|Trends & Perspectives|
While the IVD industry continues to debate and discuss FDA's guidance on analyte specific reagents (ASRs), other types of components, specifically antibodies and nucleic acid sequences labeled for “research use only” (RUO), continue to be used in clinical laboratories to develop tests. Such RUO components have not attracted nearly as much attention as ASRs.
The College of American Pathologists (CAP; Northfield, IL) has established rules for its accredited labs on using RUO reagents. According to CAP's anatomic pathology checklist, RUOs “purchased from commercial sources may be used in laboratory-developed tests only if the laboratory has made a reasonable effort to search for IVD- or ASR-class reagents. The results of that failed search should be documented by the laboratory director.”
“Our policy has been that the only circumstance under which CAP-accredited labs are allowed to use RUOs would be where there are no alternatives available,” says Patrick Fitzgibbons, MD, chairman of CAP's immunohistochemistry committee. “In other words, no ASRs and no IVDs are available. So in that setting, the laboratory directors can take responsibility for using those reagents, provided that they have fully validated the test under all the rules of CLIA, established the performance characteristics of their assay, and can document all of that. They also have to document that they have done a search for any available ASRs or IVDs and that none exist.”
The CAP checklist adds that “if the laboratory performs patient testing using Class I ASRs obtained or purchased from an outside vendor, federal regulations require that a disclaimer accompany the test result on the patient report.” Even though FDA has not established similar disclaimer requirements for RUO reagents, CAP officials said that laboratories are encouraged to use a disclaimer for RUOs.
“Our policy has been basically to follow FDA rules on the use of the disclaimer,” says Fitzgibbons. “While FDA requires a disclaimer that uses specific wording for any assay that's developed using ASRs, the agency never specified any such disclaimer or requirement for any other assays, specifically for RUOs. So CAP doesn't have a formal policy requiring labs to use such a disclaimer. But if they asked us whether they should use it or not, we would advise them that they should use some form of disclaimer to indicate that this is a laboratory-developed assay, it's been fully validated, and [it's] completely within compliance of all the CLIA regulations.”
Despite such rules and guidelines, there has been some concern in the IVD industry regarding the use of RUO reagents. One concern relates to how companies producing RUOs have an unfair advantage by not having to comply with FDA regulations.
“RUO-only companies that are not FDA registered have an open door to have their products used as diagnostics with no accountability at all to anyone,” says Tim Morken, a technical support manager at ThermoFisher Scientific (Fremont, CA). “When they sell to labs, the lab takes on all the responsibility. The RUO-only company has an advantage in that it does not have to spend money or other resources to meet FDA quality control standards, and FDA has no recourse at all toward the company in terms of medical device reporting (MDR). Indeed, there will be no MDR if there is a problem with the product. It seems that undercuts those companies that go through the FDA process.”
Another concern is the notion that CAP is effectively promoting the use of RUO reagents by not creating stricter requirements and providing further education on RUOs.
“I have not seen CAP publishing articles or going to meetings telling pathologists to use RUOs in place of available IVDs for the same target,” says Morken. “Until a couple of years ago, everyone seemed to understand that RUOs were not to be used at all in diagnostics. However, research may have hinted that certain RUO antibodies may be diagnostically useful, but no company has them available as IVDs or ASRs. I have talked to pathologists who are not aware of the differences between RUOs, ASRs, and IVDs. By opening the door to RUOs, CAP is effectively promoting their use.”
CAP officials responded that it is a mischaracterization to say they are promoting the use of RUO reagents simply because it is permitted. On the contrary, CAP's position is that RUOs could be used in diagnostic testing as a last resort if there are no alternatives.
“The vast majority of labs that are out in the community in a hospital setting are using automated immunostainers obtained from large companies, and they're going to be purchasing their reagents from those vendors and are not using RUOs either,” says Fitzgibbons. “So the great majority of labs do not use RUOs at all. I think it's a very minor issue in that sense. For us to spend a huge amount of time going around to meetings talking about not using RUOs would seem to be an unnecessary way to discuss this, and it would not have much of an impact.”
Additional information about CAP's laboratory accreditation procedures can be accessed via its Web site at www.cap.org.