NEW YORK (GenomeWeb) – As the diagnostics industry awaits the release of final regulations for lab-developed tests, some laboratories are banking on commercially available analyte-specific reagents (ASRs) as a means of simplifying their work and as a key enabler in responding to critical patient needs when tests are not otherwise available.
Realizing this market opportunity, diagnostics firm Meridian Bioscience announced last week that it was launching a new ASR product line that includes a primer set and probes to detect the target sequence associated with clarithromycin-resistant Helicobacter pylori strains and to detect H. pylori, a gram-negative bacterium usually found in the stomach.
The firm said that it has plans to grow its presence in the clinical market by expanding its menu of products that include ASRs and other early-stage diagnostic products, and that in the near future it expects to introduce additional ASRs as the company expands its product line.
There are no commercially available in vitro diagnostic products for the identification of Clarithromycin-resistant strains in the US, according to Meridian, and therefore its tests address an unmet need, allowing laboratories to develop their own tests.
"The ASRs allow our partners in centers of excellence and research facilities to expand innovation and discovery in new treatments and diagnosis," Monica Penagos, Meridian Bioscience's marketing director, told GenomeWeb. "Any labs in the US that have their own home brews, or LDTs, that are classified and qualified as highly complex are our targets for ASRs."
Laboratories use ASRs — which include polyclonal and monoclonal antibodies, ligands, specific receptor proteins, nucleic acid sequences, and similar reagents — in developing and validating their own tests. According to the US Food and Drug Administration's guidance for industry, ASRs are intended for use in diagnostic tests that identify and quantify chemical substances or ligands in biological specimens through binding or chemical reactions with substances in a specimen.
In its guidance document, the FDA stated it does not intend to provide direction on the role of clinical laboratories in the development of laboratory-developed tests.
Meridian's life sciences and Bioline molecular components businesses already provide primers and probes to manufacturers, centers of excellence, and research facilities, so the recent ASR launch is a natural extension of the company's portfolio, Penagos said.
"We see providing ASRs as not only a natural extension for our products but also as something that provides centers of excellence with high-quality reagents that meet US Food and Drug Administration high standards," Penagos said.
A range of issues, such as the FDA's pending LDT regulations, reimbursement difficulties, and investment uncertainty, have led some LDT developers to come up with innovative growth strategies including selling ASRs, which for labs could reduce the complexity of building an LDT from scratch.
"A general challenge in laboratory testing is that IVD tests are not available for everything," Sherry Dunbar, senior director of global scientific affairs at Luminex, told GenomeWeb. "What's frustrating to me is that if a patient needs a test and an IVD is not available, and the lab has no way to perform that test, then it is the patient that loses out. So, there's got to be a way to get the needed test performed in order to properly diagnose and treat the patient.
"If an IVD-cleared test is not commercially available, then the laboratory has the choice of not offering the test, sending it out to someone who is offering the test, or developing that test [itself]," said Dunbar, who was a CLIA lab director prior to joining Luminex. "Analyte specific reagents are useful if the lab decides that they want to develop their own tests."
Luminex develops, manufactures, and markets instruments and assays that use an open-architecture multi-analyte platform, and it has several tests that have been cleared for marketing by the FDA. But the company also offers a broad menu of ASRs based on its MultiCode-RTx technology for the identification and quantification of various pathogens.
Speaking from the viewpoint of a CLIA lab director, Dunbar said that if a test defined as a need by a hospital or the patient population was not commercially available, the lab would need to develop the test and validate it in-house as an LDT. When no reagents are available and laboratories develop tests from scratch, they must define targets based on published literature and then establish the sequences of primers and probes, among other materials, and the burden is on the laboratory to do a full validation of everything from all inputs to all outputs, Dunbar said. Reagents that have already been developed and are available for purchase from a commercial source can help a lab in this circumstance, she added.
"As a company providing diagnostic tests," Dunbar said, "We know that it is quite expensive to do a clinical trial study and submit that data to the FDA, so for an individual lab to do that or something like that is really cost prohibitive.
"With the pending FDA guidance regarding LDTs, it may be risky for labs to take the [LDT] route," Dunbar said. "Recently, based on FDA guidance documents, there appears to be concern that there will be more risk associated with LDTs resulting from [the] availability of next-generation sequencing and other technologies, and in particular genetic tests that may determine a treatment course."
The FDA in July released two draft guidance documents outlining how it might review the analytical and clinical validity of next-generation sequencing tests, which encompass technology that is quickly dominating genetic testing. The agency has tried to keep this work separate from the ongoing controversy surrounding its 2014 proposal to regulate LDTs, a responsibility that has been under the purview of the Centers for Medicare and Medicaid Services through the Clinical Laboratory Improvement Amendments.
In its draft guidance on regulating LDTs, the FDA proposed a risk-based regulatory framework. The agency said it planned to continue to exercise enforcement discretion for Class I devices, as well as for LDTs for rare diseases and for unmet medical needs. For Class II and Class III LDTs, or moderate- to high-risk tests, FDA would phase in registration, listing, adverse events reporting, as well as 510(k) and premarket review requirements, over a nine-year period.
As of now, the FDA has not released the final rule.
"I think the jury is still out and it remains to be seen how and where the FDA draft guidance on regulation of LDTs will be implemented and what kind of an effect the release of lab-developed test final guidelines would have on the market for analyte-specific reagents," Dunbar said. "Depending on the final decision, labs may decide to abandon doing LDTs altogether and they may decide it is too burdensome, in which case there would probably only be a few of the larger reference labs that have the capability to perform the test with a large enough infrastructure to support developing and validating an LDT per final FDA requirements for LDTs."