MICROPLATE NEONATAL GALT ASSAY

K990827 · Bio-Rad · KQP · Apr 9, 1999 · Clinical Chemistry

Device Facts

• Record ID: K990827
• Device Name: MICROPLATE NEONATAL GALT ASSAY
• Applicant: Bio-Rad
• Product Code: KQP · Clinical Chemistry
• Decision Date: Apr 9, 1999
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 862.1315
• Device Class: Class 2
• Attributes: Pediatric

Indications for Use

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 Story

The Microplate Neonatal GALT assay is an in vitro diagnostic test for infants. It uses dried blood spot (DBS) samples as input. The assay principle involves eluting the DBS in a medium containing NADP, galactose-1-phosphate, UDPG, and a tetrazolium salt. GALT in the specimen converts galactose-1-phosphate to glucose-1-phosphate, reducing NADP to NADPH. An enzyme reagent is added to convert NADPH back to NADP, simultaneously reducing the tetrazolium salt to a colored formazan dye. The device measures optical density (OD) at 550 or 570 nm before and after enzyme reagent addition. The difference in OD is used to calculate GALT activity in units/g hemoglobin or units/liter blood. The test is performed manually in a laboratory setting. Results assist clinicians in diagnosing and managing galactosemia, a hereditary disorder of galactose metabolism, allowing for early intervention.

Clinical Evidence

Bench testing only. Performance compared to the RADIAS GALT Assay and Beutler method. Concordance was 100%. Analytical sensitivity was 0.64 U/g Hb. Within-run precision ranged from 4.3% to 10.6%, and total precision ranged from 7.0% to 11.8%. No interference was observed from bilirubin, triglycerides, or protein.

Technological Characteristics

In vitro diagnostic assay using colorimetric enzymatic reaction. Reagents: NADP, galactose-1-phosphate, UDPG, tetrazolium salt, and enzyme reagent. Form factor: 96-well microplate. Detection: Spectrophotometric measurement at 550 or 570 nm. Manual processing workflow. No external calibrator required as enzyme activity is measured directly with substrates in excess.

Indications for Use

Indicated for the qualitative determination of GALT activity in dried blood spot samples to aid in the diagnosis and treatment of galactosemia in infants.

Regulatory Classification

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.

Predicate Devices

• RADIAS GALT Assay (K961432)

Reference Devices

• Beutler

Submission Summary (Full Text)

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4/9/99

K990827

# Special 510(k): Device Modification Summary

| Submitter: | Bio-Rad Laboratories, Inc.<br>4000 Alfred Nobel Drive,<br>Hercules, California 94547<br>Phone: [phone]<br>FAX: [phone] |
|------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | Juliet Carrara<br>Regulatory Affairs/Quality Assurance Manager |
| Date of Summary Preparation: | March 10, 1999 |
| Device Name: | Microplate Neonatal GALT |
| Classification Name: | Class II, Galactose-1-phosphate uridyl transferase<br>test system; 21 CFR 862.1315, 75KQP |
| Unmodified Device: | RADIAS GALT Assay<br>K961432<br>Bio-Rad Laboratories<br>Hercules, CA 94547 |
| Statement of Intended Use: | This assay is for the qualitative determination of<br>galactose-1-phosphate uridyl transferase (GALT)<br>activity in dried blood spot samples.<br>Measurements of GALT are used in the diagnosis<br>and treatment of the hereditary disease galactosemia<br>(disorder of galactose metabolism) in infants.<br>For in vitro diagnostic use only. |

## Description of Device

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.

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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 of<br>bilirubin, triglycerides,<br>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

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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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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 [phone].

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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. 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 [phone] or [phone], 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

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.

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 _