Gentian Cystatin C Immunoassay is an in-vitro diagnostic test for quantitative determination of cystatin c in human serum and plasma. The measurement of cystatin c is used in the diagnosis and treatment of renal diseases.

Device Description

The Gentian cystatin C immunoassay is a particle enhanced turbidimetric immunoassay (PETIA). The immunoparticles are made from activated polystyrene microspheres to which avian anti-human cystatin C antibodies are covalently attached. The immunoparticles and cystatin C form aggregations that change the absorbance signal, depending on the amount of cystatin C present. Measurements obtained by this device are used for the determination of Cystatin C in human serum and plasma. The Gentian C assay is calibrated with human Cystatin C calibrators. Cystatin C controls are assayed for the verification of the accuracy and precision of the Gentian cystatin C immunoassay.

AI/ML Overview

Here's a summary of the acceptance criteria and the study details for the Gentian Cystatin C Immunoassay, based on the provided text:

Acceptance Criteria and Device Performance

The core of the study is a comparison to a predicate device, the Dade Behring, Inc., N Latex Cystatin C Test Kit (K003503), rather than explicit numerical acceptance criteria for accuracy or precision. The primary acceptance criteria appear to be substantial equivalence, demonstrated by:

Acceptable correlation statistics (Slope, Intercept, R-value) when compared to the predicate device across different instruments.
Demonstration of comparable performance characteristics such as measuring range, linearity, precision, and interference.

Acceptance Criteria (Implied for Substantial Equivalence)	Reported Device Performance (Gentian Cystatin C Immunoassay vs. Predicate)
Method Comparison Regression Analysis:
Slope close to 1.0	Study 1:
	Modular P vs. BNII: 1.075
	Modular P vs. BN ProSpec: 1.048
	Study 2:
	Modular P vs. BN ProSpec: 1.021
	Architect vs. BN ProSpec: 0.975
Intercept close to 0.0	Study 1:
	Modular P vs. BNII: 0.009
	Modular P vs. BN ProSpec: 0.059
	Study 2:
	Modular P vs. BN ProSpec: -0.025
	Architect vs. BN ProSpec: -0.059
R-value close to 1.0	Study 1:
	Modular P vs. BNII: 0.986
	Modular P vs. BN ProSpec: 0.992
	Study 2:
	Modular P vs. BN ProSpec: 1.00
	Architect vs. BN ProSpec: 0.989
Measuring Range:	0.3 - 8.0 mg/L
Linearity:	0.34 - 8.4 mg/L (Modular P), 0.27 - 8.8 mg/L (Architect)
Total Imprecision CV:	4.2% (over 20 days with two lots)
Interference:	No significant interference from drugs, anticoagulants, hemoglobin (8 g/L), intralipid (11 g/L), triglycerides (14 g/L), bilirubin (420 mg/L). No RF interference.
Recovery:	99-110%
Antigen Hook Effect:	Not significant below 16 mg/L (patient samples not expected to exceed 9 mg/L)
Sample Stability:	Up to one month at 2-8°C
Reagent Stability:	At least 18 months (reagents at 2-8°C), minimum 4 weeks (reagents in use)
Limit of Detection (LoD) & Limit of Quantitation (LoQ):	Within acceptance criteria and below lowest calibrator concentration.

Study Information

Sample Size used for the test set and the data provenance:
- Study 1: 172 (Modular P vs. BNII), 174 (Modular P vs. BN ProSpec)
- Study 2: 76 (Modular P vs. BN ProSpec), 87 (Architect vs. BN ProSpec)
- Total N for method comparison: 172 + 174 + 76 + 87 = 509 samples.
- Data Provenance: Not explicitly stated, but clinical studies are generally implied to be from human blood samples. No country of origin is mentioned, nor whether samples were retrospective or prospective.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable. This is an in-vitro diagnostic (IVD) device study comparing the performance of a new assay to a legally marketed predicate assay using patient samples. The "ground truth" here is the measurement from the established predicate device, not clinical expert consensus.
Adjudication method for the test set:
- Not applicable for this type of IVD comparison study. The study involves quantitative measurements, not subjective evaluations requiring adjudication.
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 IVD device for laboratory determination of a biomarker, not an imaging or diagnostic aid for human readers/clinicians, nor does it involve AI.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this is effectively a standalone performance evaluation of the immunoassay system. It measures the device's ability to accurately quantify Cystatin C in samples.
The type of ground truth used:
- The "ground truth" for the comparative studies was the results obtained from the predicate device, the Dade Behring, Inc., N Latex Cystatin C Test Kit (K003503). This is a common method for demonstrating substantial equivalence for new IVD assays. Other performance characteristics (linearity, precision, interference) are established against internal analytical standards.
The sample size for the training set:
- The document does not explicitly mention a "training set" in the context of machine learning or algorithm development. For a turbidimetric immunoassay, the "training" equivalent would be the development and optimization of the assay reagents and conditions, as well as the calibration process with a set of known standards. The sample size for these development and calibration steps is not specified.
How the ground truth for the training set was established:
- As above, the concept of a training set with "ground truth" established by experts doesn't directly apply here. The assay is calibrated using human Cystatin C calibrators. These calibrators would have known concentrations of Cystatin C, established through highly accurate reference methods (e.g., gravimetric preparation, reference laboratories, or certified reference materials).

Summary

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NOV -- 6 2007

K071388

510(k) Summary 5.

Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination

Device description

Substantial Eguivalence

The Gentian Cystatin C immunoassay is substantially equivalent to the Dade Behring, Inc., N Latex Cystatin C Test Kit (K003503) with respect to indications for use, device design and material. The basic difference between the new device and the Dade Behring predicate device is in assay technology and the instruments used for testing. The Gentian assay is a particle enhanced turbidimetric immunoassay (PETIA), while the Dade Behring assay is a particle enhanced immunonephlometric assay (PENIA). The Gentian device can be used on all commercially available automated clinical chemistry analyzers using a light absorption detection system, while the Dade Behring test is applicable only on the Dade Behring, Inc. Nephlometer Systems. In the Gentian device avian antibodies are used and it is known by one skilled in the art that there is no interaction between Rheumatoid Factor (RF) and avian antibodies. The Dade Behring predicate device use antibodies with the inherent possibility for a false reactions with Rheumatoid Factor (RF).

Comparison to predicate device

The substantial equivalence, safety and efficacy of the Gentian cystatin C immunoassay to Dade Behring N Latex Cystatin C assay (K003503) was evaluated in two studies and on two different automated clinical chemistry analyzers. In total 4 study sites were involved. The issues addressed in these studies were the comparison between Gentian cystatin C immunoassay and the predicate device Dade Behring N Latex Cystatin C assay (K003503) (Table1). In addition external validation performance of the new device was evaluated at two study sites (Table 2).

	Instrumentapplication	Slope(95% CI)	Intercept(95% CI)	R	Cystatin Crange (mg/L)	N
Study 1	Modular P vs.BNII	1.075	0.009	0.986	0.53 - 9.47	172
	Modular P vs. BNProSpec	1.048	0.059	0.992	0.53 - 9.47	174
Study 2	Modular P vs. BNProSpec	1.021	-0.025	1.00	0.61 - 6.44	76
	Architect vs. BNProSpec	0.975	-0.059	0.989	0.51 - 7.95	87

Table 1. Summary of method comparison regression analysis

Table 2. External validation performance data

Sample	Mean cystatin C (mg/L)	Within run CV (%)	Between day CV (%)	Between site CV (%)	Between lot CV (%)	Total precision CV (%)	Recovery (%)
--------	------------------------	-------------------	--------------------	---------------------	--------------------	------------------------	--------------

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Performance characteristics

The measuring range is 0.3-8.0 mg/L. The reference range is 0.52-0.98 mg/L. Total analysis time is 10 minutes. Linearity is demonstrated over the whole assay range, the Gentian Cystatin C immunoassay is linear in the range 0.34 - 8.4 mg/L on Modular P and in the range 0.27 - 8.8 mg/L on Architect. Total imprecision CV, measured over 20 days with two lots, is 4,2%. Interference studies with drugs and anticoagulants show no significant interference, also there is no significant interference from hemoglobin (8 g/L), intralipid (11 q/L), triclycerides (14 g/L) and bilirubin (420 mg/L). Due to the use of avian antibodies, no interference with rheumatoid factor is detected. No carry-over is detected. The limit of detection (LoD) and limit of quantification (LoQ) (within CV 6%) are both within given acceptance criteria and below the lowest calibrator concentration. Sample stability is up to one month at 2-8°C. Stability of the reagents at 2-8°C is calculated to be at least 18. months. Stability of the reagents in use is minimum 4 weeks. Recovery is 99-110 %. Antigen hook effect was observed in samples with spiked cystatin C concentrations above 16 mg/L, this will have no significant impact on patient serum and plasma samples, since sample concentrations above 9 mq/l never have been reported. Serum and plasma evaluations give identical cystatin C results. Between instrument comparison regression analysis shows excellent agreement between Gentian Cystatin C when measured on Architect ci8200 and Modular P instruments.

Conclusion

When considering the comparison studies between Gentian C immunoassay and the Dade Behring, Inc., N Latex Cystatin C Test Kit (K003503) and the additional documentation supporting the Gentian cystatin C immunoassay, it can be concluded that the Gentian cystatin C immunoassay when measured on Architect ci8200 and Modular P analyzers is as safe and effective as, and substantially equivalent to the Dade Behring, Inc., N Latex Cystatin C assay.

Submitted by.

Emile Hammondi Oct. 5, 2007

Ronald G. Leonardi, Ph.D. President R & R REGISTRATIONS P.O. Box 262069, San Diego, CA 92196

Date

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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 features a stylized eagle with three overlapping wing shapes, symbolizing health, services, and people. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES . USA" is arranged in a circular pattern around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Gentian AS c/o Dr. Ronald Leonardi President of R & R Registrations 9915 Cam. Chirimolla San Diego, CA 92131

NOV - 6 2007

Re: K071388 Trade/Device Name: Gentian Cystatin C Immunoassay Regulation Number: 21 CFR 8862.1225 Regulation Name: Creatinine test system Regulatory Class: Class II Product Code: NDY Dated: October 05, 2007 Received: October 09, 2007

Dear Dr. Leonardi:

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 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 (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.

Jean 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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Indication for Use

510(k) Number (if known): K071388

Device Name: Gentian Cystatin C immunoassay

Indication For Use:

Prescription Use _ X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Carol C. Benson
Division Sign Off

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k)

Regulation Number and Section

§ 862.1225 Creatinine test system.

(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.