Search Results

The MBT Sepsityper is a qualitative in vitro diagnostic device consisting of an MBT-CA (Sepsityper) software extension and a reagent kit (MBT Sepsityper Kit US IVD) for use in conjunction with other clinical and laboratory findings to aid in the early diagnosis of bacterial and yeast infections from positively flagged blood cultures using the MALDI Biotyper CA System.

The MBT Sepsityper Kit US IVD is a disposable blood culture processing device that includes associated reagents that are intended to concentrate and purify microbial cells from blood culture samples identified as positive by a continuous monitoring blood culture system and confirmed to demonstrate the presence of a single organism as determined by Gram stain. This sample preparation manual method is performed by laboratory health professionals in a clinical diagnostic setting. Subculturing of positive blood cultures is necessary to recover organisms for identification of organisms not identified by the MBT-CA System, for susceptibility testing and for differentiation of mixed growth.

Positive MBT Sepsityper results do not rule out co-infection with organisms that may not be detected by the MBT-CA System. Results of the MBT Sepsityper should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Results of the MBT Sepsityper should be correlated with Gram stain results and used in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and yeast bloodstream infections.

Organisms recovered from positive blood culture bottles that are suitable for identification using the MBT Sepsityper Kit US IVD and MBT-CA Systems are listed in the MALDI Biotyper CA System Package Insert Reference Library.

The MALDI Biotyper CA System uses MALDI (matrix-assisted laser desorption/ionization) TOF (time of flight) mass spectrometry technology for the identification of organisms isolated from clinical samples. Identification can be performed from an isolated colony or from a cell extract. The sample material is transferred to a target plate, dried and overlaid with a matrix. The MBT FAST Shuttle US IVD is an optional hardware tool that may be used for drying the samples deposited on the MALDI target plate under controlled conditions.

The MALDI process transforms the proteins and peptides from the isolated microorganisms into positively charged ions. This is achieved by irradiating the matrix-sample composite with a UV laser. The matrix absorbs laser energy and transfers protons to the intact proteins or peptides in the gas phase. These ions are electrostatically accelerated and arrive in the flight tube at a mass-dependent speed. Because different proteins/peptides have different masses, ions arrive at the detector at different times (time of flight). The MBT-CA System measures the time (in the nanosecond range) between pulsed acceleration and the corresponding detector signal of the ions, and the time is converted into an exact molecular mass.

The highly abundant microbial ribosomal proteins result in a mass spectrum with a characteristic mass and intensity distribution pattern. This pattern is species-specific for many bacteria and yeasts and can be used as a 'molecular fingerprint' to identify a test organism. The spectrum of the unknown test organism, acquired through the software MBT Compass HT CA of the MBT-CA System, is electronically transformed into a peak list. Using a biostatistical algorithm, this peak list is compared to reference peak lists of organisms in the MBT-CA Reference Library and a log(score) between 0.00 and 3.00 is calculated. The higher the log(score), the higher the degree of similarity to a given organism in the MBT-CA Reference Library. The log(score) ranges reflect the probability of organism identification.

The FDA 510(k) submission document focuses on demonstrating substantial equivalence to an existing predicate device rather than presenting a traditional acceptance criteria study for a new device. Therefore, the "acceptance criteria" discussed are largely driven by proving that the new components (MBT Compass HT CA software and MBT FAST Shuttle US IVD) maintain or improve the performance and safety established by the predicate device.

Here's an analysis of the provided text to fulfill your request:

Acceptance Criteria and Reported Device Performance

The concept of "acceptance criteria" in this context isn't a single set of predefined thresholds for a novel device's performance against a clinical gold standard (e.g., sensitivity/specificity targets). Instead, it's about demonstrating that the new components do not negatively impact the established performance of the predicate device and potentially offer improvements (like accelerated drying time). The "reported device performance" is presented as evidence that these conditions are met.

Table 1: Acceptance Criteria (Implied) and Reported Device Performance

Study Details

Based on the provided text:

1. Sample sizes used for the test set and the data provenance:

   • MBT FAST Shuttle - Repeatability: 120 mass spectra (presumably from 12 bacterial/yeast strains * 10 repeats * 2 runs across DT, eDT, Ext, Sepsityper workflows as indicated in Table 3 headers, although the text says "each out of 2 runs" for "each workflow/method" - suggesting 10 per method/workflow per run).
   • MBT FAST Shuttle - Reproducibility (Site-to-Site): 2700 samples for MBT workflow (900 samples per study site * 3 sites) and 1350 samples for Sepsityper workflow (450 samples per study site * 3 sites). The document mentions "10 microorganisms" used per study site.
   • MBT FAST Shuttle - Reproducibility (Device-to-device): 1080 samples for MBT workflow (360 samples per MBT FAST Shuttle * 3 shuttles) and 540 samples for Sepsityper workflow (180 samples per MBT FAST Shuttle * 3 shuttles).
   • MBT FAST Shuttle - Reproducibility (Operator-to-operator): 900 samples for MBT workflow (450 samples per operator * 2 operators) and 450 samples for Sepsityper workflow (225 samples per operator * 2 operators).
   • MBT FAST Shuttle - Reproducibility (Day-to-day): 900 samples for MBT workflow (180 samples per day * 5 days) and 450 samples for Sepsityper workflow (90 samples per day * 5 days).
   • MBT FAST Shuttle - Method Comparison (Drying): 279 mass spectra for air-dried and 279 mass spectra for MBT FAST Shuttle dried from three study sites (93 mass spectra per site per drying method). Ten (10) microorganisms and a blood culture, each spotted in triplicates.
   • MBT Compass HT CA - Low Confidence Results: 15,270 spectra in total, with 1,670 yellow log(scores) re-analyzed.
   • MBT Compass HT CA - IDealTune: Data collected from 133 BTS-QC runs at Site 1 (over 17 months) and 76 BTS-QC runs at Site 2 (over 14 months).

   Data Provenance: The studies were performed at multiple sites (at least 3 for reproducibility studies), and one study explicitly mentions that microorganisms were shipped to both US study sites. This implies the data is, at least in part, prospectively collected in a multi-center setting for verification/validation. The "low confidence results" study was a retrospective non-interventional validation using data from previous clearances.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • The document does not specify the number or qualifications of experts used to establish ground truth for most of these performance studies. The studies primarily focus on performance consistency and equivalence compared to established methods using what appears to be common laboratory standards (e.g., identity confirmed organisms, BTS quality checks).
   • For the "low confidence results" study, it states: "Isolates from clinical routine were used to compare the results of the MBT-CA System against a gold standard (16S sequencing)." This suggests the ground truth was established by 16S sequencing, a molecular method, rather than solely by human experts, and then potentially interpreted by experts.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

   • No adjudication method involving multiple human readers for conflict resolution is mentioned or appears to be applicable given the nature of the device (mass spectrometry-based organism identification). The performance is assessed on the agreement with an expected identification or log(score) thresholds.

4. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

   • No MRMC or human-in-the-loop comparative effectiveness study with human readers assisting or being assisted by AI is described in this document. The device is a "clinical mass spectrometry microorganism identification and differentiation system," not an AI-assisted diagnostic imaging tool.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • Yes, the performance validation studies of the MBT FAST Shuttle US IVD and MBT Compass HT CA software are essentially standalone performance evaluations of these components within the overall MALDI Biotyper CA System. The "outputs" (identification results, log(scores)) are generated by the system (including the hardware, software, and reference library) without direct human interpretation of the raw mass spectra. Human involvement is in sample preparation and operating the system, but the core identification is algorithmic.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc):

   • For the analytical performance of organism identification, the ground truth appears to be based on:
     • Reference strains/known microorganisms: Used in repeatability and reproducibility studies.
     • 16S sequencing: Explicitly stated as the "gold standard" for comparing results in the "low confidence results" study.
     • Internal quality control standards: Like the Bacterial Test Standard (BTS) for IDealTune validation.
   • This is primarily laboratory-based "gold standard" ground truth (molecular methods, established reference cultures), rather than expert consensus on clinical cases.

7. The sample size for the training set:

   • This document describes the validation of new components for an existing system. It does not provide details about the training set size for the underlying MALDI Biotyper CA System's reference library or analytical algorithms. The "reference library" (which acts as a form of "training data" for identifying unknown spectra) is mentioned as being continually updated, but its size is not specified.

8. How the ground truth for the training set was established:

   • Similar to the above, the document does not detail how the ground truth was established for the training data (the reference library) of the overall MALDI Biotyper CA System. However, standard practice for building such libraries involves:
     • Well-characterized bacterial and yeast strains: Often from culture collections, with identity confirmed by a variety of methods including 16S rRNA gene sequencing, traditional biochemical tests, and possibly whole-genome sequencing.
     • Internal validation and verification: Ensuring the spectral patterns are consistent and representative for each species.

In summary, this 510(k) submission successfully demonstrates substantial equivalence by showing that the new components (MBT Compass HT CA software and MBT FAST Shuttle US IVD) maintain the safety and effectiveness of the predicate device, and in some cases, enhance usability (faster drying time, improved instrument maintenance) without introducing new risks or compromising diagnostic accuracy. The studies presented are analytical validations focusing on performance characteristics relevant to microorganism identification in a laboratory setting.

Ask a specific question about this device