The Randox RX Daytona Plus Alkaline Phosphatase (ALP) test system is intended for the quantitative in vitro determination of Alkaline Phosphatase (ALP) activity in serum and lithium heparinized plasma. Measurements of alkaline phosphatase are used in the diagnosis, treatment and investigation of hepatobiliary disease and in bone disease.

Device Description

The Randox RX Daytona Plus Alkaline Phosphatase (ALP) assay consists of ready to use reagent solutions.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Randox RX Daytona Plus Alkaline Phosphatase (ALP) device, based on the provided text:

Acceptance Criteria and Device Performance

Acceptance Criteria Category	Specific Criteria	Reported Device Performance
Linearity/Reportable Range	LoQ / L1 pool: ≤ 20% deviation to target	Met (linear regression r = 1.000, claimed range 8 – 918 U/L)
	L2 to L11: < 5% deviation to target	Met (linear regression r = 1.000, claimed range 8 – 918 U/L)
	Slope: 0.90 - 1.10	Met (y = 1.00x + 6.49; slope is 1.00)
	Intercept: < established LoQ	Met (intercept 6.49 is less than LoQ of 7.5 U/L)
	r: > 0.95	Met (r = 1.000)
Analytical Specificity	Control pool within 10% of decision level target	Met (Interferents did not demonstrate significant interference up to tested concentrations)
	Control and test pools recover within 10% of each other	Met (Interferents did not demonstrate significant interference up to tested concentrations)

Study Details

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

Precision/Reproducibility: Not explicitly stated for specific test sets, but 80 determinations per sample (QC or serum) were performed for each of the two reagent lots. Human serum samples (altered and unaltered, some spiked or diluted) were used. Data provenance is not explicitly stated beyond "human serum samples."
Linearity/Reportable Range: 11 levels of samples were prepared. Each level was run in replicates of five. Provenance of these samples is not specified.
Detection Limit: Not explicitly stated for a separate "test set" size, but the LoD was based on 240 determinations using 4 low-level samples. Provenance not specified.
Analytical Specificity: Not explicitly stated for a separate "test set" size for each interferent, but the study implies testing at ALP concentrations of 80 U/I and 240 U/I. Provenance not specified.
Method Comparison with Predicate Device: 106 serum patient samples. Data provenance is not explicitly stated but implies patient samples from the UK, given the manufacturer's location. The study was retrospective, comparing the new device results against an existing predicate device using collected samples.
Matrix Comparison: 46 matched patient sample pairs (serum and lithium heparin plasma). Provenance not explicitly stated.
Expected Values/Reference Range Verification: Human serum from 30 normal donors. Provenance not explicitly stated.

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

Not Applicable. This document describes the analytical performance of an in vitro diagnostic device (a laboratory test for Alkaline Phosphatase activity). The "ground truth" for such devices is typically established through reference methods, certified standards, or consensus values from established quality control materials, rather than expert interpretation of images or patient data. The document does not mention the use of experts to establish ground truth for the analytical performance studies.
- For the precision study, control materials and altered/unaltered human serum samples were used.
- For linearity, pooled samples with known concentrations were used.
- For method comparison, the predicate device (Siemens Alkaline Phosphatase (ALPAMP) Assay, K991576) served as the reference for comparison.

4. Adjudication Method for the Test Set:

Not Applicable. As noted above, this study evaluates the analytical performance of an in vitro diagnostic device, not interpretive performance requiring adjudication.

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

Not Applicable. This is an evaluation of an in vitro diagnostic device for quantitative chemical analysis, not an AI-powered diagnostic imaging system requiring human reader studies.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-loop Performance) Was Done:

Yes, a standalone study was done. The entire submission details the performance of the Randox RX Daytona Plus Alkaline Phosphatase (ALP) system itself, comprising reagents and the RX Daytona Plus analyzer. This is the inherent nature of an in vitro diagnostic test; its performance is measured independently of human interpretation of the result, though human operators perform the test and interpret the clinical significance of the result. The performance metrics (precision, linearity, detection limits, accuracy/method comparison) are all measures of the device's standalone analytical capabilities.

7. The Type of Ground Truth Used:

Reference Methods/Comparative Devices and Spiked/Diluted Samples:
- Precision and Linearity: Values derived from known concentrations in quality control materials, spiked samples, or diluted samples where the true value is calculable.
- Method Comparison: The predicate device (Siemens Alkaline Phosphatase (ALPAMP) Assay, K991576) served as the comparative "ground truth" to establish substantial equivalence.
- Detection Limits: Determined statistically using defined protocols (CLSI guideline EP17-A2).
- Analytical Specificity: Known concentrations of interferents added to known ALP concentrations.

8. The Sample Size for the Training Set:

Not Applicable. The document describes a traditional analytical performance study for an in vitro diagnostic assay, not an AI/machine learning model that requires a training set. The device is a chemical reagent and analyzer system.

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

Not Applicable. See point 8.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 April 21, 2017

RANDOX LABORATORIES LIMITED PAULINE ARMSTRONG, QA/RA MANAGER 55 DIAMOND ROAD CRUMLIN, COUNTY ANTRIM, BT29 4QY GREAT BRITAIN

Re: K162275

Trade/Device Name: Randox RX Daytona Plus Alkaline Phosphatase (ALP) Regulation Number: 21 CFR 862.1050 Regulation Name: Alkaline phosphatase or isoenzymes test system Regulatory Class: II Product Code: CJE Dated: March 21, 2017 Received: March 23, 2017

Dear Pauline Armstrong:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Kellie B. Kelm -S

for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known) K162275

Device Name

Randox RX Daytona Plus Alkaline Phosphatase (ALP)

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
-------------------------------------------------

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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K162275

510(K) SUMMARY

RANDOX RX DAYTONA PLUS ALKALINE PHOSPHATASE (ALP)

1. SAFETY AND EFFECTIVENESS AS REQUIRED BY 21 CFR 807.92 STATEMENT

This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirement 21 CFR 807.92.

SUBMITTER NAME AND ADDRESS 2.

Name: Dr. Pauline Armstrong

Address: Randox Laboratories Limited 55 Diamond Road, Crumlin, County Antrim, BT29 4QY, United Kingdom.

Telephone: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912 E-mail: Pauline.Armstrong@randox.com

Date of Summary Preparation: 20 April 2017

3. 510k NUMBER, DEVICE PROPRIETARY NAME, COMMON NAME, PURPOSE FOR SUBMISSION, REGULATORY CLASSIFCATION, PANEL, PRODUCT CODE AND 21 CFR NUMBER

510(k) No: K162275

Device Proprietary Name: Randox RX Daytona Plus Alkaline Phosphatase (ALP)

Common Name: RX Daytona Plus Alkaline Phosphatase (ALP)

Purpose for Submission: New Device

ProductCode	Regulation Name	Classification	Regulation Section	Panel
CJE	AlkalinePhosphatase orisoenzymes testsystem.	II	21 CFR 862.1050	ClinicalChemistry(75)

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4. PREDICATE DEVICE PROPRIETARY NAMES AND 510 (k) NUMBERS

Predicate Device Proprietary Name: Siemens Alkaline Phosphatase (ALPAMP)

510(k) Number: K991576

5. INTENDED USE

6. DEVICE DESCRIPTION

The Randox RX Daytona Plus Alkaline Phosphatase (ALP) assay consists of ready to use reagent solutions.

CATALOGUE NUMBER: AP8302

R1. Buffer	4 x 20 m
R2. Substrate	4 x 7 ml

REAGENT COMPOSITION

Contents	Concentrations in the Test
R1. Buffer2-amino-2-methyl-I-propanolMg2+	0.35 mol/l, pH 10.42.0 mmol/l
R2. Substratep-nitrophenylphosphate	10 mmol/l

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7. PREDICATE DEVICE COMPARISON TABLE

Table 1 - Comparison of Randox RX Daytona Plus Alkaline Phosphatase (ALP) to Predicate Device (Siemens Alkaline Phosphatase (ALPAMP)

CHARACTERISTICS	Candidate DeviceRandox RX Daytona PlusAlkaline Phosphatase (ALP) Assay(K162275)	Predicate DeviceSiemens Alkaline Phosphatase(ALPAMP) Assay(K991576)
	Similarities
INTENDED USE	For the quantitative in vitro determination ofAlkaline Phosphatase (ALP) activity in serumand plasma. Measurements of alkalinephosphatase are used in the diagnosis,treatment and investigation of hepatobilarydisease and in bone disease.	For the quantitative in vitro determination ofAlkaline Phosphatase (ALP) activity inserum and plasma. Such measurementsare used in the diagnosis and treatment ofhepatobiliary and bone disease.
ASSAY PROTOCOL	Colorimetric Method IFCC	Same
STORAGE(UNOPENED)	Reagents are stable up to the expiry datewhen stored unopened at +2 to +8°C	Same
SAMPLE TYPE	SerumPlasma (Li Heparin)	Same
REAGENTCOMPOSITION	R1. Buffer2-amino-2-methyl-l-propanol	R1.AMP
	$0.35 \text{ mol/l, (pH 10.4)}$$\text{Mg}^{2+}$$2.0 \text{ mmol/l}$	$0.438 \text{ mol/l}$$0.09%$Sodium azide
	R2. Substratep-nitrophenylphosphate$10 \text{ mmol/l}$	R2.p-nitrophenylphosphate$60 \text{ mmol/l}$Sodium azide$0.09%$
REAGENTPREPARATION	Liquid, ready to use	Same
CONTROLFREQUENCY	Randox Assayed Multisera Levels 2 & 3Two levels of control should be assayed atleast once a day	Commercially available controls arerecommendedAnalyse at least two levels of controls daily
MEASURINGRANGE	8 – 918 U/I	0 – 1100 U/I
CHARACTERISTICS	Candidate DeviceRandox RX Daytona PlusAlkaline Phosphatase (ALP) Assay(K162275)	Predicate DeviceSiemens Alkaline Phosphatase (ALPAMP)Assay(K991576)
	Differences
CALIBRATOR	Randox Calibration Serum Level 3	Fixed System Factor Value
CALIBRATIONFREQUENCY	A 2 point calibration is recommended every7 days or with a change of reagent lot	Not Required

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Table 1: Comparison of Randox RX Daytona Plus Alkaline Phosphatase (ALP) to Predicate Device (Siemens Alkaline Phosphatase (ALPAMP)

8. TEST PRINCIPLE (1)

The substrate p-nitrophenyl phosphate is hydrolyzed by Alkaline Phosphatase from the sample, in the presence of Magnesium ions, to form p-nitrophenol which is yellow in colour and can be read at 405 nm.

The intensity of colour produced is proportional to the Alkaline Phosphatase activity in the sample.

p-nitrophenyl phosphate + H2O phosphate + p-nitrophenol

1. Bowers, G.N., and R.B. Mc Comb., Clin Chem. 1975; 21: 1988.

9. PERFORMANCE CHARACTERISTICS

Analytical performance:

a. Precision/Reproducibility:
Precision was evaluated consistent with C.L.S.I documents EP5-A2

Precision studies were performed by two operators on two RX daytona plus systems using control material altered human serum samples and unaltered human serum samples that were spiked with ALP concentrations or diluted to achieve concentrations based on established ranges of 30 to 120 U/L for adults. Testing was conducted for two reagent lots of ALP, one lot on each RX daytona plus system, twice per day for 20 non-consecutive days. Two replicates per run

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were performed for each sample. Both lots yielded similar results. The results of one representative lot are summarized in the following table:

Table 2 - Precision Summary

Lot 1

			Within-Run		Total
Sample	N	ALP Mean(IU/L)	SD	%CV	SD	%CV
QC1	80	127.83	0.5	0.4	2.87	2.2
QC2	80	328.94	1.19	0.4	6.53	2.0
QC3	80	353.25	1.26	0.4	7.61	2.2
Serum 1	80	81.44	1.56	1.9	1.89	2.3
Serum 2	80	212.76	3.35	1.6	3.44	1.6
Serum 3	80	244.36	3.63	1.5	3.77	1.5
Serum 4	80	349.39	4.41	1.3	5.31	1.5
Serum 5	80	24.86	0.80	3.2	1.31	5.3
Serum 6	80	480.71	3.65	0.8	15.26	3.2
Serum 7	80	706.24	4.87	0.7	24.48	3.5
Serum 8	80	895.00	4.49	0.5	30.79	3.4

b. Linearity/assay reportable range:

Linearity studies have been carried out in accordance with C.L.S.I. standard EP6-A. Linearity studies were performed at 11 levels to determine the analytical range of an assay - that is the range where the reported result is a linear function to the analyte concentration.

Acceptance Criteria: LoQ / L1 pool ≤ 20% deviation to target L2 to L11 < 5% deviation to target Slope 0.90 - 1.10 Intercept < established LoQ r > 0.95

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The linearity samples were prepared at 11 levels. The range was from 7.50 UVI analyte concentration up to a high concentration of approximately 922 U/I. The low and high level pools were mixed to create 9 intermediate levels. Each level was run in replicates of five on two lots of ALP reagent on one RX Daytona Plus system. The results are summarized in the following table:

Analyte	ALP (U/I)
LinearRegression	$y = 1.00x + 6.49$
r	1.000

Table 3 - Linearity Summary Serum

The claimed range of the assav is 8 - 918 U/l.

c. Calibration

The use of Saline and Randox Calibration Serum Level 3 is recommended for calibration of the Randox RX Daytona Plus Alkaline Phosphatase (ALP) assay.

d. Detection limit:

Sensitivity studies have been carried out in accordance with C.L.S.I. quideline EP17-A2 'Protocols for Determination of Limits of Detection and Limits of Quantification; Approved Guideline'. A Limit of Blank (LoB), a Limit of Detection (LoD) and a Limit of Quantification (LoQ) were performed on two lots of reagents tested by two operators on one RX Daytona Plus system.

The Limit of Detection (LoD) for ALP on the RX Daytona Plus is 1.0 U/L based on 240 determinations, with 4 low level samples.

The Limit of Blank (LoB) is 0.14 U/L.

The Limit of Quantitation (LoQ) is 7.5 U/L as determined as the lowest concentration which meets an imprecision of <10% bias.

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e. Analytical Specificity:

The following analytes were tested up to the levels indicated at ALP concentrations of 80 U/I and 240 U/I and found not to interfere with the ALP assay.

Interferent	Highest concentration of substance tested which did not demonstrate significant interference
Haemoglobin	375 mg/dl
Total Bilirubin	60 mg/dl
Conjugate Bilirubin	60 mg/dl
Triglycerides	2000 mg/dl
Intralipid	750 mg/dl
Ascorbic Acid	6 mg/dl

Table 4 - ALP Interference Summary

Acceptance Criteria:

The control pool must be within 10% of the decision level target and the control and test pools must recover within 10% of each other, for the analyte to be deemed not to interfere.

f. Method comparison with predicate device:

Correlation studies were carried out in accordance with C.L.S.I. quideline EP9-A2 'Method Comparison and Bias Estimation Using Patient Samples: Approved Guideline - Second Edition'.

106 serum patient samples spanning the range 8 to 883 U/L were tested by one operator on two lots of Randox ALP reagent on one RX daytona plus analyzer and one lot of Siemens ALPAMP reagent on one Advia 1800 system, across 3 working days with each sample tested in duplicate. The test method was compared to the predicate device and the following linear regression equation was obtained:

y = 1.005x - 3.95

Correlation coefficient of r = 0.999

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q. Matrix comparison:

Matrix method comparisons for the Randox RX Daytona Plus Alkaline Phosphatase (ALP) assay was tested by one operator on one RX Daytona Plus system and was assessed for two lots of ALP reagents. Both serum and lithium heparin plasma were tested to determine whether method accuracy with lithium heparin specimens is equivalent to serum results and that lithium heparin plasma does not interfere with either the method or the system.

Patient samples were drawn in matched pairs - one sample serum (x) and the second sample lithium heparin plasma (y). A total of 46 matched patient sample pairs were analyzed spanning the 15.3 to 773.1 U/L and the following linear regression equation was obtained:

y = 1.00x - 0.13

Correlation coefficient of r = 1.00

Expected values/Reference range:

Referenced from literature

Reference intervals for ALP was verified using NCCLS C28-A3 guidelines. In a study, human serum from 30 normal donors were tested in singlicate on the RX Daytona Plus. The results obtained were ordered from lowest to highest before being examined for outliers using the Dixon test.

Upon confirmation there were no outliers, the values were compared to the quoted ranges for ALP. Results of the study indicate that all values reported in the range for Healthy Individuals.

Table 5 - Reference Ranges

Analyte	Serum
ALP (2)	Adults: 30 – 120U/L

Mosby's Manual of Diagnostic and Laboratory Tests. 3ª Edition. Pagana and Pagana, 2006, page 49.

It is recommended that each laboratory establish its own reference range to reflect the age, sex, diet and geographical location of the population.

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10. CONCLUSION

Testing results indicate that the proposed device is substantially equivalent to the predicate device.

Regulation Number and Section

§ 862.1050 Alkaline phosphatase or isoenzymes test system.

(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.