Luminescence immunoassay for the in vitro diagnostic quantitative measurement of active free progesterone (a female hormone) in saliva. Measurements obtained by this device may be used in the diagnosis and treatment of disorders of the ovaries and can be used as an aid for confirmation of ovulation.

Device Description

Luminescence immunoassay (LIA) based on the competition principle. An unknown amount of antigen present in the sample and a fixed amount of enzyme labeled antigen compete for the binding sites of the antibodies coated onto the wells. After incubation the wells are washed to stop the competition reaction. After addition of the luminescence substrate solution the intensity of the luminescence measured is inversely proportional to the amount of the antigen in the sample. Results of samples can be determined directly using the standard curve.

AI/ML Overview

IBL Progesterone LIA - Acceptance Criteria and Study Details

1. Table of Acceptance Criteria and Reported Device Performance

The provided document describes the performance characteristics of the IBL Progesterone LIA. The acceptance criteria for these characteristics are not explicitly stated as distinct thresholds in the document, but rather the reported performance values themselves serve as the demonstration of the device's capability. For this analysis, we will interpret the reported performance as meeting the implicit acceptance criteria for a device of this type.

Performance Metric	Reported Device Performance
Analytical Specificity (Cross-Reactivity)
17α-Hydroxyprogesteron	1.84%
6α-Methyl-17α-Hydroxyprogesteron	1.41%
Pregnenolone	0.41%
Deoxycorticosterone	0.28%
Androsterone Sulfat	0.25%
Androstenedion	0.20%
Androsterone	0.20%
DHEA-S	0.11%
Corticosterone	0.06%
Other substances tested	≤ 0.1 %
Analytical Sensitivity (Limit of Detection)	2.6 pg/mL (Mean signal (Zero-Standard) - 2SD)
Precision
Intra-Assay (10 measurements)	Range (pg/mL): 11.5 - 822; CV (%): 6.0 - 0.7
Inter-Assay (10 measurements)	Range (pg/mL): 10.6 - 817.1; CV (%): 18.8 - 3.4
Linearity	Range (pg/mL): 7.5 - 779; Range (%): 78 - 120; Mean (%): 97 (Serial dilution up to 1:32)
Recovery	Range (pg/mL): 27 - 1497; Range (%): 82 - 121; Mean (%): 103
Comparison Study	Correlation with a published RIA method: r² = 0.94, Regression formula: Y = 0.89 * RIA + 25.5 pg/mL
Normal Ranges (Reference Values)	Premenopausal Females (n=27 month profiles): Follicular phase: 28 - 82 pg/mL, Luteal phase (peak max): 127 - 446 pg/mL Postmenopausal Females (n=6): 18 - 51 pg/mL Males (n=49): < 59 pg/mL

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

Sample Size for Test Set:
- Clinical cycle profiling: 27 pre-menopausal women, 6 post-menopausal women, and 49 males.
- Comparison study: 97 adult healthy populations.
Data Provenance: The document does not explicitly state the country of origin for the data. It mentions the manufacturer as IBL Immuno Biological Laboratories in Hamburg, Germany, which suggests the studies were likely conducted or overseen in Germany or Europe. The study is prospective for the clinical cycle profiling (samples collected throughout menstrual cycles), and likely also prospective or from a specific collection for the healthy populations in the comparison study.

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

The document does not mention the use of "experts" in the traditional sense (e.g., radiologists, pathologists) to establish ground truth.
For the comparison study, the "ground truth" was established by a "published procedure that used a modification in the handling of saliva for a typical RIA test." This implies a reference analytical method was used as the ground truth, rather than expert clinical judgment.

4. Adjudication Method for the Test Set

Not applicable. The ground truth was established by a reference analytical method, not by human expert consensus or adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. The study focused on the analytical performance of the device and its correlation with a reference method, not on the impact of the device on human reader performance.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done

Yes, the studies reported in the document describe the standalone performance of the IBL Progesterone LIA device. The device autonomously measures progesterone levels in saliva. The comparison study assesses its agreement with a reference analytical method, which is a form of standalone performance evaluation.

7. The Type of Ground Truth Used

For Analytical Performance (Specificity, Sensitivity, Precision, Linearity, Recovery): The ground truth is inherent in the analytical standards and reference materials used to challenge the assay and measure its performance characteristics. These are established laboratory methods.
For Comparison Study: The ground truth was a published procedure using a modified RIA test for saliva progesterone. This serves as a reference method.
For Normal Ranges: The "ground truth" here is the measured progesterone levels in a defined healthy population (pre-menopausal women, post-menopausal women, males) over specific physiological periods (menstrual cycle phases).

8. The Sample Size for the Training Set

The document does not explicitly describe a "training set" in the context of an algorithm or AI. The IBL Progesterone LIA is a luminescence immunoassay, not an AI/machine learning algorithm that requires a separate training phase. All listed sample sizes (27 pre-menopausal women, 6 post-menopausal women, 49 males, and 97 adult healthy populations) are related to the evaluation/test of the device's performance characteristics and establishment of reference ranges, not for training a model.

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

As noted above, there is no explicit "training set" for an AI/machine learning model. The device is a biochemical assay. The "ground truth" for evaluating its performance (as detailed in point 7) was established through scientifically accepted analytical methods and reference procedures.

Summary

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JUL 22 2004

SUMMARY OF

SAFETY AND EFFECTIVENESS FOR IBL PROGESTERONE LIA

Manufacturer: IBL Immuno Biological Laboratories Flughafenstrasse 52A, D-22335 Hamburg Germany

Contact Information: Lehnus & Associates Gary Lehnus 150 Cherry Lane Rd. East Stroudsburg, PA 18301 Tel: (570) 620-0198

Device Name / Classification:

The device trade name is the IBL Progesterone LIA having FDA assigned name: Progesterone test system, 21 CFR, 862.1620, categorized as Class I "exempt" medical devices for the Clinical Chemistry and Clinical Toxicology Panel, as Product Code JLS.

Device Description:

Device Intended Use:

Device Performance:

Studies were performed to establish levels of progesterone throughout the menstrual cvcles of pre-menopausal women. Saliva samples were collected from apparently healthy females known to be pre-menopausal and using no contraceptives. Three saliva samples were collected per day and pooled and frozen prior to running the Progesterone LIA assay. Collection began at the last day of bleeding and continued daily until first day of bleeding. A total of 27 premenopausal women, six postmenopausal women and 49 males were evaluated for the studies.

Comparison studies were performed using saliva samples from 97 adult healthy populations. These samples were tested with the IBL Progesterone LIA and compared to a published procedure that used a modification in the handling of saliva for a typical RIA test. Results from measuring the saliva samples in both methods yielded a correlation of r2 = 0.94 with a regression formula of Y=0.89*RIA + 25.5 pg/mL.

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Analytical Specificity(Cross Reactivity)	Substance	% Cross-reactivity
	17α-Hydroxyprogesteron	1.84
	6α-Methyl-17α-Hydroxyprogesteron	1.41
	Pregnenolone	0.41	Cross-reactivity ofother substancestested ≤ 0.1 %
	Deoxycorticosterone	0.28
	Androsterone Sulfat	0.25
	Androstenedion	0.20
	Androsterone	0.20
	DHEA-S	0.11
	Corticosterone	0.06
	Analytical Sensitivity(Limit of Detection)	2.6 pg/mL	Mean signal (Zero-Standard) - 2SD
Precision	Range (pg/mL)	CV (%)
Intra-Assay (10)	11.5 - 822	6.0 - 0.7
Inter-Assay (10)	10.6 - 817.1	18.8 - 3.4
Linearity	Range (pg/mL)	Range (%)	Mean (%)	Serial dilution up to
	7.5 - 779	78 - 120	97	1 : 32
Recovery	Range (pg/mL)	Range (%)	Mean (%)
	27 - 1497	82 - 121	103

The overall performance of the IBL Progesterone LIA is shown below:

ﺑﺮﻧﺎﻣ

Normal ranges	Progesterone (pg/mL)
♀	Premenopausal(n = 27 month profiles)	Follicular phase28 - 82 pg/mLLuteal phase(peak max) 127 - 446 pg/mL
♀	Postmenopausal, n = 6	18 - 51 pg/mL
♂	n = 49	< 59 pg/mL

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/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" around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, a traditional symbol of medicine, with three wavy lines representing the branches of government.

JUL 22 2004

Food and Drug Administration 2098 Gaither Road

Public Health Service

Rockville MD 20850

IBL-Hamburg c/o Mr. Gary Lehnus Lehnus & Associates Consulting 150 Cherry Lane Rd. East Stroudsburg, PA 18301

K040923 Re:

Trade/Device Name: IBL Progesterone LIA Test Regulation Number: 21 CFR 862.1620 Regulation Name: Progesterone test system Regulatory Class: Class I Product Code: JLS Dated: June 10 2004 Received: June 17, 2004

Dear Mr. Lehnus:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your betermined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the energy of 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 r ou may a we se 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 Parts 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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Page 2

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,

feain M. Cooper, US, DVM.

Jean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K040923

Device Name: ____IBL_Progesterone LIA Test

Indications For Use:

Luminescence immunoassay for the in vitro diagnostic quantitative measurement of Editinoooonoo inimanoad and hormone) in saliva. Measurements obtained by this device may be used in the diagnosis and treatment of disorders of the ovaries and can be used as an aid for confirmation of ovulation.

The IBL SaliCap Set is used for the collection, handling, and storage of saliva used in the Progesterone LIA assay.

Prescription Use __X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________ (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

Office of In Vitro Diagnostic

510(k)

Office of In Vitro Diagnostic
Device Evaluation and Safety

Page 1 of ____________________________________________________________________________________________________________________________________________________________________

Regulation Number and Section

§ 862.1620 Progesterone test system.

(a)
Identification. A progesterone test system is a device intended to measure progesterone (a female hormone) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of disorders of the ovaries or placenta.(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.