VITROS IMMUNODIAGNOSTIC PRODUCTS FOLATE REAGENT PACK 1/2, VITROS IMMUNODIAGNOSTIC PRODUCTS VITAMIN B12/FOLATE REAGENT P3

K984166 · Ortho-Clinical Diagnostics, Inc. · CGN · Feb 5, 1999 · Clinical Chemistry

Device Facts

• Record ID: K984166
• Device Name: VITROS IMMUNODIAGNOSTIC PRODUCTS FOLATE REAGENT PACK 1/2, VITROS IMMUNODIAGNOSTIC PRODUCTS VITAMIN B12/FOLATE REAGENT P3
• Applicant: Ortho-Clinical Diagnostics, Inc.
• Product Code: CGN · Clinical Chemistry
• Decision Date: Feb 5, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1295
• Device Class: Class 2

Intended Use

1. & 2. The VITROS Immunodiagnostic Products Folate Reagent Pack 1/2 and the VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3 - for the in vitro quantitative measurement of folate in human serum and plasma (heparin) and whole blood (red cell folate), to aid in the differential diagnosis of anemia. 3. The VITROS Immunodiagnostic Products Folate Calibrators - for in vitro use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of folate in human serum and plasma (heparin). 4. The VITROS Immunodiagnostic Products Red Cell Folate Pack - for whole blood sample preparation, to allow the in vitro quantitative measurement of red cell folate using the VITROS Immunodiagnostic System.

Device Story

VITROS Immunodiagnostic System performs quantitative/semi-quantitative folate analysis in human serum, plasma, and whole blood. System uses coated microwells as solid-phase separation; luminescence as signal. Process: sample (53 µL) incubated with reagents (73 mins at 37°C for folate; 90 mins at room temperature for whole blood prep); enzyme-labeled tracer used instead of radioisotopes. Operated by laboratory personnel in clinical settings. Output: quantitative folate concentration. Healthcare providers use results to aid in differential diagnosis of anemia. Benefits: automated immunoassay workflow; eliminates radioactive waste associated with traditional radioassays.

Clinical Evidence

Bench testing only. Performance compared to predicate using patient specimens across clinical categories. Deming's regression showed correlation (r=0.979 for red cell folate). Analytical sensitivity, specificity, precision, linearity, and expected values were established. No clinical prospective/retrospective trials reported.

Technological Characteristics

Solid-phase immunoassay using coated microwells. Energy source: VITROS Immunodiagnostic System instrumentation. Detection: luminescence. Tracer: enzyme-labeled. Binding protein: bovine milk-derived folate binding protein. Sample volume: 53 µL. Connectivity: dedicated to VITROS Immunodiagnostic System. Sterilization: N/A (reagents).

Indications for Use

Indicated for in vitro quantitative measurement of folate in human serum, plasma (heparin), and whole blood (red cell folate) to aid in differential diagnosis of anemia.

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

• Bio-Rad Quantaphase II Folate Radioassay (K935286)

Submission Summary (Full Text)

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### 510(k) Summary

# (a) VITROS Folate assay

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92

The assigned 510(k) number is: طبط / 1 / 984 / 1

### 1. Submitter name, address, contact Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive

Rochester, New York 14626-5101 [phone]

Contact Person: Anne Zavertnik

Date 510(k) prepared: November 18th, 1998

#### 2. Device Name

#### (a) Folate assay

Trade or Proprietary Name: VITROS Immunodiagnostic Products Folate assay Common Name: Serum folate assay Classification Name: Folate assay for the in vitro quantitative measurement of folate in human serum and plasma (heparin).

### 3. Predicate Device

The VITROS Immunodiagnostic Products Folate assay is substantially equivalent to Bio-Rad Quantaphase II Folate Radioassay (K935286).

### 4. Device Description

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum, plasma and urine. Coated microwells are used as the solid phase separation system.

VITROS Immunodiagnotic Products Folate Assay and Red Cell Folate Pack

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The system is comprised of three main elements:

- 1. The VITROS Immunodiagnostic Products range of products, in this case VITROS Immunodiagnostic Products Folate Reagent Pack, VITROS Immunodiagnostic Products Folate Calibrators and the VITROS Immunodiagnostic System. The VITROS Folate Reagent Pack consists of: The VITROS Immunodiagnostic Products Folate Reagent Pack 1/2 and the VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3
- 2. The VITROS Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).
- 3. Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 510(k) pre-market notification (K984310).

The VITROS System and common reagents are dedicated specifically only for use with the VITROS Immunodiagnostic Products range of immunoassay products.

#### 5. Device Intended Use

The VITROS Folate assay is intended for the in vitro quantitative measurement of folate in human serum and plasma (heparin) and whole blood (red cell folate), to aid in the differential diagnosis of anemia.

#### 6. Comparison to Predicate Device

The VITROS Immunodiagnostic Products Folate assay is substantially equivalent to Bio-Rad Quantaphase II Folate Radioassay (predicate device), which was cleared by FDA (K935286) for IVD use.

The relationship between the VITROS Folate assay and the predicate device, determined by Deming's Regression, is:

VITROS Folate assay =0.999 x Bio-Rad Quantaphase II Folate Radioassay + 0.676 ng/mL Comparisons of the VITROS Folate assay and the predicate device were performed with samples from a variety of clinical categories.

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In addition to the studies mentioned above, tests were performed to obtain analytical sensitivity, specificity, precision, dilution and expected values. Refer to the VITROS Folate assay package insert for VITROS Folate assay results.

Table 1 lists the similarities and differences of the device characteristics between the VITROS Folate assay with the predicate device, Bio-Rad Quantaphase II Folate Radioassay.

| Device<br>Characteristic | VITROS Folate assay | Predicate<br>Device |
|------------------------------------|-------------------------------------------------------|--------------------------------|
| Calibration range | 0 – 20 ng/ml | 0-20 ng/mL |
| Basic principle | Solid phase assay | Radioassay |
| Tracer | Enzyme labeled | 125Iodine |
| Instrumentation | VITROS<br>Immunodiagnostic System | Gamma Counter |
| Sample type | Serum, plasma (heparin) | Serum or plasma (EDTA) |
| Binding protein | Folate binding protein,<br>purified from bovine milk. | Folate binding protein |
| Sample volume | 53 µL | 200 µL |
| Incubation time and<br>temperature | 73 mins at 37 °C | 1 hour at room<br>temperature. |

Table 1 List of the assay characteristics

#### 7. Conclusions

The data presented in the pre-market notification demonstrate that the VITROS Folate assay performs substantially equivalent to the predicate device, that was cleared by FDA (K935286) for IVD use.

Equivalence was demonstrated using currently commercially available reagents along with patient specimens covering a variety of clinical categories.

The data presented in the premarket notification provide a reasonable assurance that the VITROS Folate assay is safe and effective for the stated intended use.

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# (b) VITROS Red Cell Folate Pack

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92

The assigned 510(k) number is: __________________

### 1. Submitter name, address, contact

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 [phone]

Contact Person: Anne Zavertnik

Date 510(k) prepared: November 18th, 1998

#### 2. Device Name

Trade or Proprietary Name: VITROS Immunodiagnostic Products Red Cell Folate Pack (performed using the Vitros Folate Reagent Pack 1/2, VITROS Vitamin B12/Folate Reagent Pack 3 and the VITROS Red Cell Folate Pack)

Common Name: Red cell folate assay.

Classification Name: Red cell folate assay for the in vitro quantification of folate in human whole blood.

#### 3. Predicate Device

The VITROS Immunodiagnostic Products Red Cell Folate assay, is substantially equivalent to Bio-Rad Quantaphase II Folate Radioassay used with the Bio-Rad Red Cell Folate Reagent Pack (K935286).

### 4. Device Description

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum. plasma and urine. Coated microwells are used as the solid phase separation system.

The system is comprised of three main elements:

- 1. The VITROS Immunodiagnostic Products (in this case VITROS Immunodiagnostic Products Red Cell Folate Pack, VITROS Immunodiagnostic Products Folate Pack 1/2, VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3, VITROS Immunodiagnostic Products Folate Calibrators, which are combined by the VITROS Immunodiagnostic System to perform the VITROS Red Cell Folate assay).
VITROS Immunodiagnotic Products Folate Assay and Red Cell Folate Pack

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- 2. The VITROS Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).
- 3. Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 510(k) pre-market notification (K984310).

The VITROS System and common reagents are dedicated specifically only for use with the VITROS Immunodiagnostic Products range of immunoassay products.

#### 5. Device Intended Use

The Vitros Red Cell Folate Pack is intended for use in whole blood sample preparation to allow the in vitro quantitative measurement of red cell folate using the VITROS Immunodiagnostic System.

### 6. Comparison to Predicate Device

The VITROS Immunodiagnostic Products Red Cell Folate assay, is substantially equivalent to Bio-Rad Quantaphase II Folate Radioassay (predicate device), used with the Bio-Rad Red Cell Folate Reagent Pack, that was cleared by FDA (K935286) for IVD use.

The relationship between the VITROS Red Cell Folate assay and the predicate device, determined by Deming's Regression, is:

VITROS Red Cell Folate assay =1.17 x Bio-Rad Ouantaphase II Folate assay (used with the Bio-Rad Red Cell Folate Reagent Pack ) + 4.0 (ng/mL)

Comparisons of the VITROS Red Cell Folate assay and the predicate device were performed with samples from a variety of clinical categories.

Although there was a good correlation between the assays (r = 0.979), the VITROS assay showed an overall 17% positive bias. The results reflect true numerical differences for red cell folate measurement between the VITROS and Bio-Rad Quantaphase II assays.

In addition to the studies mentioned above, tests were performed to obtain precision, linearity and expected values. Refer to the VITROS Red Cell Folate Pack package insert for VITROS Red Cell Folate assay results.

Table 1 lists the similarities and differences of the device characteristics between the VITROS Red Cell Folate assay with the predicate device, Bio-Rad Quantaphase II Folate assay (used with the Bio-Rad Red Cell Folate Reagent Pack ).

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| | | | | | | | Table 1 List of the assay characteristics |
|--|--|--|--|--|--|--|-------------------------------------------|
|--|--|--|--|--|--|--|-------------------------------------------|

| Device<br>Characteristic | VITROS Red Cell Folate<br>assay | Predicate<br>Device |
|------------------------------------|-------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------|
| Calibration range | 0 - 20 ng/ml | 0 - 20 ng/ml |
| Basic principle | Solid phase assay | Radioassay |
| Tracer | Enzyme labeled | 125I |
| Instrumentation | VITROS<br>Immunodiagnostic System | Gamma Counter |
| Sample type | Whole blood (EDTA or<br>heparin) | Whole blood (EDTA) |
| Binding Protein | Folate binding protein | Folate binding protein |
| Sample volume | 53 µL | 200 µL |
| Incubation time and<br>temperature | 90 minutes at room<br>temperature (whole blood<br>preparation); 73 minutes at<br>37° C (folate assay) | 90 minutes at room<br>temperature (whole blood<br>preparation); 60 minutes<br>at room temperature<br>(folate assay). |

### 7. Conclusions

The data presented in the pre-market notification demonstrate that the VITROS Red Cell Folate assay performs substantially equivalent to the predicate, that was cleared by FDA (K935286) for IVD use.

Equivalence was demonstrated using currently commercially available reagents along with patient specimens covering a variety of clinical categories.

The data presented in the premarket notification provide a reasonable assurance that the VITROS Red Cell Folate assay is safe and effective for the stated intended use.

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Image /page/6/Picture/10 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" around the perimeter. Inside the circle is a stylized symbol that resembles a human figure in profile, with three overlapping heads or faces.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB 5 1999

Ms. Anne Zavertnik Regulatory Affairs Associate Ortho-Clinical Diagnostics A•Johnson & Johnson Company 100 Indigo Creek Drive Rochester, New York 14626-5101

Re: K984166 Trade Name: VITROS Immunodiagnostic Products Folate Assay Product Code: CGN Regulatory Class: II 118 II Dated: January 6, 1999 Received: January 7, 1999

Dear Ms. Zavertnik:

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 [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 vours.

Steven Autman

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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# Chapter 1 - Summary Information

# Indications for Use Statement

Page 1 of 1

### 510(k) Number (if known)

.

{

| Device Name: | 1. VITROS Immunodiagnostic Products Folate Reagent Pack 1/2<br>2. VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent<br>Pack 3<br>3. VITROS Immunodiagnostic Products Folate Calibrators |
|----------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | 4. VITROS Immunodiagnostic Products Red Cell Folate Pack |
| Indications for Use: | 1. & 2. The VITROS Immunodiagnostic Products Folate Reagent Pack<br>1/2 and the VITROS Immunodiagnostic Products Vitamin B12/Folate<br>Reagent Pack 3 - for the <i>in vitro</i> quantitative measurement of folate in<br>human serum and plasma (heparin) and whole blood (red cell folate), to<br>aid in the differential diagnosis of anemia. |
| | 3. The VITROS Immunodiagnostic Products Folate Calibrators - for <i>in vitro</i> use in the calibration of the VITROS Immunodiagnostic System<br>for the quantitative measurement of folate in human serum and plasma<br>(heparin). |
| | 4. The VITROS Immunodiagnostic Products Red Cell Folate Pack - for<br>whole blood sample preparation, to allow the <i>in vitro</i> quantitative<br>measurement of red cell folate using the VITROS Immunodiagnostic<br>System. |

.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Sean Cooper

(Division Sign-Off)

Division of Clinical Laboratory Devices

| 510(k) Number | K 984166 |
|---------------|----------|
|---------------|----------|

| Prescription Use (Per 21 CFR 801.109) | OR | Over-The-Counter Use |
|---------------------------------------|----|----------------------|
|---------------------------------------|----|----------------------|

(Optional Format 1-2-96)

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