Editors: Olga Pozdnyakova, MD, PhD, Geoffrey Wool, MD, PhD, David Bernard, MD, PhD & Raul S. Gonzalez, MD
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Q. When we receive new immunohistochemistry antibodies or DAB kits, they undergo a quality control process. Every institution where I have worked has done this task a little differently. When a laboratory receives a new antibody, what is the correct QC process? What if we receive two units of the same antibody from the same lot but one came in on Thursday and one on Friday?
A. May 2026—A laboratory’s process to confirm acceptable performance of new reagent lots should comply with CAP checklist requirement ANP.22760 New Reagent Lot Confirmation of Acceptability. Specifically, new lots of reagents for an antibody or detection system must be compared to the previous lot using at least one known positive and one known negative control tissue. This comparison should be made on slides cut from the same control block.
Reagent lot numbers can be confirmed by reviewing the package insert and/or packaging materials for the reagents received. Reagents from the same lot that arrive at the laboratory on separate days do not require testing of both reagents and may not require testing of either if the lot is the same as that of reagents that were previously confirmed by the lab. Conversely, multiple reagent packages for the same antibody or detection system received in the lab on the same day each require confirmation of acceptable performance if they are from different lots.
Each laboratory must develop processes for recording and monitoring the lot numbers of reagents received and identify when reagents from new lots are required for clinical testing, confirm acceptable performance for new lots of reagents, and maintain corresponding records as evidence of compliance with the CAP checklist requirement. Laboratories are permitted to determine which processes they use to achieve these requirements in a manner that is sensitive to their workflow and other needs.
Emily Meserve, MD, MPH
Pathologist
Spectrum Healthcare Partners
Portland, Me.
Vice Chair, CAP Immunohistochemistry Committee
Q. Should clinical laboratories treat FDA class I devices like FDA-cleared or -approved devices or laboratory-developed tests?
A. Medical devices are classified by the FDA as class I (low risk), class II (moderate risk), or class III (high risk) based on their intended use and risk profile. Class I devices are subject to general controls, while class II devices are subject to general and special controls and follow the FDA’s premarket notification (i.e. 510[k]) process. Class III devices require general controls and more extensive premarket authorizations.
Information on devices that are listed, cleared, and/or approved by the FDA can be found in several public FDA databases.1,2 FDA medical device classification reflects the manufacturer’s intended use, risk profile, and regulatory obligations. Whether a test is treated as an FDA-cleared or -approved assay or a laboratory-developed test (LDT) depends on how the laboratory incorporates the device into patient testing and whether its use is consistent with its FDA-cleared or -approved labeling.
Regulatory descriptions for many class I medical devices listed in the U.S. Code of Federal Regulations (CFR) note that the devices may be “exempt from premarket notification procedures.” Refractometer for clinical use (21 CFR §862.2800) is an example of a class I medical device in the federal regulations that includes this language.3 However, because many class I devices have not gone through FDA clearance or approval processes, how clinical laboratories handle them from the standpoint of CLIA regulatory compliance may cause confusion. In 2003, the Centers for Medicare and Medicaid Services provided some clarity on this topic in the Federal Register, noting that the term FDA-cleared or -approved test system “includes test systems exempt from FDA premarket clearance or approval.”4 In this context, clinical laboratories may consider class I devices—when used consistent with their description in the CFR—to be treated similarly to those that are FDA cleared or approved.
There is an important caveat to this perspective. As noted above, class I devices are subject to FDA general controls, which require manufacturers of such devices to register with the FDA and list their devices in an FDA database.5 More simply stated, a manufacturer’s piece of equipment or reagent is only a class I device if the FDA classified it as such based on its intended use and risk profile, it is registered and listed with the FDA, and the manufacturer follows other general controls.
Similar equipment or reagents that do not meet the aforementioned criteria may be available from life science manufacturers. These manufacturers are prohibited from marketing such products for clinical use, as doing so would be considered misbranding and subject the manufacturer to legal penalties and enforcement action under the Federal Food, Drug, and Cosmetic Act. Yet high-complexity CLIA laboratories are not prohibited from incorporating such life science products into LDTs, although the laboratory assumes legal responsibility for their use.