(26 days)
The Optilite IgM Kit is intended for the quantitative in vitro measurement of IgM in human serum, lithium heparin or EDTA plasma using the Binding Site Optilite analyser. Measurement of IgM aids in the diagnosis of abnomal protein metabolism and the body's lack of ability to resist infectious agents. The test results are to be used in conjunction with other clinical and laboratory findings.
The Optilite IgM Kit comprises the following reagents: Antiserum: Goat anti IgM supplied in stabilised liquid form. Preservatives: 0.099% sodium azide, 0.1% E-amino-n-caproic acid (EACA), 0.5% BSA and 0.01% benzamidine. Calibrator and Controls: Pooled human serum, supplied in stabilised liquid form. Contain 0.099% sodium azide, 0.1% EACA and 0.01% benzamidine as preservatives. The concentration given on the quality control certificate has been obtained by comparison with the DA470k international reference material. Reaction Buffer: Containing 0.099% sodium azide as a preservative.
The provided text describes a 510(k) submission for the Optilite IgM Kit, which is a quantitative in vitro measurement system for IgM in human serum, lithium heparin, or EDTA plasma. The submission is a modification to an existing device (K082129). The core of the submission revolves around demonstrating that the modified device maintains performance comparable to the previously cleared device, rather than proving initial efficacy or diagnostic accuracy.
Based on the provided text, here's an analysis of the acceptance criteria and study proving the device meets them:
Key Takeaway: This 510(k) submission is for a modification to an existing device (change of antibody source and buffer). Therefore, the "acceptance criteria" and "study" are primarily focused on demonstrating that this modification does not negatively impact the performance compared to the original, already cleared device. There is no new clinical effectiveness study to establish diagnostic accuracy against a disease state from scratch.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally framed as "no change in performance compared to the device cleared in K082129" or meeting specific pre-defined quantitative thresholds (e.g., allowable CV, limits of agreement).
| Acceptance Criteria Category | Specific Acceptance Criteria (implicit/explicit) | Reported Device Performance and Conclusion |
|---|---|---|
| Precision/Reproducibility | No significant change in repeatability, within-laboratory, between-instrument, and between-lot precision compared to the predicate (K082129). (Implicit, demonstrated through comparison of observed CVs and SDs to historical or expected performance, as guided by CLSI EP5-A3). For example, meeting specific CV targets for different levels. | Repeatability and Within Laboratory: |
| • Level 1: Total CV 4.9% | ||
| • Level 5: Total CV 7.0%. | ||
| Between Instrument: | ||
| • Level 1: CV 5.2% | ||
| • Level 5: CV 6.9%. | ||
| Between Lot: | ||
| • Level 1: CV 0.7% | ||
| • Level 5: CV 1.5%. | ||
| Conclusion: "The above results do not indicate any change in performance compared to the device cleared in K082129. The precision claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended." | ||
| Linearity/Assay Reportable Range | No significant change in linearity compared to the predicate (K082129). Demonstrated by strong correlation coefficient (r value) of the linear regression. (Implicit, based on historical performance). | Linear Regression Equation: y = 1.029 x – 0.1752 g/L |
| r value: 0.998. | ||
| Conclusion: "These results are comparable to those currently presented in the product insert and therefore do not indicate any change in performance compared to the device cleared in K082129. The linearity claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended." | ||
| Kit Stability (Accelerated) | Stability claim of 12 months (365 days) at 4°C verified with a maximum allowable difference of ±15% (per EP25-A). | Achieved Stability (equivalent at 4°C): |
| • IR: 507 days | ||
| • Low Control: 531 days | ||
| • High Control: 878 days | ||
| • Samples 1-3: 561 days. | ||
| Decision: All "Pass." | ||
| Conclusion: Verified stability claim. (Real-time study ongoing for further support). | ||
| Detection Limit (LoQ, LoD, LoB) | LoQ validated by all samples reporting within an allowable CV of 8%. No significant change in LoD or LoB from the predicate (0.01 g/L and 0.007 g/L respectively). (Implicit, based on historical performance as per EP17-A2). | LoQ: All tested samples were within the acceptance criteria of allowable CV of 8%. |
| LoD: No change in performance observed after antisera change. | ||
| LoB: No change in performance observed after antisera change. | ||
| Conclusion: "The results generated do not indicate any change in performance compared to the device cleared in K082129. The LoB, LoD and LoQ claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended." | ||
| Method Comparison with Predicate Device | Agreement between the modified and predicate device, evidenced by low bias, tight limits of agreement, high correlation coefficient, and appropriate Passing Bablok regression results to demonstrate equivalence. | Bland Altman Mean Bias: -2.13% |
| 95% Limits of Agreement: -9.63% to 5.36% | ||
| Passing Bablok: y= 0.9775x + 0.009 (Slope 95% CI: 0.971 to 0.983; Intercept 95% CI: 0.001 to 0.016) | ||
| Correlation coefficient: 0.999. | ||
| Conclusion: "The above results do not indicate any change in performance compared to the device cleared in K082129. The comparison claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended." | ||
| Expected Values/Reference Range | Transferred reference interval accepted if ≤2 samples fall outside the limits of the reference interval. | Of 20 samples, 18 gave results within the reference interval (0.35 – 2.42 g/L). Two samples were slightly below the lower boundary (0.305 g/L and 0.319 g/L). |
| Conclusion: "The results of this study therefore meet the acceptance criteria and indicate that the reference interval can be transferred from the originally cleared device." |
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision Studies (Repeatability and Within Laboratory):
- Sample Size: 5 different samples. For each level, N=80 for Repeatability/Within Lab Summary (20 working days * 2 runs/day * 2 reps/run).
- Data Provenance: Not explicitly stated, but typically internal lab data (e.g., from the manufacturer's R&D or QC labs).
- Precision Studies (Between Instrument):
- Sample Size: 5 different samples. For each level, N=24 (6 working days * 2 runs/day * 2 reps/run).
- Data Provenance: Not explicitly stated, typically internal lab data.
- Precision Studies (Between Lot):
- Sample Size: 5 different samples. For each level, N=24 (6 working days * 2 runs/day * 2 reps/run).
- Data Provenance: Not explicitly stated, typically internal lab data.
- Linearity Study:
- Sample Size: Dilution series from a high pool (8.44 g/L) and a low pool (0.17 g/L). Each diluted sample tested in 3 replicates.
- Data Provenance: Not explicitly stated, typically internal lab data.
- Kit Stability (Accelerated):
- Sample Size: 6 replicates of controls, internal reference, and samples.
- Data Provenance: Not explicitly stated, typically internal lab data.
- Detection Limit (LoQ) Study:
- Sample Size: Four samples.
- Data Provenance: Not explicitly stated, typically internal lab data.
- Method Comparison with Predicate Device:
- Sample Size: 120 serum samples and 60 plasma samples (total 180 samples).
- Data Provenance: Not explicitly stated, but typically clinical samples or commercial samples purchased for the study. Given the medical context, these would be human samples. The study was conducted as per pre-submission meeting Q171503, implying a prospective design for this specific comparative testing.
- Expected Values/Reference Range:
- Sample Size: 20 samples from apparently healthy US donors.
- Data Provenance: Prospective collection of samples from US donors.
Overall Data Provenance: The document explicitly mentions "20 samples from apparently healthy US donors" for the reference range study. For other analytical performance studies (precision, linearity, stability, detection limit), the provenance is not specified, but these are typically conducted in-house by the manufacturer (retrospective analysis vs. new data collection is not detailed, but likely new data generation for the modified kit).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This device is an in vitro diagnostic (IVD) for quantitative measurement of IgM. The "ground truth" for IVDs of this nature is established by the reference measurement procedure or the assigned/target values of calibrators and controls used in the analytical performance studies, not by clinical expert consensus in the way a diagnostic imaging AI might establish ground truth from radiologists.
- For Analytical Studies (Precision, Linearity, LoD/LoQ, Stability): The ground truth for these samples are their known or reference concentrations, which are determined by highly accurate laboratory methods or traceable standards (e.g., ERM-DA470k/IFCC for IgM). No clinical experts are involved in establishing this type of ground truth.
- For Method Comparison: The "ground truth" in this context is the result obtained from the predicate device (the unmodified K082129 kit), as the goal is to show agreement between the modified and unmodified kit.
- For Reference Range Study: The "ground truth" is the established reference interval for IgM in a healthy population. The study assessed whether the modified kit's results for healthy individuals fell within this known range.
Therefore, the concept of "experts establishing ground truth" as it applies to reader studies for imaging devices does not directly apply here.
4. Adjudication Method for the Test Set
Given that this is an IVD kit for quantitative measurement and not an imaging device requiring human interpretation, there is no mention of an adjudication method among multiple human readers. The analytical performance is evaluated against quantitative measurements, established standards, or the performance of the predicate device.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. MRMC studies are specific to diagnostic performance, typically for imaging devices where multiple readers interpret cases with and without AI assistance. This submission is for an IVD kit that provides a quantitative measurement, not an interpretative diagnosis requiring human readers in the loop. The "comparison" done was a method comparison between the modified kit and the predicate kit.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, in essence. The "device" here is the Optilite IgM Kit used on the Optilite analyser. Its performance is evaluated analytically (precision, linearity, limits, stability) and comparatively against its predicate. This is a standalone performance assessment of the kit, which automatically provides quantitative results. There is no human interpretative step that the kit is assisting or replacing within its intended use.
7. The Type of Ground Truth Used
- For Analytical Performance (Precision, Linearity, LoD/LoQ, Stability):
- Traceability: ERM-DA470k/IFCC (a certified reference material for immunoglobulins). This is a highly robust form of ground truth based on international standards.
- Known Concentrations: Samples and controls with established or assigned target values.
- For Method Comparison:
- Predicate Device Results: The results from the previously cleared Optilite IgM Kit (K082129) served as the reference for comparison to demonstrate equivalence.
- For Reference Range Study:
- Established Reference Interval: The pre-determined reference range (0.35 – 2.42 g/L) for IgM in a healthy population served as the ground truth against which results from healthy donors were compared.
There is no pathology confirmation or outcomes data mentioned, as these are typically used for assessing clinical accuracy or impact on patient management, which is beyond the scope of this 510(k) for a modified quantitative IVD.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of an AI/ML algorithm. This submission is for an immunoturbidimetric test kit, not an AI-powered diagnostic system. The "training" of such a system would refer to the development and optimization of the reagent formulation and methods, which involves extensive R&D and internal testing, often with many samples. However, the document provided focuses on the validation testing required for regulatory submission.
The section M. Performance Characteristics details the validation experiments for the modified kit. These are the test sets to prove performance, not training sets.
9. How the Ground Truth for the Training Set Was Established
As noted above, there is no "training set" in the AI/ML sense described. For the development of the original device and its subsequent modifications, the "ground truth" would be established through:
- Reference materials: Calibrating the assay against international reference standards (e.g., ERM-DA470k/IFCC).
- Internal validation: Testing against well-characterized in-house samples and controls with known concentrations.
- Method optimization: Iteratively adjusting reagent concentrations and reaction parameters to achieve desired analytical performance (sensitivity, specificity, precision, linearity) based on these known samples and reference materials.
The provided document focuses on the verification and validation studies for a pre-defined modified product, demonstrating its performance against regulatory requirements, rather than the developmental phase of the original or modified kit's creation.
§ 866.5510 Immunoglobulins A, G, M, D, and E immunological test system.
(a)
Identification. An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.(b)
Classification. Class II (performance standards).