This assay is for the qualitative determination of galactose-1-phosphate uridyl transferase (GALT) activity in dried blood spot samples. Measurements of GALT are used in the diagnosis and treatment of the hereditary disease galactosemia (disorder of galactose metabolism) in infants. For in vitro diagnostic use only.

Device Description

The Microplate Neonatal GALT assay utilizes dried blood spot samples (DBS) eluted in a medium containing 8-nicitinamide adenine dinucleotide phosphate (NADP), galactose-1phosphate, uridine-5-diphosphoglucose (UDPG), and a tetrazolium salt. During elution, GALT present in the specimen converts galactose-1-phosphate to glucose-1-phosphate, with the eventual reduction of NADP to NADPH. After elution, an aliquot of the eluate is transferred to a microwell. The optical density (OD) is read, then Enzyme Reagent is added. During the incubation that follows, the Enzyme Reagent converts NADPH generated by GALT and endogenous red cell enzymes to NADP, and the tetrazolium salt to a colored formazan dye which is detected at 550 or 570 nm. The OD is read again and the difference between the two OD readings is determined. GALT activity, in units/g hemoglobin or units/liter blood, is calculated from the difference in signal between the two absorbance readings. A unit is defined as the quantity of GALT that catalyzes the formation of 1 micromole of UDP galactose per gram of hemoglobin or per Liter blood per hour at 37℃. An external calibrator is not necessary because enzyme activity is measured directly with substrates in excess.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study information for the Microplate Neonatal GALT assay, based on the provided document:

Acceptance Criteria and Reported Device Performance

Performance Tests	Acceptance Criteria	Microplate Assay (Reported Performance)	RADIAS Assay (Reported Performance)
Concordance	100%	100% (to RADIAS)	100% (To Beutler)
Analytical Sensitivity	< 0.80 U/g Hb	0.64 U/g Hb	0.51 U/g Hb.
Within-run Precision	< 12 %	4.3% - 10.6%	4.5% - 14.5%
Total Precision	< 15 %	7.0% - 11.8%	8.5% - 22.5%
Interference of bilirubin, triglycerides, and protein	No Interference	No Interference	No Interference

Study Information

Sample size used for the test set and the data provenance:
The document does not explicitly state the sample size for the test set. It mentions comparison "to RADIAS" and "To Beutler" for concordance, implying samples were tested on existing methods. The data provenance (country of origin, retrospective/prospective) is not specified.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not provided. The "ground truth" seems to be established by comparison to existing methods (RADIAS Assay and Beutler method), rather than through expert consensus on a test set.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
Not applicable, as the ground truth was established by comparison to existing methods, not by human adjudication of independent readings.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
Not applicable. This is an in vitro diagnostic device for measuring enzyme activity, not an AI-powered image analysis or diagnostic aid for human readers.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, this is a standalone device ("algorithm only") as it is an in vitro diagnostic assay that directly measures GALT activity. Its performance is reported in laboratory-centric metrics (sensitivity, precision, concordance) without human interpretation as part of the core measurement.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
For concordance, the ground truth was established by comparison to legally marketed predicate devices/methods: the RADIAS GALT Assay (K961432) and the Beutler method. For analytical sensitivity and precision, the ground truth is based on the inherent analytical capabilities of the method, likely determined against known controls or reference materials.
The sample size for the training set:
Not applicable. This is an in vitro diagnostic assay based on chemical reactions, not a machine learning or AI model that requires a training set.
How the ground truth for the training set was established:
Not applicable, as there is no training set for this type of device.

Summary

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4/9/99

K990827

Special 510(k): Device Modification Summary

Submitter:	Bio-Rad Laboratories, Inc.4000 Alfred Nobel Drive,Hercules, California 94547Phone: (510) 741-6188FAX: (510) 741-6471
Contact Person:	Juliet CarraraRegulatory Affairs/Quality Assurance Manager
Date of Summary Preparation:	March 10, 1999
Device Name:	Microplate Neonatal GALT
Classification Name:	Class II, Galactose-1-phosphate uridyl transferasetest system; 21 CFR 862.1315, 75KQP
Unmodified Device:	RADIAS GALT AssayK961432Bio-Rad LaboratoriesHercules, CA 94547
Statement of Intended Use:	This assay is for the qualitative determination ofgalactose-1-phosphate uridyl transferase (GALT)activity in dried blood spot samples.Measurements of GALT are used in the diagnosisand treatment of the hereditary disease galactosemia(disorder of galactose metabolism) in infants.For in vitro diagnostic use only.

Description of Device

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After elution, an aliquot of the eluate is transferred to a microwell. The optical density (OD) is read, then Enzyme Reagent is added. During the incubation that follows, the Enzyme Reagent converts NADPH generated by GALT and endogenous red cell enzymes to NADP, and the tetrazolium salt to a colored formazan dye which is detected at 550 or 570 nm. The OD is read again and the difference between the two OD readings is determined. GALT activity, in units/g hemoglobin or units/liter blood, is calculated from the difference in signal between the two absorbance readings. A unit is defined as the quantity of GALT that catalyzes the formation of 1 micromole of UDP galactose per gram of hemoglobin or per Liter blood per hour at 37℃. An external calibrator is not necessary because enzyme activity is measured directly with substrates in excess.

RADIAS

Technical Characteristics Compared to Unmodified Device

The technical characteristics are summarized in the flow chart below:

Microplate

Manual Steps: Manual steps: Punch 1/8 inch DBS into microtiter well す Add 200 ul Substrate/Color Reagent + Incubate 3 Hrs at 37 C + + RADIAS steps: Mix and transfer 120 ul into clean wells + Read at 570 nm Read at 550 nm + Add 50 ul Enzyme Reagent → + Incubate 37 C, 10 min. + Read at 570 nm Read at 550 nm

Punch 3/16 inch DBS into 12 X 75 tubes Add 350 ul Substrate/Color Reagent Incubate 3 Hrs at 37 C Transfer 120 ul into clean wells Add 60 ul Enzyme Reagent Incubate 37 C, 20 min.

The main differences between the protocols are where the Microplate Neonatal GALT format uses 1/8 inch DBS in 200 ul Elution reagent rather than a 3/16 inch DBS in 350 ul elution reagent (RADIAS format). After 3 hours of elution the Microplate format continues processing the test in a manual mode whereas the RADIAS format completes the test by automation. No significant changes were made in the assay reagents or procedure.

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Performance Characteristics

Performance Tests	Acceptance Criteria	Microplate Assay	RADIAS Assay
Concordance	100%	100%(to RADIAS)	100%(To Beutler)
Analytical Sensitivity	< 0.80 U/g Hb	0.64 U/g Hb	0.51 U/g Hb.
Within-run Precision	< 12 %	4.3% - 10.6%	4.5% - 14.5%
Total Precision	< 15 %	7.0% - 11.8%	8.5% - 22.5%
Interference ofbilirubin, triglycerides,and protein	No Interference	No Interference	No Interference

When considering the similarities of the intended use, general characteristics of the two assays, the use of the same technology and the excellent concordance between the two methods, it can be concluded that the RADIAS GALT Test and the Microplate Neonatal GALT Assay are substantially equivalent. Based on the establishment of substantial equivalence, the safety and effectiveness of the Microplate Neonatal GALT Assay is confirmed.

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Public Health Service

Image /page/3/Picture/2 description: The image shows a partial view of a logo or emblem. The visible portion features a stylized depiction of an eagle or similar bird with outstretched wings, rendered in black. The word "DEPARTMENT" is partially visible along the left edge of the image, oriented vertically. The overall design suggests an official or governmental affiliation.

APR 9 1999 Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Ms. Juliet Carrara Regulatory Affairs/Ouality Assurance Manager Bio-Rad Laboratories, Inc. Diagnostics Group 4000 Alfred Nobel Drive Hercules, California 94547-1803

K990827 Re:

Trade Name: Microplate Neonatal GALT Assay Regulatory Class: II Product Code: KOP Dated: March 10, 1999 Received: March 12, 1999

Dear Ms. Carrara:

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 legally marketed predicate 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 of the Act. The general controls provisions of the Act include requirements for annual registration, 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 Regulations, Title 21, Parts 800 to 895. A 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 regulation (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 regulation may result in regulatory 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 premarket notification"(21 CFR 807.97). Other general 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/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

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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Statement of Indications for Use

510(k) Number:

Device Name:

Indications for Use:

K990827

Bio-Rad Microplate Neonatal GALT Test

For in vitro diagnostic use only.

Cent (Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number . K 99082

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescriptive Use
(Per 21 CFR 801.109)
OR over-th

OR over-the-counter Use _

Regulation Number and Section

§ 862.1315 Galactose-1-phosphate uridyl transferase test system.

(a)
Identification. A galactose-1-phosphate uridyl transferase test system is a device intended to measure the activity of the enzyme galactose-1-phosphate uridyl transferase in erythrocytes (red blood cells). Measurements of galactose-1-phosphate uridyl transferase are used in the diagnosis and treatment of the hereditary disease galactosemia (disorder of galactose metabolism) in infants.(b)
Classification. Class II.