The ImmunoDip™ Urinary Albumin Screen tests for the presence of elevated levels of albumin in urine. Elevated urinary albumin is also known as microalbuminuria. Elevated albumin is an early sign of possible kidney damage. Detection of elevated urinary albumin can aid in the early detection and monitoring of the course of incipient nephropathy in diabetics and hypertensive patients. For IN VITRO diagnostic use.

Device Description

ImmunoDip™ Urinary Albumin Screen is an immunochromatographic test strip which is encased in a plastic housing. The ImmunoDip™ Urinary Albumin Screen is placed into a urine sample for at least three minutes and is then removed and read. Results are determined by visually comparing the relative color intensity of two blue bands to obtain a semi-quantitative result of Negative (<= 18 mg/L) or Positive (>18 mg/L).

ImmunoDip™ Urinary Albumin Screen is an immunochromatographic test strip containing monoclonal mouse antibodies against human serum albumin bound to colored latex beads. Human albumin is fixed in a band at the bottom half of the testing region. Goat anti-mouse antibodies are fixed in a band at the top half of the testing region. The dipstick is encased in an open-ended plastic housing.

When the dipstick is placed into a urine sample cup, the urine sample migrates up the test strip. Albumin present in the urine binds with blue colored latex beads present in the strip. Both beads and albumin are carried up the device by capillary action. At low levels of albumin, the great majority of blue beads are bound at the lower band containing human albumin. At higher levels of albumin, many of the beads pass through the lower band and are bound at the upper band. Levels of albumin above the decision level value of 18 mg/L will produce color on the upper band which is darker than the lower band. By observing the appearance of the two lines, the user can semi-quantitatively determine the urine microalbumin concentration as either Negative (<=18 mg/L), or Positive (>18 mg/L).

AI/ML Overview

The ImmunoDip™ Urinary Albumin Screen is an immunochromatographic test strip intended to detect elevated levels of albumin in urine (microalbuminuria), which can indicate early kidney damage in high-risk patients.

Here's a breakdown of the acceptance criteria and study information provided:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implied)	Reported Device Performance
Precision: 100% agreement between operators and observers	100% agreement obtained between two operators and two additional observers across within-day, between-day, within-run, and between-run testing (internal 20-day study with two albumin levels).
Accuracy (POL Users): High overall agreement with expected results over a clinically relevant range of concentrations.	91% overall agreement with expected results (range 89%-94%) for POL users across 6 proficiency samples (4.5 mg/L, 9.0 mg/L, 15 mg/L, 22 mg/L, 36 mg/L, 72 mg/L). Exceeded 98% accuracy when 15 mg/L and 22 mg/L samples were excluded.
Accuracy (Trained Lab Personnel): High overall agreement with expected results.	95% overall agreement (range 93%) for trained laboratory personnel across 6 proficiency samples.
Equivalence to Predicate Methods: Comparable specificity, sensitivity, and efficiency to existing urinary albumin assay methods.	Specificity: 95-97%Sensitivity: 95% (against both Beckman Array and Kamiya assays)Efficiency: 95-97%

2. Sample Size Used for the Test Set and Data Provenance

Precision Study: The sample size for the "test set" in the precision study is not explicitly stated in terms of number of urine samples. It refers to "two levels of albumin in urine" and "all instances of within-day, between-day, within-run and between-run testing" with 100% agreement.
POL Studies: "Six proficiency samples over a clinically relevant range of concentrations (4.5 mg/L, 9.0 mg/L, 15 mg/L, 22 mg/L, 36 mg/L and 72 mg/L)." The number of users (professional and POL users) and the number of replicates (15 replicates within-run, 5 different days between-runs, 3 POL sites between sites) contribute to the overall sample size but the exact number of unique "test set" samples is not provided.
Clinical Studies: For comparison against predicate methods, "clinical urine samples" were used, but the specific number of these samples is not mentioned.
Data Provenance: The document does not explicitly state the country of origin for the data. The submitter is based in Canada. The POL studies involved "Physician Office Laboratory (POL) studies" and "3 POL sites," implying real-world settings, but whether these were prospective or retrospective is not specified for all studies. The precision study was an "internal 20 day precision study."

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

Precision Study: "two operators and two additional observers" were involved in determining agreement. Their qualifications are not specified beyond "operators" and "observers."
POL Studies: "expected results" were used as the ground truth for the 6 proficiency samples. The method or expertise used to establish these "expected results" is not detailed.
Clinical Studies: The "ground truth" was established by two predicate quantitative methods: the Beckman Array (K922273) and the Kamiya (Crestat) Microalbumin Assay (K934146), and one semi-quantitative method, the DCLare™ ImmunoDip™ Stick for Microalbuminuria (K972337).

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method (e.g., 2+1, 3+1).
In the precision study, 100% agreement was obtained between "two operators and two additional observers," implying direct consensus or agreement without needing a tie-breaker.
For the POL and clinical studies, the results were compared against an "expected result" or predicate device results, not against a human adjudicated consensus derived from multiple readers of the ImmunoDip device itself.

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

A formal MRMC comparative effectiveness study, as typically understood in the context of comparing human readers with and without AI assistance, was not conducted.
The studies involved comparing the ImmunoDip device's performance by "POL users" versus "trained laboratory personnel" and against established "predicate methods." There is no mention of an "AI assistance" component or an effect size for human readers improving with AI.

6. Standalone (Algorithm Only) Performance

The ImmunoDip™ Urinary Albumin Screen is a visual immunochromatographic test strip read by a human. Therefore, a standalone "algorithm only" performance study in the sense of a fully automated AI system without human interaction was not conducted, as the device itself is not a software algorithm. Its performance is the "standalone" performance based on visual interpretation.

7. Type of Ground Truth Used

Precision Study: The ground truth was based on the consensus ("100% agreement") among two operators and two observers for known albumin levels (two levels specified).
POL Studies: The ground truth for the proficiency samples was "expected results," which implies they were pre-determined values for the proficiency samples. The method of determination for these "expected results" is not specified but would typically come from a reference method or certified values.
Clinical Studies: The ground truth was established by two full quantitative predicate methods (Beckman Array, Kamiya Microalbumin Assay) and one semi-quantitative predicate method (DCLare™ ImmunoDip™ Stick for Microalbuminuria).

8. Sample Size for the Training Set

The document implies that the device is a test strip read visually by a human, not a machine learning or AI algorithm that requires a "training set" in the typical sense. Therefore, the concept of a "training set" as it relates to AI development is not applicable here. The studies described are for validation of the chemical-biological test strip and human interpretation.

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

As the device is not an AI algorithm requiring a training set, this question is not applicable.

Summary

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510(K) Notification

Diagnostics Chemicals Limited

Product Cat. No. 790-01, 790-15

Image /page/0/Picture/4 description: The image shows a logo with two stylized letters. The letters appear to be "d" and "d", with the first "d" having a rounded rectangular shape and a vertical line extending upwards. The second "d" is similar but has a curved element at the top, creating a hook-like shape. The logo is black against a white background.

20.0 510(k) SMDA 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:	K994035
Prepared:	November 22, 1999
Summiteer:	Diagnostic Chemicals Limited
Address:	West Royalty Industrial ParkCharlottetownP.E.I., C0A 1B0Canada(902) 566-1396
Contact:	Karen Callbeck
Device:	Trade Name:ImmunoDip™ Urinary Albumin ScreenCommon Name:Test for microalbuminuria	Trade Name:	ImmunoDip™ Urinary Albumin Screen	Common Name:	Test for microalbuminuria
Trade Name:	ImmunoDip™ Urinary Albumin Screen
Common Name:	Test for microalbuminuria
Classification:	Division of Clinical Laboratory DevicesPanel- Clinical ChemistryClassification Code- 75 JIR (Urinary Protein or Albumin)
Predicate Devices:	DCLare™ ImmunoDip™ stick for Microalbuminuria (Diagnostic ChemicalsLimited- K972337),Microalbumin Assay/Array® Analyzer (Beckman Instruments Inc.-K922273), N-Assay TIA Microalbumin (Crestat Diagnostics/KamiyaBiomedical Company- K934146),BeSure Plus OneStep Ovulation Prediction test (Syntron Bioresearch, Inc,K983113),One Step Ovulation Predictor (Selfcare, Inc.-K991386)MiniClinic Ovulation Predictor (Vanguard Biomedical- K960233), andClearplan Easy Ovulation Test (Whitehall Labs- K981271).

Device Description:

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510(K) Notification

Diagnostics Chemicals Limited

Product Cat. No. 790-01. 790-15

Image /page/1/Picture/4 description: The image shows a stylized, bold, and black graphic of the letters 'ddj'. The letters are interconnected, with the 'd' on the left and the 'j' on the right sharing a common vertical stroke. The overall design is simple and modern, with a focus on the interplay of positive and negative space.

Intended Use:

The ImmunoDip™ Urinary Albumin Screen tests for the presence of elevated levels of albumin in urine. Elevated urmary albumin is also known as microalbuminuria. Elevated albumin is an early sign of possible kidney damage. Detection of elevated urinary albumin can aid in the early detection and monitoring of the course of incipient nephropathy in diabetics and hypertensive patients. For IN VITRO diagnostic use.

Technological Characteristics:

ImmunoDip™ Urmary Albumin Screen is an immunochromatographic test strip containing monoclonal mouse antibodies against human serum albumin bound to colored latex beads. Human albumin is fixed in a band at the bottom half of the testing region. Goat anti-mouse antibodies are fixed in a band at the top half of the testing region. The dipstick is encased in an open-ended plastic housing.

When the dipstick is placed into a urine sample cup, the urine sample migrates up the test stip, Albumin present in the urine binds with blue colored latex beads present in the strip. Both beads and albumin are carried up the device by capillary action. At low levels of albumin, the great majority of blue beads are bound at the lower band containing human albumin. At higher levels of albumin, many of the beads pass through the lower band and are bound at the upper band. Levels of albumin above the decision level value of 18 mg/L will produce color on the upper band which is darket than the lower band. By observing the appearance of the two lines, the user can semi-quantitatively determine the urine microalbumin concentration as either Negative (s18 mg/L), or Positive(>18 mg/L),

Assessment of Performance:

The performance characteristics on the ImmunoDip™ Urinary Albumin Screen were evaluated in precision studies to determine the within-day, between -day, within-run and between-run precision. Physician Office Laboratory (POL) studies were carried out in which the performance of trained laboratory technicians was compared against that of POL users. Clinical studies which compared results obtained with the Urinary Albumin Screen against three existing uring albumm assay methods were also carried out.

In an internal 20 day precision study utilizing two levels of albumin in urine, 100% agreement was obtained between two operators and two additional observers in all instances of within-day, betweenday, within-run and between-run testing.

In the POL studies, professional and POL users participated in the evaluations of six proficiency samples over a clinically relevant range of concentrations (4.5 mg/L, 9.0 mg/L, 15 mg/L, 22 mg/L, 36 mg/L and 72 mg/L). The POL results showed an overall agreement with expected results of 91% (range of 89% 94%). This was not significantly different form the results obtained with trained laboratory personnel who reported overall agreement of 95% (range 93%).

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510(K) Notification

Diagnostic Chemicals Limited

Product Cat. No. 790-01. 790-15

The majority of deviations from expected results were observed at the two sampling levels nearest the 18 mg/L level that separate the positive and negative results. Excluding the 15 and 22 mg/L samples, both groups exceeded 98% accuracy. No significant differences were observed withinrun (15 replicates), between-runs (5 different days), or between sites (3 POL sites). Results demonstrated that lay users can obtain results equivalent to those obtained by trained laboratory workers.

The performance of ImmunoDip™ Urinary Albumin Screen on clinical urine samples was compared against that of two predicate methods; the sem-quantitative DCLare™ ImmunoDip™ Stick for Microalbuminuria (K972337) and full quantitative urinary albumin testing using the Beckman Array (K922273) and the Kamiya (Crestat) Microalbumin Assay (K934146). Specificity ranged from 95-97%. Sensitivity was 95% against both methodologies. Efficiency ranged from 95-97%. These results indicate that the ImmunoDip™ Urinary Albumin Screen gives performance which is substantially equivalent to that of existing methods for urinary albumin measurement.

CONCLUSION:

The ImmunoDip™ Urinary Albumin Screen provides a convenient method for screening for microalbuminuria. Studies indicate that use of the device by POL users provides results which are comparable to the results obtained by trained laboratory personnel. The ImmunoDip Urinary Albumin Screen provides results which are comparable to other methods currently used in chical laboratories and physicians office laboratories ..

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Image /page/3/Picture/1 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" arranged around the top half of the circle. Inside the circle is a stylized symbol resembling three overlapping lines that curve upwards, often interpreted as representing people. The logo is presented in black and white.

FEB 1 2000

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Karen Callbeck, R.T., B.Sc. Regulatory Affairs Coordinator, Diagnostic Division Diagnostics Chemicals Limited 16 McCarville Street Charlottetown. PE, CIE 2A6 CANADA

Re: K994035

Trade Name: ImmunoDip Urinary Albumin Screen Regulatory Class: I reserved Product Code: JIR Dated: November 29, 1999 Received: November 29, 1999

Dear Ms. Callbeck:

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

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 (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 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 (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

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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INDICATIONS FOR USE

510(k) Number (if known): K994035

Device Name: ImmunoDip Urinary Albumin Screen

Indications for Use:

There are several kidney disease conditions that can produce high levels of albumin in urine (1). Determining albumin in the wine at the low lowels measured by this test is helpful for early detection and trestment of petients it risk for reast (Listany) disease. Low but eleveled urinary albuminuria, refers to a level of the human protein albumin in nime shout 18 mg . Levels above 18 mg L are not normally found in healthy individuals. These low bet eigificant levels are not detectable with older dipstick assuys. The ImmoDig™ Uniony Albumin Screen classifies samples as postive or negative based on their being above or below a level of 18 mg/L.

Conditions in which elevated levels of albumin in urine may be present include: Type 1 and Type 2 diabetes (2-8); bypertension (9, 10); and real disease found in pregancy (11). There are other best as well. Distans is the largest single cause. One study found 45% of the insulin-timental disbetics develop secious kidney disease (3). Testing for elevelod levels of albumin in wine helps to identify those diabetics who are prone to kidney disease. Scientifics studies indicate that proper control of blood sugar) levels and blood pressure help slow or prevent kidney damage (1,9).

References:

Viberti, G. C., Hill, R. D., Jazett, R. J., Argyzopoulos, A., Mahmud, U. & Keen, H. Loncer 1982; i: 1430-1432. ﻠ Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellibus.
Viberti, G. C., Pickup J. C., Jazett, R. J., Keen, H. N Engl J Med 1979; 300: 638-41. Effect of control of blood 2 glucose on urinary excretion of albumin and fi-microglobulin in insulin-dependent diabetes.
Mogensen, C. E. & Christensen, C. K. N Engl J Med 1984; 311: 89-93. Predicting diabetic nephropathy in insulin-3. dependent patients.
Mogasen, C. E. N. Engl J Med 1984; 310: 356-360. Microalbuminuta proceinuria and early 4. mortality in maturity-onset diabetes.
Deckert, T., Feldt-Rasmussen, B., Borch-Johnsen, K., Jensen, T. & Kofoel-Ezevaldsen, A. Diobetologio 1989; 32. રું. 219-226. Albuminuria reflects widespread vascular damage. The Steno hypothesis.
Waller, K. V., Ward, K. M., Mahan, J. D. & Wissmatt, D. K. Clin Chem 1989; 35: 755-765. Curcat concepts in ર. proteinuria.
Mattock, M. B., Keen, H., Viberti, G. C., El-Gohsti, M. R., Murrells, T. J., Scott, G. S., Wing, J. R. & Jackson, P. 7. G. Diaberalogia 1988; 31: 82-87. Coronary heart disease and urinary excention rate in Type 2 (non-insulindependent) diabetic patients.
Alzaid, A. A., Diobetes Care 1996; 19: 79-89. MicrosIbuminuta in patients with NDDM: An Overview. 8.
Mathiesen, E. R., Rom, B., Jensen, T., Storm, B. & Decker, T. Diabeter 1990; 39: 245-249. Relationship between 9. blood pressure and urinary albumin excretion in development of microslbuminuris.

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Concurrence of CDRH, Office of Device Evaluation (ODE)

Patricia Bernhart for M.J. Cooper
(Division Sign-Off)

Division of Clinical Laboratory Devices 510(k) Number_K 994035

Prescription Use
(Per 21 CFR 801.109)

Over the Counter Use

Regulation Number and Section

§ 862.1645 Urinary protein or albumin (nonquantitative) test system.

(a)
Identification. A urinary protein or albumin (nonquantitative) test system is a device intended to identify proteins or albumin in urine. Identification of urinary protein or albumin (nonquantitative) is used in the diagnosis and treatment of disease conditions such as renal or heart diseases or thyroid disorders, which are characterized by proteinuria or albuminuria.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.