(207 days)
The ACE BUN/Urea Reagent is intended for the quantitative determination of blood urea nitrogen (BUN) concentration in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. BUN measurements are used in the diagnosis and treatment of certain renal and metabolic diseases. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE Creatinine Reagent is intended for the quantitative determination of creatinine concentration in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE Uric Acid Reagent is intended for the quantitative determination of uric acid concentration in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Uric acid measurements are used in the diagnosis and treatment of numerous renal and metabolic disorders, including renal failure, gout, leukemia, psoriasis, starvation or other wasting conditions and of patients receiving cytotoxic drugs. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE CK Reagent is intended for the quantitative determination of creatine kinase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Measurement of creatine kinase is used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
In the ACE BUN/Urea Reagent assay, urea in serum is hydrolyzed in the presence of urease to yield ammonia and carbon dioxide. The ammonia formed then reacts in the presence of glutamate dehydrogenase with 2-oxoglutarate and NADH to yield glutamate and NAD. NADH absorbs strongly at 340 nm, whereas NAD+ does not. The initial rate of decrease in absorbance, monitored bichromatically at 340 nm/647 nm, is proportional to the urea concentration in the sample.
In the ACE Creatinine Reagent assay, creatinine reacts with picric acid in an alkaline medium to form a red-orange colored complex, which absorbs strongly at 505 nm. The rate of complex formation, determined by measuring the increase in absorbance bichromatically at 505 nm/573 nm during a fixed time interval, is directly proportional to the creatinine concentration in the sample.
In the ACE Uric Acid Reagent assay, uric acid in serum is oxidized by uricase to allantoin and hydrogen peroxide. The hydrogen peroxide then acts to oxidatively couple dichlorohydroxybenzene sulfonic acid and 4-aminoantipyrine in a reaction catalyzed by peroxidase, producing a red colored quinoneimine complex, which absorbs strongly at 505 nm. The amount of chromogen formed is determined by measuring the increase in absorbance bichromatically at 505 nm/610 nm, and is directly proportional to the uric acid concentration in the sample.
In the ACE CK Reagent assay, serum creatine kinase initiates the conversion of creatine phosphate to creatine with the transfer of a phosphate group to adenosine diphosphate (ADP), forming ATP. The ATP is then used in the phosphorylation of D-glucose to form D-glucose-6-phosphate and ADP. This reaction is catalyzed by hexokinase. The enzyme glucose-6-phosphate dehydrogenase catalyzes the reduction of D-glucose-6-phosphate and nicotinamide adenine dinucleotide phosphate (NADP+). The series of reactions triggered by serum creatine kinase and ending in the formation of NADPH. NADPH strongly absorbs at 340 nm, whereas NADP+ does not. Therefore, the rate of conversion of NADP+ to NADPH can be determined by monitoring the increase in absorbance bichromatically at 340 nm/378 nm. This rate of conversion from NADP+ to NADPH is a function of the activity of CK in the sample.
Here's a summary of the acceptance criteria and supporting studies for the Alfa Wassermann ACE Reagents (BUN/Urea, Creatinine, Uric Acid, CK), based on the provided 510(k) summary.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly derived from comparisons to a predicate device (Alfa Wassermann ACE K930104 reagents) and performance characteristics such as precision, accuracy (correlation/regression with predicate), linearity, detection limits, and interference. The reported device performance is from in-house studies and Point-of-Care (POL) studies.
Note: The document does not explicitly state "acceptance criteria" numerical targets. Instead, it presents performance data for the candidate device, implying that the data's comparability to the predicate and established analytical standards is the basis for acceptance. I will present the reported performance, which demonstrates the device's meeting the necessary equivalency.
| Characteristic | Acceptance Criteria (Implied) | Reported Device Performance (Candidate Device) |
|---|---|---|
| Intended Use | Same as predicate (quantitative determination in serum) | BUN: Quantitative determination in serum and lithium heparin plasma. |
| Creatinine: Quantitative determination in serum and lithium heparin plasma. | ||
| Uric Acid: Quantitative determination in serum and lithium heparin plasma. | ||
| CK: Quantitative determination in serum and lithium heparin plasma. | ||
| (Extended to lithium heparin plasma compared to predicate, requiring performance studies in this matrix) | ||
| Platforms | Compatible with ACE Clinical Chemistry System | ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. (Expanded platforms compared to predicate) |
| Method | Photometric (Same as predicate) | Photometric (Same as predicate) |
| Calibration Stability | 7 days (BUN), 2 days (Creatinine), 30 days (Uric Acid) | Same |
| On-Board Stability | 30 days (BUN), 10 days (Creatinine), 30 days (Uric Acid), 25 days (CK) | Same |
| Sample Type | Serum (per predicate) | Serum and lithium heparin plasma (Candidate device demonstrates equivalence in both) |
| Sample Volume | 3 µL (BUN, Uric Acid), 20 µL (Creatinine), 5 µL (CK) | Same |
| Reaction Volume | 333 µL (BUN), 240 µL (Creatinine), 243 µL (Uric Acid), 170 µL (CK) | Same |
| Expected Values | Same as predicate | Same |
| Measuring Range | 3-100 mg/dL (BUN), 0.33-25.0 mg/dL (Creatinine), 1.5-16.0 mg/dL (Uric Acid), 11-1350 U/L (CK) | Same |
| Sample Stability | Same as predicate (storage conditions) | Same |
| Precision | Low, Mid, High %CV and SD comparable to predicate/clinical needs | In-House Serum/Plasma: Generally 0.98, Slope ~1, Intercept ~0) |
| Creatinine: R > 0.99, Slope 1.003-1.050, Intercept -0.077 to 0.005. | ||
| Uric Acid: R > 0.98, Slope 1.008-1.028, Intercept -0.29 to -0.09. | ||
| CK: R > 0.99, Slope 0.978-1.006, Intercept -0.5 to 0.1. (See pages 8-9) | ||
| Method Comparison (POL) | Comparison to In-House ACE results: Slope, Intercept, Correlation (R) and Std Error Est. demonstrating equivalence to predicate system (e.g., R > 0.98, Slope ~1, Intercept ~0). | BUN: R > 0.99, Slope 0.989-1.039, Intercept -0.1 to 1.4. |
| Creatinine: R > 0.99, Slope 0.977-1.051, Intercept -0.085 to 0.037. | ||
| Uric Acid: R > 0.99, Slope 0.936-1.034, Intercept 0.02 to 0.58. | ||
| CK: R > 0.99, Slope 0.962-1.053, Intercept -16.5 to 1.1. (See pages 14-15) | ||
| Detection Limits (LoB, LoD, LoQ) | Low values demonstrating capability to measure analytes at clinically relevant low concentrations. | BUN: LoB 1.53, LoD 1.97, LoQ 3.0 mg/dL. |
| Creatinine: LoB 0.14, LoD 0.18, LoQ 0.33 mg/dL. | ||
| Uric Acid: LoB 1.11, LoD 1.34, LoQ 1.50 mg/dL. | ||
| CK: LoB 4.68, LoD 8.30, LoQ 11.0 U/L. (See page 16) | ||
| Linearity | Wide linear range covering clinical needs, with high correlation. | BUN: Linear to 100.0 mg/dL, R² 0.9991. |
| Creatinine: Linear to 25.0 mg/dL, R² 0.9981. | ||
| Uric Acid: Linear to 16.0 mg/dL, R² 0.9939. | ||
| CK: Linear to 1350.0 U/L, R² 0.9975. (See page 16) | ||
| Interferences | No significant interference at specified levels of common interferents. | Demonstrated no significant interference from icterus, hemolysis, lipemia/triglycerides, and ascorbic acid at clinically relevant concentrations for all four analytes. (See page 17) |
Studies Proving Acceptance Criteria:
The studies are described under "Performance Data" and "Device Comparison with Predicate" sections of the 510(k) summary. These studies aim to demonstrate substantial equivalence to the previously cleared predicate device (Alfa Wassermann ACE BUN/Urea Reagent, ACE Creatinine Reagent, ACE Uric Acid Reagent, and ACE CK Reagents, K930104).
2. Sample Size Used for the Test Set and Data Provenance
-
Test Set (Matrix Comparison: Serum vs. Plasma):
- BUN: 95 pairs (ACE), 96 pairs (Alera), 51 pairs (Axcel)
- Creatinine: 102 pairs (ACE), 102 pairs (Alera), 55 pairs (Axcel)
- Uric Acid: 97 pairs (ACE), 95 pairs (Alera), 55 pairs (Axcel)
- CK: 94 pairs (ACE), 96 pairs (Alera), 55 pairs (Axcel)
- Data Provenance: The document states "In-House Precision" and "In-House Matrix Comparison". This typically implies that the data was generated within the manufacturer's laboratory or a testing facility under their control. The country of origin is not explicitly stated but is implicitly the US, given the 510(k) submission to the FDA. The data is retrospective, as it's being used to characterize reagent performance.
-
Test Set (POL - Method Comparison):
- BUN: 53-54 samples per POL lab for comparison with In-House ACE.
- Creatinine: 51 samples per POL lab for comparison with In-House ACE.
- Uric Acid: 49 samples per POL lab for comparison with In-House ACE.
- Creatinine Kinase: 48-50 samples per POL lab for comparison with In-House ACE.
- Data Provenance: "POL - Method Comparison" indicates data from Physician Office Laboratories (POLs), likely external to the main testing facility but still considered part of the overall validation. The document refers to "In-House ACE (x) vs. POL 1 ACE (y)", "POL 2 ACE (y)", etc., indicating comparisons against internal reference methods. The data is retrospective.
-
Test Set (Detection Limits, Linearity, Interferences, Alera Precision): The sample sizes for these specific studies are not explicitly detailed in the provided summary beyond "Low level tested," "Upper level tested," and "number of replicates for precision measurements (i.e. '3.2, 4.0%') implies multiple measurements. These are likely in-house, retrospective studies.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This information is not provided in the document. For in vitro diagnostic devices like these reagents, the "ground truth" is typically established by reference methods or validated comparative methods, often run on established clinical chemistry analyzers. The expertise lies in operating these reference instruments and ensuring proper laboratory practices, rather than expert interpretation of images or clinical cases.
4. Adjudication Method for the Test Set
This concept is not applicable to this type of device. Adjudication methods (like 2+1, 3+1) are common in studies involving subjective interpretations (e.g., medical image analysis by radiologists) where discrepancies among readers need to be resolved to establish ground truth. For quantitative IVD reagents, the reference method provides a direct numerical result, not a subjective interpretation requiring adjudication.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
This is not applicable to this type of device. MRMC studies are used to assess the effectiveness of an AI system (or any diagnostic aid) for human readers, particularly in medical imaging. The current device is a diagnostic reagent, which directly measures chemical concentrations, not an AI intended to assist human interpretation of cases.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
This is not applicable in the context of an IVD reagent. The "algorithm" here is the chemical reaction and photometric measurement itself. The performance data presented (precision, linearity, method comparison, etc.) is the standalone performance of the reagent on the specified analyzers, without human interpretive input altering the result.
7. Type of Ground Truth Used
The ground truth for all performance studies (precision, matrix comparison, method comparison, linearity) is established by comparison against a reference method or a substantially equivalent predicate method performed on existing, validated clinical chemistry analyzers (specifically, the predicate ACE Clinical Chemistry System and the candidate ACE, ACE Alera, and ACE Axcel systems themselves acting as the "reference" for their own performance claims, and for method comparisons, the "In-House ACE" results). This is a common and accepted approach for demonstrating substantial equivalence for IVD reagents.
8. Sample Size for the Training Set
This information is not provided and is generally not applicable in the way it is asked for AI/ML devices. These are chemical reagents, not AI/ML algorithms that require "training sets" in the conventional sense of machine learning. The development process would involve formulation, optimization, and internal testing to define assay parameters, which is a different concept than an AI training set.
9. How the Ground Truth for the Training Set Was Established
As stated above, the concept of a "training set" with established ground truth in the AI/ML sense is not applicable to these chemical reagents. The "ground truth" during their development and optimization would be based on established analytical chemistry principles and performance measurements against known standards or reference materials.
§ 862.1770 Urea nitrogen test system.
(a)
Identification. A urea nitrogen test system is a device intended to measure urea nitrogen (an end-product of nitrogen metabolism) in whole blood, serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of certain renal and metabolic diseases.(b)
Classification. Class II.