(43 days)
The products encompassed by this request are intended for in vitro diagnostic use and are intended for use in the quantitative determinations of Nat K . Cl . and CO., Beckman Instrument is the Original Equipment Manufacturer of the Chemistry Analyzers and of the predicate Reagents. The Beckman Chemistry Analyzers perform a broad array of tests. ALKO manufactures the ISE Reagents, wherein samples are analyzed for quantitative determinations of Nat, K, Cl and CO2 by ISE method. These Reagents are intended to be used with equivalent Beckman Chemistry Analyzers. As such, ALKO products are intended to serve as direct replacements to like named products manufactured by Beckman Instrument Inc.
The Electrolyte Buffer is intended to provide constant ionic strength for measuring electrolytes in the samples. As such, it is diluted with Wash Solution and introduced into the sample and/or calibrator, for quantitative determination of Nat, K*, Cl and CO., The Electrolyte Reference Reagent is intended to provide reference points for Na , K , Cl and CO2. The CO2 Acid Reagent is intended to release CO2 from serum and plasma samples and/or calibrators. The CO, Alkaline Buffer is to provide a constant CO, concentration as reference for the CO, Electrode. The Wash Concentrate is intended to be diluted with deionized water. The prepared Wash Solution is used to wash the systems sample flow path and to dilute reagents on equivalent Beckman CX® Systems.
The products encompassed by this 510(k) submission are Class II (75JIX) In Vitro Diagnostic Solutions manufactured by ALKO Diagnostic Corporation, 333 Fiske Street, Holliston, MA 01746. The Reagents are intended for use on equivalent Beckman Analyzers. Beckman Instrument is the original equipment manufacturer (OEM) of the analyzers and of predicate reagents which are necessary for the continued operation and use of the analyzers.
Information herein will support ALKO's position for the intended use of these products to the equivalent Beckman Chemistry Analyzers. The Beckman Chemistry Añalyzers perform a broad array of tests. ALKO manufactures the ISE Reagents, wherein samples are analyzed for quantitative determinations of Nat, K', Cl ' and CO, by ISE method. These Reagents are intended to be used with equivalent Beckman Chemistry Analyzers. As such, ALK O products are intended to serve as direct replacements to like named products manufactured by Beckman Instrument Inc.
The Electrolyte Buffer is intended to provide constant ionic strength for measuring electrolytes in the samples. As such, it is diluted with Wash Solution and introduced into the sample and/or calibrator, for quantitative determination of Nat, K., Cl - and CO2. The Electrolyte Reference Reagent is to provide reference points for Nat, K*, Cl and CO, The CO, Acid Reagent is to release CO, from serum and plasma samples and/or librators. The CO, Alkaline Buffer is to provide a constant CO2 concentration as reference for the CO2 * Electrode. The Wash Concentrate is intended to be diluted with de-ionized water. The prepared Wash Solution is used to wash the systems sample probe and to dilute reagents on equivalent Beckman CX® Systems.
- ALKO product A443-325 (Electrolyte Buffer) is equivalent to Beckman Instrument product 443325 . (Electrolyte Buffer).
- ALKO product A443-315 (Electrolyte Reference Reagent), is equivalent to Beckman Instrument product . 443315 (Electrolyte Reference Reagent).
- ALKO product A443-330 (CO2 Acid Reagent), is equivalent to Beckman Instrument product 443330 . (CO2 Acid Reagent).
- ALKO product A443-320 (CO2 Alkaline Buffer), is equivalent to Beckman Instrument product 443320 . (CO2 Alkaline Buffer).
- ALKO product A443-335 (Wash Concentrate), is equivalent to Beckman Instrument product 443335 . (Wash Concentrate).
ALKO uses a similar composition, description and packaging design as that used by Beckman Instrument Inc. in its products.
Acceptance Criteria and Study for ALKO Reagents on Beckman CX® Series Analyzers
This document describes the acceptance criteria and study proving equivalence for ALKO Reagents when used on Beckman CX® Series and equivalent analyzers. The goal is to demonstrate that ALKO products can serve as direct replacements for Beckman Instrument Inc. reagents for quantitative determination of Na+, K+, Cl-, and CO2 by ISE method.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the performance characteristics demonstrated to be equivalent to the predicate Beckman reagents. For the purposes of this summary, the key performance characteristics are precision and correlation with Beckman reagents.
Acceptance Criteria for Precision (implicitly defined by demonstrated performance)
The acceptance criteria for precision are implicitly based on the observed Coefficient of Variation (CV%) values, which are considered acceptable for quantitative electrolyte measurement in clinical diagnostics.
| Analyte | Sample Type/Level | Metric | Acceptance Criteria (Implied) | Reported Performance (Total CV%) |
|---|---|---|---|---|
| Na+ | Serum (Normal) | CV% | Clinically acceptable range | 0.9596% |
| Na+ | Serum (Abnormal) | CV% | Clinically acceptable range | 0.7698% |
| Na+ | Urine (Level 1) | CV% | Clinically acceptable range | 1.2544% |
| Na+ | Urine (Level 2) | CV% | Clinically acceptable range | 1.0267% |
| K+ | Serum (Normal) | CV% | Clinically acceptable range | 1.1071% |
| K+ | Serum (Abnormal) | CV% | Clinically acceptable range | 0.8462% |
| K+ | Urine (Level 1) | CV% | Clinically acceptable range | 1.2944% |
| K+ | Urine (Level 2) | CV% | Clinically acceptable range | 1.2567% |
| Cl- | Serum (Normal) | CV% | Clinically acceptable range | 1.2643% |
| Cl- | Serum (Abnormal) | CV% | Clinically acceptable range | 0.8451% |
| Cl- | Urine (Level 1) | CV% | Clinically acceptable range | 1.3918% |
| Cl- | Urine (Level 2) | CV% | Clinically acceptable range | 1.0690% |
| CO2 | Serum (Normal) | CV% | Clinically acceptable range | 4.0549% |
| CO2 | Serum (Abnormal) | CV% | Clinically acceptable range | 1.9268% |
Acceptance Criteria for Correlation with Beckman Reagents (implicitly defined by demonstrated performance)
The acceptance criteria for correlation are implicitly based on high R-squared values (close to 1), slopes close to 1, and intercepts close to 0, indicating strong agreement and similar performance to the Beckman reagents.
| Analyte | Analyzer (CX®3) | Acceptance Criteria (Implied) | Reported Performance (R-Squared) | Reported Performance (Slope) | Reported Performance (Intercept) |
|---|---|---|---|---|---|
| Na+ | CX®3 | R² > 0.99, Slope ≈ 1, Intercept ≈ 0 | 0.9992 | 1.0048 | -0.6344 |
| K+ | CX®3 | R² > 0.99, Slope ≈ 1, Intercept ≈ 0 | 0.9995 | 0.9840 | 0.0846 |
| Cl- | CX®3 | R² > 0.99, Slope ≈ 1, Intercept ≈ 0 | 0.9991 | 0.9801 | 1.5534 |
| CO2 | CX®3 | R² > 0.99, Slope ≈ 1, Intercept ≈ 0 | 0.9956 | 0.9738 | 0.6117 |
| Na+ | CX®5 | R² > 0.99, Slope ≈ 1, Intercept ≈ 0 | 0.9961 | 0.9727 | 3.7055 |
| K+ | CX®5 | R² > 0.99, Slope ≈ 1, Intercept ≈ 0 | 0.9993 | 0.9807 | 0.0447 |
| Cl- | CX®5 | R² > 0.99, Slope ≈ 1, Intercept ≈ 0 | 0.9991 | 0.9369 | 5.0960 |
| CO2 | CX®5 | R² > 0.99, Slope ≈ 1, Intercept ≈ 0 | 0.9988 | 0.9885 | 0.2429 |
| Na+ | Urine (CX®3) | R² > 0.99, Slope ≈ 1, Intercept ≈ 0 | 0.9997 | 0.9984 | 0.0968 |
| K+ | Urine (CX®3) | R² > 0.99, Slope ≈ 1, Intercept ≈ 0 | 0.9991 | 0.9602 | 1.0587 |
| Cl- | Urine (CX®3) | R² > 0.99, Slope ≈ 1, Intercept ≈ 0 | 0.9978 | 0.9764 | 1.7695 |
2. Sample Sizes Used for the Test Set and Data Provenance
Precision Study:
- Sample Size (Test Set): For each analyte (Na+, K+, Cl-, CO2), there were 60 measurements for each control level (serum normal, serum abnormal, urine level 1, urine level 2) for "Total" precision, derived from 20 runs performed in triplicate per run. For "Run to Run" precision, N=20 (representing 20 individual runs).
- Data Provenance: The document does not explicitly state the country of origin. Given the FDA 510(k) submission, it is likely that the study was conducted in the US or under US regulatory standards. The study appears to be prospective as it involved measurements over a defined period (20 runs over 30 days).
Correlation Study:
- Serum/Plasma Samples (Beckman CX®3): 68+ serum and plasma samples were used across the analytes, with specific N values: Na+ (72), K+ (74), Cl- (77), CO2 (68).
- Serum Samples (Beckman CX®5): 34+ serum samples were used across the analytes, with specific N values: Na+ (38), K+ (40), Cl- (34), CO2 (38).
- Urine Samples (Beckman CX®3): 54+ urine samples were used across the analytes, with specific N values: Na+ (54), K+ (54), Cl- (55).
- Data Provenance: The document does not explicitly state the country of origin. This study appears to be prospective as it involved measuring samples with ALKO reagents and comparing them to measurements with Beckman reagents on the same analyzers.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This type of study (comparative performance of IVD reagents) does not typically involve human experts establishing "ground truth" in the same way imaging or clinical decision support AI devices do. The "ground truth" or reference standard for this study is the performance of the predicate Beckman reagents on the same analyzer. There are no human experts involved in determining the analytical accuracy or precision of the measurements.
4. Adjudication Method for the Test Set
Not applicable. As described above, this study focuses on analytical performance characteristics (precision, correlation) of diagnostic reagents, not clinical interpretation that would require expert adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This study pertains to in vitro diagnostic reagents, which measure analytes (Na+, K+, Cl-, CO2) directly. MRMC studies are typically performed for clinical decision support or imaging interpretation devices where human interpretation is a critical component influencing diagnostic accuracy.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, this study presents standalone performance of the ALKO reagents in conjunction with the Beckman analyzers. The measurements are performed by the automated ISE module of the analyzers, calibrated with either ALKO or Beckman reagents, without human interpretation of the raw analytical results being the primary endpoint of the study. The performance characteristics (precision, correlation) are inherent to the reagent-analyzer system.
7. The Type of Ground Truth Used
The "ground truth" for the correlation study is established by the measurements obtained using the predicate Beckman reagents on the same Beckman CX® Series analyzers. The study aims to show that the ALKO reagents produce results that are statistically equivalent and highly correlated with those from the established and legally marketed Beckman reagents. For the precision study, there is no external "ground truth"; rather, the assay's own reproducibility is assessed.
8. The Sample Size for the Training Set
This document describes a performance validation study for in vitro diagnostic reagents. In this context, there isn't a "training set" in the sense of machine learning algorithms. The reagents themselves are "trained" or optimized during their development and manufacturing process to meet certain specifications. The data presented here are validation data used to demonstrate that the final manufactured product performs as intended and equivalently to the predicate.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of a machine learning algorithm. The "ground truth" for the development of ALKO reagents would involve internal R&D and quality control processes to ensure the chemical properties and performance characteristics meet design specifications and are comparable to market leaders like Beckman.
§ 862.1150 Calibrator.
(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.