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510(k) Data Aggregation
(87 days)
Optilite® Freelite Mx Kappa Free Kit:
The Optilite Freelite Mx Kappa Free Kit is intended for the quantitative in vitro measurement of Kappa free light chains in serum and urine using the Binding Site Optilite analyser. Measurement of free light chains in serum and urine aids in the diagnosis and monitoring of multiple myeloma, lymphocytic neoplasms, Waldenström's macroglobulinaemia, AL amyloidosis, light chain deposition disease and connective tissue diseases such as systemic lupus erythematosus (SLE); and in serum aids in the evaluation of monoclonal gammopathy of undetermined significance (MGUS). Results of the free light chain measurements should always be interpreted in conjunction with other laboratory and clinical findings.
Optilite® Freelite Mx Lambda Free Kit:
The Optilite Freelite Mx Lambda Free Kit is intended for the quantitative in vitro measurement of Lambda free light chains in serum and urine using the Binding Site Optilite analyser. Measurement of free light chains in serum and urine aids in the diagnosis and monitoring of multiple myeloma, lymphocytic neoplasms, Waldenström's macroglobulinaemia, AL amyloidosis, light chain deposition disease and connective tissue diseases such as systemic lupus erythematosus (SLE); and in serum aids in the evaluation of monoclonal gammopathy of undetermined significance (MGUS). Results of the free light chain measurements should always be interpreted in conjunction with other laboratory and clinical findings.
The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed a portion of the light is transmitted and focused onto a photodiode by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument.
The provided FDA 510(k) clearance letter and its associated 510(k) Summary pertains to the Optilite Freelite Mx Kappa Free Kit and Optilite Freelite Mx Lambda Free Kit. The submission sought to add a claim for the evaluation of Monoclonal Gammopathy of Undetermined Significance (MGUS) to the intended use statement (in serum).
Here's an analysis of the acceptance criteria and the study proving the device meets these criteria, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly list acceptance criteria in terms of pre-defined numerical thresholds for sensitivity, specificity, or positive/negative rates that were required to be met for the MGUS claim. Instead, it describes clinical performance studies designed to demonstrate the utility of the device for MGUS evaluation. The conclusion states that "The studies generated successful results where all pre-defined acceptance criteria were met," implying these criteria were internal to the manufacturer's study design and not explicitly detailed in the public document as numerical targets.
However, we can infer the de facto "reported device performance" based on the results of Study 1 and Study 2.
Inferred Performance/Results:
| Performance Metric | Freelite Mx Kappa & Lambda Kits (for MGUS evaluation) | Commentary |
|---|---|---|
| Study 1: Determination of Positive Rate Ratio in MGUS | This study aimed to show the "positive rate" of the test in clinically confirmed MGUS patients. The "positive rate" here refers to the percentage of MGUS patients whose FLC ratio was abnormal based on the device's reference intervals. It is not a traditional sensitivity as it's not classifying all MGUS cases, but rather indicating how often the FLC ratio is abnormal within the MGUS population. | |
| All MGUS positive | 56.3% (n=129/N=229) | Implies that 56.3% of confirmed MGUS patients had an abnormal FLC ratio according to the device's criteria. |
| Light chain MGUS | 100.0% (n=10/N=10) | Shows that the device identified all LC-MGUS cases as "abnormal" (test-positive). This is a strong indicator for this specific subtype. |
| Non-light chain only MGUS | 54.3% (n=119/N=219) | Shows the positive rate for MGUS cases that are not LC-MGUS. |
| Study 1: Determination of Negative Rate Ratio in Disease Controls (non-MGUS) | This study aimed to show the "negative rate" of the test in non-MGUS patients with other conditions. The "negative rate" here refers to the percentage of non-MGUS patients whose FLC ratio was within the normal reference interval. It is not a traditional specificity as it's not classifying all non-MGUS cases as negative, but rather indicating how often the FLC ratio is normal in a disease control group. | |
| Disease Controls (Non-MGUS) | 91.9% (n=125/N=136) | Implies that 91.9% of patients with polyclonal hypergammaglobulinemia (non-MGUS disease controls) had a normal FLC ratio. |
| Study 2: Evaluation of MGUS Progression (Stable vs. Progressive) | This study retrospectively evaluated the ability of the device to track stable versus progressive MGUS based on FLC changes. The acceptance criteria here would likely revolve around the consistency of FLC results with the clinical status (stable or progressive). | |
| Stable MGUS test positive patients | 95.6% (n=43/N=45) | This indicates that 95.6% of patients with clinically stable MGUS showed FLC results consistent with stability (i.e., less than 25% increase in involved FLC). |
| Progressive MGUS test positive patients | 50.0% (n=2/N=4) | This indicates that 50.0% of patients with clinically progressive MGUS (converting to MM) showed FLC results consistent with progression (i.e., FLC ratio outside reference interval AND >= 25% increase in involved FLC from baseline). The small sample size (N=4) for progressive MGUS patients should be noted for this metric. |
2. Sample Sizes Used for the Test Set and Data Provenance
-
Study 1 (Evaluation of MGUS and disease controls at single time points):
- MGUS Test Set: 229 samples from patients with clinically confirmed MGUS.
- Disease Control Test Set (non-MGUS): 136 samples from patients with polyclonal hypergammaglobulinemia.
- Provenance: Retrospective study. The country of origin is not explicitly stated, but the submitter (The Binding Site Ltd) is based in the United Kingdom.
-
Study 2 (Evaluation of MGUS progression):
- Total Patients: 49 MGUS patients.
- Stable MGUS Cohort: 45 patients.
- Progressive MGUS Cohort: 4 patients (who progressed from MGUS to MM).
- Total Samples: 185 samples (up to 4 individual draws for stable, up to 6 for progressive).
- Provenance: Retrospective study. Country of origin not explicitly stated.
- Total Patients: 49 MGUS patients.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- The document states that the clinical diagnostic criteria for MGUS and disease controls were "confirmed with each site" and "as practiced clinically."
- For the progressive MGUS study, changes were defined as clinical progression from MGUS to MM.
- No specific number of experts or their qualifications (e.g., "Radiologist with 10 years of experience") are mentioned in the provided text. The ground truth relies on "clinical diagnosis" or "clinical truth," which typically implies the consensus opinion of treating clinicians or established diagnostic criteria within the medical community (e.g., IMWG guidelines for MGUS/MM).
4. Adjudication Method for the Test Set
- The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for establishing the clinical ground truth. It relies on "clinical diagnosis" or "clinical truth" established by the sites providing the samples.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC study was done. This device is an in vitro diagnostic (IVD) kit for quantitative measurement of biomarkers, not an image-based AI device that would typically involve human readers interpreting images. The closest analog would be a clinical utility study comparing outcomes with and without the FLC test, but that is beyond the scope of a 510(k) for an IVD kit unless explicitly requested for a novel claim.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- This is a standalone study. The Optilite Freelite Mx Kappa and Lambda Free Kits are laboratory assays. The "performance data" presented (positive rates, negative rates, tracking of progression) are derived solely from the measurements made by the device (Optilite Analyser) on patient samples, compared against established clinical diagnoses (ground truth). There is no "human-in-the-loop" aspect to the device's direct measurement and result generation. The results are then interpreted by clinicians in conjunction with other findings, but the device's output itself is standalone.
7. Type of Ground Truth Used
- The ground truth used was clinical diagnosis/clinical truth.
- For Study 1: "clinically confirmed MGUS" and "polyclonal hypergammaglobulinemia confirmed by study testing... with supporting clinical information." The diagnostic criteria for MGUS were stated to align with or be similar to those outlined by the International Myeloma Working Group (IMWG).
- For Study 2: "clinically determined stable or progressive status" for MGUS patients, with progression defined as conversion from MGUS to Multiple Myeloma (MM) based on clinical diagnosis. FLC results criteria adapted from IMWG guidelines were used for evaluation of the device's performance, but the patient's status (stable/progressive) was the "clinical diagnosis."
8. Sample Size for the Training Set
- The document states, "The devices in this submission have not materially changed since originally cleared under K150658." This implies that the core analytical performance studies (e.g., analytical measuring range, precision, accuracy) were previously established and referenced from prior 510(k) submissions (K173732 and K150658).
- For the new MGUS claim, the performance data presented are for clinical validation on the test sets described in points 1 and 2.
- The document does not describe a distinct "training set" for the clinical claim of MGUS evaluation, nor is it typical for IVD kits to have a "training set" in the machine learning sense for their clinical claims. The performance studies demonstrate the device's ability to measure FLCs in patient populations relevant to MGUS, and these measures are compared against clinical ground truth. The assay itself (reagents, instrument) would have been "trained" (i.e., optimized and validated analytically) during its initial development and previous clearances.
9. How the Ground Truth for the Training Set Was Established
- As a "training set" for the clinical claim is not explicitly mentioned or relevant for this type of IVD 510(k), this question is not directly applicable. For the device itself, analytical validation and calibration would have established its operational parameters, but this isn't "ground truth" in the diagnostic performance sense. The clinical ground truth for the test sets was derived from established clinical diagnoses and diagnostic criteria.
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(265 days)
The Optilite Freelite Kappa Free Kit is intended for the quantitative in vitro measurement of Kappa free light chains in serum using the Binding Site Optilite analyser. Measurement of free light chains aids in the diagnosis and monitoring of multiple myeloma, lymphocytic neoplasms, Waldenström's macroglobulinaemia, AL amyloidosis, light chain deposition disease and connective tissue diseases such as systemic lupus erythematosus (SLE), and aids in the evaluation of monoclonal gammopathy of undetermined significance (MGUS). Results of the free light chain measurements should always be interpreted in conjunction with other laboratory and clinical findings.
The Optilite Freelite Lambda Free Kit is intended for the quantitative in vitro measurement of Lambda in serum using the Binding Site Optilite analyser. Measurement of free light chains aids in the diagnosis and monitoring of multiple myeloma, lymphocytic neoplasms, Waldenstrom's macroglobulinaemia, AL amyloidosis, light chain deposition disease and connective tissue diseases such as systemic lupus erythematosus (SLE), and aids in the evaluation of monoclonal gammopathy of undetermined significance (MGUS). Results of the free light chain measurements should always be interpreted in conjunction with other laboratory and clinical findings.
The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed a portion of the light is transmitted and focused onto a photodiode by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument.
Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary for the Optilite Freelite Kappa Free Kit and Optilite Freelite Lambda Free Kit:
Context: This submission is for a modification to a previously cleared device (K150658) to extend its indications for use to "aid in the evaluation of Monoclonal Gammopathy of Undetermined Significance (MGUS)". The core device technology and its principles (immunoturbidimetry for quantitative measurement of free light chains) remain unchanged. Therefore, the performance data provided specifically addresses the new MGUS claim.
Acceptance Criteria and Reported Device Performance
Device: Optilite® Freelite® Kappa Free Kit and Optilite® Freelite® Lambda Free Kit
Intended Use Extension: Aid in the evaluation of Monoclonal Gammopathy of Undetermined Significance (MGUS).
| Acceptance Criteria (Pre-defined) | Reported Device Performance |
|---|---|
| Study 1: Clinical Performance - Sensitivity | |
| Sensitivity for all MGUS samples: at least 30% | 59.4% (95% CI: 53.0 - 65.5%) |
| Sensitivity for Light Chain MGUS (LC-MGUS): Not explicitly listed, but the study highlighted this subgroup. | 100% (95% CI: 75.8 - 100%) |
| Sensitivity for non-LC-MGUS samples: Not explicitly listed, but the study highlighted this subgroup. | 57.2% (95% CI: 50.6 - 63.5%) |
| Study 1: Clinical Performance - Specificity | |
| Specificity for non-MGUS disease controls: at least 85% | 86.4% (95% CI: 79.8 - 91.1%) |
| Study 2: Evaluation of MGUS Progression (Stable) | |
| Correct categorization of clinically stable MGUS by FLC testing: at least 80% | 93.3% of stable patients were categorized as "test positive" (meaning FLC stable based on criteria) |
| Study 2: Evaluation of MGUS Progression (Progressive) | |
| Correct categorization of clinically progressive MGUS by FLC testing: at least 30% | 50.0% of progressive patients were categorized as "test positive" (meaning FLC progressive based on criteria) |
Study Details:
1. Sample Sizes and Data Provenance:
- Study 1 (Sensitivity and Specificity):
- MGUS Samples (Sensitivity): 234 samples from patients with clinically confirmed MGUS.
- Disease Controls (Specificity): 140 samples from patients with polyclonal hypergammaglobulinemia (non-MGUS).
- Data Provenance: Retrospective testing of residual samples. The country of origin is not explicitly stated, but the company (The Binding Site Ltd.) is based in the United Kingdom.
- Study 2 (MGUS Progression):
- Total Samples: 185 samples from 49 MGUS patients (45 stable, 4 progressive). Up to 4 individual sample draws for stable, up to 6 for progressive per patient.
- Data Provenance: Retrospective testing of residual samples. Country of origin not explicitly stated.
2. Number of Experts and Qualifications for Ground Truth:
- The document states that the clinical diagnostic criteria that clinicians used to establish the "clinical truth" of MGUS positive samples were confirmed with each site.
- The ground truth for non-MGUS samples was based on "clinically confirmed polyclonal hypergammaglobulinemia" and "supporting clinical information."
- For the progression study, "clinically determined stable or progressive status" was the basis.
- The number of experts and their specific qualifications (e.g., radiologist with 10 years of experience) are not explicitly provided in the summary. It generally refers to "clinicians" and "clinical diagnosis."
3. Adjudication Method for the Test Set:
- Not explicitly mentioned. Given that the ground truth relies on "clinical diagnosis" and "clinically confirmed MGUS," it implies that the diagnostic criteria were applied by the treating clinicians at the respective sites prior to the retrospective study. There is no indication of an independent multi-expert adjudication process specifically for this study's test set.
4. MRMC Comparative Effectiveness Study:
- No. This submission is for an in-vitro diagnostic (IVD) device (a laboratory test), not an AI-assisted diagnostic tool that would directly assist human readers in image interpretation. Therefore, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study to measure improvement in human readers with AI assistance is not applicable and was not performed.
5. Standalone Performance (Algorithm Only without Human-in-the-Loop):
- Yes. The study evaluates the performance of the device (Optilite Freelite Kappa and Lambda Free Kits on the Optilite Analyser) in measuring FLC levels and deriving the kappa:lambda ratio. The performance metrics (sensitivity, specificity, categorization of stable/progressive) are reported for the device's output itself, compared to the clinical ground truth. This is a standalone performance assessment of the IVD test.
6. Type of Ground Truth Used:
- Clinical Diagnosis / Clinical Findings:
- For MGUS positive samples: "clinically confirmed MGUS" based on diagnostic criteria, including those outlined by the 'International Myeloma Working Group (IMWG)' consensus.
- For non-MGUS samples: "polyclonal hypergammaglobulinemia confirmed by study testing (total IgG/lgA/lgM and serum IFE), with supporting clinical information."
- For stable/progressive MGUS: "clinically determined stable or progressive status" based on patient follow-up and conversion to MM or stable status over time. This includes evaluation criteria based on IMWG guidelines for multiple myeloma regarding FLC changes.
7. Sample Size for the Training Set:
- Not applicable. This submission focuses on the performance of a lab-based immunoassay kit, not a machine learning or AI algorithm that requires a "training set" in the conventional sense. The test method is immunoturbidimetry, which relies on chemical reactions and optical detection, not an algorithm that learns from data.
8. How Ground Truth for the Training Set Was Established:
- Not applicable, as there is no "training set" for this type of device. The method is a validated laboratory assay.
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