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.

Device Description

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.

AI/ML Overview

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.

Summary

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MAR 1 9 1998

Submitter's Name:

Address:

Telephone: FAX: Contact Person:

Date Summary Prepared:

NAME OF DEVICE

510(k) Summary

IDENTIFICATION

Astoria-Pacific, Inc.

503-657-3010

503-655-7367

February 3, 1998

14600 SE 82nd Drive

Raymond L. Pavitt, President

Clackamas, OR 97015-0830, USA

Lester B. Garrison, Diagnostics Manager

Tyrosine 50-Hour Reagent Kit Proprietary Name: Common Name: Free Tyrosine Test System 1-Nitroso-2-naphthol (Fluorometric), Free Tyrosine Classification Name:

LEGALLY MARKETED DEVICE EQUIVALENT TO PROPOSED DEVICE

The Tyrosine 50-Hour Reagent Kit is substantially equivalent to a legally marketed predicate device, Technicon Tyrosine test.

DESCRIPTION OF PROPOSED DEVICE

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.

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The materials provided and their components are listed below.

Reagent	Active Component(s)	Concentration	Volume
Extraction Buffer	Succinate Buffer	6.0 mM	1000 mL
Saline Diluent, 0.9%	Sodium ChlorideTriton X-100	154. mM0.05%	600 mL
Complex Reagent	1-Nitroso-2-NaphtholDMSO	1.5 mM3.5 M	500 mL
Sodium Nitrite, 2.5%	Sodium Nitrite	0.36 M	10 mL
Nitrous Acid	Nitric Acid, 10%Sodium Nitrite, 2.5%	50 mL0.25 mL -Added before use	50 mL
Sodium Metabisulfite	Sodium Metabisulfite	0.26 M	500 mL
Tyrosine Stock Standard, L-Tyrosine10 mg/dL	Hydrochloric Acid	0.55 mM6.0 mM	50 mL

INTENDED USE

This method is for the quantitative determination of the amino acid tyrosine in whole blood saturated filter paper disks using the API™ 300 SPOTCHECK® Analyzer or the RFA 300 System. 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.

SUMMARY OF TECHNOLOGICAL CHARACTERISTICS OF DEVICE COMPARED TO PREDICATE DEVICE

Similarities with Predicate Device

The Astoria-Pacific SPOTCHECK® Tyrosine 50-Hour Reagent Kit is similar to the predicate device, Technicon Tyrosine test, having the same technological characteristics and intended use. Both are diagnostic reagent kits to be used for the quantitative, automated. fluorometric determination of the amino acid tyrosine in blood; both have the same chemical principles and reaction mechanism.

The reagents are identical, and there are no new reagents. The proposed device uses approximately the same temperatures, time and ratios of reagents as the predicate device.

Differences from Predicate Device

While the method and reagents are identical for the proposed and predicate devices, there are minor variations in the surfactants. The Technicon device uses Brij-35, while the proposed device uses Triton X-100, as it is available in a purified grade. In addition, the sample for the proposed device is whole blood spotted on filter paper and extracted with a

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buffer; the sample for the predicate device is not specified. The proposed device is designed for a sampling rate of 90 per hour vs. 50 per hour for the predicate device.

There are also slight differences in the temperature of the assay and the wavelengths of the excitation and emission filters. The temperature of the assay, which affects the level of fluorescence produced, is 80°C for the 50-Hour Reagent Kit and 90°C for the Technicon Tyrosine test; temperatures from 55°C to 90°C are cited in the literature for this reaction. The Proposed device designates 450 nm and 550 nm for the excitation and emission wavelengths, respectively: the predicate device uses 440 nm and 540 nm, respectively. Because there is a broad bandpass of about 40 nm for the filters, and the emitted fluorescent light is broad spectrum, this difference is not consequential.

Other differences include concentration range (0-200 mg/L for Astoria-Pacific vs. 0-2 mg/L for Technicon), detection limit and upper limit of the assay, Also, the Technicon Tyrosine test required the user to prepare all reagents; in the 50-Hour Reagent Kit, the reagents are either pre-made or pre-weighed.

The minor differences between the Astoria-Pacific SPOTCHECK® Tyrosine 50-Hour Reagent Kit and the Technicon Tyrosine test raise no questions of safety or efficacy.

BRIEF DISCUSSION OF NONCLINICAL TESTS

Because there is such a strong similarity between the Astoria-Pacific SPOTCHECK® Tyrosine 50-Hour Reagent Kit and the Technicon Tyrosine test, no nonclinical testing has been performed to demonstrate substantial equivalence to the predicate device.

BRIEF DISCUSSION OF CLINICAL TESTS

Clinical testing has been performed on whole blood saturated filter paper disks. These test include 1,096 specimens analyzed by the State of California's Genetic Disease Laboratory, of which 532 were normal neonatal blood samples and 521 were spiked samples. Results correlated well with the expected values for the spiked samples; all normal neonatal blood samples yielded tyrosine values within the normal range. Other testing is described in the product labeling.

CONCLUSIONS DRAWN FROM THE NONCLINICAL AND CLINICAL TESTS

The clinical tests demonstrate that the proposed device, the Astoria-Pacific SPOTCHECK® Tyrosine 50-Hour Reagent Kit, is safe and performs as well as or better than the predicate device.

OTHER INFORMATION

No other information has been requested by the FDA at this time.

End of 510(k) SUMMARY.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle or bird-like figure with three curved lines representing its head and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the bird figure.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 19 1998

Raymond L. Pavitt . President Astoria-Pacific, Inc. 14600 SE 82nd Drive Clackamas, Oregon 97015-0830

Re: K970093 Tyrosine 50-Hour Reagent Kit Requlatory Class: II Product Code: CDR February 4, 1998 Dated: February 5, 1998 Received:

Dear Mr. Pavitt:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act of the Act. include requirements for annual reqistration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. ਸੁ substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General requlation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in requlatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note:

this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 510 (k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to Other qeneral information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Sitman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page _ of _

510(k) Number (if known):_____________________________________________________________________________________________________________________________________________________ o Harr Reagent Kit. Device Name: Indications For Use:

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

(Division Sigri-Off)
Division of
510(k) Number. 12970092

Over-The-Counter Use

(Optional Format 1-2-96)

MAR-13-1998 છેર: 18 301 5945949

વડાદ

Regulation Number and Section

§ 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.