INSTRINSIC FACTOR AB, CALIBRATORS, AND QC ON THE ACCESS IMMUNOASSAY SYSTEMS, MODELS 387992, 387993, 387999

K033603 · Beckman Coulter, Inc. · LIG · Dec 19, 2003 · Clinical Chemistry

Device Facts

• Record ID: K033603
• Device Name: INSTRINSIC FACTOR AB, CALIBRATORS, AND QC ON THE ACCESS IMMUNOASSAY SYSTEMS, MODELS 387992, 387993, 387999
• Applicant: Beckman Coulter, Inc.
• Product Code: LIG · Clinical Chemistry
• Decision Date: Dec 19, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1810
• Device Class: Class 2

Intended Use

The Access Intrinsic Factor Ab assay is for the detection of intrinsic factor antibody in human serum and plasma using the Access Immunoassay systems. Intrinsic factor antibodies are measured as an aid in the diagnosis of pernicious anemia.

Device Story

Access Intrinsic Factor Ab assay is a paramagnetic particle, chemiluminescent immunoassay used on Access Immunoassay Systems (Access, Access 2, Synchron LXi 725, UniCel Dxl 800). Input: human serum or plasma. Principle: binding of intrinsic factor antibody to alkaline phosphatase enzyme-conjugated intrinsic factor, followed by competitive binding reaction with monoclonal antibody on paramagnetic solid-phase particles. Detection: dioxetane-based chemiluminescent substrate measuring light production. Used in clinical laboratory settings by trained personnel. Output: quantitative or qualitative detection of intrinsic factor antibodies. Results aid clinicians in diagnosing pernicious anemia. Benefits: automated, non-radioactive alternative to traditional radioimmunoassays.

Clinical Evidence

Clinical study used samples from healthy subjects to establish an upper reference limit (1.20 AU/mL) and ROC analysis to determine a positive cutoff (1.53 AU/mL). Method comparison study of 127 patient samples (including 67 positive) compared the Access assay to a predicate radioimmunoassay. Results: 100% negative agreement, 96.4% positive agreement, and 92.1% overall agreement. Analytical studies included imprecision (total CV 4.6-5.3%), dilution linearity, and specificity testing (no interference from bilirubin, hemoglobin, albumin, triglycerides, or vitamin B12 < 1500).

Technological Characteristics

Paramagnetic particle-based chemiluminescent immunoassay. Utilizes alkaline phosphatase enzyme conjugate and dioxetane-based substrate. Solid phase: paramagnetic particles. Detection: light measurement via chemiluminescence. System: Access Immunoassay Systems (Access, Access 2, Synchron LXi 725, UniCel Dxl 800). Reagents/calibrators stable for 56 days; calibration stable for 14 days.

Indications for Use

Indicated for the detection of intrinsic factor antibody in human serum and plasma as an aid in the diagnosis of pernicious anemia.

Regulatory Classification

Identification

A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.

Predicate Devices

• DPC IFbAb (k811927)

Submission Summary (Full Text)

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# 510(k) SUMMARY

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: K033603

# Submitter's Name and Address

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: [phone] Fax: [phone] Contact: Valynda Machen

Date Prepared: November 14, 2003

## Device Names

- Intrinsic Factor Ab, Intrinsic Factor Ab Calibrators, and Proprietary Name: Intrinsic Factor Ab QC on the Access® Immunoassay Systems
- Immunoassay for the detection of intrinsic factor antibody Common Name:

Classification Name: Vitamin B12 Test System

## Predicate Device

DPC IFbAb

Diagnostic Products Corporation

5700 West 96th Street

Los Angeles, CA 90045-5597

510(k) Number: k811927

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# Device Description

The Access Intrinsic Factor Ab reagents, calibrators, QC, and the Access Immunoassay Analyzers (Access, Access 2, Synchron LXi 725, and UniCel Dxl 800) comprise the Access Immunoassay Systems for the detection of intrinsic factor antibody in human serum and plasma.

#### Intended Use

The Access Intrinsic Factor Antibody assay is a paramagnetic particle, chemiluminescent immunoassay for the detection of intrinsic factor antibody in human serum and plasma using the Access Immunoassay Systems.

# Comparison of Technological Characteristics

| Attribute | DPC IFbAb RIA | Access IFAb |
|---------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended<br>Use | For the detection of intrinsic<br>factor blocking antibody in<br>serum. | For the detection of intrinsic<br>factor antibody in human<br>serum and plasma. |
| Assay<br>Principles | DPC's IF bAb procedure<br>detects anti-intrinsic factor<br>blocking antibody in serum by<br>its effect on the vitamin B12-<br>binding capacity of the solid-<br>phase intrinsic factor binder. | Utilizes the binding of intrinsic<br>factor antibody to alkaline<br>phosphatase enzyme<br>conjugated to intrinsic factor,<br>followed by a competitive<br>binding reaction with<br>monoclonal antibody coupled<br>to the solid phase. |
| Solid<br>Support | Microcrystalline cellulose<br>particles | Paramagnetic particles |
| Detection<br>System | Utilizes ⁵⁷ Cobalt labeled<br>vitamin B12; Measures bound<br>radioactivity with a gamma<br>counter | Utilizes dioxetane-based<br>chemiluminescent substrate;<br>Measures light production from<br>a chemiluminescent reaction |
| Calibrator | Single level negative reference<br>of liquid pooled human serum<br>negative for intrinsic factor<br>blocking antibody. | Single level calibrator of liquid<br>synthetic matrix with an<br>intrinsic factor antibody<br>concentration of 1.00 AU/ml. |

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### Summary of Analytical Studies

Imprecision: Imprecision was tested for concentrations from approximately 1.1 to 14.2 AU/mL. The within run imprecision ranged from 1.3% CV to 1.5% CV. Between-run assay imprecision ranged from 4.4% CV to 5.1% CV. Total imprecision ranged from 4.6% CV to 5.3% CV.

Dilution Recovery (Linearity): Linearity studies performed by diluting serum patient samples at various levels with Access intrinsic Factor Ab S0 Calibrator show that serial dilutions transform a positive sample result to a negative sample result.

Methods Comparison: A comparison of 127 values using the Access Intrinsic Factor Ab assay and a commercially available radioimmunoassay kit gave the following statistical data: Negative agreement=100%, Positive agreement =96.4%, and Overall Agreement = 92.1%.

Analytical Specificity: There was no significant interference from potential sample contaminants (bilirubin, hemoglobin, human serum albumin, and triglycerides). In addition, samples with vitamin B12 values of < 1500 do not interfere with the assay.

Stability: Intrinsic Factor Ab reagents, calibrators, and QC are stable for 56 days after opening. The calibration is stable for 14 days.

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Image /page/3/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a black circle with two curved white lines inside, resembling a stylized eye or a wave pattern. To the right of the circle, the words "BECKMAN" and "COULTER" are stacked vertically in a bold, sans-serif font.

## Summary of Clinical Studies

Samples from an apparently healthy subject population were used to set the upper reference limit (URL) for the Access Intrinsic Factor Ab assay. A 99% nonparametric determination of results gave a URL value of 1.20 AU/mL.

The positive cutoff value was determined by Receiver Operator Curve (ROC) analysis of negative, equivocal, and positive samples. The positive cutoff was determined to be 1.53 AU/mL.

Patient samples (67 positive) from a clinical site were then used to measure agreement between the Access Intrinsic Factor Ab Assay and the predicate device.

The agreement between the two devices was calculated using an equivocal category. The negative agreement was 100%; the positive agreement was 96.4%; and the overall agreement was 92.1%.

#### Conclusion

Intrinsic Factor Ab, Intrinsic Factor Ab Calibrators, and Intrinsic Factor Ab QC on the Access Immunoassay Systems is substantially equivalent to DPC IFbAb RIA for the detection of intrinsic factor antibody in human serum and plasma.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 1 9 2003

Ms. Valynda Machen Senior Regulatory Specialist Beckman Coulter, Inc, 1000 Lake Hazeltine Drive Chaska, MN 55318-1084

k033603 Re:

> Trade/Device Name: Intrinsic Factor Ab, Intrinsic Factor Ab Calibrators, and Intrinsic Factor Ab QC on the Access Immunoassay Systems Regulation Number: 21 CFR 862.1810 Regulation Name: Vitamin B12 test system Regulatory Class: Class II Product Code: LIG; JJX, JIT Dated: November 14, 2003 Received: November 17, 2003

Dear Ms. Machen:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA), 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer 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 Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known): K033603

Intrinsic Factor Ab, Intrinsic Factor Ab Calibrators, and Intrinsic Device Name: Factor Ab QC on the Access Immunoassay Systems

# Indications For Use:

The Access Intrinsic Factor Ab assay is a paramagnetic particle, chemiluminescent immunoassay for the detection of intrinsic factor antibody in human serum and plasma using the Access Immunoassay Systems. It is intended for in vitro diagnostic use as an aid in the diagnosis of pernicious anemia.

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Concurrence of CDRH, Office of Device Evaluation (ODE)
Carol Benson & Jean Cooper, DVM
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety

| 510(k) | K033603 |
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| Prescription Use<br>(Per 21 CFR 801.109) | X |
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OR

| Over-The Counter Use | ________________ |
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(Optional Format 1-2-96)