K Number

Device Name

HCG ER METHOD FOR THE TECHNICON IMMUNO 1 SYSTEM IN-VITRO DIAGNOSTIC CLINICAL METHOD

Manufacturer

BAYER CORP.

Date Cleared

1996-06-03

(59 days)

Product Code

DHA

Regulation Number

862.1155

Intended Use

This in vitro diagnostic procedure is intended to quantitatively measure human chorionic gonadotropin (hCG) in human serum on the Technicon Immuno 1º system. Measurements of human chorionic gonadotropin are used for the detection of pregnancy. This method is an adaptation of an existing Technicon Immuno 1 hCG method and has an extended range from 800 mIU/mL to 100,000 mIU/mL. This diagnostic method is not intended for use on any other system.

Device Description

This method is a double antibody immunoassay. hCG Antibody Conjugate 1 (R1) and hCG Antibody Conjugate 2 (R2) are reacted with patient sample (or calibrator containing hCG) and incubated on the Technicon Immuno 1 system at 37℃. The mIMP Reagent (monoclonal ImmunoMagnetic Particle) is added and a second incubation occurs during which the antibody complex is bound. The mIMP/antibody complex is then washed and the pNPP (para nitrophenylphosphate) substrate is added. The alkaline phosphatase (ALP) in the antibody conjugate reacts with the pNPP to form para-nitrophenoxide and phosphate. Increasing absorbance, due to the formation of para-nitrophenoxide, is monitored at 405 nm and 450 nm. A sample having no hCG will have the minimum label bound, while samples containing high hCG concentrations will have maximum label bound. Thus the dose/response curve is directly proportional to the hCG in the sample. The hCG ER method is an adaptation of the existing Technicon Immuno 1 hCG method. They both use the identical hCG Reagent, Part No. T01-2966-51. The hCG ER Calibrators, Part No. T03-3668-01, are identical in formulation to the Technicon SET point Reproductive Calibrators, Part No. T03-3148-01, which are used for the standard hCG method. There are no changes in either reagent or callbrator formulation. The hCG ER method differs from the standard hCG method in three ways: - 1. The hCG ER calibrators, are reconstituted in 1.0 mL of Reproductive Calibrator Diluent while the Reproductive Calibrators are reconstituted in 2.0mL of Reproductive Calibrator Diluent. This doubles the concentrations of hCG in the calibrator from 0 -1000 mIU/mL to 0 - 2000 mIU/mL. - 2. 65uL of calibrator are reacted with reagent, while 1.3uL of any other sample, serum or control, are reacted. 65uL of the highest calibrator, 2000 mIU/mL, corresponds to 130 total mIU of hCG. A corresponding serum sample with 130 total mIU of hCG, at 1.3uL volume, would have 100,000 mIU/mL concentration. Thus a serum sample at 100,000 mIU/mL reacts the same total quantity of hCG, and produces the same amount of p-nitrophenoxide, as does calibrator at 2,000 mIU/mL. - 3. The concentrations of all samples other than calibrator are automatically multiplied by a factor of 50, which is the difference in volume between 65uL and 1.3uL.

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Predicate Devices

Not Found

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes a standard immunoassay method and its adaptation, focusing on chemical reactions, incubation times, and absorbance measurements. There is no mention of AI or ML in the device description, intended use, or performance studies.

Therapeutic

No
The device is described as an "in vitro diagnostic procedure" intended to "quantitatively measure human chorionic gonadotropin (hCG) in human serum" for "detection of pregnancy." This indicates it is used for diagnostic purposes, not for treating or preventing disease.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states "This in vitro diagnostic procedure is intended to quantitatively measure human chorionic gonadotropin (hCG)...Measurements of human chorionic gonadotropin are used for the detection of pregnancy." The text also refers to it as a "diagnostic method."

SaMD (Software as a Medical Device)

The device description clearly outlines a double antibody immunoassay procedure involving reagents, calibrators, incubations on a physical system (Technicon Immuno 1), and monitoring absorbance. This indicates a physical in vitro diagnostic device, not a software-only device.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The "Intended Use / Indications for Use" section explicitly states: "This in vitro diagnostic procedure is intended to quantitatively measure human chorionic gonadotropin (hCG) in human serum on the Technicon Immuno 1º system."

This statement clearly identifies the device as an in vitro diagnostic device, as it is intended for use outside of the body to examine specimens (human serum) to provide information for diagnostic purposes (detection of pregnancy).

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

This in vitro diagnostic procedure is intended to quantitatively measure human chorionic gonadotropin (hCG) in human serum on the Technicon Immuno 1 system. Measurements of human chorionic gonadotropin are used for the detection of pregnancy. This method is an adaptation of an existing Technicon Immuno 1 hCG method and has an extended range from 800 mIU/mL to 100,000 mIU/mL. This diagnostic method is not intended for use on any other system.

Product codes (comma separated list FDA assigned to the subject device)

Not Found

Device Description

The hCG ER method is an adaptation of the existing Technicon Immuno 1 hCG method. They both use the identical hCG Reagent, Part No. T01-2966-51. The hCG ER Calibrators, Part No. T03-3668-01, are identical in formulation to the Technicon SET point Reproductive Calibrators, Part No. T03-3148-01, which are used for the standard hCG method. There are no changes in either reagent or calibrator formulation. The hCG ER method differs from the standard hCG method in three ways:

1. The hCG ER calibrators, are reconstituted in 1.0 mL of Reproductive Calibrator Diluent while the Reproductive Calibrators are reconstituted in 2.0mL of Reproductive Calibrator Diluent. This doubles the concentrations of hCG in the calibrator from 0 -1000 mIU/mL to 0 - 2000 mIU/mL.
1. 65uL of calibrator are reacted with reagent, while 1.3uL of any other sample, serum or control, are reacted. 65uL of the highest calibrator, 2000 mIU/mL, corresponds to 130 total mIU of hCG. A corresponding serum sample with 130 total mIU of hCG, at 1.3uL volume, would have 100,000 mIU/mL concentration. Thus a serum sample at 100,000 mIU/mL reacts the same total quantity of hCG, and produces the same amount of p-nitrophenoxide, as does calibrator at 2,000 mIU/mL.
1. The concentrations of all samples other than calibrator are automatically multiplied by a factor of 50, which is the difference in volume between 65uL and 1.3uL.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Imprecision Study:

Study type: Imprecision evaluation (within-run and total imprecision).
Sample size: N=129 to 147 replicates per sample type (two commercial controls and three serum pools). Overall, 20 days of testing on two systems using two lots of hCG reagent.
Key results:
- Serum Pool 1: Mean 978 mIU/mL, Within Run C.V. 3.8%, Total C.V. 5.5%
- Control 1: Mean 9707 mIU/mL, Within Run C.V. 3.5%, Total C.V. 6.2%
- Control 2: Mean 28658 mIU/mL, Within Run C.V. 3.8%, Total C.V. 6.8%
- Serum Pool 2: Mean 26746 mIU/mL, Within Run C.V. 3.6%, Total C.V. 4.8%
- Serum Pool 3: Mean 83756 mIU/mL, Within Run C.V. 3.2%, Total C.V. 6.2%

Correlation Study:

Study type: Method comparison (correlation) between Technicon Immuno 1 hCG and hCG ER methods.
Sample size: 104 serum samples.
Key results:
- hCG values ranged from 840 mIU/mL to 88,500 mIU/mL.
- Linear regression equation: Y = 1.11 X + 323 where Y = Immuno 1 hCG ER X = Immuno 1 hCG.
- Correlation coefficient: r = 0.998.

Sample Dilution / Parallelism:

Study type: Parallelism study using diluted serum samples.
Sample size: Three unique serum samples with hCG values close to 100,000 mIU/mL.
Key results: Mean observed values were all within 95%-107% of expected.

Sample Dilution / Linearity:

Study type: Linearity study using co-diluted high and low hCG serum samples.
Sample size: Three unique pairs of high and low hCG serum samples.
Key results: The observed recoveries were all within 99%-107% of expected.

Reagent & Calibrator Stability:

Study type: Stability study for reconstituted calibrators.
Sample size: Three sets of calibrators tested weekly for five weeks.
Key results: Serum pool recoveries were calculated from week 0, weekly, and fresh reconstituted calibrations, indicating stability.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Precision/Imprecision:
- Within-run %CV: 3.2% to 3.8%
- Total %CV: 4.8% to 6.8%
Correlation: Pearson's r = 0.998
Accuracy/Recovery (Parallelism): 95%-107% of expected
Accuracy/Recovery (Linearity): 99%-107% of expected
Lowest Reportable Result: 800 mIU/mL

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

standard Technicon Immuno 1 deg. hCG method

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 862.1155 Human chorionic gonadotropin (HCG) test system.

(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)Identification. A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.

Summary

K961351

Attachment 3

JUN - 3 1996

Summary of Safety and Effectiveness

hCG Extended Range (hCG ER) Method for the Technicon Immuno 1° system

Listed below is a comparison of the performance of the Technicon Immuno 1° hCG ER method and a similar method granted clearance of substantial equivalence (standard Technicon Immuno 1° hCG method). The information below was extracted from the Technicon Immuno 1 hCG ER method sheet, the Technicon Immuno 1 hCG method sheet, and data on file at Bayer Corporation.

Intended Use

| Part Number | Technicon
Immuno 1º
hCG ER
T01-2966-51 | Technicon
Immuno 1º
hCG
T01-2966-51 | | |
|-------------------------------------------------|-------------------------------------------------|----------------------------------------------|------------------|------|
| Reference Range | 800 - 100,000 mIU/mL | 0.5 - 1000 mIU/mL | | |
| Precision, within-run
(n = 130 over 20 days) | mean
(mIU/mL) | %CV | mean
(mIU/mL) | %CV |
| | 978 | 3.8% | 18.3 | 2.4% |
| | 9,707 | 3.5% | 55.7 | 2.2% |
| | 26,746 | 3.6% | 195.8 | 2.1% |
| | 28,658 | 3.8% | | |
| | 83,756 | 3.2% | | |
| Precision, total
(n = 130 over 20 days) | mean
(mIU/mL) | %CV | mean
(mIU/mL) | %CV |
| | 978 | 5.5% | 18.3 | 4.0% |
| | 9,707 | 6.2% | 55.7 | 3.7% |
| | 26,746 | 4.8% | 195.8 | 3.7% |
| | 28,658 | 6.8% | | |
| | 83,756 | 6.2% | | |

Regression Equation

Y = 1.11 X + 323 where Y = Immuno 1 hCG ER X = Immuno 1 hCG n = 104 sera r = 0.998

. .

Assay Description

The hCG ER method is an adaptation of the existing Technicon Immuno 1 hCG method. They both use the identical hCG Reagent, Part No. T01-2966-51. The hCG ER Calibrators, Part No. T03-3668-01, are identical in formulation to the Technicon SET point Reproductive Calibrators, Part No. T03-3148-01, which are used for the standard hCG method. There are no changes in either reagent or callbrator formulation. The hCG ER method differs from the standard hCG method in three ways:

1. The hCG ER calibrators, are reconstituted in 1.0 mL of Reproductive Calibrator Diluent while the Reproductive Calibrators are reconstituted in 2.0mL of Reproductive Calibrator Diluent. This doubles the concentrations of hCG in the calibrator from 0 -1000 mIU/mL to 0 - 2000 mIU/mL.
1. 65uL of calibrator are reacted with reagent, while 1.3uL of any other sample, serum or control, are reacted. 65uL of the highest calibrator, 2000 mIU/mL, corresponds to 130 total mIU of hCG. A corresponding serum sample with 130 total mIU of hCG, at 1.3uL volume, would have 100,000 mIU/mL concentration. Thus a serum sample at 100,000 mIU/mL reacts the same total quantity of hCG, and produces the same amount of p-nitrophenoxide, as does calibrator at 2,000 mIU/mL.
1. The concentrations of all samples other than calibrator are automatically multiplied by a factor of 50, which is the difference in volume between 65uL and 1.3uL.

Image /page/3/Figure/0 description: The image is a plot titled "hCG ER Dose Response Curve". The x-axis is labeled "hCG Concentration (mIU/mL)" and ranges from 0 to 2000. The y-axis is labeled "Reaction Rate (mA/min)" and ranges from 0.00 to 6.00. The plot shows a linear relationship between hCG concentration and reaction rate.

Conc.	Rate
mlU/mL	mA/min
0	0.0042
20	0.0812
80	0.3074
200	0.7286
1000	2.9533
2000	5.0696

Imprecision

Within run and total imprecision were evaluated by testing two commercial controls and three serum pools for twenty days on two systems using two lots of hCG reagent. For both systems, twenty days of data, one run a day, were collected with one reagent lot and 17 days of data were collected with the other reagent lot . The mean rate for each reagent lot was used to generate calibration curves, and concentrations for each lot were calculated from their respective calibration curves. The within-run variance was calculated daily. The among day variance was equal to the variance of the daily means minus the within-run variance divided by the number of reps per day. Total variance was equal to the among day variance plus the within-run variance. Standard deviations were the square roots of the variances.

| Product | Number
of
Replicates | Mean
mlU/mL | Within Run
S.D.
mlU/mL | Within Run
C.V. | Total
S.D.
mlU/mL | Total
C.V. |
|--------------|----------------------------|----------------|------------------------------|--------------------|-------------------------|---------------|
| Serum Pool 1 | 129 | 978 | 38 | 3.8% | 54 | 5.5% |
| Control 1 | 147 | 9707 | 343 | 3.5% | 585 | 6.2% |
| Control 2 | 130 | 28658 | 1083 | 3.8% | 1926 | 6.8% |
| Serum Pool 2 | 132 | 26746 | 955 | 3.6% | 1262 | 4.8% |
| Serum Pool 3 | 129 | 83756 | 2732 | 3.2% | 5212 | 6.2% |

Imprecision Results

Correlation

104 serum samples were assayed for hCG on the Technicon Immuno 1 with the hCG and hCG ER methods. All samples were assayed undiluted in the hCG ER method. Samples that read between 800 and 1000 mIU/mL were assayed undiluted in the standard hCG method. Those that read greater than 1000 mIU/mL were manually diluted with Technicon Immuno 1 Sample Diluent B (Product # T03-3574-01) before assaying. Two researchers separately diluted each sample in order to minimize individual biases in dilution.

hCG values ranged from 840 mIU/mL to 88,500 mIU/mL. Results were calculated using linear regression.

Image /page/5/Figure/3 description: This image is a method comparison of hCG vs. hCG ER on Technicon Immuno 1. The scatter plot shows the correlation between the two methods, with hCG on the x-axis and hCG ER on the y-axis, both measured in mIU/mL. A regression line is plotted through the data points, and the equation of the line is given as hCG = 1.11(hCG ER) + 323, with a correlation coefficient of r = 0.998, based on 104 serum samples.

Interfering Substances/ Specificity

The hCG ER method has the identical reagent and calibrator formulation as the standard hCG method. However the hCG ER method uses 1.3uL of sample while the standard method uses 50uL. With 1/38th the sample volume of the standard method, the hCG ER method has 1/38th the amount of interfering or cross-reacting substances added to the reaction. Assay specificities are expected to be the same as for the standard method.

Expected Values

The hCG ER method has the same expected values as the standard hCG method. The only difference between the two methods is that the standard hCG method reports hCG values between 0.5 and 1000 mIU/mL and the hCG ER method reports hCG values between 800 and 100,000 mIU/mL.

Sample Dilution / Parallelism

For parallelism, three unique serum samples with hCG values close to 100,000 mIU/mL were diluted with Sample Diluent B. The mean observed values were all within 95%-107% of expected.

Image /page/7/Figure/2 description: The image contains three graphs, each titled "hCG-ER - Parallelism" with different sample labels: A, B, and C. Each graph plots "Recovery (mIU/mL)" on the y-axis against "Percent Serum" on the x-axis, showing observed data points connected by a dotted line representing the expected values. The graphs include percentage values at each data point, such as 105.0%, 95.8%, 100.1%, and 101.2% for Sample A, indicating the recovery rate at different serum percentages.

Sample Dilution / Linearity

Three unique pairs of high and low hCG serum samples were co-diluted and assayed. The observed recoveries were all within 99%-107% of expected.

Image /page/8/Figure/2 description: The image contains three line graphs, each titled "HCG-ER LINEARITY" with a different number (#1, #2, and #3). Each graph plots "Recovery (mIU/mL)" on the y-axis against "Linearity Pool" on the x-axis, ranging from -2 to 2. Each graph shows an "Expected" line with "Observed" data points marked with percentages indicating the recovery rate at different linearity pool values, such as 102% at -1, 99% at 0, 101% at 1, and 107% at 2.

Reagent & Calibrator Stability

The same hCG reagent is used for the hCG ER method as for the standard method. No additional stability studies are necessary.

The hCG ER calibrators, Part No. T03-3668-01, are identical in formulation to the Technicon SET point Reproductive Calibrators, Part No. T03-3148-01. Shelf life and shipping stability are not necessary.

The hCG ER calibrators are stable for 30 days after reconstitution. Three sets of calibrators were reconstituted and tested individually at Time 0. The three sets were not pooled. Their rates were combined and used for "Week 0" calibration. At weekly intervals only one set of open vial calibrator was tested along with a freshly reconstituted set. A different set was used weekly for five weeks. Serum pool recoveries were calculated from week 0, weekly, and fresh reconstituted calibrations.

Image /page/10/Figure/0 description: The image contains three line plots that show the stability of hCG ER Reconstituted Calibrator for Serum Pools 1, 2, and 3. Each plot shows the recovery in mIU/mL over a period of 5 weeks. The plots include data points for Fresh Recon, Week 0 Calibration, and Weekly Calibration, as well as a -2SD Range line.

Minimal Detectable Concentration

The hCG ER method has a lowest reportable result of 800 mIU/mL. Minimal detectable dose is not determined. The lowest reportable result is used to determine the lower limit of detection rather than minimal detectable dose.