(a) Identification. Zika virus serological reagents are in vitro diagnostic devices that consist of antigens or antibodies for the detection of Zika virus or Zika antibodies in human specimens from individuals who have signs and symptoms consistent with Zika virus infection and/or epidemiological risk factors. The detection aids in the diagnosis of current or recent Zika virus infection or serological status. Negative results obtained with this test do not preclude the possibility of Zika virus infection, past or present. Positive results should be interpreted with consideration of other clinical information and laboratory findings and should not be used as the sole basis for treatment or other patient management decisions.

(b) Classification. Class II (special controls). The special controls for this device are:

(1) The labeling required under § 809.10(b) of this chapter must include:

(i) An intended use with a detailed description of what the device detects (Zika IgM antibodies, other Zika antibodies, or Zika antigens), the type of results provided to the user, the specimen type for which testing is indicated (e.g., serum, whole blood), the clinical indications appropriate for test use, and the specific population(s) for which the test is intended.

(ii) Performance characteristics from analytical and clinical studies required under paragraphs (b)(2)(ii) and (iii) of this section.

(iii) A detailed explanation of the interpretation of results and criteria for validity of results (e.g., criteria that internal or external quality controls must meet in order for a test/test run to be valid, minimum signal strength that the sample has to yield to be interpretable as a valid result).

(iv) Limiting statements indicating that:

(A) Results are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. The test results should be interpreted in conjunction with clinical observations, patient history, epidemiological information, and other laboratory evidence.

(B) Device results are intended to be followed up according to the latest professional guidelines (e.g., recommendations from the Centers for Disease Control and Prevention) for the diagnosis of Zika virus infection.

(C) Negative test results do not preclude the possibility of Zika virus infection, past or present.

(D) Specimens can result in false negative results on the device if collected outside of the appropriate response window for specific Zika virus antigens or antibodies, as determined by scientific evidence (e.g., for IgM <7 days post symptom onset (pso) or risk of exposure and if collected past 84 days pso).

(v) Detailed instructions for use that minimize the risk of generating a false positive or false negative result (e.g., co-testing of other matrices).

(2) Design verification and validation must include:

(i) A detailed device description, including all device parts (e.g., Zika antigen target, other flavivirus antigen target, capture antibodies), instrument requirements, ancillary reagents required but not provided, and the technological characteristics, including all pre-analytical methods for specimen processing.

(ii) Detailed documentation and results from analytical performance studies including: characterization of the cut-off(s), analytical sensitivity to a standardized reference material that FDA has determined is appropriate (e.g., World Health Organization reference standard or the Centers for Disease Control and Prevention reference standard), class specificity for human antibodies (e.g., IgM or IgG), analytical specificity (cross reactivity including cross reactivity to other flaviviruses), interference, carryover/cross contamination, specimen stability, hook effect (if applicable), matrix equivalency (if applicable), freeze-thaw studies (if applicable), and reproducibility.

(iii) Detailed documentation and results from clinical studies, including the clinical study protocol (with a description of the testing algorithm and results interpretation table), detailed clinical study report, including line data of the clinical study results, and other appropriate statistical analysis. The samples used in the clinical study must be collected from subjects representative of the full spectrum of the intended use population (e.g., endemic and non-endemic regions if both are indicated).