(20 days)
Binding assay for the in vitro quantitative determination of vitamin B12 in human serum and plasma. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 2010 and MODULAR ANALYTICS E170 (Elecsys module) immunoassay analyzers.
A Vitamin B12 test system is a device intended to measure Vitamin B12 in serum, plasma. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.
Elecsys Vitamin B12 CalSet II is used for calibrating the quantitative Elecsys Vitamin B12 assay on the Elecsys 2010 and MODULAR ANALYTICS E170 immunoassay analyzers.
For use in the verification of the calibration established by the Elecsys Vitamin B12 reagent on Elecsys 2010 and MODULAR ANALYTICS E170 immunoassay analyzers.
(1) The Elecsys Vitamin B12 Assay employs a competitive test principle using intrinsic factor specific for Vitamin B12. Vitamin B12 in the sample competes with the added Vitamin B12 labeled with biotin for the binding sites on the ruthenium-labeled intrinsic factor complex. Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent barcode.
(2) The Elecsys Vitamin B12 CalSet II is a lyophilized product consisting of human serum with added Vitamin B12 in two concentration ranges. During manufacture, the analyte is spiked into the matrix at the desired concentration levels.
(3) The Elecsys Vitamin B12 CalCheck is a lyophilized product consisting of human serum with added Vitamin B12. During manufacture, the analyte is spiked into the matrix at the desired concentration levels.
The provided document describes the Elecsys Vitamin B12 Test System, which includes the Elecsys Vitamin B12 Immunoassay, Elecsys Vitamin B12 CalSet II, and Elecsys Vitamin B12 CalCheck. This system is intended for the in vitro quantitative determination of Vitamin B12 in human serum and plasma, used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.
The document is a 510(k) Premarket Notification summary, seeking substantial equivalence to previously cleared devices. It primarily focuses on comparing the new device (modified device) to its predicates and detailing the differences and similarities. It does not explicitly state pre-defined acceptance criteria for the modified device's performance, nor does it present a study designed to explicitly prove the device meets such acceptance criteria as a primary outcome.
Instead, the document presents analytical performance data (precision and method comparison) for the modified device and compares it to the predicate device. The goal of this submission is to demonstrate that the changes implemented do not raise new questions of safety and effectiveness, and that the modified device remains substantially equivalent to the predicate.
Given this, I will extract the available performance data and structure the answer to reflect what is present in the document. Since explicit acceptance criteria are not provided for the modified device in the context of a new study to prove "acceptance," I will highlight the reported performance parameters and the context of their presentation (comparison to predicate).
1. Table of Acceptance Criteria and Reported Device Performance
As explicit acceptance criteria for the modified device are not stated in the provided text, the table below presents the reported performance of the modified device alongside that of the predicate device for comparison. The underlying assumption in a 510(k) submission for modifications is that the modified device's performance should be comparable to or better than the predicate, or that any differences do not negatively impact safety and effectiveness.
| Performance Characteristic | Acceptance Criteria (Implicit for 510(k) Substantial Equivalence - generally comparable to predicate) | Elecsys Vitamin B12 (Modified Device) Performance | Elecsys Vitamin B12 (Predicate Device K973702) Performance |
|---|---|---|---|
| Precision (Within-Run) | |||
| Elecsys 2010 | Comparable to Predicate | HS 1: 8.7% (232 pg/mL); HS 2: 4.4% (818 pg/mL); HS 3: 3.0% (1,245 pg/mL) | Human Serum 1: 6.9% (203 pg/mL); Human Serum 2: 4.2% (481 pg/mL); Human Serum 3: 2.7% (1,499 pg/mL) |
| PCA 1: 8.3% (226 pg/mL); PCA 2: 4.0% (610 pg/mL); PCA 3: 3.1% (1,369 pg/mL) | Control 1: 2.8% (1,119 pg/mL); Control 2: 4.3% (471 pg/mL) | ||
| MODULAR ANALYTICS E170 | Comparable to Predicate | HS 1: 1.2% (267 pg/mL); HS 2: 2.9% (887 pg/mL); HS 3: 1.5% (1,308 pg/mL) | Human Serum 1: 2.4% (155 pg/mL); Human Serum 2: 2.8% (359 pg/mL); Human Serum 3: 0.6% (1,162 pg/mL) |
| PCA 1: 1.7% (308 pg/mL); PCA 2: 1.0% (710 pg/mL); PCA 3: 0.8% (1,524 pg/mL) | PreciControl U1: 0.9% (667 pg/mL); PreciControl U2: 4.3% (399 pg/mL) | ||
| Precision (Total) | |||
| Elecsys 2010 | Comparable to Predicate | HS 1: 9.5% (232 pg/mL); HS 2: 5.1% (818 pg/mL); HS 3: 3.7% (1,245 pg/mL) | Human Serum 1: 7.6% (203 pg/mL); Human Serum 2: 4.4% (481 pg/mL); Human Serum 3: 3.2% (1,499 pg/mL) |
| PCA 1: 8.0% (226 pg/mL); PCA 2: 5.2% (610 pg/mL); PCA 3: 3.4% (1,369 pg/mL) | Control 1: 3.2% (1,119 pg/mL); Control 2: 4.6% (471 pg/mL) | ||
| MODULAR ANALYTICS E170 | Comparable to Predicate | HS 1: 8.4% (269 pg/mL); HS 2: 3.3% (853 pg/mL); HS 3: 2.5% (1,261 pg/mL) | Human Serum 1: 6.1% (157 pg/mL); Human Serum 2: 3.6% (349 pg/mL); Human Serum 3: 2.2% (1,128 pg/mL) |
| PCA 1: 7.5% (239 pg/mL); PCA 2: 3.7% (658 pg/mL); PCA 3: 2.4% (1,415 pg/mL) | PreciControl 1: 2.8% (671 pg/mL); PreciControl 2: 4.2% (391 pg/mL) | ||
| Method Comparison | |||
| Predicate vs. Commercially available radiobinding assay | N/A | N/A | N = 345, Passing Bablok: y = -9.2 + 1.06x, r = 0.977, SD(md68) = 45.7; Linear regression: y = 7.4 + 1.02x, r = 0.977, Sy.x = 75.5. Range: 30 - 1,798 pg/mL |
| Modified Device (E170 w/ CalSet II) vs. Predicate (E170 w/ CalSet) | Comparable to Predicate method comparison results (e.g., strong correlation, desirable slope/intercept) | N = 101, Passing Bablok: y = 0.982x - 0.018, r = 0.977, SD(md68) = 8.05; Linear regression: y = 0.968x + 5.77, r = 0.999, Sy.x = 9.63. Range: 49 - 1,691 pg/mL | N/A |
Note on "Acceptance Criteria": This 510(k) submission is for a modified device demonstrating substantial equivalence. The "acceptance criteria" for such a submission are typically implicit: the modified device's performance data (precision, method comparison, etc.) should demonstrate that the changes do not adversely affect the device's safety and effectiveness compared to the predicate, and that the device performs as intended within clinically acceptable limits. Explicit numerical acceptance criteria are not presented in this summary.
2. Sample Size Used for the Test Set and Data Provenance
-
Precision Study:
- The sample sizes for the human serum samples and controls are not explicitly stated as a single "test set" number for the precision study. Instead, the results are presented for multiple individual samples (HS 1, HS 2, HS 3, PCA 1, PCA 2, PCA 3 for the modified device; Human Serum 1, 2, 3, Control 1, 2 for the predicate) each run multiple times to determine within-run and total precision (CV%). The number of replicates is not specified.
- Data Provenance: Not explicitly stated (e.g., country of origin). It is a laboratory study to assess analytical performance.
- Retrospective/Prospective: Not specified, but analytical performance studies like precision are typically conducted prospectively.
-
Method Comparison Study:
- Modified Device Study Sample Size: N = 101 (comparison of MODULAR ANALYTICS E170 calibrated with Elecsys Vitamin B12 CalSet II vs. E170 calibrated with Elecsys Vitamin B12 CalSet).
- Predicate Device Study Sample Size: N = 345 (comparison of Elecsys Vitamin B12 with a commercially available radiobinding Vitamin B12 assay).
- Data Provenance: Not explicitly stated (e.g., country of origin).
- Retrospective/Prospective: Not specified.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This type of submission (for an in vitro diagnostic assay) does not typically involve "experts to establish ground truth" in the same way imaging or clinical decision support AI devices do. The "ground truth" for Vitamin B12 assays is the actual concentration of Vitamin B12 in the samples. For method comparison, an existing, accepted method (predicate device or another commercially available assay) serves as the reference. Therefore, this section is not applicable in the context of this device and study type.
4. Adjudication Method for the Test Set
Not applicable. As described above, this is an analytical performance study for an in vitro diagnostic, not a study involving human interpretation with adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, a multi-reader, multi-case (MRMC) comparative effectiveness study was not performed. This type of study is relevant for imaging devices or AI tools that assist human readers in interpretation. The Elecsys Vitamin B12 Test System is an automated in vitro diagnostic assay.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done
Yes, the studies presented (precision and method comparison) are essentially "standalone" performance evaluations of the assay system itself. The assay is an automated electrochemiluminescence immunoassay (ECLIA) run on Roche Elecsys 2010 and MODULAR ANALYTICS E170 analyzers. Its output is a quantitative measurement of Vitamin B12, not a diagnostic interpretation that requires human-in-the-loop interaction for its primary function.
7. The Type of Ground Truth Used
The "ground truth" for the performance studies shown is:
- Precision: The inherent value of the assayed samples (human serum and controls) determined by repetitive measurements.
- Method Comparison: Values obtained from a previously cleared or commercially available (reference) Vitamin B12 assay. For the modified device, the predicate device calibrated with the original CalSet serves as the reference for method comparison with the modified device using CalSet II.
8. The Sample Size for the Training Set
This information is not provided in the document. This submission describes an in vitro diagnostic device, not a machine learning or AI algorithm that typically has a distinct training set. The "training" for a device like this would involve calibration procedures using specific calibrators (Elecsys Vitamin B12 CalSet II) and master curves, often established during development and manufacturing, rather than a "training set" of patient data in the AI sense.
9. How the Ground Truth for the Training Set was Established
As noted above, this device does not have a "training set" in the context of machine learning. The "ground truth" for instrument calibration is established by using calibrators (Elecsys Vitamin B12 CalSet II) which are "lyophilized product[s] consisting of human serum with added Vitamin B12." These calibrators "are used for calibrating the quantitative Elecsys Vitamin B12 assay." The concentrations of Vitamin B12 in these calibrators are determined during manufacturing and are traceable to a standardization process, which for the modified device is "standardized against the Elecsys Vitamin B12 assay."
§ 862.1810 Vitamin B
12 test system.(a)
Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.(b)
Classification. Class II.