(a) Identification. A mutation detection test for myeloproliferative neoplasms is an in vitro diagnostic device intended for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from whole blood. The test is intended for use as an adjunct to evaluation of suspected polycythemia vera in conjunction with other clinicopathological factors.

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

(1) Design verification and validation must include:

(i) A detailed description of all components in the test, including the following:

(A) A detailed description, including illustrations or photographs of non-standard equipment or methods, of the test components, including all required reagents, instrumentation, and equipment.

(B) Detailed documentation of the device software, including standalone software applications and hardware-based devices that incorporate software.

(C) A detailed description of methodology and assay procedures including appropriate internal and external quality controls that are recommended or provided. The description must identify those control elements that are incorporated into the testing procedure.

(D) A detailed specification for sample collection, processing, and storage.

(E) A description of the criteria for test result interpretation and reporting including result outputs, analytical sensitivity of the assay, and the values that will be reported.

(ii) Information that demonstrates the performance characteristics of the test, including:

(A) For indications for use based on a threshold established in a predicate device of this generic type, device performance data from either a method comparison study to the predicate device or through a clinical study demonstrating clinical validity using well-characterized prospectively or retrospectively obtained clinical specimens, as appropriate, representative of the intended use population.

(B) For indications for use based on a threshold not established in a predicate device of this generic type, device performance data from a clinical study demonstrating clinical validity using well-characterized prospectively or retrospectively obtained clinical specimens, as appropriate, representative of the intended use population.

(C) Device reproducibility data generated, using a minimum of three sites, of which at least two sites must be external sites, with two operators at each site. Each site must conduct a study that includes at least two operators per site, two runs per operator per day over a minimum of three non-consecutive days evaluating a sample panel that contains allelic frequencies that span the claimed measuring range, and include the clinical threshold allelic frequency. Pre-specified acceptance criteria must be provided and followed.

(D) Information on device traceability and a description of the value assignment process for calibrators and controls.

(E) Device precision data using clinical samples and controls to evaluate the within-lot, between-lot, within-run, between-run, and total variation.

(F) Device linearity data generated from samples covering the device measuring range and for any standards used in the quantitation of allelic frequencies.

(G) Device analytic sensitivity data, including limit of blank and limit of detection.

(H) Device specificity data, including interference and cross-contamination.

(I) Device and clinical specimen stability data, including real-time stability (long-term storage and in-use stability) and stability evaluating various storage times, temperatures, and freeze-thaw conditions, as appropriate.

(iii) Identification of risk mitigation elements used by the device, including a detailed description of all additional procedures, methods, and practices incorporated into the instructions for use that mitigate risks associated with testing using the device.

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

(i) An intended use statement, including an indication for use that includes the variant(s) for which the assay was designed and validated, for example, JAK2 G1849T.

(ii) A detailed description of the performance studies conducted to comply with paragraph (b)(1)(ii) of this section and a summary of the results.