Reagents: The ARCHITECT® SHBG assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of sex hormone binding globulin (SHBG) in human serum and plasma on the ARCHITECT i System. The ARCHITECT SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.
Calibrators: The ARCHITECT® SHBG Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of SHBG in human serum and plasma.
Controls: ARCHITECT® SHBG Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of SHBG in human serum and plasma. For in vitro diagnostic use.

Device Description

The ARCHITECT SHBG assay is a two-step immunoassay to determine the presence of SHBG in human serum and plasma using CMIA technology with flexible assay protocols, referred to as Chemiflex®. In the first step, sample, assay diluent, and anti-SHBG coated paramagnetic microparticles are combined. SHBG present in the sample binds to anti-SHBG coated microparticles. After washing, the SHBG binds to the anti-SHBG acridinium-labeled conjugate that is added in the second step. Following another wash cycle, pretrigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). A direct relationship exists between the amount of SHBG in the sample and the RLUs detected by the ARCHITECT i System optics. The concentration of SHBG in the sample is determined by comparing the chemiluminescent signal in the reaction to the ARCHITECT SHBG calibration.

AI/ML Overview

The ARCHITECT® SHBG assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of sex hormone binding globulin (SHBG) in human serum and plasma. The study conducted to demonstrate its substantial equivalence compared its performance against the Elecsys® SHBG Immunoassay System (Roche, k#031717).

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

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a quantitative table format. Instead, it describes characteristics that are evaluated for substantial equivalence. The key performance indicator for the assay itself is the correlation coefficient for method comparison.

Performance Metric	Acceptance Criteria (Implied by Substantial Equivalence to Predicate)	Reported ARCHITECT® SHBG Performance
Method Comparison (Correlation Coefficient)	High correlation (e.g., typically >0.95 for quantitative assays in IVD)	0.98
Precision	Substantially equivalent to predicate	Substantially Equivalent
Linearity	Substantially equivalent to predicate	Substantially Equivalent
Interferences	Substantially equivalent to predicate	Substantially Equivalent
Measuring Range	Comparable to predicate (0.1 – 250 nmol/L for device vs 0.350 - 200 nmol/L for predicate)	0.1 – 250 nmol/L
Analytical Sensitivity	Comparable to predicate (0.1 nmol/L for device vs 0.35 nmol/L for predicate)	0.1 nmol/L
Analytical Specificity	No detectable cross-reactivities with specified substances	No detectable cross-reactivities

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

Sample Size: 626 specimens
Data Provenance: Not explicitly stated, but clinical studies for such devices typically involve prospective or retrospectively collected human samples. The document does not specify the country of origin. Given the applicant is in Spain, it's plausible the data originates from Europe, but this is an inference.

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

This information is not provided in the document. For an immunoassay like this, the "ground truth" would typically refer to the reference values or results obtained from a well-established and validated reference method (the predicate device in this case, Elecsys® SHBG). It doesn't involve the interpretation of images or other subjective assessments that would require a panel of human experts in the same way an imaging AI might.

4. Adjudication Method for the Test Set:

Not applicable. The ground truth for this type of quantitative assay is established by comparison to a reference method (the predicate device), not through human adjudication of subjective interpretations.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:

No. An MRMC study is not relevant for this type of in vitro diagnostic device. MRMC studies are typically used for evaluating diagnostic imaging systems where human readers interpret medical images, and the AI's role is to assist these readers. This device is a quantitative blood assay.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

Yes, implicitly. The method comparison study is a standalone performance evaluation of the ARCHITECT® SHBG assay algorithm (the device) against the predicate device. The results (e.g., correlation coefficient) represent the performance of the ARCHITECT® SHBG system on its own. Human intervention during the assay process is for operation of the instrument, not for interpretation of the result in a way that significantly influences the quantitative outcome.

7. The Type of Ground Truth Used:

The ground truth used was comparison to a legally marketed predicate device (Elecsys® SHBG Immunoassay System). The predicate device's results serve as the reference standard against which the new device's performance is measured.

8. The Sample Size for the Training Set:

This information is not provided in the document. For an immunoassay, the "training set" concept is usually applied to the development and optimization phase of the assay (e.g., reagent concentrations, reaction times), rather than a distinct, retrospectively defined data set for algorithm training as seen in machine learning. The document focuses on the validation of the finalized assay.

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

This information is not provided and is generally not applicable in the same way as it would be for an AI algorithm that learns from data. For a traditional immunoassay, the "ground truth" during development would be established through meticulous analytical validation using known standards, spiked samples, and comparison to established reference methods to ensure the assay accurately reflects the analyte's concentration.

Summary

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SHBG

510(k) Summary (Summary of Safety and Effectiveness)

This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of CFR

The Assigned 510(k) Number is: __

Preparation date: February 21st, 2006

Applicant Name:

Mr. Joan Guixer Director of Quality Assurance and Regulatory Affairs Biokit S.A. Llica d'Amunt Barcelona, Spain 08186

Device Name:

Reagent

Classification Name: Radioimmunoassay, testosterones and dihydrotestosterone Trade Name: ARCHITECT® SHBG Device Classification: 21 CFR 862 1680 Device Class: Class I Classification Panel: Clinical Chemistry Product Code: CDZ

Calibrators

Classification Name: Calibrator, Secondary Trade Name: ARCHITECT® SHBG Calibrators Device Classification: 862.1150 Device Class: Class II Classification Panel: Clinical Chemistry Product Code: JIT

Controls

Classification Name: Single (Specified) Analyte Controls (assayed and unassayed) Trade Name: ARCHITECT® SHBG Controls Device Classification: 862.1660 Device Class: Class I Classification Panel: Clinical Chemistry Product Code: JJX

ldentification of Predicate Device:

Elecsys® SHBG Immunoassay System (Roche, k#031717)

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Intended Use of Device:

The ARCHITECT® SHBG Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of SHBG in human serum and plasma.

The ARCHITECT® SHBG Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of SHBG in human serum and plasma.

Description of Device:

Comparison of Technological Characteristics:

The ARCHITECT® SHBG assay is a chemiluminiscent microparticle immunoassay (CMIA) method for the quantitative determination of the SHBG in human serum or plasma.

Summary of Non-Clinical Performance:

The ARCHITECT® SHBG assay is substantially equivalent to the Elecsys® SHBG assay in terms of precision, linearity and interferences as demonstrated in non-clinical performance data in this 510(k) submission.

Summary of Clinical Performance:

The ARCHITECT® SHBG assay demonstrated substantially equivalent performance to the Elecsys® SHBG indicated by a method comparison with a correlation coefficient of 0.98.

ARCHITECT SHBG February, 2006

510(k) Summarv

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Reagents:

・

Similarities:
Characteristics	Device	Predicate
Product Type	Immunoassay	Immunoassay
Methodology	Chemiluminescent MicroparticleImmunoassay (CMIA)	Chemiluminescence a solidphase enzyme immunoassay
Intended Use	The ARCHITECT® SHBG assayis a chemiluminescentmicroparticle immunoassay(CMIA) for the quantitativedetermination of sex hormonebinding globulin (SHBG) inhuman serum and plasma onthe ARCHITECT / System.	Immunoassay for the in vitroquantitative determination of sexhormone-binding globulin inhuman serum and plasma. TheECLIA is intended for use on theRoche Elecsys® 1010/2010 andMODULAR ANALYTICS E170(Elecsys module) immunoassayanalyzers.
Where Used	Clinical Laboratories	Clinical Laboratories
Assay Protocol	Two-step direct sandwichimmunoassay	Sandwich principle
Specimen Type	Human serum or plasma(Lithium Heparin, SodiumHeparin, Ammonium Heparin,Potassium EDTA)	Human Serum and LithiumHeparin Plasma
Interpretation of Results	Standard Curve	Standard Curve
Interferences	Non significant interferenceswith:Hemoglobin, bilirubin,triglycerides, protein	Non significant interferenceswith:Bilirubin, hemolysis, lipemia,biotin
Measuring Range	0.1 – 250 nmol / L	0.350 - 200 nmol / L
Analytical Sensitivity	0.1 nmol / L	0.35 nmol / L
Analytical Specificity	Non detectable cross-reactivities were found for:AFP, cortisol, 11-Deoxycortisol,Estradiol, testosterone, 5-dihydrotestosterone, TG, TBGand transferrin.	Non detectable cross-reactivities were found for:AFP, CBG, DHT, estradiol,fibrinogen, human IgA, humanIgG, plasminogen, TBG,testosterone, TG, transferrinand TSH.
Method Comparison	ARCHITECT SHBG was compared to the predicate device.626 specimens ranging 6.5 nmol/L to 1072.0 nmol/L wereevaluated and the correlation coefficient obtained was 0.98.

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Differences:

Characteristics	Device	Predicate
Platform	ARCHITECT / System	ROCHE Elecsys® 1010/1020Analyzer and MODULARANALYTICS E170
Components	Microparticles	Microparticles
	1or 4 Bottle(s) (6.6 mL each)	1 bottle of 6.5mL.
	Anti-SHBG(mouse monoclonal)coated microparticles in TRISbuffer.Preservative: sodium azide.	Streptavidin-coatedmicroparticles, 0.72 mg/mL;binding capacity: 470 ngbiotin/mg microparticles.Preservative.
	Conjugate	R1 - Anti-SHBG-Ab~biotin -
	1or 4 Bottle(s) (5.9 mL each)	1 bottle (10.0 mL)
	Anti-SHBG(mouse,monoclonal)acridinium-labeled conjugate inphosphate buffer with protein(mouse, bovine) stabilizer.Preservative: sodium azide.	Biotinylated monoclonal anti-SHBG antibody (mouse) 1.25mg/L; phosphate buffer 100mmol/L, pH 7.2.Preservative.
	Assay Diluent	R2 - Anti-SHBG-Ab~Ru
	1or 4 Bottle(s) (8.0 mL each)	1 bottle, 10 mL
	SHBG Assay Diluent containingphosphate buffer with protein(mouse,bovine) stabilizer.Preservative: sodium azide.	Monoclonal anti-SHBGantibody (mouse) labeled withruthenium complex 1.25 mg/L;phosphate buffer 100mmol/L,pH 7.2. Preservative

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Calibrators:

Similarities: Predicate Characteristics Device ARCHITECT® Elecsys® SHBG CalSet is used

for calibrating the quantitative Intended Use The SHBG Calibrators for the are Elecsys SHBG assay on the calibration of the ARCHITECT i Elecsys immunoassay systems. System when used for the quantitative determination of SHBG in human serum and plasma. Against the first International Traceable to the WHO Standardization/Traceability Standard for SHBG from the Standard Material NIBSC National Institute for Biological CODE: 95/560. Standards and Control (NIBSC) code 95/560.

Differences:

Characteristics	Device	Predicate
Calibrator Components	6 Bottles (2.0 mL each) ofARCHITECT SHBGCalibrators. Calibrator Acontains phosphate bufferedsaline with protein (goat)stabilizer. Calibrators B to Fcontain SHBG in phosphatebuffered saline with protein(goat) stabilizer. Preservatives:sodium azide and ProClin® 300.	SHBG Cal1 and Cal2 (1.0 mLeach) The concentration ofSHBG Cal1 is approximately0.0 nmol/L; SHBG Cal2contains approximately 40nmol/L human SHBG in ahuman serum matrix.
Calibrator Concentrations	CAL A - 0.0 nmol/LCAL B - 2.0 nmol/LCAL C - 6.0 nmol/LCAL D - 25.0 nmol/LCAL E - 125.0 nmol/LCAL F - 250.0 nmol/L	0.0 and 40 nmol/L
Matrix	Purified Human SHBG in aphosphate buffered saline	Lyophilized equine serum (cal1)and human serum (cal2). Bothcontaining SHBG.

ARCHITECT SHBG February, 2006

510(k) Summary

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Controls:

Similarities:
Characteristics	Device	Predicate
Intended Use	The ARCHITECT® SHBGControls are for the verificationof the accuracy and precision ofthe ARCHITECT i Systemwhen used for the quantitativedetermination of SHBG inhuman serum and plasma.	Elecsys® PreciControl Universalis used for quality control ofElecsys immunoassay on theElecsys immunoassay systems.
Methodology	ChemiluminescentMicroparticle Immunoassay(CMIA)	Chemiluminescence a solidphase enzyme immunoassay
Matrix	Purified Human SHBG in buffer	SHBG human serum in buffer

Differences:

Characteristics	Device	Predicate
Control Components	3 Bottles (4.0 mL each) ofARCHITECT SHBG Controlscontain SHBG (human,purified) in phosphate bufferedsaline with protein (goat)stabilizer. Preservatives:sodium azide and ProClin®300.	SHBG Controls (LSHC1,LSHC2)Two vials of lyophilized SHBGin a nonhuman protein/buffermatrix.
Control Concentrations	Low – 9.0 nmol/LMedium – 25.0 nmol/LHigh – 150.0 nmol/L	Target values andconcentration range areindicated in a value sheet.

Conclusion:

As summarized above the ARCHITECT® SHBG Reagents, Calibrators (A-F) and Controls (Low, Medium and High) are substantially equivalent to the ROCHE Elecsys® SHBG Reagents, Calibrators and Controls. Substantial equivalence for the reagents and calibrators has been demonstrated as recommended by the FDA guidance for Industry "Format for Traditional and Abbreviated 510(k)s" (Issued on: August 12, 2005) and for controls as recommended by the FDA Guidance for Industry "Points to Consider Document on Assayed and Unassayed Quality Control Material" (Draft Guidance released for comment on February 3, 1999).

ARCHITECT SHBG February, 2006

510(k) Summary

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Image /page/6/Picture/0 description: The image is a seal for the Department of Health & Human Services in the USA. The seal is circular and contains the department's logo. The logo is a stylized representation of a human figure embracing a globe. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the perimeter of the circle.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Joan Guixer Quality Assurance and Regulatory Affairs Director Biokit S.A. Can Malè s/n Llissa d'Amunt, Barcelona, 08186 Spain

JAN 2 3 2007

K060818 Re: Trade/Device Name: ARCHITECT® SHBG Reagents, Calibrators (A-F) and ARCHITECT® SHBG Controls (Low, Medium, High) Regulation Number: 21 CFR§ 862.1680 Regulation Name: Testosterone test system Regulatory Class: Class I, reserved Product Code: CDZ, JIT, JJX Dated: December 20, 2006 Received: December 26, 2006

Dear Mr. Guixer:

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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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 vour 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 (240) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean m. Cooper, M.S., D.V.M.

Sean M. Cooper, M.S., 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 Statement

510(k) Number (if known): K060818

Device Name: ARCHITECT® SHBG REAGENTS, CALIBRATORS (A-F) and ARCHITECT® SHBG CONTROLS (LOW, MEDIUM, HIGH)

Indications for Use:

Reagents

The ARCHITECT SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.

Calibrators

The ARCHITECT® SHBG Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of SHBG in human serum and plasma.

Controls

ARCHITECT® SHBG Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of SHBG in human serum and plasma.

For in vitro diagnostic use.

Prescription Use × (Part 21 CFR 801 Subpart D) 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)

rision Sign-Off

fire of In Vitro Diagnostic Device valuation and Safety

060818

Regulation Number and Section

§ 862.1680 Testosterone test system.

(a)
Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.(b)
Classification. Class I.