The intended use of Chiron Diagnostics ACS:180 Ferritin Assay is for the quantitative determination of Ferritin in serum or plasma using the Chiron Diagnostics ACS:180® Automated Chemiluminescence Systems. It is to be used to aid in the diagnosis of iron deficiency anemia and iron overload.

Device Description

The Chiron Diagnostics ACS:180 Ferritin assay is a two-site sandwich immunoassay using direct, chemiluminometric technology, which uses constant amounts of two anti-ferritin antibodies. The first antibody, in the Reagent, is a polyclonal goat anti-ferritin antibody labeled with acridinium ester. The second antibody, in the Solid Phase, is a monoclonal mouse anti-ferritin antibody, which is covalently coupled to paramagnetic particles. The ACS:180 system automatically performs the following steps:

dispenses 25 uL of sample into a cuvette .
. dispenses 100 µL of Lite Reagent and 450 µL of Solid Phase and incubates for 7.5 minutes at 37°C
. separates, aspirates, and washes the cuvettes with reagent water4
. dispenses 300 uL each of Reagent 1 and Reagent 2 to initiate the chemiluminescent reaction
. reports results according to the selected option, as described in the system operating instructions or in the online help system

A direct relationship exists between the amount of ferritin present in the patient sample and the amount of relative light units (RLUs) detected by the system.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and supporting study for the Chiron Diagnostics ACS:180 Ferritin assay:

The document is a 510(k) summary for a medical device submitted to the FDA, which focuses on demonstrating substantial equivalence to a predicate device rather than setting new, explicit acceptance criteria in the same way a clinical trial might. However, performance characteristics are presented that implicitly serve as acceptance criteria for regulatory clearance based on equivalence.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implicit from Predicate Equivalence)	Reported Device Performance (Chiron Diagnostics ACS:180 Ferritin)
Intended Use: Quantitative determination of Ferritin in serum/plasma to aid in diagnosis of iron deficiency anemia and iron overload.	Intended Use: Matches the criteria; the device quantifies Ferritin for iron deficiency anemia and iron overload diagnosis.
Sensitivity (Detection Limit): Implied to be comparable to predicate or clinically acceptable.	Sensitivity: 0.5 ng/mL (1 pmol/L) minimal detectable concentration.
Reportable Range: Implied to be comparable to predicate or clinically acceptable.	Reportable Range: Up to 1650 ng/mL (3630 pmol/L).
Method Comparison (Correlation with Predicate/Reference Method): High correlation expected.	Method Comparison: Correlation coefficient (r) = 1.00 against an alternate chemiluminescent method for 276 samples (3.1 to 1621 ng/mL). Equation: ACS:180 Ferritin = 1.01 (alternate chemiluminescent method) + 1.84 ng/mL.
Precision (Within-Run & Total %CV): Expected to be within clinically acceptable limits for different concentration levels.	Precision:- Mean 13.1 ng/mL: Within-run %CV = 2.76, Total %CV = 4.98- Mean 54.8 ng/mL: Within-run %CV = 2.64, Total %CV = 6.07- Mean 162.7 ng/mL: Within-run %CV = 2.73, Total %CV = 4.68- Mean 359.5 ng/mL: Within-run %CV = 3.62, Total %CV = 5.08
Expected Results in Healthy and Diseased Populations: Values should align with known physiological ranges.	Expected Results:- Normal Males (N=142): Geo. Mean = 94 ng/mL, 95th Percentile = 22-322 ng/mL- Normal Females (N=134): Geo. Mean = 46 ng/mL, 95th Percentile = 10-291 ng/mL- Iron Deficiency (N=60): Geo. Mean = 11.6 ng/mL, Total Observed Range = 0.68-34.5 ng/mL- Other Anemias (N=7): Geo. Mean = 610.8 ng/mL, Total Observed Range = 13.0-1390.8 ng/mL- Iron Overload (N=44): Geo. Mean = 1899.6 ng/mL, Total Observed Range = 334.6-8573.0 ng/mL- Renal Dialysis (N=31): Geo. Mean = 312.3 ng/mL, Total Observed Range = 31.3-1321.2 ng/mL- Chronic Liver Disease (N=34): Geo. Mean = 1967.1 ng/mL, Total Observed Range = 7.9-12826.0 ng/mL

2. Sample Size for the Test Set and Data Provenance

Method Comparison: 276 samples in the range of 3.1 to 1621 ng/mL were used for comparison against an alternate chemiluminescent method.
Precision: 4 samples were assayed, each 3 times in 8 assays.
Expected Results (Reference Ranges):
- Normal Males: 142 subjects
- Normal Females: 134 subjects
- Iron Deficiency: 60 patients
- Other Anemias: 7 patients
- Iron Overload: 44 patients
- Renal Dialysis: 31 patients
- Chronic Liver Disease: 34 patients

Data Provenance: The document does not explicitly state the country of origin or whether the studies were retrospective or prospective. Given the nature of a 510(k) submission for an in-vitro diagnostic, these studies are typically conducted by the manufacturer as prospective analytical and clinical performance evaluations, but specific details are not provided.

3. Number of Experts and Qualifications for Ground Truth

Not applicable. This device is an in-vitro diagnostic assay for quantitative measurement. Its "ground truth" is established through analytical validation against reference methods, known concentrations, and correlation with clinical diagnoses rather than expert interpretation of images or clinical cases. The reference ranges for healthy and sick populations are derived from the observed values in those cohorts, where the diagnosis of the condition itself would have been made by medical professionals, but this isn't "expert adjudication" of device output.

4. Adjudication Method for the Test Set

Not applicable. As noted above, this is a quantitative immunoassay, not a diagnostic imaging or interpretive device that requires expert adjudication of its output.

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

Not applicable. This is an IVD for quantitative measurement of a biomarker, not a diagnostic imaging aid for human interpretation. Therefore, an MRMC study comparing human readers with and without AI assistance is not relevant to this device.

6. Standalone (Algorithm Only) Performance

Yes, the studies presented are standalone performance studies of the assay device. The "Method Comparison" and "Precision" sections directly evaluate the analytical performance of the ACS:180 Ferritin assay without human-in-the-loop interpretation of its quantitative results. The "Expected Results" section provides reference ranges and observed values in different patient populations, demonstrating the device's ability to produce diagnostically relevant results on its own.

7. Type of Ground Truth Used

Analytical Performance (Sensitivity, Reportable Range, Precision): Ground truth is established through known concentrations of ferritin controls, international reference standards (if applicable, though not specified here), and replicate measurements using the device itself.
Method Comparison: The "ground truth" for method comparison is the results obtained from an "alternate chemiluminescent method," suggesting an established, comparable method already in use.
Expected Results: The ground truth for the clinical categories (e.g., "Normal Males," "Iron Deficiency," "Iron Overload") is based on clinical diagnosis of the subjects/patients included in those cohorts. The document states, "The following values for patients with several diagnosed conditions were determined," implying the patients were already diagnosed with these conditions through standard clinical practice before their samples were tested.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI development. For an immunoassay like this, the development process involves reagent formulation and optimization, calibration, and internal validation studies. The reported performance characteristics likely represent the outcome of extensive internal development and validation, but specific "training set" sizes are not applicable as there isn't an algorithm being trained in the typical AI sense.

9. How Ground Truth for the Training Set was Established

Not applicable for this type of device. As explained in point 8, the concept of a "training set" and associated ground truth establishment (in the AI/ML context) is not relevant for the development and validation of a traditional immunoassay device. The assay development would involve ensuring accurate measurement through chemical and immunological principles, using calibrated materials, and verifying performance through analytical and clinical validation studies as detailed in the document.

Summary

{0}------------------------------------------------

AUG - 5 1999

K992157

Summary of Safety and Effectiveness

As required by.21 CFR 807.92, the following 510(k) Summary is provided:

1. Submitters Information

Contact person:	William J. PignatoDirector of Regulatory Affairs
Address:	Chiron Diagnostics Corporation63 North StreetMedfield, MA 02052
Phone:Faxe-mail	(508) 359-3825(508) 359-3356william.pignato.b@bayer.com
Date Summary Prepared:	June 22, 1999

2. Device Information

Proprietary Name:	Chiron Diagnostics ACS: 180 Ferritin
Common Name:	Ferritin Immunological Test System
Device Classification:	Class II: 21 CFR 866.5350

3. Predicate Device Information

Name:	Chiron Diagnostics ACS: 180 Ferritin Immunoassay
Manufacturer:	Chiron Diagnostics Corporation

4. Device Description

Ferritin plays a significant role in the absorption, storage, and release of iron. As the storage form of iron, ferritin remains in the body tissues until it is needed for erythropoiesis. When needed, the iron molecules are released from the apoferritin shell and bind to transferrin, the circulating plasma protein that transports iron to the erythropoietic cells.

Although dietary iron is poorly absorbed, the body conserves its iron stores carefully, reabsorbing most of the iron released from the breakdown of red blood cells. As a result, the body normally loses only 1 to 2 mg of iron per day, which is generally restored by the iron absorbed in the small intestine from dietary sources.

Ferritin is found in serum in low concentrations and is directly proportional to the body's iron stores. Serum ferritin concentration, when analyzed with other factors such as serum iron, iron-binding capacity, and tissue iron stores, is valuable in the diagnosis of iron-deficiency anemias, anemias of chronic infection, and conditions such as thalassemia and hemochromatosis that are associated with iron overload. Measurement of serum ferritin is

{1}------------------------------------------------

particularly valuable in distinguishing iron-deficiency anemias caused by low iron stores from those resulting from inadequate iron utilization.

5. Statement of Intended Use

The intended use of Chiron Diagnostics ACS:180 Ferritin Assay is for the quantitative determination of Ferritin in serum or plasma using the Chiron Diagnostics ACS:180® Automated Chemiluminescence Systems; to aid in the diagnosis of iron deficiency anemia and iron overload.

6. Summary of Technological Characteristics

dispenses 25 uL of sample into a cuvette .
. dispenses 100 µL of Lite Reagent and 450 µL of Solid Phase and incubates for 7.5 minutes at 37°C
. separates, aspirates, and washes the cuvettes with reagent water4
. dispenses 300 uL each of Reagent 1 and Reagent 2 to initiate the chemiluminescent reaction
. reports results according to the selected option, as described in the system operating instructions or in the online help system

A direct relationship exists between the amount of ferritin present in the patient sample and the amount of relative light units (RLUs) detected by the system.

6. Performance Characteristics

Expected Results

In clinical studies, the following values for apparently healthy male and female subjects with normal liver function enzyme tests, bilirubin, and serum iron tests, were determined:

Category	N	Geo. Mean (ng/mL)	Geo. Mean (pmol/L)	95th Percentile Range (ng/mL)	95th Percentile Range (pmol/L)
Normal Males	142	94	207	22-322	48-708
Normal Females	134	46	101	10-291	22-640

The following values for patients with several diagnosed conditions were determined:

Category	N	Geo. Mean(ng/mL)	(pmol/L)	Total Observed Range(ng/mL)	(pmol/L)
Iron Deficiency	60	11.6	26	0.68-34.5	1.5-76
Other Anemias	7	610.8	1344	13.0-1390.8	29-3060

{2}------------------------------------------------

Iron Overload	44	1899.6	4178	334.6-8573.0	736-18861
Renal Dialysis	31	312.3	687	31.3-1321.2	68.9-2907
Chronic Liver Disease	34	1967.1	4328	7.9-12826.0	17-28217

As with all diagnostic assays, each laboratory should determine its own reference range(s) for the diagnostic evaluation of patient results.

Sensitivity and Assay Reportable Range

The ACS:180 Ferritin assay measures ferritin concentrations up to 1650 ng/mL (3630 pmol/L) with a minimum detectable concentration of 0.5 ng/mL (1 pmol/L).

Method Comparison

For 276 samples in the range of 3.1 to 1621 ng/mL (6.8 to 3566.2 pmol/L), the relationship between the ACS:180 Ferritin assay and an alternate chemiluminescent method is described by the equation:

ACS:180 Ferritin = 1.01 (alternate chemiluminescent method) + 1.84 ng/mL Correlation coefficient (r) = 1.00

Precision

Four samples were assayed 3 times in 8 assays. The following results were obtained:

Mean(ng/mL)	Mean(pmol/L)	Within-run% CV	Total% CV
13.1	29	2.76	4.98
54.8	121	2.64	6.07
162.7	358	2.73	4.68
359.5	791	3.62	5.08

{3}------------------------------------------------

Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, stacked on top of each other.

AUG - 5 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. William J. Pignato Director of Regulatory Affairs Chiron Diagnostics Corporation (A Bayer Diagnostics Corporation) 63 North Street Medfield, Massachusetts 02052

Re: K992157

Trade Name: Chiron Diagnostics ACS: 180 FERRITIN Assay Regulatory Class: II Product Code: DBF Dated: June 22, 1999 Received: June 25, 1999

Dear Mr. Pignato:

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.

{4}------------------------------------------------

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 (770)488-7655.

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" (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 (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Sutman

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

{5}------------------------------------------------

Page of

510(k) Number (if known): _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Device Name: Chiron Diagnostics ACS:180 FERRITIN Assay

Indications for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Division Sign-Off
Division of Clinical Laboratory Devices
510(k) Number	K992157

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

Regulation Number and Section

§ 866.5340 Ferritin immunological test system.

(a)
Identification. A ferritin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron-storing protein) in serum and other body fluids. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia.(b)
Classification. Class II (performance standards).