As government agencies partner with industry in a race to save countless lives in a growing Ebola outbreak, two hurdles loom large for companies lining up for the run, the FDA's Luciana Borio told a House subcommittee Wednesday.

The first involves preclinical work that has to be done in a high-containment lab, which necessitates a public-private partnership. "No one can go it alone," she testified before the Energy and Commerce Health Subcommittee. The second is the lack of a health care infrastructure in the West African countries where the outbreak is raging. Before clinical trials can begin, that infrastructure must be beefed up to support the studies.

National Institute of Health (NIH) officials are in Liberia now, preparing for a phase II/III vaccine trial that's slated to start in mid-January, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), said as he updated the lawmakers on progress being made in the development of medical products targeting Ebola.

Meanwhile, the Biomedical Advanced Research and Development Authority (BARDA) is helping scale up production of Mapp Biopharmaceutical Inc.'s Zmapp, an experimental antibody cocktail. Vials of the drug, which has been used on a compassionate-use basis in nine Ebola patients, will be filled in Indiana over the next few weeks in preparation for clinical trials in West Africa. BARDA Director Robin Robinson told the subcommittee that he anticipates significant challenges when the trials begin in January.

Overcoming the hurdles as the Ebola crisis continues to grow requires a lot of partnering with other agencies, regulators and industry. As a result of the coordination and the sense of urgency, Robinson said processes that normally take two to three years have been compressed into a year or 18 months.

The FDA, for instance, is taking unprecedented steps, Borio said. The agency has assigned more than 300 staff to work full-time on expediting its response to Ebola issues, including the granting of export permission for Zmapp and emergency use authorization of six diagnostics. One of the diagnostics was developed by the Defense Department, two by the Centers for Disease Control and Prevention (CDC) and three by industry.

The agency also has approved proposed studies in just a few days and granted compassionate use of experimental products within 24 hours. And it is working with the NIH to develop flexible, innovative and adaptive trials for multiple products under a common protocol. The $25 million in emergency funding the FDA is requesting would help it sustain its aggressive response to the crisis, Borio said.

To deal with the "incredible demands" the epidemic has placed on the FDA, the agency has explored multiple ways to be "responsive and adaptive to the complex range of issues that this constantly changing epidemic has presented," FDA spokeswoman Jennifer Rodrigiez told BioWorld Today. In some instances, it may have to prioritize activities across its centers, "but more often this has just meant our dedicated staff is just working harder and longer, including on evenings and weekends," Rodriguez added.

DIAGNOSTIC PROGRESS

Despite the challenges, the progress being made is palpable. On the diagnostics front, NIAID is supporting Corgenix Medical Corp.'s development of rapid immunodiagnostics using genomic technology to produce recombinant viral proteins. NIAID also is advancing development of other diagnostics, including novel technologies such as microfluidics, optofluidics and nanophotonics, which can detect an array of viruses, including Ebola.

Working with the CDC, NIAID scientists have established and staffed diagnostic laboratory field sites in Liberia to gather real-time data critical to patient care and monitoring of the epidemic. NIAID and CDC researchers also are collaborating with public health institutes in Mali, the latest country hit by the outbreak, to provide training in laboratory testing for identification of Ebola and other fever-causing viruses.

The World Health Organization (WHO) put out an urgent plea this week for rapid, sensitive and simple-to-use diagnostics, saying efforts to contain the outbreak are "currently hampered by cumbersome, slow and complex diagnostic tests that impose a number of additional logistical challenges, including requirements for a high level of laboratory biosafety and staff expertise in using sophisticated machines."

The standard molecular assays being used include the reverse-transcriptase polymerase chain reaction test, which requires a number of laborious procedures, takes from two to six hours and costs about $100. "These requirements are difficult to meet in resource-constrained West African settings," the WHO said.

To speed the development of rapid diagnostics, the FDA contacted several companies that have the capability to quickly develop an Ebola test and encouraged them to join the effort. A number of them are in discussions with the agency, Borio said.

VACCINE DEVELOPMENT

As the NIH and CDC prepare for advanced vaccine trials in Liberia and Sierra Leone, NIAID-supported phase I trials are ongoing in the U.S. and Europe of vaccine candidates developed by Glaxosmithkline plc. NIAID also is collaborating with the Defense Department on phase I trials of a vaccine developed by the Public Health Agency of Canada and licensed to Newlink Genetics Corp. (See BioWorld Today, Sept. 8, 2014.)

Other NIH efforts in vaccine development include:

• Crucell Holland BV's recombinant adenovirus-vectored Ebola vaccine and Crucell's recent vaccine collaboration with Bavarian Nordic, which should lead to phase I trials early next year (see BioWorld Today, Oct. 23, 2014);

• a collaboration with Thomas Jefferson University scientists to produce a vaccine candidate based on an existing rabies vaccine that would also generate immunity to Ebola and Marburg. The vaccine candidates, which are expected to begin clinical trials next year, were licensed to Exxell Bio;

• Profectus Biosciences Inc.'s preclinical development of a second recombinant VSV-vectored vaccine candidate against Ebola and Marburg viruses;

• a collaboration with the Galveston National Laboratory & Institute for Human Infections and Immunity at the University of Texas Medical Branch at Galveston on a paramyxovirus-based Ebola vaccine that's expected to progress to clinical trials in mid-2015;

• early development efforts involving a DNA vaccine targeting Ebola and Marburg viruses, an adenovirus-5-based intranasal Ebola vaccine and a combination virus-like particle/DNA vaccine targeting Ebola and Marburg viruses to be delivered by microneedle patch.

While the NIH generally funds early development of vaccines and other medical countermeasures, BARDA steps in at late-stage development and helps fund manufacturing of the products, Robinson said. If Congress approves the president's request for $6.2 billion in emergency funding to respond to the Ebola epidemic, BARDA will be able to support four of the five vaccine candidates currently being developed with NIH help, Robinson noted. The agency already has the funding necessary to support diagnostics candidates.

As more volunteer health care workers and military troops respond to the epidemic, the need for a vaccine is becoming even more pressing. "We really do owe them the development of a vaccine," Rep. Michael Burgess said. Some of those workers may choose to participate in January's vaccine trial.

Editor's note: This is the first part of a two-part series. Part 2 will look at the progress being made on drugs and devices to fight Ebola and provide an outlook on the epidemic.