Mutation Detection Test Classification for Blood Cancers

Summary

The Food and Drug Administration (FDA, the Agency, or we) is classifying the mutation detection test for myeloproliferative neoplasms into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for classification of the mutation detection test for myeloproliferative neoplasms. We are taking this action because we have determined that classifying the device into class II will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

Compliance Requirements

1. #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.; 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.; 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.; 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.; Information on device traceability and a description of the value assignment process for calibrators and controls.; Device precision data using clinical samples and controls to evaluate the within-lot, between-lot, within-run, between-run, and total variation.; Device linearity data generated from samples covering the device measuring range and for any standards used in the quantitation of allelic frequencies.; Device analytic sensitivity data, including limit of blank and limit of detection.; Device specificity data, including interference and cross-contamination.; 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.; 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.; 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.; The labeling required under § 809.10(b) of this chapter must include: (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.; This device is subject to premarket notification requirements under section 510(k) of the FD&C Act.; For a device to fall within this classification, and thus avoid automatic classification in class III, it would have to comply with the special controls named in this final order.

Market Impacts

• Reclassification from class III to class II with special controls reduces regulatory burden and enables market access through 510(k) pathway rather than premarket approval; Device can now serve as predicate for future substantially equivalent devices, enabling other sponsors to use 510(k) process rather than De Novo classification or PMA; Special controls requirements create technical and validation barriers that must be met for market access, including extensive performance validation and quality control requirements; Mandatory compliance with specific performance validation requirements including multi-site reproducibility studies, analytical sensitivity/specificity testing, and detailed labeling requirements

Validated Company Impacts