(433 days)
This method is for the quantitative determination of the amino acid tyrosine in whole blood saturated filter paper disks using the APF™ 300 SPOTCHECK® Analyzer or the RFA 300 System. Measurements obtained by this device are used primarily to screen newborns for congenital tyrosinemia, a disease that can cause liver/kidney disorders.
The proposed device, Tyrosine 50-Hour Reagent Kit, is a set of reagents to be used with the API™ 300 SPOTCHECK® Analyzer or the RFA 300 System for the quantitative determination of the amino acid tyrosine (Tyr) in whole blood saturated filter paper disks. The amount of Tvr is determined by measuring the fluorescent compound produced in the reaction of tyrosine with 1-nitroso-2-naphthol, catalyzed by nitrous acid at 80°C. The excitation wavelength of the product is 450 nm and emission is measured at 550 nm. The method is specific for para-substituted phenolic compounds. Excess 1-nitroso-2-naphthol is removed from the reaction mixture by reduction with sodium m-bisulfite.
The method is designed for mass screening, with enough reagents in each 50-Hour ' Reagent Kit for 1 week plus start-up (50 hours total) of run time. It is packaged to reduce storage space and to require a minimum of time to prepare. Each component is packaged with the correct weight to prepare the required volume of reagent. The standard is in a concentrated form, to permit easy dilution to prepare a standard curve.
Here's an analysis of the provided text to extract the acceptance criteria and study information:
Acceptance Criteria and Device Performance for Tyrosine 50-Hour Reagent Kit
The provided document describes the Tyrosine 50-Hour Reagent Kit, which is a set of reagents for the quantitative determination of the amino acid tyrosine in whole blood saturated filter paper disks. The device is intended for mass screening, primarily for newborns, to diagnose and treat diseases such as congenital tyrosinemia.
The submission claims substantial equivalence to a predicate device, the Technicon Tyrosine test. The acceptance criteria are implicitly based on demonstrating performance as well as or better than this predicate device, particularly through clinical correlation.
1. Table of Acceptance Criteria and Reported Device Performance
Given the nature of the submission (510(k) for a reagent kit claiming substantial equivalence), explicit numerical acceptance criteria (e.g., minimum sensitivity, specificity thresholds) are not formally stated in the provided text. Instead, the performance is evaluated by demonstrating good correlation with expected values and accurate identification within normal ranges, in comparison to the predicate device.
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Correlation with expected values for spiked samples | "Results correlated well with the expected values for the spiked samples." |
| Accuracy in detecting normal neonatal blood samples | "All normal neonatal blood samples yielded tyrosine values within the normal range." |
| Safety and Efficacy (compared to predicate device) | "The clinical tests demonstrate that the proposed device... is safe and performs as well as or better than the predicate device." |
| Functional equivalence to predicate device: | |
| - Quantitative, automated, fluorometric determination | Met: Both devices perform this. |
| - Same chemical principles and reaction mechanism | Met: "both have the same chemical principles and reaction mechanism." |
| - Similar reagents | Met: "The reagents are identical, and there are no new reagents." (Minor variation in surfactants noted as not consequential). |
| - Similar temperatures, time, and reagent ratios | Met: "The proposed device uses approximately the same temperatures, time and ratios of reagents as the predicate device." (Slight temperature difference noted as not consequential, within literature range for reaction). |
| Concentration Range (implicitly acceptable based on use case for screening) | 0-200 mg/L (This is different from the predicate's 0-2 mg/L but the document implies this difference is acceptable for the intended screening application, allowing for a broader range suitable for identifying elevated levels). |
| Detection Limit / Upper Limit | Not explicitly stated as acceptance criteria, but stated as a difference from the predicate that did not raise safety/efficacy concerns. |
| Ease of Use / Preparation | Improved: "reagents are either pre-made or pre-weighed" in the proposed device, while predicate required user preparation. |
| Sample Throughput | Improved: "sampling rate of 90 per hour vs. 50 per hour for the predicate device." |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: 1,096 specimens
- Normal Neonatal Blood Samples: 532
- Spiked Samples: 521
- Data Provenance: The specimens were analyzed by the State of California's Genetic Disease Laboratory. The data appears to be retrospective as the samples were "analyzed" by an existing laboratory. The country of origin is the USA.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- The document does not specify the number of experts or their qualifications used to establish ground truth for the test set.
- However, the samples were analyzed by the "State of California's Genetic Disease Laboratory," implying analysis by qualified laboratory personnel, but no explicit number or credentialing of medical experts (e.g., geneticists, pathologists) involved in establishing the 'true' tyrosine levels for the samples is provided.
4. Adjudication Method
- The document does not specify an adjudication method (e.g., 2+1, 3+1, none). The ground truth for spiked samples would be based on the known concentration of the spike, and for normal samples, on established normal ranges from the collaborating laboratory.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described.
- The study focuses on the performance of the device itself in quantitative measurements, rather than human reader interpretation with or without AI assistance. The device is a reagent kit for an automated system, not an AI-powered image interpretation tool where human-in-the-loop studies are common.
6. Standalone Performance Study
- Yes, a standalone performance study was done for the algorithm (the reagent kit and its associated method). The clinical tests described (1,096 specimens) represent the performance of the proposed device without human intervention beyond the standard operation of the API™ 300 SPOTCHECK® Analyzer or the RFA 300 System.
- The study demonstrated that the device correlated well with expected values and produced results within the normal range for normal neonatal samples.
7. Type of Ground Truth Used
- For Spiked Samples: The ground truth was based on the known concentration of the spiked tyrosine.
- For Normal Neonatal Blood Samples: The ground truth was based on established normal ranges for tyrosine in neonatal blood, as determined by the State of California's Genetic Disease Laboratory. This could be considered a form of clinical consensus/laboratory reference range.
8. Sample Size for the Training Set
- The document does not explicitly mention a separate "training set" for the device, as it is a reagent kit and not a machine learning algorithm in the modern sense that requires explicit training data to learn parameters from scratch.
- The development of such a kit typically involves internal validation and optimization, but not a distinct 'training set' as used in AI/ML terminology. The "clinical tests" described are implicitly the demonstration of the final product's performance, which in a regulatory context serves as the validation against ground truth.
9. How the Ground Truth for the Training Set Was Established
- As a distinct training set (in the AI/ML sense) is not mentioned, therefore, how its ground truth was established is not applicable or described in the document. The development of the kit would be based on established chemical principles and optimization to match the performance of the predicate device.
§ 862.1730 Free tyrosine test system.
(a)
Identification. A free tyrosine test system is a device intended to measure free tyrosine (an amono acid) in serum and urine. Measurements obtained by this device are used in the diagnosis and treatment of diseases such as congenital tyrosinemia (a disease that can cause liver/kidney disorders) and as an adjunct to the measurement of phenylalanine in detecting congenital phenylketonuria (a disease that can cause brain damage).(b)
Classification. Class I.