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.

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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Access Intrinsic Factor Ab assay based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance (Access IFAb)	Predicate Device (DPC IFbAb)
Imprecision	Not explicitly stated	Within-run: 1.3% CV to 1.5% CV	Not directly comparable
		Between-run: 4.4% CV to 5.1% CV
		Total: 4.6% CV to 5.3% CV
Dilution Recovery (Linearity)	Not explicitly stated	Serial dilutions transform positive sample results to negative. (Demonstrated linearity)	Not explicitly stated
Methods Comparison (Agreement with Predicate)	High agreement with predicate device for substantial equivalence	Negative agreement: 100%
		Positive agreement: 96.4%
		Overall agreement: 92.1%
Analytical Specificity	No significant interference from common substances	No significant interference from bilirubin, hemoglobin, human serum albumin, triglycerides.	Not explicitly stated
		Samples with vitamin B12 values < 1500 do not interfere.
Stability (Reagents, Calibrators, QC)	Not explicitly stated	56 days after opening	Not explicitly stated
Stability (Calibration)	Not explicitly stated	14 days	Not explicitly stated
Upper Reference Limit (URL)	99% nonparametric determination	1.20 AU/mL	Not explicitly stated
Positive Cutoff Value	Determined by ROC analysis	1.53 AU/mL	Not explicitly stated

Note: The acceptance criteria are largely implied by the statement of "substantial equivalence" to the predicate device, especially regarding the agreement studies. Specific quantitative acceptance criteria for each analytical performance parameter (e.g., maximum CV for imprecision) are not explicitly stated in this summary.

2. Sample Size and Data Provenance for Test Set

Sample Size: 127 values were used for the methods comparison with the predicate device. For the clinical study measuring agreement, 67 positive patient samples were used, in addition to an unspecified number of negative and equivocal samples to calculate ROC analysis for the positive cutoff.
Data Provenance: The text does not explicitly state the country of origin. It mentions "patient samples (67 positive) from a clinical site," suggesting prospective or retrospective samples collected from a clinical setting.
Retrospective/Prospective: Not explicitly stated, but "patient samples from a clinical site" could imply either.

3. Number of Experts and Qualifications for Ground Truth for Test Set

The document does not mention the use of experts to establish ground truth for the test set. Instead, the ground truth for comparison appears to have been established by the predicate device (DPC IFbAb RIA).

4. Adjudication Method for the Test Set

Not applicable, as expert adjudication for ground truth establishing is not mentioned. The comparison is made against the results of the predicate device.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This document describes an in vitro diagnostic device (an immunoassay), and such studies are typically performed for imaging or pathology devices where human readers interpret results.

6. Standalone (Algorithm Only) Performance Study

Yes, the studies described are standalone (algorithm only) performance studies. The device is an automated immunoassay system, and its performance (imprecision, linearity, specificity, stability, and agreement with a predicate device) is assessed independently of human interpretation of the assay results themselves. Human involvement would be in sample collection and running the assay, but not in interpreting the raw signal for diagnosis.

7. Type of Ground Truth Used

The primary type of "ground truth" used for validation in this submission is the results obtained from the predicate device (DPC IFbAb RIA). For the clinical performance, the agreement between the new Access IFAb assay and the predicate device was evaluated. Additionally, "an apparently healthy subject population" was used to establish the upper reference limit.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or algorithm development, as this is an immunoassay. The development of the assay itself would involve optimization and calibration using various samples, but these are not referred to as a "training set" in the same way as for AI/ML algorithms.

9. How the Ground Truth for the Training Set Was Established

As this is an immunoassay rather than an AI/ML device, the concept of a "training set" and its associated ground truth is not explicitly discussed in this 510(k) summary. The assay's performance characteristics are established through analytical and clinical studies as detailed above, using samples where results from the predicate device or clinical status (e.g., "apparently healthy subject population," "67 positive patients") serve as reference.

Summary

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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: (952) 368-1383 Fax: (952) 368-7610 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

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
IntendedUse	For the detection of intrinsicfactor blocking antibody inserum.	For the detection of intrinsicfactor antibody in humanserum and plasma.
AssayPrinciples	DPC's IF bAb proceduredetects anti-intrinsic factorblocking antibody in serum byits effect on the vitamin B12-binding capacity of the solid-phase intrinsic factor binder.	Utilizes the binding of intrinsicfactor antibody to alkalinephosphatase enzymeconjugated to intrinsic factor,followed by a competitivebinding reaction withmonoclonal antibody coupledto the solid phase.
SolidSupport	Microcrystalline celluloseparticles	Paramagnetic particles
DetectionSystem	Utilizes ⁵⁷ Cobalt labeledvitamin B12; Measures boundradioactivity with a gammacounter	Utilizes dioxetane-basedchemiluminescent substrate;Measures light production froma chemiluminescent reaction
Calibrator	Single level negative referenceof liquid pooled human serumnegative for intrinsic factorblocking antibody.	Single level calibrator of liquidsynthetic matrix with anintrinsic factor antibodyconcentration 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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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 (301) 594-3084. 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 (800) 638-2041 or (301) 443-6597 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:

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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(Per 21 CFR 801.109)	X
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Over-The Counter Use	________________
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(Optional Format 1-2-96)

Regulation Number and Section

§ 862.1810 Vitamin B

12 test system.(a)
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.(b)
Classification. Class II.