Manufacturers of commercial IHC assay reagents, kits, instruments, and computer software are federally regulated, with requirements based on risk level classification. The Code of Federal Regulations, 21CFR 864.1860, regulates immunohistochemistry reagents and kits.
For IHC:
- Class I: “…provide the pathologist with adjunctive diagnostic information…”“…minimal potential for harm to the user.”
- Class II: “…provide prognostic or predictive data…”“…mandatory performance standards…”
Many IHC test systems are FDA-approved for in vitro diagnostic (IVD) use. Other predictive marker tests are laboratory-developed tests using analyte-specific reagents (ASRs). The FDA defines ASRs as "antibodies, both polyclonal and monoclonal, specific receptor proteins, ligands, nucleic acid sequences, and similar reagents which, through specific binding or chemical reaction with substances in a specimen, are intended for use in a diagnostic application for identification and quantification of an individual chemical substance or ligand in biological specimens." ASRs are not subject to preclearance by the FDA; however, testing performed using ASRs does require test method validation.
The laboratory must verify or validate the performance of these test systems before use in patient testing. The extent of validation varies with the FDA status. Specific validation guidelines apply to predictive markers. Currently, the minimum standard evaluates 20 positive and 20 negative cases during the validation phase of implementation of new ER, PR, and HER2 testing. Validation is followed by a correlation study where the validated assay is compared or correlated with another previously validated similar assay. The College of American Pathologists further outlines the acceptable correlation values and numbers of cases to be associated depending on assay type. All steps must be completed and documented before the testing for patient diagnosis is performed.
