(221 days)
VITEK® MS PRIME is a mass spectrometry system using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) for the identification of microorganisms cultured from human specimens.
The VITEK® MS PRIME 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.
This 510(k) submission introduces the VITEK®MS PRIME System. The VITEK® MS PRIME is intended for laboratory use by professional users who are trained in microbiology and good laboratory practices.
The VITEK® MS PRIME makes microorganism identifications via matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF MS) technology, which includes the three basic principles of ionization, separation, and detection,
As a first step, a VITEK® MS-DS Target Slide is prepared in accordance with the instructions for use.
NOTE: Depending on the culture, the analyte sample (i.e. microorganism from cultured media) may be directly spotted to a target slide, or for Mycobacterium. Nocardia and mould it must be processed/inactivated before adding to the target slide.
Once the specimen (cultured from the appropriate media) is spotted to the target slide, a matrix is added for the purpose of easy sublimation and strong absorbance in the laser wavelength employed by theinstrument.
NOTE: The VITEK® MS PRIME is a Class 1 laser product, containing a Class 4 Neodymium-doped yttrium lithium fluoride (Nd:YLF) laser – the laser operates at a wavelength of 349 nm.
The prepared slide is then loaded onto the VITEK®MS PRIME instrument. where a laser targets the sample spot and pulses the isolate spot, resulting in vibrational excitation of matrix and analyte molecules. The matrix transfer protons to the analyte resulting in a positive charge. So as part of the first basic principle, the ionized molecules are then accelerated in an electromagnetic field and a grid electrode in the ionization chamber.
The acceleration in the electromagnetic field is the beginning of the second basic principle (i.e. the separation process that is based of the time-of-flight principle). The velocity of the molecules depends on the mass-to-charge (m/z) ratio of the analyte, with heavier molecules having a higher moment of inertia resulting in a lower velocity.
As a final step in the basic principle of MALDI-ToF technology (i.e. detection) the time of flight is measured precisely by the ions arrival at a particle detector. This speed of the ions in flight depends on their mass - with heavier molecules having a higher moment of inertia resulting in a lower velocity. The time of transit is measured precisely by the ions' arrival at a particle detector. Based on the time of flight, the m/z ratio of each particle can be determined, and a mass spectrum of the analyte sample mixture is generated. The recorded signal is processed and presented as a spectrum of intensity versus mass in Daltons (Da). The mass spectrum displays results as a series of peaks (spectrum) which correspond to the ionized proteins derived from the analyte sample. And for identification of an unknown organism, the resulting mass spectra are sufficiently distinctive to allow taxonomic characterization at the genus and species when compared against the VITEK® MS Knowledge Base.
Here's a breakdown of the acceptance criteria and study information for the VITEK® MS PRIME, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (Minimum Agreement) | Reported Device Performance (VITEK® MS PRIME) |
|---|---|---|
| Biological Equivalency | 95% Agreement (compared to reference method) | 99.7% Agreement (1456/1461, excluding discordant IDs and No IDs) |
| Correct single choice ID or low discrimination to correct genus (Gram-positive) | Not explicitly stated, but within overall 95% | 99.0% |
| Correct single choice ID or low discrimination to correct genus (Gram-negative) | Not explicitly stated, but within overall 95% | 97.2% |
| Correct single choice ID or low discrimination to correct genus (Yeast) | Not explicitly stated, but within overall 95% | 100% |
| Correct single choice ID or low discrimination to correct genus (Mycobacteria - solid culture) | Not explicitly stated, but within overall 95% | 100% |
| Correct single choice ID or low discrimination to correct genus (Mycobacteria - liquid culture) | Not explicitly stated, but within overall 95% | 97.62% |
| Correct single choice ID or low discrimination to correct genus (Moulds) | Not explicitly stated, but within overall 95% | 97.4% |
| Correct single choice ID or low discrimination to correct genus (Nocardia) | Not explicitly stated, but within overall 95% | 100% |
| Discordant Identification Rate (Biological Equivalency) | Not explicitly stated, but implied to be low | 0.3% (5/1461) |
| No Identification Rate (Biological Equivalency) | Not explicitly stated, but implied to be low | 1.6% (23/1461) |
| Clinical Performance Evaluation (Overall, including/excluding No IDs) | 95% Agreement (compared to reference method) | 98.4% (492/500) |
| Clinical Performance (Overall, excluding No ID results) | 95% Agreement (compared to reference method) | 99.6% (492/494) |
| Correct single choice ID or low discrimination to correct genus (Gram-positive) | Not explicitly stated, but within overall 95% | 99.3% |
| Correct single choice ID or low discrimination to correct genus (Gram-negative) | Not explicitly stated, but within overall 95% | 98.8% |
| Correct single choice ID or low discrimination to correct genus (Yeast) | Not explicitly stated, but within overall 95% | 95.3% |
| Correct single choice ID or low discrimination to correct genus (Mycobacteria) | Not explicitly stated, but within overall 95% | 100% |
| Correct single choice ID or low discrimination to correct genus (Moulds) | Not explicitly stated, but within overall 95% | 98.0% |
| Correct single choice ID or low discrimination to correct genus (Nocardia) | Not explicitly stated, but within overall 95% | 100% |
| Discordant Identification Rate (Clinical Performance) | Not explicitly stated, but implied to be low | 0.4% (2/500) |
| No Identification Rate (Clinical Performance) | Not explicitly stated, but implied to be low | 1.2% (6/500) |
| Challenge Isolate Results | Not explicitly stated, but implied to be high agreement, no misidentifications/no IDs | 100.0% (100/100) agreement, no No IDs, no discrepant results |
| Quality Control Results | Not explicitly stated, but implied to be high agreement | 98.3% agreement |
| Reproducibility Results | Not explicitly stated, but implied to be high agreement | 99.5% agreement |
2. Sample Sizes Used for the Test Set and Data Provenance:
-
Biological Equivalency Study:
- Sample Size: 1461 samples (representing 487 unique tests in triplicate).
- Data Provenance: Not explicitly stated, but the strains tested included "critical pathogens" for the 479 claimed species. It is likely a combination of well-characterized laboratory strains and potentially some clinical isolates, given the reference to "clinically validated isolates." retrospective or prospective is not mentioned.
-
Clinical Performance Evaluation:
- Sample Size: 500 clinical isolates (from 100 species with five strains each).
- Data Provenance: "clinical isolates tested from all sites combined." The specific countries of origin are not specified, but the data is explicitly from "clinical isolates," suggesting data from human specimens. The study design of using "clinical isolates" usually implies retrospective or prospectively collected samples from clinical settings. It refers to "reference identification obtained during previous clinical studies," suggesting a retrospective use of previously characterized clinical data.
-
Challenge Isolate Results:
- Sample Size: 100 challenge strains.
- Data Provenance: Not specified, but "challenge strains" often refers to a curated set of difficult-to-identify or representative strains used for rigorous testing.
-
Quality Control Results:
- Sample Size: Not explicitly stated, but refers to "all quality control strains tested at all sites."
-
Reproducibility Results:
- Sample Size: Not explicitly stated, but refers to "Reproducibility strains."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:
- The document does not directly state the number of experts or their qualifications.
- For the Clinical Performance Evaluation, the ground truth was established by "a one choice or multiple choice (more than one species) reference identification obtained during previous clinical studies." This implies that the reference identifications were well-established and accepted, likely through conventional microbiological methods and expert interpretation from those previous studies. The nature of these "previous clinical studies" (e.g., whether they involved expert consensus or a gold standard method) is not detailed.
4. Adjudication Method for the Test Set:
- The document does not explicitly describe an adjudication method for the test set results. The ground truth for the clinical performance evaluation was "reference identification obtained during previous clinical studies," implying that disagreements with a single reference standard were likely noted as discordant results rather than undergoing a separate adjudication process within this specific study.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No MRMC comparative effectiveness study is mentioned. This device (VITEK® MS PRIME) is an automated system for microorganism identification using MALDI-TOF MS technology, which does not involve human readers interpreting results in the same way an imaging AI algorithm would. Its performance is compared to a reference method, not to human readers' performance with and without AI assistance.
6. Standalone Performance:
- Yes, a standalone performance study was done. Both the "Biological Equivalency study" and "Clinical Performance Evaluation" describe the performance of the VITEK® MS PRIME system alone (algorithm only) in identifying microorganisms, comparing its results to a ground truth or reference identification. The stated agreement rates (e.g., 98.4% clinical agreement) are measures of this standalone performance. The device is described as "a qualitative in vitro diagnostic device indicated for use in conjunction with other clinical and laboratory findings," but the performance metrics provided are for the device's identification capability itself.
7. Type of Ground Truth Used:
- The ground truth used appears to be reference identification by accepted microbiological methods (which implicitly includes expert consensus in their establishment).
- For the Biological Equivalency study, performance was measured "in comparison with the reference method."
- For the Clinical Performance Evaluation, performance was determined by comparing the VITEK® MS PRIME identification to "a one choice or multiple choice (more than one species) reference identification obtained during previous clinical studies." This "reference identification" would be established through a combination of traditional culture-based methods, molecular methods, and expert interpretation/consensus over time, serving as the gold standard for organism identification. "Outcomes data" or "pathology" as the direct ground truth are not mentioned for identifying the microorganisms themselves, though the device aids in diagnosis of infections.
8. Sample Size for the Training Set:
- The document does not explicitly state the sample size for the training set. It refers to a "VITEK® MS Knowledge Base" (KB v3.2) against which the mass spectra are compared. This knowledge base is the "training set" or reference library. The complexity and size of this knowledge base are not detailed in terms of number of samples/isolates used to build it.
9. How the Ground Truth for the Training Set Was Established:
- The document states that identifications are made "when compared against the VITEK® MS Knowledge Base." While it doesn't describe the exact process for building this KB, such knowledge bases for MALDI-TOF MS systems are typically built by:
- Acquisition of mass spectra from a large collection of well-characterized and phenotypically/genetically confirmed (often by sequencing, biochemical tests, or other gold-standard methods) reference strains across various species.
- Each reference strain's identity is verified by expert microbiologists using established methods before being added to the database.
- The collection process ensures reproducibility and representation of intra-species variability.
- Thus, the ground truth for the training set (Knowledge Base) is established through a rigorous process of expert-validated identification using traditional and molecular microbiological gold standards.
§ 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.