(a) Identification. A clinical mass spectrometry microorganism identification and differentiation system is a qualitative in vitro diagnostic device intended for the identification and differentiation of microorganisms from processed human specimens. The system acquires, processes, and analyzes spectra to generate data specific to a microorganism(s). The device is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infection.

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

(1) The intended use statement must include a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended, when applicable.

(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt with an indication for in vitro diagnostic use.

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

(i) A detailed device description, including all device components, control elements incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology and all pre-analytical methods for processing of specimens, and algorithm used to generate a final result. This must include a description of validated inactivation procedure(s) that are confirmed through a viability testing protocol, as applicable.

(ii) Performance characteristics for all claimed sample types from clinical studies with clinical specimens that include prospective samples and/or, if appropriate, characterized samples.

(iii) Performance characteristics of the device for all claimed sample types based on analytical studies, including limit of detection, inclusivity, reproducibility, interference, cross-reactivity, interfering substances, carryover/cross-contamination, sample stability, and additional studies regarding processed specimen type and intended use claims, as applicable.

(iv) A detailed explanation of the interpretation of test results for clinical specimens and acceptance criteria for any quality control testing.

(4) The device's labeling must include a prominent hyperlink to the manufacturer's website where the manufacturer must make available their most recent version of the device's labeling required under § 809.10(b) of this chapter, which must reflect any changes in the performance characteristics of the device. FDA must have unrestricted access to this website, or manufacturers must provide this information to FDA through an alternative method that is considered and determined by FDA to be acceptable and appropriate.

(5) Design verification and validation must include:

(i) Any clinical studies must be performed with samples representative of the intended use population and compare the device performance to results obtained from an FDA-accepted reference method and/or FDA-accepted comparator method, as appropriate. Documentation from the clinical studies must include the clinical study protocol (including predefined statistical analysis plan, if applicable), clinical study report, and results of all statistical analyses.

(ii) Performance characteristics for analytical and clinical studies for specific identification processes for the following, as appropriate:

(A) Bacteria,

(B) Yeasts,

(C) Molds,

(D) Mycobacteria,

(E) Nocardia,

(F) Direct sample testing (e.g., blood culture),

(G) Antibiotic resistance markers, and

(H) Select agents (e.g., pathogens of high consequence).

(iii) Documentation that the manufacturer's risk mitigation strategy ensures that their device does not prevent any device(s) with which it is indicated for use, including incorporated device(s), from achieving their intended use (e.g., safety and effectiveness of the functions of the indicated device(s) remain unaffected).

(iv) A detailed device description, including the following:

(A) Overall device design, including all device components and all control elements incorporated into the testing procedure.

(B) Algorithm used to generate a final result from raw data (e.g., how raw signals are converted into a reported result).

(C) A detailed description of device software, including validation activities and outcomes.

(D) Acquisition parameters (e.g., mass range, laser power, laser profile and number of laser shots per profile, raster scan, signal-to-noise threshold) used to generate data specific to a microorganism.

(E) Implementation methodology, construction parameters, and quality assurance protocols, including the standard operating protocol for generation of reference entries for the device.

(F) For each claimed microorganism characteristic, a minimum of five reference entries for each organism (including the type strain for microorganism identification), or, if there are fewer reference entries, a clinical and/or technical justification, determined by FDA to be acceptable and appropriate, for why five reference entries are not needed.

(G) DNA sequence analysis characterizing all type strains and at least 20 percent of the non-type strains of a species detected by the device, or, if there are fewer strain sequences, then a clinical and/or technical justification, determined by FDA to be acceptable and appropriate, must be provided for the reduced number of strains sequenced.

(H) As part of the risk management activities, an appropriate end user device training program, which must be offered as an effort to mitigate the risk of failure from user error.