CEDIA RED BLOOD CELL FOLATE (NO BOIL REAGENT PACK)

K960800 · Boehringer Mannheim Corp. · CGN · Jul 26, 1996 · Clinical Chemistry

Device Facts

• Record ID: K960800
• Device Name: CEDIA RED BLOOD CELL FOLATE (NO BOIL REAGENT PACK)
• Applicant: Boehringer Mannheim Corp.
• Product Code: CGN · Clinical Chemistry
• Decision Date: Jul 26, 1996
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1295
• Device Class: Class 2

Indications for Use

The CEDIA® Red Blood Cell Folate (No Boil) Reagent Pack to be used in combination with the CEDIA® Folate (No Boil) Assay is a homogeneous enzyme binding assay for the quantitation of folate in red blood cells.

Device Story

In-vitro homogeneous enzyme immunoassay for quantitative folate determination in red blood cells. Uses CEDIA® (Cloned Enzyme Donor Immunoassay) technology based on genetically engineered β-galactosidase fragments. Fragments reassociate to form active enzyme, which cleaves o-nitrophenyl-β-D-galactopyranoside (ONPG) substrate, producing a color change measured spectrophotometrically at 415 nm. Folate-specific binding protein inhibits enzyme reassociation; sample folate competes with enzyme-donor-bound folate for binding sites, making enzyme activity directly proportional to folate concentration. Used in clinical laboratory settings by trained personnel. Provides quantitative results to assist in folate status assessment.

Clinical Evidence

Bench testing only. Precision studies performed with intra-assay CVs ranging from 4.4% to 6.0% across three patient sample levels. Method comparison against the CEDIA B12/Folate Assay (n=96) yielded a correlation coefficient of 0.96, slope of 1.20, and intercept of -30.6.

Technological Characteristics

Homogeneous enzyme immunoassay. Principle: Competitive protein binding using genetically engineered β-galactosidase fragments. Detection: Spectrophotometric measurement of ONPG hydrolysis at 415 nm. Reagents include human serum albumin-based low calibrator and ascorbic acid (stable 90 days at 2-8°C).

Indications for Use

Indicated for the quantitative determination of folate in human anticoagulated whole blood (red blood cells).

Regulatory Classification

Identification

A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow.

Predicate Devices

• CEDIA® Red Blood Cell Folate Reagent Pack

Reference Devices

• Bio-Rad Quantaphase II® B12/Folate Assay

Submission Summary (Full Text)

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K960800
JUL 26 1996
510(k) SUMMARY

| Subject: | Premarket Notification, 510(k)
CEDIA® Red Blood Cell Folate (No Boil) Reagent Pack:
Safety and Effectiveness Summary |
| --- | --- |
| Manufacturer: | Boehringer Mannheim Corporation
2400 Bisso Lane
P.O. Box 4117
Concord CA 94524-4117
Phone [phone]
Fax [phone] |
| | Boehringer Mannheim Corporation
9115 Hague Road
Indianapolis, IN 46256
Phone [phone] |
| Contact: | Mary Koning, Regulatory Affairs Specialist |
| Date: | 23 February 1996 |
| Proprietary Name | CEDIA® Red Blood Cell Folate (No Boil) Reagent Pack |
| Common Name | Homogeneous Enzyme Immunoassay for the Quantitative
Determination of Folate in Red Blood Cells. |
| Classification Name | Folate Test System |
| Predicate Device | CEDIA® Red Blood Cell Folate Reagent Pack |
| Device Description | CEDIA® Technology |
| | The CEDIA® Red Blood Cell Folate (No Boil) Reagent Pack to be
used in combination with the CEDIA® Folate (No Boil) Assay is an in-
vitro homogeneous enzyme immunoassay used for the quantitative
determination of folate in red blood cells. The assay is |

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Diagnostics

# 510(k) SUMMARY cont.

| Device Description, cont. | based on the bacterial enzyme β-galactosidase, which has been genetically engineered into two inactive fragments. These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically.
Folate specific binding protein, by binding to folate on the enzyme donor will inhibit enzyme reassociation thereby regulating the level of β-galactosidase formed. Folate present in the sample will compete with the folate bound to the enzyme donor subunit for the limited number of specific binding sites further regulating the level of active enzyme formed. Concentrations of folate are directly proportional to the amount of enzyme formed as monitored by the hydrolysis of the substrate o-nitrophenyl-β-D-galactopyranoside (ONPG). | |
| --- | --- | --- |
| Intended Use | The CEDIA® Red Blood Cell Folate (No Boil) Reagent Pack to be used in combination with the CEDIA® Folate (No Boil) Assay is a homogeneous enzyme binding assay for the quantitation of folate in red blood cells. | |
| Statement of Similarities and Differences | The following table outlines the similarities and differences between the BioRad Quantaphase II B12/Folate Radioassay and CEDIA® Red Blood Cell Folate (No Boil) Reagent Pack. | |
| Parameter | Bio-Rad Quantaphase II® B12/Folate Assay | CEDIA® Red Blood Cell Folate (No Boil) Reagent Pack |
| Basic Principle | Competitive Protein Binding (CPB) | Competitive Protein Binding (CPB) |
| Methodology | Radioimmunoassay | Homogeneous Enzyme Immunoassay |
| Intended Use | Quantitative determination of Folate in human anticoagulated whole blood | Quantitative determination of Folate in human anticoagulated whole blood |
| Monitoring System | Bound radioactivity ⁵⁷Co and ¹²⁵I with the pellet counted | β-galactosidase hydrolysis of ONPG |

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Diagnostics

510(k) SUMMARY, cont.

| Statement of Similarities and Differences, cont. | | |
| --- | --- | --- |
| Parameter | CEDIA® Red Blood Cell Folate Reagent Pack | CEDIA® Red Blood Cell Folate (No Boil) Reagent Pack |
| Detection Mechanism | Gamma counter | Spectrophotometer at 415 nm |
| Reagents | Protein diluent
Ascorbic Acid | Human serum albumin based Low calibrator (0 ng Folate/mL)
Ascorbic Acid |
| Sample Type | EDTA | Heparin |
| Working Concentration of Ascorbic Acid | 0.4% | 0.2% |
| Protocol
Dilution
Incubation
Temperature | 1:11
90 minutes
20 - 25°C | 1:100
20 - 60 minutes
20 - 25°C |
| Stability of Ascorbic Acid | Prepare daily. | Stable for 90 days when stored at 2 - 8 °C |
| Stability of Hemolysate | Sample is stable for 10 days at -20°C | Sample is stable for 24 hours at -20°C |
| Expected Values | 95 - 570 ng/mL | 193 - 964 ng/mL |

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Diagnostics

# 510(k) SUMMARY, cont.

| Statement of Similarities and Differences, cont. | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Parameter | BioRad Quantaphase II® B12/Folate Assay | | | CEDIA® Red Blood Cell Folate (No Boil) Reagent Pack | | |
| Precision | Intra -assay: Patient Samples | | | Intra -assay: Patient Samples | | |
| Level | 1 | 2 | 3 | 1 | 2 | 3 |
| Within-Run (ng/mL) | 818 | 385 | 290 | 502.2 | 481.7 | 344.4 |
| %CV | 3.7 | 6.5 | 5.2 | 5.1 | 4.4 | 6.0 |
| Method Comparison | N/A | | | versus CEDIA B12/Folate Assay | | |
| Number = Correlation = Slope = Intercept = | | | | 96
0.96
1.20
-30.6 | | |
| The performance information establishes the basis for substantial equivalence to the predicate device. | | | | | | |