In situ hybridization test systems for use with a corresponding approved oncology therapeutic product.

(a) Identification. In situ hybridization (ISH) test systems indicated for use with a corresponding approved oncology therapeutic product are identified as prescription in vitro diagnostic devices consisting of nucleic acid probes intended for the qualitative or quantitative detection of specific nucleic acid sequences in human clinical specimens to provide information related to the use of a corresponding approved oncology therapeutic product as described in the corresponding approved oncology therapeutic product labeling. (b) Classification. Class II (special controls). The special controls for this device are: (1) Design verification and validation must include: (i) Specification for risk mitigation elements intended to mitigate risks associated with testing and results interpretation, including controls, procedures, and user training requirements, as appropriate. (ii) Specification of the criteria for test result interpretation and reporting, including device cut-off(s) ( i.e., clinical threshold(s) or the medical decision point(s) between positive and negative results) or other relevant criteria that distinguishes positive and negative or quantitative results. This information must include the rationale for the chosen cut-off(s) to include the upper reference of normal, or other relevant criteria and results supporting validation of the cut-off(s) evaluating borderline samples around the clinical threshold(s). Scoring criteria for all applicable signals must be included. (iii) Device performance data demonstrating appropriate analytical sensitivity from studies using interphase nuclei from intended use specimen type(s) that are considered karyotypically normal, or through an alternative approach, as determined to be appropriate by FDA ( e.g., probe sensitivity and probe limits). (iv) Device performance data demonstrating appropriate analytical specificity of the device for the intended use specimen type(s), as determined to be appropriate by FDA ( e.g., probe specificity, interference study, cross-reactivity and cross contamination testing). (v) Device performance data demonstrating appropriate precision and reproducibility of the device using clinical specimens representing the intended use specimen type(s) and intended use biomarker(s) from the intended use population and investigating major sources of variability ( e.g., multiple reagent lots, operators, instruments over multiple days, and inter- and intra-reader precision). Surrogate samples that adequately represent the intended use specimen type(s) and intended use biomarker(s) may be appropriate, as determined by FDA, to supplement clinical specimens. If the device will be used at more than one site, data must demonstrate adequate reproducibility across multiple intended use sites. Additionally, precision and reproducibility of the device must be evaluated with specimens near the clinical decision threshold(s) and near the limits of reportable range. Additionally, device performance data demonstrating appropriate precision must be included from studies evaluating the different signals and associated cut-offs and controls, as determined to be appropriate by FDA. Furthermore, precision of the device must be evaluated per specimen and in aggregate. (vi) Device performance data demonstrating appropriate device robustness, as determined to be appropriate by FDA. The study must assess the tolerance ranges for various critical test and specimen parameters, as applicable. (vii) Device performance data demonstrating linearity of quantitative results using samples covering the device measuring range, as applicable. (viii) Device performance data demonstrating appropriate specimen stability based on the intended use specimen type(s) of the device, as applicable. (ix) Clinical data generated using well-characterized clinical specimens representative of the intended use population demonstrating appropriate clinical performance of the device for its intended use, as determined to be appropriate by FDA. (2) Labeling must include: (i) An appropriate summary, as determined by FDA, of the performance studies performed and the results of those studies, including those that relate to all design verification and validation special controls. (ii) A limiting statement, as appropriate, that explains that the test results are intended to be interpreted by a qualified or appropriately trained reader in conjunction with other diagnostic laboratory test results and/or pathology test results, relevant clinical information, and proper controls. (iii) Language indicating that the test system is indicated for use with a corresponding FDA-approved oncology therapeutic product and device labeling must be consistent with the information set forth in the corresponding FDA-approved oncology therapeutic product labeling. [91 FR 53190, Aug. 17, 2026]