Mission Creatinine Reagent Kit is for the quantitative determination of creatinine in serum, plasma, or urine on the Beckman Synchron CX® & CX® Delta Systems. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in renal dialysis, and as a calculation basis for measuring other urine analytes.

Device Description

Creatinine is determined by mixing a sample with the alkaline picric reagent, Creatinine from the sample combines with the reagent to produce a red-colored complex. Absorbance readings are taken at both 520 nm and 560 nm at 25.6 seconds after sample addition. The differential absorbance is a direct measure of the concentration of Creatinine in the sample.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information based on the provided text, structured to address your specific questions:

Acceptance Criteria and Device Performance

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the comparison to the predicate device and the specified guidelines (NCCLS EP5-A and EP9-A2). The "acceptance" is demonstrated by the Mission Creatinine Reagent exhibiting "similar" performance characteristics to the Beckman Creatinine Reagent.

Performance Metric	Acceptance Criteria (Implied/Compared)	Reported Device Performance (Mission Reagent)
Precision	Meeting NCCLS Guideline EP5-A standards (typical ranges for clinical assays) and showing comparable precision to the predicate device.	Serum Control 1 (1.6 mg/dL): Swr (within run sd) = 0.07 mg/dL (4.4% CV) ST (Total sd) = 0.14 mg/dL (8.4% CV) Serum Control 2 (6.9 mg/dL): Swr (within run sd) = 0.10 mg/dL (1.5% CV) ST (Total sd) = 0.62 mg/dL (8.9% CV) Urine Control 1 (89 mg/dL): Swr (within run sd) = 0.7 mg/dL (0.8% CV) ST (Total sd) = 10.9 mg/dL (12.3% CV) Urine Control 2 (217 mg/dL): Swr (within run sd) = 2.2 mg/dL (1.0% CV) ST (Total sd) = 9.5 mg/dL (4.4% CV)
Method Comparison (Serum)	Good correlation with the predicate device (Beckman Reagent) as per NCCLS Guideline EP9-A2, with a strong linear relationship (r² close to 1) and small systematic/proportional bias.	Mission = 1.000 x Beckman + 0.003 Range = 0.2 to 11.8 mg/dL r² = 0.998 df = 70 n = 71 S(yx) = 0.13 mg/dL
Method Comparison (Urine)	Good correlation with the predicate device (Beckman Reagent) as per NCCLS Guideline EP9-A2, with a strong linear relationship (r² close to 1) and small systematic/proportional bias.	Mission = 0.988 x Beckman + 0.634 Range = 10 to 400 mg/dL r² = 0.999 df = 44 n = 45 S(yx) = 3.17 mg/dL
Recovery to Expected Values (Serum)	Similar recovery to the predicate device, ideally within a clinically acceptable range (e.g., 90-110%).	Range of average % Recovery: 85.7 - 105.3 Overall Mean Recovery: 98.5 Comparable to Beckman's 93.4 - 114.3 range and 104.2 mean
Recovery to Expected Values (Urine)	Similar recovery to the predicate device, ideally within a clinically acceptable range.	Range of average % Recovery: 87 - 102.1 Overall Mean Recovery: 96 Comparable to Beckman's 83 - 102.9 range and 96.2 mean
Functional Sensitivity	Lowest level where %CV is less than 20% should be adequate for clinical use and comparable to the predicate.	Lowest level with %CV < 20% observed at expected 0.9 mg/dL Creatinine (which measured 0.57 mg/dL with Mission, 0.79 mg/dL with Beckman). At 0.57 mg/dL, Mission's %CV was 12.9%. (Beckman at 0.79 mg/dL had 7.0 %CV). This suggests the functional sensitivity for Mission is around 0.6 mg/dL, which is comparable to the predicate's 0.8 mg/dL, for the criterion of %CV < 20%.

Study Details

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

Precision:
- Sample Size: 80 for each control (Serum Control 1, Serum Control 2, Urine Control 1, Urine Control 2). Total of 320 observations.
- Data Provenance: Not explicitly stated, but clinical laboratory controls are typically pooled human or synthetic samples. The study was conducted following NCCLS Guideline EP5-A. Likely prospective, as samples were run over 20 days.
Method Comparison:
- Serum: n = 71 samples (serum samples were spiked or diluted).
- Urine: n = 45 samples (urine controls were spiked or diluted).
- Data Provenance: Not explicitly stated, but the comparison involves running samples with both the Mission and Beckman reagents simultaneously. Likely prospective, generated for this study.
Recovery to Expected Values:
- Serum: Varying dilutions from a high of 9.04 mg/dL to a low of 0.20 mg/dL. The number of samples/dilutions isn't a single 'n' but represents a range of tested concentrations.
- Urine: Varying dilutions from 400 mg/dL to 10 mg/dL.
- Data Provenance: Not explicitly stated, but involved spiking and diluting pooled serum and urine controls. Likely prospective, generated for this study.
Functional Sensitivity:
- Sample Size: Each dilution was tested as 4 samples per run over 5 calibrated runs. For the 0.90 mg/dL expected value, N=20; for 0.30 mg/dL, N=20; for 0.18 mg/dL, N=20; for 0.04 mg/dL, N=5 (Mission) and N=2 (Beckman); for 0.00 mg/dL, N=9 (Mission) and N=11 (Beckman).
- Data Provenance: Dilutions of serum samples and a zero. Likely prospective, generated for this study.

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

This information is not applicable as the device is an in-vitro diagnostic (IVD) reagent for quantitative chemical analysis. Ground truth is established by the known concentration of controls/spiked samples or by comparison to a legally marketed predicate device, not by expert interpretation.

4. Adjudication method for the test set

This information is not applicable for this type of IVD device. Adjudication is relevant for scenarios involving human interpretation, often clinical or imaging diagnosis, where discrepancies between readers or between reader and ground truth need to be resolved. For quantitative chemical measurements, the output is a numerical value which is then compared against known values or a predicate.

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 information is not applicable. This is an IVD reagent, not an AI-assisted diagnostic tool that involves human readers.

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

This is an IVD reagent, so the "device" (reagent) operates standalone in conjunction with the analytical instrument (Beckman Synchron CX & CX Delta Systems). The performance data presented (precision, correlation, recovery, functional sensitivity) inherently represents the standalone performance of the reagent on the specified instrument.

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

The ground truth for this device's performance evaluation was established using:

Known concentrations: For control materials (serum/urine controls) used in precision studies.
Expected values: For spiked or diluted samples in method comparison and recovery studies. Creatinine was added gravimetrically for some recovery samples.
Predicate Device: The Beckman Creatinine Reagent served as the reference standard against which the Mission Reagent's performance was compared for correlation, recovery, and functional sensitivity. The premise is that the predicate device is already recognized as providing accurate measurements.

8. The sample size for the training set

This information is not applicable. This is a chemical reagent, not a machine learning model, so there is no "training set" in the computational sense. The "development" of the reagent would involve chemical formulation and optimization, not data-driven machine learning training.

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

This information is not applicable for the same reasons as point 8.

Summary

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K033058

JAN § 0 2004

510(k) Summary for Mission Diagnostic Creatinine Reagents on Beckman Synchron CX® & CX® Delta Systems

1. Submitter's Name & Address	Mission Diagnostics331 Fiske StHolliston MA 01746FAX: 508-429-0452
	Contact Person:
	Linda StundtnerQA/RA Manager508-429-0450




Establishment Registration Number:	3003656721
Date of Preparation:	Jan 19, 2009
2. Identification of the Device:
Proprietary/Trade name:	Creatinine Reagent Kit for Beckman Synchron CX®& CX® Delta Systems
Common or usual name	Creatinine Reagent, Alkaline Picric Reagent
Classification name:	Creatinine test system
Device Classification	II
Regulation Number:	21 CFR § 862.1225

Chemistry (75)

Mission manufactures reagents intended to serve as direct replacements to like named products . manufactured by Original Equipment Manufactures (OEM)

Predicate Device: 3.

Panel:

Product Code:

Mission claims substantial equivalence to the OEM Reagents listed below: .
CGX

Substantial Equivalence Table of Product PN's & Trade Names

Mission Product		OEM Equivalent
BK-443340D	Creatinine Reagent -	443340	Creatinine Reagent -
BK-443340AD	Alkaline Buffer	443340	Alkaline Buffer
BK-443340BD	Picric Acid	443340	Picric Acid

4. Device Description:

Creatinine is determined by mixing a sample with the alkaline picric reagent, Creatinine from . the sample combines with the reagent to produce a red-colored complex. Absorbance readings are taken at both 520 nm and 560 nm at 25.6 seconds after sample addition. The differential absorbance is a direct measure of the concentration of Creatinine in the sample.
Intended Use: .
Mission Creatinine Reagent is for the quantitative determination of Creatinine in serum, . plasma or urine on the Beckman Synchron CX® & CX® Delta.
- Creatinine measurements are used in the diagnosis and treatment of renal diseases, in . renal dialysis, and as a calculation basis for measuring other urine analytes.

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The reagents are intended for use in place of predicate devices. .
The original equipment manufacturer (OEM) of the instruments and the predicate reagents, . which are necessary for the continued operation and use of the instruments.
Mission uses a similar composition, description and packaging as that used by the OEM in its . products, as shown in the packaging section of this submission.

5. Performance Characteristics:

Precision and correlation data are collected per:

SOP23-01-02 Performance Study Protocol for 510(k) Submission .

Precison and Correlation are summarized below:

Precision data was collected following the guidelines of NCCLS Guideline EP5-A

Samples were run for 20 days, 2 runs per day, 2 observations per run on an instrument . operated according to the manufacturers instructions. The following data was obtained:

	N	Test Meanmg/dL	Swrwithin run sd	% CV	STTotal sd	%CV
Serum Control 1	80	1.6	0.07	4.4	0.14	8.4
Serum Control 2	80	6.9	0.10	1.5	0.62	8.9
Urine Control 1	80	89	0.7	0.8	10.9	12.3
Urine Control 2	80	217	2.2	1.0	9.5	4.4

Method Comparison of Mission Creatinine Reagent to Beckman Reagent following the guidelines of NCCLS Guideline EP9-A2 was conducted.

Serum samples were spiked or diluted and run in triplicate and tested with each reagent, Mission Creatinine Reagent and Beckman Creatinine Reagent in separate calibrated runs. Recoveries of individual observations were compared by least squares regression. The following statistics were obtained:

Mission = 1.000 x Beckman + 0.003 Range = 0.2 to 11.8 mg/dL; r2 = 0.998; df = 70; n = 71; S(yx) = 0.13 mg/dL

Urine controls were spiked or diluted and run in triplicate and tested with each reagent, Mission Creatinine Reagent and Beckman Creatinine Reagent in separate calibrated runs. Recoveries of individual observations were compared by least squares regression. The following statistics were obtained:

Mission = 0.988 x Beckman + 0.634 Range = 10 to 400 mg/dL; r2 = 0.999; df = 44; n = 45; S(yx) = 3.17 mg/dL

Recovery to Expected Values was evaluated for each matrix; serum & urine. Dilutions of the respective matrices were made and measured with Mission and Beckman reagent.

Pooled Serum was spiked to an expected value of 10 mg/dL by adding Creatinine gravimetrically. . Dilutions were made using the spiked serum, serum, and/or Human serum albumin (HmSA).
Urine recovery samples were made by mixing Urine Control 2 (expected value = 400 mg/dL), Urine . Control 1 (expected value = 90 mg/dL), and/or Normal saline.

% Recovery = (Measured/expected) x100 was calculated for both Mission and Beckman. Mission and Beckman exhibited similar recoveries across the range of values in all matrices. See table below:

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Matrix	Range of Conc.Expected, mg/dL	Reagent	Range of average %Recovery	Overall MeanRecovery
Serum	9.04 - 0.20 mg/dL	Mission	85.7 - 105.3	98.5
Serum	9.04 - 0.20 mg/dL	Beckman	93.4 - 114.3	104.2
Urine	400 - 10 mg/dL	Mission	87 - 102.1	96
Urine	400 - 10 mg/dL	Beckman	83 - 102.9	96.2

Functional sensitivity was evaluated on dilutions of serum samples made from a starting serum of an approximately concentration of 0.9 mg/dL; and dilutions of 1:3, 1:5.1:11 and a zero. Dilutions were tested as 4 samples per run over 5 calibrated runs.

The lowest level where the % CV was less than 20% was with the dilution at an expected . value of 0.9 mg/dL Creatinine which measured/recovered as:
- 0.6 mg/dL with Mission reagent .
- . 0 8 mg/dL with Beckman reagent.

The CX Delta reports Creatinine values to 0.1 mg/dL.

Dilution	Expected value mg/dL	Mission Reagent				Beckman Reagent
		Mean	sd	N	%CV	Mean	sd	N	%CV
1	0.90	0.57	0.07	20	12.9	0.79	0.06	20	7.0
2	0.30	0.18	0.04	20	25.4	0.22	0.06	20	28.0
3	0.18	0.08	0.04	20	51.3	0.11	0.03	20	28.0
4	0.04	0.04	0.05	5	136.9	0.00	0.00	2	NA
5	0.00	0.11	0.11	9	94.9	0.09	0.09	11	103.8

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Image /page/3/Picture/1 description: The image shows a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES" written around the edge. Inside the circle is a symbol consisting of three stylized, curved lines that resemble a person or a flame. The seal appears to be a logo or emblem, possibly representing a government agency or organization related to health and human services.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 5 0 2004

Ms. Linda M. Stundtner QA/RA Manager Diamond Diagnostics Mission Diagnostics Division 331 Fiske St. Holliston. MA 01746

K033058 Re:

Trade/Device Name: Mission Diagnostic Creatinine Reagent for Beckman Synchron CX

& Delta Analyzers Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: Class II Product Code: CGX Dated: December 22, 2003 Received: December 24, 2003

Dear Ms. Stundtner:

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 for association to May 28, 1976, the enactment date of the Medical Device Amendments, or to conimer 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 of any I ecolul statutes and regisments, 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 (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,

Jean M. Cooper, US, DVM.

Yean 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): ____________________________________________________________________________________________________________________________________________________

Device Name: Mission Diagnostic Creatinine Reagent for Beckman Synchron CX & Delta Analyzers

Indications For Use:

Mission Creatinine Reagent Kit is for the quantitative determination of creatinine in serum, . Mission Creathine Reagent Kit is for the qualificano assimilar
plasma, or urine on the Beckman Synchron CX® & CX® Delta Systems.
Creatinine measurements are used in the diagnosis and treatment of renal diseases, in . Creatinine measuremonts are acculation basis for measuring other urine analytes.

Prescription Use (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)

Carol C Benam for Jean Cooper, DVM
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K033058

Page 1 of 1

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.