IMMULITE 2000 FOLIC ACID, MODEL L2KF02, L2KF06

K993254 · Diagnostic Products Corp. · CGN · Nov 12, 1999 · Clinical Chemistry

Device Facts

• Record ID: K993254
• Device Name: IMMULITE 2000 FOLIC ACID, MODEL L2KF02, L2KF06
• Applicant: Diagnostic Products Corp.
• Product Code: CGN · Clinical Chemistry
• Decision Date: Nov 12, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1295
• Device Class: Class 2

Indications for Use

IMMULITE 2000 Folic Acid is for in vitro diagnostic use with the IMMULITE 2000 Analyzer - for the quantitative measurement of folic acid in serum, heparinized plasma or ascorbic acid-treated whole blood, as an aid in clinical diagnosis and treatment of anemia.

Device Story

IMMULITE 2000 Folic Acid is an in vitro diagnostic reagent system used with the IMMULITE 2000 Automated Immunoassay Analyzer. It measures folic acid levels in serum, heparinized plasma, or ascorbic acid-treated whole blood. The assay uses a competitive chemiluminescent immunoassay principle. Patient samples undergo on-board treatment with dithiothreitol and NaOH/KCN to release folic acid from binding proteins. The treated sample competes with ligand-labeled folic acid for binding to a murine anti-folate binding protein antibody-coated polystyrene bead. After incubation and washing, alkaline phosphatase-labeled anti-ligand is added, followed by a chemiluminescent substrate (phosphate ester of adamantyl dioxetane). The resulting photon output is inversely proportional to the folic acid concentration. The system is operated by laboratory personnel in clinical settings. Results assist clinicians in diagnosing and managing anemia by identifying folate deficiency.

Clinical Evidence

Bench testing only. Method comparison studies were conducted comparing the IMMULITE® 2000 Folic Acid to the predicate IMMULITE® Folic Acid. Serum analysis (n=156) yielded a correlation coefficient of r=0.996 with a regression equation of y=0.96x - 0.54 ng/mL. Hemolysate analysis (n=49) yielded a correlation coefficient of r=0.981 with a regression equation of y=1.18x - 29 ng/mL. No clinical prospective or retrospective studies were required.

Technological Characteristics

Chemiluminescent immunoassay; solid phase: polystyrene bead coated with murine monoclonal antibody; detection system: alkaline phosphatase-labeled anti-ligand; substrate: phosphate ester of adamantyl dioxetane; automated sample pretreatment (dithiothreitol, NaOH/KCN); quantitative measurement; intended for use on IMMULITE 2000 Automated Immunoassay Analyzer.

Indications for Use

Indicated for the quantitative measurement of folic acid in serum, heparinized plasma, or ascorbic acid-treated whole blood as an aid in the clinical diagnosis and treatment of anemia in patients.

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

• IMMULITE® Folic Acid (K943705)

Submission Summary (Full Text)

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K993254

Nov 1 2 1999

# 510(k) Summary of Safety and Effectiveness

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

| Name: | Diagnostic Products Corporation |
|-----------------------------------------------|---------------------------------------------------------------------------------------------------------------------|
| Address: | 5700 West 96th Street<br>Los Angeles, California 90045-5597 |
| Telephone Number:<br>Facsimile Number: | [phone]<br>[phone] |
| Contact Person: | Edward M. Levine, Ph.D.<br>Director of Clinical Affairs |
| Date of Preparation: | October 26, 1999 |
| Device Name: | IMMULITE® 2000 Folic Acid |
| Trade: | Reagent system for the determination of folic acid<br>in serum, heparinized plasma, or whole blood. |
| Catalog Number: | L2KFO2 (200 tests); L2KFO6 (600 tests) |
| Classification: | Class II device (862.1295, 75CGN) |
| Manufacturer: | Diagnostic Products Corporation<br>5700 West 96th Street<br>Los Angeles, California 90045-5597 |
| Establishment Registration #: | DPC's Registration # is 2017183 |
| Substantially Equivalent<br>Predicate Device: | DPC's IMMULITE® Folic Acid (K943705) |
| Description of Device: | IMMULITE® 2000 Folic Acid is a clinical device<br>for use with the IMMULITE® 2000 Automated<br>Immunoassay Analyzer |

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Intended Use of the Device:

IMMULITE 2000 Folic Acid is for in vitro diagnostic use with the IMMULITE 2000 Analyzer - for the quantitative measurement of folic acid in serum, heparinized plasma or ascorbic acid-treated whole blood, as an aid in clinical diagnosis and treatment of anemia.

# Summary and Explanation of the Test:

Folic acid (folate) and vitamin B12 are nutrients essential to hematopoiesis. Megaloblastic anemia is almost always due to lack of one of these two vitamins. Circulating folate levels are usually normal or elevated in vitamin B12 deficiency, but red cell folate levels are frequently low in this condition.

Folate deficiency is commonly encountered as a result of dietary deficiency (as in alcoholism) or increased demand for this vitamin (as in pregnancy). Unlike vitamin B12, folate is a heat-labile vitamin susceptible to loss by prolonged cooking. Accordingly, the prevalence of folate deficiency exhibits major demographic variations, apparently reflecting differences in-dietary and culinary habits.

Circulating folate levels, being strongly influenced by recent intake, are unreliable as an index to tissue stores. Thus, folate levels measured in serum or plasma may be normal in the face of folate deficiency. Conversely, circulating levels may be low long before tissue stores have been exhausted. Accordingly, it is important to measure red cell folate levels whenever serum or plasma levels are measured.

# Performance Equivalence - Technology Comparison:

IMMULITE® and IMMULITE® 2000 Folic Acid are chemiluminescent immunoassays. The technology in DPC's IMMULITE® 2000 Folic Acid is a unique combination of technologies employed in previously cleared and commercially marketed DPC products.

The IMMULITE 2000 Folic Acid assay begins with a 2-cycle, on-board sample treatment of patient serum, plasma or ascorbic acid-treated whole blood (for measuring red cell folate). The sample, along with ligand-labeled folic acid, is first treated with dithiothreitol (DTT), in a reaction tube containing no bead, and then with sodium hydroxide/potassium cyanide (NaOH/KCN), in a second treatment cycle. The treated sample is transferred to a second reaction tube containing a murine anti-folate binding protein antibody-coated polystyrene bead and folate binding protein (FBP). During a 30-minute incubation, folic acid released from binding proteins in the patient sample competes with ligand-labeled folic acid for binding with FBP. The bead is washed and alkaline phosphatase labeled anti-ligand is added. During the final 30-minute incubation, the alkaline phosphatase anti-ligand binds to the ligand-labeled folate that was bound to the bead during the first incubation. The unbound enzyme conjugate is removed by centrifugal wash. Substrate is then added.

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## Technology Comparison (continued):

The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, is then added and the test unit is incubated for a further 10 minutes. The chemiluminescent substrate undergoes hydrolysis in the presence of alkaline phosphatase to vield an unstable intermediate. Production of this intermediate results in a sustained emission of light. The bound complex - and thus also the photon output - is inversely proportional to the concentration of folic acid in the sample.

IMMULITE® Folic Acid is a boil, competitive, ligand-labeled, protein binding chemiluminescent assay with in situ immobilization, and with an anti-ligand detection system. The solid phase, a polystyrene bead enclosed within an IMMULITE Test Unit, is coated with a murine monoclonal antibody specific for folic acid binding protein. The sample is pretreated by boiling in the presence of dithiothreitol to denature endogenous binding proteins to release folic acid. The treated patient sample, ligand-labeled folic acid analog and folic acid binding protein are simultaneously introduced into the Test Unit, and incubated for approximately 30 minutes at 37 °C with intermittent agitation. During this time, folic acid in the sample competes with the ligand-labeled folic acid analog for a limited amount of folic acid binding protein, and the folic acid binding protein is captured by the antibody on the bead. Unbound analog is then removed by a centrifugal wash, after which an alkaline phosphatase-anti-ligand conjugate is introduced and the test unit is incubated for an additional 30 minute cvcle. The unbound enzyme conjugate is removed by a centrifugal wash.

The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, is then added and the test unit is incubated for a further 10 minutes. The chemiluminescent substrate undergoes hydrolysis in the presence of alkaline phosphatase to vield an unstable intermediate. Production of this intermediate results in a sustained emission of light. The bound complex - and thus also the photon output - is inversely proportional to the concentration of folic acid in the sample.

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## Method Comparison

#### Serum

The IMMULITE® 2000 Folic Acid procedure was compared to DPC's IMMULITE® Folic Acid on 156 serum samples, with folic acid concentrations ranging from 1.8 to 20 ng/mL.

8.3 ng/mL (IMMULITE® 2000) Means: 9.2 ng/mL (IMMULITE®)

Linear regression analysis of folic acid values yielded the following statistics:

(IMMULITE® 2000) = 0.96 (IMMULITE®) - 0.54 ng/mL r = 0.996

## Hemolysates

The IMMULITE® 2000 Folic Acid procedure was also compared to DPC's IMMULITE® Folic Acid on 49 samples, with folic acid concentrations ranging from 46 to 260 ng/mL.

| Means: | 128 ng/mL (IMMULITE® 2000 Folic Acid) | |
|--------|---------------------------------------|--|
| | 134 ng/mL (IMMULITE® Folic Acid) | |

Linear regression analysis of folic acid values yielded the following statistics:

(IMMULITE® 2000) = 1.18 (IMMULITE®) - 29 ng/mL r = 0.981

### Conclusion:

The data presented in this summary of safety and effectiveness is the data the Food and Drug Administration used in granting DPC substantial equivalence for IMMULITE® 2000 Folic Acid.

Edward A. Fessier

Edward M. Levine, Ph.D Director of Clinical Affairs

10/26/89

Date

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circle 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

NOV 1 2 1999

Edward M. Levine, Ph.D. Director of Clinical Affairs Diagnostic Products Corporation 5700 West 96th Street Los Angeles, California 90045-5597

Re: K993254 Trade Name: Immulite® 2000 Folic Acid Regulatory Class: II Product Code: CGN Dated: September 24, 1999 Received: September 28, 1999

Dear Dr. Levine:

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 (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic OS 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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# 510(k) Number (if known): Device Name: IMMULITE® 2000 Folic Acid

Indications For Use:

IMMULITE 2000 Folic Acid is for in vitro diagnostic use with the IMMULITE 2000 Analyzer – for the quantitative measurement of folic acid in serum, heparinized plasma or ascorbic acid-treated whole blood, as an aid in clinical diagnosis and treatment of anemia.

Cooper
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K993254

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109)

OR

Over-The-Counter Use

(Optional Format 1-2-96)