(203 days)
The MALDI Biotyper CA System is a mass spectrometer system using matrix-assisted laser desorption/ionization - time of flight (MALDI-TOF) for the identification and differentiation of microorganisms cultured from human specimens.
The MALDI Biotyper CA System is a qualitative in vitro diagnostic device indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infections.
The MBT-CA System consists of the Microflex LT/SH mass spectrometer, reference library, kit reagents (US IVD HCCA, US IVD Bacterial Test Standard), US IVD 48 Spot Target or MBT Biotarget 96 US IVD plate, and software. The MALDI Biotyper CA System with closed safety covers is a Class 1 Laser product. With the safety cover opened it becomes a Class 4 Laser product.
The MALDI Biotyper CA System reference library was established by analyzing the type strain from each claimed species combined with 4 to ~30 additional strains from the same species provided by clinical laboratories or commercial strain collections. Currently a total of 3029 strains (covering 334 species / groups with 294 bacteria plus 40 yeasts) are contained in the clinically validated MBT-CA library.
Implementation methodology, construction parameters and quality assurance protocols use a standard operating protocol for generation of reference entries and all testing parameters are the same.
MBT-CA microorganism identification is based on isolate MALDI spectra using Bruker reference libraries with a 1:1 comparison of unknown MALDI spectra against each single entry of a given reference library. During a single identification event, an unknown MALDI spectra is compared against each single reference entry producing individual log(score) results. This number of log(scores) is sorted based on their value and the highest one is used to generate the final result. The addition of new reference entries does not influence the already included entries. If no reference entries are removed within a library update the log(score) calculation remains unchanged for the same MALDI spectra.
MALDI Biotyper CA System client software displays a user-interface which guides the user through the MALDI Biotyper CA System workflow. The MALDI Biotyper CA System client also interfaces to the flexControl software for automated acquisition of mass spectra on the microflex LT/SH instrument.
The MALDI Biotyper CA System server communicates with the MALDI Biotyper CA System client and the MBT-DB server. It performs preprocessing on acquired spectra, and matches peak lists against the Main Spectrum (reference pattern, (MSP)) for matching and calculates the score value (log (score)).
The MBT-DB server stores all information for the MALDI Biotyper CA System. The MBT-DB maintains spectra data (creation information and mass/intensity lists), project data (results of defined and executed runs), method data (parameter lists for spectra preprocessing and identification), user management data, reference patterns and other peak lists plus additional maintenance data.
GTPS firmware communicates with the flexControl PC software, controls and monitors the vacuum, moves the sample carrier and performs the docking of the target plate, controls and monitors high voltages in the ion source, generates trigger signals, and monitors instrument status.
The flexControl acquisition software communicates with the MALDI Biotyper CA System client, loads automatic run jobs, communicates with the GTPS firmware, communicates with the laser in the microflex LT/SH instrument, sets the acquisition parameters in the digitizer and reads the acquired data from the digitizer, performs automated data acquisition, evaluates acquired spectra, adjusts the laser power during automatic data acquisition, performs a re-calibration of the time-of-flight to mass transformation, stored acquired spectra on disk and performs source cleaning. The flexControl software does not display a user interface.
The optional Honeywell (Hyperion 1300g) Barcode Reader USB cable is connected to the MALDI Biotyper CA System computer. The barcode reader scans the unique ten-digit target ID which appears in the Target ID box on the target plate. After the target ID has been entered, the a new Run page opens and the ten-digit target ID appears as the Plate ID and is appended to the Run name. Sample identifications are entered into the computer corresponding to the target plate position for that run.
Here's a breakdown of the acceptance criteria and study information for the MALDI Biotyper CA System, extracted from the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document describes performance for the addition of Candida auris to the existing MBT-CA reference library, rather than a full de novo clearance study of the entire device. Therefore, the "acceptance criteria" here refer to the performance required for the inclusion of this new organism into the established system.
| Criteria (for C. auris identification) | Reported Device Performance (C. auris identification) |
|---|---|
| High confidence organism ID (log(score) $\ge$ 2.0) | 22 out of 22 (100%) correctly identified |
| Low confidence organism ID (log(score) $\ge$ 1.7 - |
§ 866.3378 Clinical mass spectrometry microorganism identification and differentiation system.
(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.