The Serum CrossLaps™ One Step ELISA assay is intended for in vitro diagnostic use as an indication of human bone resorption and may be used as an aid in : Monitoring bone resorption changes of A. 1.) Anti-resorptive therapies in postmenopausal women: a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs b) Bisphosphonate therapies 2. ) Anti-resorptive therapies in individuals diagnosed with osteopenia; a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs b) Bisphosphonate therapies B. Predicting skeletal Response (Bone Mineral Density) in postmenopausal woman under going anti-resorptive therapies a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs b) Bisphosphonate therapies

Device Description

The Serum CrossLaps™ One Step ELISA kit was developed for the quantitative measurement of Type I Collagen C-Telopeptide (CrossLaps™) in human plasma and serum. The EIA format is a non-competitive binding protein assay. The Serum CrossLaps 114 One Step ELISA is based on two highly specific monoclonal antibodies against the amino acid sequence of EK AHD-B-GGR, where the aspartic acid residue (D) is ß-isomerized. In order to obtain a specific signal in the Serum CrossLaps 114 One Step ELISA, two chains of EK AHD-S-GGR must be cross-linked Standards, control, or unknown serum samples are pipetted into the appropriate microtitre wells coated with streptavidin, followed by application of a mixture of a biotinylated antibody and a peroxidase-conjugated antibody. Then, a complex between CrossLaps 110 antigens, biotinylated antibody and peroxidase-conjugated antibody is generated, and this complex binds to the streptavidin surface via the biotinylated antibody. Following the one-step incubation at room temperature, the wells are emptied and washed. A chromogenic substrate is added and the colour reaction is stopped with sulfuric acid. Finally, the absorbance is measured at 450 nm.

AI/ML Overview

The provided text describes the Serum CrossLaps™ One Step ELISA device and its pre-market notification (K990843) for FDA clearance. However, the document does not contain a detailed study proving the device meets specific acceptance criteria with reported device performance metrics. Instead, it focuses on demonstrating substantial equivalence to a previously cleared predicate device (CrossLaps™ ELISA, K972788).

Therefore, I cannot fully complete all sections of your request based solely on the provided text. I will fill in the information that is available and indicate where data is missing.

Acceptance Criteria and Study Proving Device Meets Acceptance Criteria

The primary study detailed in this pre-market notification is a demonstration of substantial equivalence to a legally marketed predicate device (CrossLaps™ ELISA, K972788). This type of submission relies on showing that the new device is as safe and effective as the predicate device, not necessarily by meeting pre-defined numerical acceptance criteria for novel performance.

Please note: The document explicitly states the "pre-market notification includes clinical data demonstrating that" without elaborating on the specifics of this data or presenting numerical acceptance criteria or performance metrics directly from that data. The focus is on the intent for use and equivalence.

1. Table of acceptance criteria and the reported device performance

Acceptance Criteria	Reported Device Performance (as explicitly stated in provided text)
(Not explicitly stated in terms of numerical performance metrics)	Substantially equivalent to previously cleared CrossLaps™ ELISA (K972788).
Intended Use: Quantitation of Type I Collagen C-Telopeptide (CrossLaps™) in human plasma and serum as an indication of human bone resorption.	Device developed for quantitative measurement of Type I Collagen C-Telopeptide (CrossLaps™) in human plasma and serum. Intended for in vitro diagnostic use for: - Monitoring bone resorption changes in: a) Postmenopausal women undergoing anti-resorptive therapies (HRT, Bisphosphonate). b) Individuals with osteopenia undergoing anti-resorptive therapies (HRT, Bisphosphonate). - Predicting skeletal response (Bone Mineral Density) in postmenopausal women undergoing anti-resorptive therapies (HRT, Bisphosphonate).
Performance equivalent to predicate device (K972788) for the stated indications for use.	Clinical data demonstrates substantial equivalence to predicate device K972788 (details of this data or specific performance metrics are not provided in the summary).

2. Sample size used for the test set and the data provenance

Sample size for test set: Not explicitly stated in the provided text. The document mentions "clinical data demonstrating that" without specifying the number of samples or subjects used in this clinical data.
Data provenance: Not explicitly stated in the provided text (e.g., country of origin). The data is described as "clinical data," implying human subjects, but specifics are missing. It is implied to be retrospective or prospective as part of a pre-market notification, but this is not explicitly stated.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not provided in the given text. The device measures a biochemical marker (Type I Collagen C-Telopeptide). Ground truth for such a device would typically involve comparing its measurements to established reference methods or clinical outcomes, rather than expert consensus on images.

4. Adjudication method for the test set

This information is not provided in the given text, as the context is a biochemical assay, not an imaging device requiring expert adjudication of results.

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

This question is not applicable to the described device. The Serum CrossLaps™ One Step ELISA is an in vitro diagnostic (IVD) assay for measuring a biochemical marker, not an AI-assisted diagnostic imaging device that involves human readers.

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

This question is not applicable in the AI sense. The device is a standalone diagnostic assay (an ELISA kit) that provides quantitative results without human interpretation of complex patterns, thus already "algorithm only" in its biochemical analysis. It's not an AI algorithm but a laboratory test.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth would most likely be established by comparison to existing, validated methods for measuring Type I Collagen C-telopeptides or correlation with clinical outcomes data relevant to bone resorption (e.g., Bone Mineral Density changes, fracture rates). However, the specific type of ground truth used in the substantial equivalency demonstration is not detailed in the provided text. The submission relies on "clinical data demonstrating" equivalence to a predicate device, which implies the predicate device's established performance serves as a benchmark rather than a new 'ground truth' being established from scratch.

8. The sample size for the training set

This information is not provided in the given text. For an ELISA kit, "training set" doesn't apply in the same way it would for an AI algorithm. Development and validation would involve studies to establish assay linearity, precision, accuracy, etc., potentially using various sample types and concentrations, but these are not explicitly referred to as a "training set" with a specified size.

9. How the ground truth for the training set was established

This information is not provided and is not applicable in the AI sense for this type of device. The "ground truth" for developing an ELISA method is typically based on the known concentrations of target analytes in reference materials or samples, or by comparison to established gold standard methods for the biochemical measurement.

Summary

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Image /page/0/Picture/1 description: The image shows a sequence of handwritten characters and numbers. The sequence starts with the letter 'K', followed by the numbers '990843'. The handwriting style appears casual, with some variations in stroke thickness.

Summery of Safety and Effectiveness:

Name of Device:	Serum CrossLaps™ One Step ELISA
Classification Name:	Enzyme immunoassay, Type I Collagen C-Telopeptide
Analyte Code and Name:	JMM
Submitter:	Osteometer BioTech A/SHerlev Hovedgade 207DK-2730 Herlev
Date:	March 9th, 1999

The Serum CrossLaps™ One Step ELISA kit was developed for the quantitative measurement of Type I Collagen C-Telopeptide (CrossLaps™) in human plasma and serum.

The EIA format is a non-competitive binding protein assay.

The Serum CrossLaps 114 One Step ELISA is based on two highly specific monoclonal antibodies against the amino acid sequence of EK AHD-B-GGR, where the aspartic acid residue (D) is ß-isomerized. In order to obtain a specific signal in the Serum CrossLaps 114 One Step ELISA, two chains of EK AHD-S-GGR must be cross-linked

Standards, control, or unknown serum samples are pipetted into the appropriate microtitre wells coated with streptavidin, followed by application of a mixture of a biotinylated antibody and a peroxidase-conjugated antibody. Then, a complex between CrossLaps 110 antigens, biotinylated antibody and peroxidase-conjugated antibody is generated, and this complex binds to the streptavidin surface via the biotinylated antibody. Following the one-step incubation at room temperature, the wells are emptied and washed. A chromogenic substrate is added and the colour reaction is stopped with sulfuric acid. Finally, the absorbance is measured at 450 nm.

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This pre-market notification demonstrates that the Serum CrossLaps™ One Step ELISA for the quantitative measurement of Type I Collagen C-telopeptides in plasma and serum is substantially equivalent to CrossLaps™ ELISA that was cleared by FDA in a previous submission (#K972788).

This pre-market notification includes clinical data demonstrating that

The CrossLaps™ ELISA assay is intended for in vitro diagnostic use as an indication of human bone resorption and may be used as an aid in :

Monitoring bone resorption changes of A.

1.) Anti-resorptive therapies in postmenopausal women:
a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs
b) Bisphosphonate therapies

2.) Anti-resorptive therapies in individuals diagnosed with osteopenia;

a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs
b) Bisphosphonate therapies

B. Predicting skeletal Response (Bone Mineral Density) in postmenopausal woman under going anti-resorptive therapies

a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs
b) Bisphosphonate therapies

...

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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 arrangement of text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA". Inside the circle is a stylized symbol that resembles a triple helix or a series of flowing lines, often interpreted as representing the department's mission related to health and well-being.

JUL - 9 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Eva Gamwell Henriksen Head of Regulatory Affairs and Quality Assurance OSTEOMETER BIOTECH A/S HERLEV HOVEDGADE 207 DK-2730 HERLEV, DENMARK

Re: K990843

Trade Name: Serum CrossLaps™ One Step ELISA Regulatory Class: I reserved Product Code: JMM Dated: May 25, 1999 Received: May 27, 1999

Dear Ms. Henriksen:

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 (OS) 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

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 (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/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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510(k) Number (if known):_

Serum CrossLaps™ One Step ELISA Device Name:

Indications for use:

The Serum CrossLaps™ One Step ELISA assay is intended for in vitro diagnostic use as an indication of human bone resorption and may be used as an aid in :

K990843

Monitoring bone resorption changes of A.
- 1.) Anti-resorptive therapies in postmenopausal women:
- a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs
- b) Bisphosphonate therapies
- 1. ) Anti-resorptive therapies in individuals diagnosed with osteopenia;
- a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs
- b) Bisphosphonate therapies
B.

Predicting skeletal Response (Bone Mineral Density) in postmenopausal woman under going anti-resorptive therapies

a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs
b) Bisphosphonate therapies

Sean Cooper

(Division Sign-Off) (Division of Clinical Laborator) 89908

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

(Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription use
(Per 21 CFR 801.109)

✓

Over-The-Counter Use

(Optional Format 1-2-96)

0011

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.