For the in vitro quantitative determination of degradation products of type I collagen in human serum and plasma, for assessing individual bone resorption. The test may be used as an aid in monitoring anti-resorptive therapies (e.g. bisphosphonates, hormone replacement therapy - HRT) in postmenopausal women and individuals diagnosed with osteopenia. The elecrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche ELECSYS 1010 and 2010 immunoassay analyzers.

Device Description

The ELECSYS® β-CrossLaps/serum Test is based on a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve provided with the reagent bar code card.

AI/ML Overview

This document describes a 510(k) submission for the ELECSYS® β-CrossLaps/serum Immunoassay, seeking substantial equivalence to a predicate device. It does not contain a study proving the device meets specific acceptance criteria in the traditional sense of a clinical trial with pre-defined performance thresholds for accuracy, sensitivity, or specificity against a ground truth.

Instead, the submission focuses on demonstrating "substantial equivalence" to a legally marketed predicate device (Osteometer Serum CrossLaps™ One Step ELISA) by comparing various performance characteristics. The acceptance criteria are implicitly defined by the comparable performance of the predicate device.

Here's an analysis of the provided information:

1. Table of Acceptance Criteria (Implicit) and Reported Device Performance

Since this is a substantial equivalence claim, the "acceptance criteria" are the performance characteristics of the predicate device, and "reported device performance" is the performance of the ELECSYS® β-CrossLaps/serum Immunoassay.

Feature	Acceptance Criteria (Predicate Device)	Reported Device Performance (ELECSYS® β-CrossLaps/serum Immunoassay)
Within-Run Precision (%CV)	Serum samples:	Human sera:
	5.4% at 1737 pM	4.6% at 0.08 ng/mL
	5.0% at 2694 pM	1.8% at 0.39 ng/mL
	5.1% at 3415 pM	1.0% at 3.59 ng/mL
		Controls:
		3.4% at 0.15 ng/mL
		1.6% at 0.84 ng/mL
		2.2% at 3.18 ng/mL
Total Precision (%CV)	Serum samples:	Human sera:
	8.1% at 1963 pM	4.7% at 0.08 ng/mL
	5.4% at 2820 pM	4.3% at 0.39 ng/mL
	6.5% at 3503 pM	1.6% at 3.59 ng/mL
		Controls:
		3.4% at 0.15 ng/mL
		1.9% at 0.84 ng/mL
		2.5% at 3.18 ng/mL
Analytical Sensitivity	94 pM	0.01 ng/mL
Interferences	No interference from ditaurobiliribin up to 60 mg/dL	No interference from bilirubin up to 65 mg/dL
	No interference from hemoglobin up to 1.0 g/dL	No interference from hemoglobin up to 0.5 g/dL
	No interference from intralipid up to 1000 mg/dL	No interference from intralipid up to 1500 mg/dL
		No interference from biotin up to 90 ng/mL
		No interference from rheumatoid factor up to 1500 U/mL
		No high dose hook effect up to 150 ng/mL
Measuring Range	94 – 20,000 pM	0.010 – 6.00 ng/mL
Assay Protocol	1-step sandwich assay	2-step sandwich assay
Detection Protocol	ELISA/Absorbance reading	Electrochemiluminescence
Instrument	Microtiter Plate Reader	ELECSYS® 2010 and 1010 Immunoassay Analyzers
Procedure	Manual	Automatic
Calibration Frequency	Calibration with each run	ELECSYS® 2010: after 1 month (same lot), after 7 days (same kit). ELECSYS® 1010: with every reagent kit, after 7 days (20-25°C), after 3 days (25-32°C).

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

The document does not explicitly state the total sample size used for the performance characteristic studies (e.g., precision, analytical sensitivity, interference).

Precision: "Human sera" and "Controls" are mentioned, implying multiple samples were tested at different concentrations. Specific numbers are not provided.
Interference: Various substances were tested for interference, but the number of samples or specific experimental setup for these tests is not detailed.

The data provenance (country of origin, retrospective/prospective) is not mentioned. Given it's a submission to the FDA, it's likely the studies were conducted under good laboratory practices, but the location is not specified.

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

This type of immunoassay does not typically involve human experts establishing a "ground truth" in the same way an imaging device might. The "ground truth" for an immunoassay is typically established by:

Reference materials/standards: The analytical sensitivity and calibration are based on purified peptides and internal reference standards.
Clinical correlation: While the intended use includes monitoring therapies, the document primarily focuses on analytical performance. Clinical correlation studies (e.g., comparing results to patient outcomes) are not detailed here as the primary "ground truth" for the device's technical performance.

Therefore, this question is not directly applicable to the type of device and study described.

4. Adjudication Method for the Test Set

Not applicable. This is an immunoassay, and measurements are quantitative. There's no human interpretation or subjective assessment of results that would require an adjudication method.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve With AI vs Without AI Assistance

Not applicable. This is an in vitro diagnostic immunoassay, not an AI-assisted diagnostic imaging device for human readers.

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

Yes, the performance characteristics (precision, analytical sensitivity, interference) provided are for the device (ELECSYS® β-CrossLaps/serum Immunoassay) operating in a standalone mode on the ELECSYS 1010 and 2010 immunoassay analyzers, without human-in-the-loop performance influencing the measurement itself. Humans operate the machines and interpret the results, but the analytical performance data are intrinsic to the device.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

The "ground truth" for an immunoassay's analytical performance (as presented here) relies on:

Reference standards/Calibrators: Purified peptide standards are used for calibration and traceability. These are the fundamental "ground truth" for achieving accurate quantitative measurements.
Validated measurement methods: The performance characteristics are measured against established laboratory practices and often using validated control materials.

For the intended use of "assessing individual bone resorption" and "monitoring anti-resorptive therapies," the ultimate ground truth would involve clinical factors like bone mineral density (BMD) changes, fracture rates, or other clinical outcomes. However, this submission focuses on the analytical equivalence of the assay itself, not a full clinical outcome study.

8. The Sample Size for the Training Set

Not applicable. This device is an immunoassay, not a machine learning or AI algorithm that requires a "training set" in the conventional sense of developing a model. The "training" for such a device involves establishing calibration curves and optimizing manufacturing processes, which utilizes internal quality control and validation data rather than a distinct "training set" for an algorithm.

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

Not applicable, as there is no "training set" for an algorithm in this context. The "ground truth" for the device's operational parameters (e.g., calibration curve) is established using validated controls and reference materials with known concentrations of the analyte (degradation products of type I collagen).

Summary

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JUL 2 4 2000

510(k) Summary

K 993706

According to the requirements of 21 CFR 807.92, the following Introduction information provides sufficient detail to understand the basis for a determination of substantial equivalence

Submitter name, address, contact

Roche Diagnostics Corporation 9115 Hague Rd Indianapolis IN 46250 (317) 576 3723

Contact person: Priscilla A. Hamill

Date prepared: October 28, 1999

Predicate device

The ELECSYS β-CrossLaps/serum Immunoassay is substantially equivalent to other devices marketed in the United States. We claim equivalence to the Osteometer Serum CrossLaps™ One Step ELISA (K990843).

Device name

Proprietary name	ELECSYS® β-CrossLaps/serum Immunoassay
Common name	Electrochemiluminescence Immunoassay, β-CrossLaps / Serum
Classification name	Column Chromatography & Color Development, Hydroxyproline

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and the comments of the country

and the comments of the comments of

Devicedescription	The ELECSYS® β-CrossLaps/serum Test is based on a two stepsandwich immunoassay with streptavidin microparticles andelectrochemiluminescence detection.Results are determined using a calibration curve that is generatedspecifically on each instrument by a 2-point calibration and a mastercurve provided with the reagent bar code card.
Intended use	Immunoassay for the in vitro quantitative determination of degradationproducts of type I collagen in human serum and plasma.
Indication for use	• For assessing individual bone resorption• As an aid in monitoring anti-resorptive therapies (eg. bisphosphates,hormone replacement therapy-HRT) in postmenopausal women andindividuals diagnosed with ostepenia
Substantialequivalence	The ELECSYS® β-CrossLaps/serum Immunoassay is equivalent to otherdevices legally marketed in the United States. We claim equivalence tothe Osteometer Serum CrossLaps™ One Step ELISA (K990843).

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Substantial equivalence similarities

The following table compares the ELECSYS® ß-CrossLaps/serum Immunoassay with the predicate device.

Feature	ELECSYS® β-CrossLaps/serumImmunoassay	Predicate Device
Intended use	for the quantitativedetermination ofdegradation products oftype I collagen	for the quantitativedetermination ofdegradation products ofC-terminal telopeptidesof type I collagen
Indication for use	For assessingindividual boneresorption. As an aid inmonitoring anti-resorptive therapies(bisphosphonates orhormone replacementtherapy HRT)in postmenopausalwomen individualsdiagnosed withosteo-penia	Diagnosis of human boneresorption as an aid in: Monitoring boneresoprtion changes underhormone replacementtherapy (HRT) orbisphosphonate therapyin Anti-resorptivetherapies inpostmenopausalwomen Anti-resorptivetherapies inindividuals diagnosedwith osteopenia Predicting skeletalresponse (Bone MineralDensitiy) inpostmenopausal womanundergoing anti-resorptive therapies

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Feature	ELECSYS® β-CrossLaps/serumImmunoassay	Predicate Device
Specimencollection	fasting morning bloodsamples arerecommended longterminvestigations:samples should bealways taken under thesame conditions as thebaseline sample	fasting morningblood samples arerecommended longterminvestigations:samples should bealways taken underthe same conditionsas the baselinesample
Sample type	Human serum and plasma	Human serum andplasma
Antibodies	2 monoclonal antibodiesagainst the amino-acidsequence of EKAHD-β-GGR	2 monoclonalantibodies against theamino-acid sequence ofEKAHD-β-GGR

11:00 PM

Substantial equivalence – similarities, continued

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Substantial equivalence differences

The following table compares the ELECSYS® ß-CrossLaps/serum Immunoassay with the predicate device.

Feature	ELECSYS® β-CrossLaps/serumImmunoassay	Predicate Device
Assay protocol	2-step sandwich assay	1-step sandwich assay
Detection protocol	Electrochemiluminescence	ELISA/Absorbance reading
Instrument	ELECSYS® 2010 and1010 ImmunoassayAnalyzers	Microtiter Plate Reader
Procedure	Automatic	Manual
Measuring range	0.010 – 6.00 ng/mL	94 – 20,000 pM
Traceability /Standardization	Internal referencestandards (purifiedpeptide): traceable byweight	No information in thepackage insert.

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Substantial equivalence performance characteristics

The Performance characteristics of the ELECSYS® ß-CrossLaps/serum Immunoassay and the predicate device are compared in the table below.

Feature	ELECSYS® β-CrossLaps Test System	Predicate Device
Within-Rum precision (%CV)	Human sera:4.6% at 0.08 ng/mL1.8% at 0.39 ng/mL1.0% at 3.59 ng/mLControls:3.4% at 0.15 ng/mL1.6% at 0.84 ng/mL2.2% at 3.18 ng/mL	Serum samples:5.4% at 1737 pM5.0% at 2694 pM5.1% at 3415 pM
Total precision (%CV)	Human sera:4.7% at 0.08 ng/mL4.3% at 0.39 ng/mL1.6% at 3.59 ng/mLControls:3.4% at 0.15 ng/mL1.9% at 0.84 ng/mL2.5% at 3.18 ng/mL	Serum samples:8.1% at 1963 pM5.4% at 2820 pM6.5% at 3503 pM
Analytical sensitivity	0.01 ng/mL	94 pM
Feature	ELECSYS® β-CrossLapsTest System	Predicate Device
Limitations	No interference from bilirubin up to 65 mg/dL No interference from hemoglobin up to 0.5 g/dL No interference from intralipid up to 1500 mg/dL No interference from biotin up to 90 ng/mL No interference from rheumatoid factor up to 1500 U/mL No high dose hook effect up to 150 ng/mL	No interference from ditaurobiliribin up to 60 mg/dL No interference from hemoglobin up to 1.0 g/dL No interference from intralipid up to 1000 mg/dL
On-board stability	ELECSYS® 2010: 8 weeksELECSYS® 1010: 4 weeks(stored alternately in the refrigerator and analyzer at ambient temperature 20-25°C; up to 20hr opened in total)	NA
Calibrationfrequency	ELECSYS® 2010:after 1 month (same lot) after 7 days (same kit) ELECSYS® 1010: with every reagent kit after 7 days (20-25°C) after 3 days (25-32°C)	Calibration with each run

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Substantial equivalence – performance characteristics, continued

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/7/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 perimeter. Inside the circle is a stylized image of an eagle or bird-like figure with three curved lines representing its body and wings.

JUL 2 4 2000

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Priscilla Hamill Regulatory Affairs, Laboratory Systems Roche Diagnostics Corporation 9115 Hague Road PO Box 50457 Indianapolis, Indiana 46250-0457

Re: K993706

Trade Name: Elecsys® Serum B-CrossLaps/serum Immunoassay Regulatory Class: I reserved Product Code: JMM Dated: June 16, 2000 Received: June 19, 2000

Dear Ms. Hamill:

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/cdrl/dsma/dsmamain.html".

Sincerely yours,

Steven Gutman

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 STATEMENT

510(k) Number (if known): NHA K99370 C

Device Name: ELECSYS® Serum β-CrossLaps/serum Immunoassay

Indications For Use: For the in vitro quantitative determination of degradation products of type I collagen in human serum and plasma, for assessing individual bone resorption. The test may be used as an aid in monitoring anti-resorptive therapies (e.g. bisphosphonates, hormone replacement therapy - HRT) in postmenopausal women and individuals diagnosed with osteopenia. The elecrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche ELECSYS 1010 and 2010 immunoassay analyzers.

Dean Cooper

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number 4993706

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

Concurrence of CDRH, Office of Device Evaluation (ODE) Prescription Use OR Over-The-Counter Use (Per 21 CFR 801.109)

(Optional Format 1 -

2-96)

Regulation Number and Section

§ 862.1400 Hydroxyproline test system.

(a)
Identification. A hydroxyproline test system is a device intended to measure the amino acid hydroxyproline in urine. Hydroxyproline measurements are used in the diagnosis and treatment of various collagen (connective tissue) diseases, bone disease such as Paget's disease, and endocrine disorders such as hyperparathyroidism and hyperthyroidism.(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.