SILVER SPRING, Md. – Can the development of antimicrobials and susceptibility tests be coordinated more effectively? Yes, according to attendees of an FDA workshop Thursday on challenges and opportunities for getting clearance for antimicrobial susceptibility tests (ASTs) shortly after antimicrobial drug approval.

"It takes a village," was a phrase tossed out several times during the event, in which clinicians, laboratory representatives, regulators, and members of the pharmaceutical and medical device industries offered potential solutions.

The meeting came about a week after the release of draft guidance that is intended to give the FDA recommendations on interactions between pharmaceutical companies and device companies for coordinated development of a new microbial drug and an AST.

Ribhi Shawar, branch chief of the general bacteriology and antimicrobial susceptibility branch within Center for Devices and Radiological Health (CDRH), set the stage by emphasizing that "this is not co-development," or companion diagnostics. Rather, it is coordinated development to bring drug approval and test clearance closer together.

Shawar said other key messages from the draft document are that the FDA is encouraging joint meetings involving the drug sponsor and device manufacturer, as well as representatives from the Center for Drug Evaluation and Research and CDRH. Either the AST device manufacturer or drug sponsor may request these meetings.

He also stressed that review of the new antimicrobial drug product and AST device will remain independent. ASTs are class II devices, subject to a 90-day review cycle.

Amy Mathers, associate professor at the University of Virginia, put the issue in perspective, noting that patient safety is paramount. She described her experience treating patients without the benefit of susceptibility data. She told the story of a woman in her 20s with cystic fibrosis with an infection. Lacking a susceptibility test, Mathers started one treatment, but within a few days, the patient developed neurological toxicity.

Trying another treatment proved futile, demonstrating to Mathers that "it is really difficult to use a drug" without susceptibility data. Indeed, as several presenters noted, doctors often are reluctant to use new antimicrobials without such data.

"We really need to close the [development] gap," said Mary Motyl of Merck & Co., adding that two- to three-year delay between the two processes has not decreased, remaining the same as it was 15 years ago.

Motyl said internal delays in getting agreements signed between drug and device companies are "interminably long," with lawyers on each side taking months to come to an agreement. Darcie Carpenter of Beckman Coulter Inc. agreed, adding that lawyers also must redraw contracts if the pharmaceutical company sells an antimicrobial agent to another firm.

She also highlighted the complexity of device development, particularly as many rely on software during the interpretation process. While the device may be cleared, the company may need to wait for the software update before it can be used, she said.

Merck's strategy for working with AST developers involves using a company-established susceptibility testing development team for Zerbaxa, an antibacterial drug product approved in 2014 to treat complicated intra-abdominal infections and complicated urinary tract infections. The team meets with each device manufacturer to follow progress and expedite any delays, according to Motyl. She said the company also plans to review basic information about future antibiotic development with all of the device manufacturers simultaneously.

Looking at the issue as a whole, she recommended there be incentives for device makers to develop tests for new antibiotics – a point with which many participants agreed.

Unlike on the drug side, there is the lack of incentives for developing these tests. For example, under the Generating Antibiotics Incentives Now Act, antibacterials and antifungals intended to treat serious or life-threatening infections may be designated as a qualified infectious disease product. This designation allows a candidate to gain priority review and fast track review status. Recommendations

Two presenters came armed with suggestions for the FDA. Carpenter and Bill Brasso, senior staff scientist at BD Diagnostic Systems, part of Becton, Dickinson, and Co., recommended the agency continue to have meetings to gain stakeholder input.

In addition, they said, antimicrobial drug sponsors should give AST device manufacturers access to clinical trial isolates. These isolates can serve as a significant part of AST device manufacturers' data collection.

Speaking on behalf of the Susceptibility Testing Manufacturing Association, the two also provided some suggestions on the draft guidance. They suggested clarifying whether it would change when the AST device manufacturer can submit an FDA 510(k) application.

Further, they asked about breakpoint changes, which are used to define susceptibility and resistance, and whether the document could be changed to address them.

Steve Gitterman, deputy director of the Division of Microbiology Devices, Office of In Vitro Diagnostics and Radiological Health within CDRH, tried to get participants to think beyond regulatory solutions, as they are not enough to spur development.

"We're not impotent, but we're not omnipotent," Gitterman said. He encouraged the audience to look at the draft guidance through the regulatory, legislative, and advocacy perspective.

Regarding the suggestions made in Basso and Carpenter's presentation, he said FDA officials, "have talked about moving forward on every one of these issues, but it's really tough."

In particular, he emphasized that the draft guidance is about tearing down barriers and allowing AST developers to submit applications while drugs are still in development.