(16 days)
This assay is for the qualitative determination of galactose-1-phosphate uridyl transferase activity in dried blood spot samples using the Bio-Rad CODA Analyzer. 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.
The CODA GALT assay utilizes dried blood spot samples (DBS) eluted in a medium containing B-nicotinamide adenine dinucleotide phosphate (NADP), galactose-1-phosphate, uridine-5diphosphoglucose (UDPG), and a tetrazolium salt. During the manual elution step, GALT present in the specimen converts galactose-1-phosphate to glucose-1-phosphate, with the eventual reduction of NADP to NADPH.
After elution, the samples are placed on the CODA instrument and 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 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.
The CODA instrument is an integrated immunoassay analyzer intended for the automation of microplate based assays for in vitro diagnostic use.
Acceptance Criteria and Device Performance Study
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Tests | Acceptance Criteria | CODA Assay (Reported Performance) | Microplate Assay (Comparator) |
|---|---|---|---|
| Concordance | 100% | 100% (to Manual) | NA |
| Analytical Sensitivity | < 1.0 U/g Hb | 0.31 U/g Hb | 0.64 U/g Hb |
| Within-run Precision | < 12 % | 6.2% - 8.8% | 4.3% - 10.6% |
| Total Precision | < 15 % | 5.8% - 12.5% | 7.0% - 11.8% |
| Interference of bilirubin, triglycerides, and protein | No Interference | No Interference | No Interference |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the specific sample sizes used for each performance test in the "Testing To Establish Substantial Equivalence" section. It primarily focuses on comparing the new CODA assay's performance against the existing Microplate Neonatal GALT Assay.
- Sample Size: Not explicitly stated for the test set.
- Data Provenance: The document does not provide details on the country of origin of the data or whether the study was retrospective or prospective. Given the context of a 510(k) submission for a device modification, the studies were likely conducted internally by Bio-Rad Laboratories, Inc.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This information is not provided in the document. The study primarily involves analytical performance comparisons rather than clinical evaluation requiring expert interpretation of results.
4. Adjudication Method for the Test Set
Not applicable. The study focuses on analytical performance characteristics and concordance with a predicate device, not clinical outcomes requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic assay, and the evaluation focuses on its analytical performance and equivalence to a predicate device, not on human reader performance with or without AI assistance.
6. Standalone (Algorithm Only) Performance
Yes, a standalone performance study was done for the CODA Neonatal GALT Assay, as indicated by the "CODA Assay (Reported Performance)" column in the table. The reported values for Analytical Sensitivity, Within-run Precision, Total Precision, and Interference are measurements of the device's performance in isolation.
7. Type of Ground Truth Used
The "ground truth" for the performance tests appears to be established by:
- Concordance: Comparison to a "Manual" method (likely a reference laboratory method or a prior established manual GALT assay).
- Analytical Sensitivity, Precision, and Interference: These are quantitative measurements against established analytical standards and internal controls. The document states 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℃," indicating a well-defined chemical/enzymatic basis for measurement.
8. Sample Size for the Training Set
The document does not mention a "training set" in the context of developing the CODA Neonatal GALT Assay. This assay is a modification to an existing one, not a novel AI/machine learning algorithm that typically requires a distinct training phase.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as no training set (in the context of machine learning) is mentioned or implied for this device modification. The device's underlying principles are based on established biochemical reactions, not on learning from a dataset.
{0}------------------------------------------------
K93536
Special 510(k): Device Modification Summary Bio-Rad CODA Neonatal GALT Assay
| Submitter: | Bio-Rad Laboratories, Inc.4000 Alfred Nobel Drive,Hercules, California 94547Phone: (510) 741-6298FAX: (510) 741-6471 |
|---|---|
| Contact Person: | Elizabeth TangRegulatory Affairs Specialist |
| Date of Summary Preparation: | October 18, 1999 |
| Device Name: | Bio-Rad CODA Neonatal GALT Assay |
| Classification Name: | Galactose-1-phosphate uridyl transferase test system |
| Predicate Device: | Microplate Neonatal GALT AssayK998027Bio-Rad Laboratories, Inc.RADIAS GALT AssayK961432Bio-Rad Laboratories, Inc. |
| Statement of Intended Use: | This assay is for the qualitative determination of galactose-1-phosphate uridyl transferase activity in dried blood spotsamples using the Bio-Rad CODA Analyzer.Measurements of GALT are used in the diagnosis andtreatment of the hereditary disease galactosemia (disorderof galactose metabolism) in infants.For in vitro diagnostic use only. |
Description of Device
The CODA GALT assay utilizes dried blood spot samples (DBS) eluted in a medium containing B-nicotinamide adenine dinucleotide phosphate (NADP), galactose-1-phosphate, uridine-5diphosphoglucose (UDPG), and a tetrazolium salt. During the manual elution step, GALT present in the specimen converts galactose-1-phosphate to glucose-1-phosphate, with the eventual reduction of NADP to NADPH.
After elution, the samples are placed on the CODA instrument and an aliquot of the eluate is transferred to a microwell. The optical density (OD) is read, then Enzyme Reagent is added.
{1}------------------------------------------------
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 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.
The CODA instrument is an integrated immunoassay analyzer intended for the automation of microplate based assays for in vitro diagnostic use.
Testing To Establish Substantial Equivalence
To establish substantial equivalence to an existing device, and thus establish the safety and effectiveness. the CODA Neonatal GALT Assay is compared to the Microplate Neonatal GALT Assay. A review of the intended use of each system shows them to be the same. The only differences between the protocols are the size of dried blood spots and volume of Substrate/Color reagent used. No significant changes were made in the assay reagents or procedure.
The CODA assay will use the same kit configuration as the 510(k) cleared Microplate GALT Assay (#K990827). Those using the kit for the CODA application will follow the instructions of a separate CODA application instruction note. This note will refer them to the main kit insert for all other information about the assay.
| Performance Tests | Acceptance Criteria | CODA Assay | Microplate Assay |
|---|---|---|---|
| Concordance | 100% | 100%(to Manual) | NA |
| Analytical Sensitivity | < 1.0 U/g Hb | 0.31 U/g Hb | 0.64 U/g Hb |
| Within-run Precision | < 12 % | 6.2% - 8.8% | 4.3% - 10.6% |
| Total Precision | < 15 % | 5.8% - 12.5% | 7.0% - 11.8% |
| Interference ofbilirubin, triglycerides,and protein | No Interference | No Interference | No Interference |
Performance Characteristics
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 Microplate GALT Test and the CODA Neonatal GALT Assay are substantially equivalent. Based on the establishment of substantial equivalence, the safety and effectiveness of the CODA Neonatal GALT Assay is confirmed.
{2}------------------------------------------------
Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol featuring three abstract human figures, represented by curved lines, positioned closely together.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
NOV - 4 1999
Ms. Elizabeth Tang Regulatory Affairs Specialist Bio-Rad Laboratories, Inc. Diagnostics Group 4000 Alfred Nobel Drive Hercules, California 94547
Re: K993536
Trade Name: Bio-Rad CODA® Neonatal GALT Assay Regulatory Class: II Product Code: KQP Dated: October 18, 1999 Received: October 19, 1999
Dear Ms. Tang:
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.
{3}------------------------------------------------
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 Sutman
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
{4}------------------------------------------------
Statement of Indications for Use
510(k) Number:
Device Name:
Indications for Use:
Bio-Rad CODA Neonatal GALT Assay
This assay is for the qualitative determination of galactose-1-phosphate uridyl transferase activity in dried blood spot samples using the Bio-Rad CODA Analyzer. 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.
Cooper
(Division Sign-Off)
Division of Clinical Laboratory vices
510(k) Number K993536
(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-The-counter Use _
§ 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.