vaccines that can be marketed. One of those vaccines, for prevention of Japanese encephalitis, followed that scenario and was licensed in 2011. It is now available for soldiers and dependents being deployed to regions of the world where the disease is endemic.”

 

Conclusion

Many of WRAIR CRADAs are with pharmaceutical companies, some of which are international. Davis said many partnerships derive from their own PIs, who keep up on what’s happening in cutting-edge research in their areas.

“They may come to my office about partnering with some other agency. Or the personnel in my office may hear about something interesting and approach the PIs. And sometimes others contact the ORTA business office to ask about partnering with us, because of something they’re working on or something they’ve read in a WRAIR-published paper,” she said.

“There are always new CRADAs and agreements going into place. There is no end game to research – you’ll never come up with a product that fully solves the medical problem permanently. You may make it faster, cheaper, more effective, but even if you have a vaccine that works, you are never done, always looking for something better.”

“There are always new CRADAs and agreements going into place. There is no end game to research – you’ll never come up with a product that fully solves the medical problem permanently. You may make it faster, cheaper, more effective, but even if you have a vaccine that works, you are never done, always looking for something better.”

WRAIR utilizes a host of agreement types – commercial test agreements, clinical trial agreements, cooperative agreements, memoranda of agreement, and interagency agreements with other federal agencies – each appropriate to a specific relationship and with its own legal nuances.

“There is a toolbox of agreements and details and we try to ensure we are using the right tool for the job based on the unique case, which often isn’t known until you actually get into agreement discussions,” Davis said. “I think we get better with experience and continue to develop our staff and network with other ORTAs. I don’t think our methodologies, as such, have changed and we work hard to ensure our collaborations are mission aligned. We do more CRADAs and partnerships and agreements each year, including more across the federal government.

“Missions always change, of course, and we take our direction from our higher headquarters, who take direction from their higher headquarters and DoD. We also have BRAC 2005, which segregated the missions of the various institutes within MRMC [U.S. Army Medical Research and Materiel Command] and greatly redefined the missions, but all our work remains centered on the advancement of mission-aligned medical research. We are, for the most part, looking into methods of prevention for deployed soldiers. Every current drug involved with treatment or prevention of malaria has had WRAIR involvement, in some way, shape or form. And those were supported by CRADAs.”
MRMC already is looking at requirements related to the Pacific pivot and WRAIR already is conducting medical research in Asia. The military medical mission, as determined by Army leadership, will determine future partnerships or change in focus on diseases specific to that region. A weak economy and shrinking DoD budgets have raised concerns and left WRAIR uncertain about the future of its research, partnerships, and collaborations.

“Looking at current trends, we’re still growing strong and signing as many CRADAs as last year, with no impact on our ability to partner. So I’m not getting pessimistic – yet. I think we will be getting busier, that our PIs will be looking for new ways to do their mission,” Davis said. “We have, however, seen impact on our investigators, largely driven by travel limitations for DoD personnel, which have been alleviated somewhat lately.

“But our ability to communicate what we need and want to potential partners may have an impact on future agreements. If our investigators don’t have the opportunity to go out and network, it’s hard to move forward. Many of our agreements get their start at scientific meetings, after presentations that show where we have common interests – but if we aren’t there and the light bulbs don’t go off, we won’t have CRADAs resulting from those. The number of CRADAs is not going down, but that doesn’t mean we have not lost opportunities by not being out there because we don’t know what we don’t know.”

In the future as in the past, the scope of WRAIR’s efforts and partnerships is broad, depending on the disease under investigation.

“We usually work and exist within that space that is not being addressed by industry or academia. Success to date is ‘not enough’ or we wouldn’t be working on it. Expectations of continuing research depend upon the fate of research funding within DoD,” noted Col. Peter Weina, WRAIR deputy commander, adding that includes partnerships with organizations such as the CDC and WHO.

“There is an ecosystem of interactions with multiple different groups. There is no real way to tease out where one starts and the other ends. It is part of a continuum, like a fragile ecosystem; affecting one part of the system has impact on all other parts.”

“There is an ecosystem of interactions with multiple different groups. There is no real way to tease out where one starts and the other ends. It is part of a continuum, like a fragile ecosystem; affecting one part of the system has impact on all other parts.”

Braverman sums up the future as one in which collaboration and partnerships will be even more important to WRAIR’s success.

“I’ve really come to appreciate the importance of the OCONUS labs and clinical research networks we have in our partner countries, not only for DoD and Army efforts, but for international efforts to find treatments for malaria and HIV,” he concluded.

“Without those networks and the capabilities we bring to the table, it would be very difficult for the international community to replicate the clinical trials we do. So we have built a network that is truly important to global health as well as to the DoD.”

This article first appeared in Walter Reed Army Institute of Research: 120 Years of Advances for Military and Public Health.