Health leaders call for manufacturers to consider the customer when developing diagnostic tests and discuss the need to develop direct-from-specimen tests to characterize pathogens.
Brad Spring, BS (Vice President, Regulatory Affairs & Compliance, BD Life Sciences, Baltimore, Maryland) and John Besser, PhD (Deputy Chief, Enteric Diseases Laboratory Branch, Centers for Disease Control and Prevention [CDC], Atlanta, Georgia) were among a panel of speakers in a recent webinar on using culture-independent diagnostic tests (CIDTs) to track infectious diseases.
Mr. Spring shared an industry perspective on developing laboratory tests. He noted that, although new multiplexed diagnostic tests offer several benefits, they may also prevent preservation of viable microorganisms for further public health-related activities.
He stressed the importance of incorporating the voice of the customer in efforts to develop laboratory tests, in particular during the concept and definition phases. Manufacturers typically conduct interviews with clinicians, laboratory personnel, administrators, and other key stakeholders, to identify customer must haves for a new product such as a laboratory-developed test (LDT). Manufacturers then translate these preferences into product specification, he said. However, conflicting customer requirements can also create challenges for manufacturers—for example, a requirement to use cell lysis in the LDT versus a requirement for the test to preserve a viable organism.
Moving forward, Mr. Spring therefore emphasized the need for manufacturers to engage public health laboratories, such as the CDC, in these voice-of-customer activities. In this way, manufacturers will be equipped to better understand and incorporate public health needs into the product development process, he said. In particular, this type of collaboration will help to manage conflicting product requirements.
He discussed opportunities for improvement in product development, noting that future trends in technology (such as metagenomics, proteomics, and next-generation sequencing [NGS]) may align better with public health needs.
Mr. Spring highlighted the need for continued collaborations between manufacturers, public health laboratories, and agencies such as the US Food and Drug Administration (FDA), to continue to explore measures to improve disease surveillance efforts. Once again, educational outreach is key, and manufacturers can improve collaborations with public health laboratories, microbiology groups, and stakeholders in industry, specifically by providing educational materials about new LDTs, and by holding in-service training sessions for new tests.
He also discussed opportunities to improve collection and preservation of isolates. Because Clinical Laboratory Improvement Amendment regulations require laboratories to follow manufacturers’ instructions, Mr. Spring stated that manufacturers should provide information that reinforces the need to preserve isolates for submission to public health laboratories; this might also include information about the need for clinical laboratories to contact their state public health laboratory for isolate submission guidelines for cases involving reportable pathogens.
The FDA can also contribute to manufacturers’ efforts to improve understanding of the CIDT landscape, Mr. Spring said. For example, the agency could share a list on the FDA website of new molecular diagnostic tests that are approved or cleared for detection of gastrointestinal microorganisms, he concluded.
John Besser, PhD, Deputy Chief, Enteric Diseases Laboratory Branch, CDC, Atlanta, Georgia, discussed the need to develop direct-from-specimen tests to characterize pathogens. Two important reasons for this, he explained, are to ensure specimen compatibility with commercial systems, and to reduce the time to actionable results. “After an individual eats contaminated food, confirmation of a case outbreak can be a lengthy process,” he said.
However, LDTs are difficult to develop. According to Dr. Besser, stool specimens are complex and can contain significant amounts of DNA and RNA from various sources— from the patient, from dietary plants and animals, and from bacteria and other microorganisms in the stool. Indeed, every gram of stool contains about 100 billion organisms, he said. Adding to this challenge, some pathogens, such as Salmonella and STEC are also genetically similar to commensal organisms.
Dr. Besser discussed three strategies that could help overcome these limitations, and that may represent future approaches to pathogen characterization using direct-from-stool tests. Amplicon sequencing is a targeted approach using readily available NGS technology to analyze genetic variation in specific regions of the genome. It has been shown to improve strain identification and characterization of E. coli 0157:H7, said Dr. Besser. Shotgun metagenomics is also widely used for characterizing microbiomes. This technology allows unbiased sequencing of all nucleic acids recovered directly from an environment such as stool, and, although it is an expensive and slow method that produces a lot of data, its potential power cannot be underestimated, said Dr. Besser. Single-cell sequencing is a third technology that can help to investigate these complex microbial specimens. This method uses an optical probe to sort individual cells based on selected characteristics, thereby allowing researchers to analyze genomic data from individual cells of interest in a clinical specimen.
Dr. Besser emphasized that direct-from-specimen tests could improve compatibility between CIDTs and public health, adding that continued research effort will help to overcome current technological limitations. These tests will also help to improve the efficiency and effectiveness of PulseNet, a national laboratory network that connects cases of foodborne illness to detect outbreaks, he added.
Continued collaborations between all stakeholders—including laboratory test developers, manufacturers, and public health laboratories—is the solution to develop better diagnostic tests to benefit patient care and public health, Dr. Besser concluded.
Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.