The Optilite C-Reactive Protein Reagent is intended for the quantitative in vitro determination of C-reactive protein (CRP) concentration in serum using the Binding Site Optilite analyser. Measurement of C-Reactive Protein aids in evaluation of the amount of injurv to body tissues and for evaluation of infection, tissue injurv, and inflammatory disorders. This test should be used in conjunction with other laboratory and clinical findings.

The Optilite C-Reactive Protein Calibrator is intended for the calibration of the Optilite C-Reactive Protein Reagent on the Optilite analyser.

The Optilite C-Reactive Protein Controls are intended for use in quality control by monitoring accuracy and precision for the Optilite C-Reactive Protein Reagent.

Device Description

The Optilite C-Reactive Protein Reagent is comprised of a dual wedge containing the following:

Antiserum: Supplied in stabilised liquid form. Preservatives: 0.099% sodium azide, TRIS pH 8.0.

Reaction Buffer: Containing 0.099% sodium azide, TRIS pH 7.5 as preservatives.

The Optilite C-Reactive Protein Calibrator is comprised of the following: Pooled human serum, supplied in stabilised liquid form. Containing 0.099% sodium azide, as preservative.

The Optilite C-Reactive Protein Controls are comprised of the following: Pooled human serum, supplied in stabilised liquid form. Containing 0.099% sodium azide, as preservative.

AI/ML Overview

The Binding Site Optilite C-Reactive Protein Reagent, Calibrator, and Controls have several performance characteristics, and the report details the studies conducted to verify these characteristics against pre-defined acceptance criteria.

1. Table of Acceptance Criteria and Reported Device Performance:

Performance Characteristic	Acceptance Criteria	Reported Device Performance
Precision/Reproducibility	Total precision (%CV < 10%), Within-run precision (%CV < 5%), Between-run precision (%CV < 8%), Between-day precision (%CV < 8%)	Sample 1 (6.8 mg/L): Total %CV 6.2, Within-run %CV 2.7, Between-run %CV 1.4, Between-day %CV 5.4, Between-batch %CV 0.6, Between-instrument %CV 3.0 Sample 2 (9.5 mg/L): Total %CV 4.3, Within-run %CV 1.2, Between-run %CV 1.3, Between-day %CV 3.9, Between-batch %CV 1.9, Between-instrument %CV 0.7 Sample 3 (21.5 mg/L): Total %CV 2.6, Within-run %CV 1.0, Between-run %CV 0.8, Between-day %CV 2.2, Between-batch %CV 2.6, Between-instrument %CV 0.8 Sample 4 (65.4 mg/L): Total %CV 3.1, Within-run %CV 0.7, Between-run %CV 0.8, Between-day %CV 2.9, Between-batch %CV 2.9, Between-instrument %CV 2.5 All reported values meet the acceptance criteria.
Linearity/Assay Reportable Range	%CV for each sample ≤ 8%, Allowable nonlinearity: 0.5mg/L up to 5mg/L, and ± 10% above 5mg/L (Visual inspection confirms all results within acceptable %CV for the provided data).	The reported %CV values for 14 samples ranging from 2.70 mg/L to 316.03 mg/L are all below 8% (ranging from 0.1% to 3.7%). The study states "Results met the Acceptance criteria for CV<8%."
Detection Limit (Limit of Quantitation - LoQ)	Not explicitly stated as an "acceptance criteria" but 5.0 mg/L is presented as the determined LoQ.	LoB = 1.35 mg/L, LoD = 2.66 mg/L, LoQ = 5.0 mg/L.
Analytical Specificity (Interference)	Mean results from spiked samples must be within 10% of the mean of the control samples.	The assay was not affected by: - Haemoglobin (5g/L) - Bilirubin (200mg/L) - Triglyceride (500mg/dL) - Intralipid (250mg/dL) - Rheumatoid Factor (2417IU/mL) - 14 therapeutic drugs at specified concentrations. All reported findings indicate the acceptance criteria for non-interference were met.
Method Comparison with Predicate Device (Clinical Concordance)	Not explicitly stated as a numerical acceptance criterion, but the intention is to demonstrate strong agreement.	98.4% of samples tested gave clinically concordant results on both analysers (Optilite and predicate). Regression statistics (Weighted Linear, Passing-Bablok, Weighted Deming) also show good correlation.

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

Precision/Reproducibility: 4 sera samples. The provenance is not specified (e.g., country of origin or retrospective/prospective).
Linearity/Assay Reportable Range: A series of 14 samples. The provenance is not specified.
Detection Limit: LoB and LoD were based on 4 serum samples, while LoQ was determined from 4 serum samples. The provenance is not specified.
Analytical Specificity (Interference): Serum samples with CRP concentrations at approximately 9mg/L, 60mg/L, and 150mg/L. The provenance is not specified.
Method Comparison: 193 serum samples, including 83 normal donors and 110 clinical samples. The provenance is not specified.
Expected values/Reference range verification: 50 adult donor samples. The provenance is not specified.

All studies appear to be prospective in nature, as they involve testing the device under controlled conditions to determine its performance characteristics.

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

Not applicable. This device is an in vitro diagnostic (IVD) assay for measuring C-Reactive Protein concentration. Ground truth is established by the analytical method itself (e.g., precise dilution, reference methods, or spiking with known quantities) rather than expert interpretation of images or clinical data. Therefore, experts in human diagnosis are not directly involved in establishing the ground truth for these analytical performance studies. The studies followed established CLSI guidelines for laboratory assay validation.

4. Adjudication method for the test set:

Not applicable. As described above, the studies focus on analytical performance where ground truth is intrinsically known or established through controlled experimental design and reference methods, not through 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:

Not applicable. This is an IVD device for quantitative measurement of a biomarker (CRP). It does not involve human readers interpreting images or clinical cases, nor does it incorporate AI assistance.

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

Yes, the studies described are standalone performance evaluations of the analytical device (Optilite CRP Reagent, Calibrator, Controls) on the Optilite analyser. The performance metrics (precision, linearity, detection limit, specificity) are inherently algorithm-only or instrument-only performance measures, as the human involvement is in operating the instrument and interpreting the numerical output, not in making a diagnostic interpretation that the instrument assists.

7. The type of ground truth used:

Precision/Reproducibility: The "ground truth" for precision studies are the known concentrations of the sera samples, which are then measured repeatedly to assess variability.
Linearity/Assay Reportable Range: The "ground truth" is the known concentration gradient created by mixing high and low concentration pools, or by spiking with pure protein, allowing for comparison with the measured values.
Detection Limit: The "ground truth" is based on statistical calculations from repeated measurements of blank and low-concentration samples.
Analytical Specificity: The "ground truth" involves comparing results from samples with known interfering substances added to those without, to assess if the interfering substances impact expected CRP values.
Method Comparison: The "ground truth" is the result obtained from the legally marketed predicate device (Roche Diagnostics Tina-Quant C-Reactive Protein Gen. 3) when assaying the same samples.
Traceability: The assay calibration is traceable to the international reference standard ERM-DA474, which serves as the "ground truth" for CRP concentration.

8. The sample size for the training set:

Not applicable. This is not a machine learning or AI-driven device that requires a distinct training set. The calibration curve is established using known calibrator materials according to standard IVD practices, not a machine learning training process.

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

Not applicable, as there is no machine learning training set. For the instrument's calibration, the Optilite C-Reactive Protein Calibrator is used. This calibrator consists of pooled human serum, and its concentrations are traceable to the international reference standard ERM-DA474. This traceability ensures that the instrument's measurements relate to a globally recognized standard for CRP.

Summary

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Optilite C-Reactive Protein Reagent, Calibrator and Controls 510(k) Summary

A. 510(k) Number:

K172868

B. Purpose for Submission:

New device

C. Measurand:

C-Reactive Protein

D. Type of Test:

Quantitative immunoturbidimetry

E. Applicant:

The Binding Site

F. Proprietary and Established Names:

Optilite® C-Reactive Protein Reagent, Optilite®C-Reactive Protein Calibrator, Optilite® C-Reactive Protein Controls.

G. Regulatory Information:

1. Requlation section:
  21 CFR 866.5270, C-reactive protein immunological test system.
1. Classification:
  Class II
1. Product code:
  DCN, System, Test, C-Reactive Protein
1. Panel:
  Immunology (82)

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H. Intended use:

1. Intended use(s):
  The Optilite C-Reactive Protein Reagent is intended for the quantitative in vitro determination of C-reactive protein (CRP) concentration in serum using the Binding Site Optilite analyser. Measurement of C-Reactive Protein aids in evaluation of the amount of injurv to body tissues and for evaluation of infection, tissue injurv, and inflammatory disorders. This test should be used in conjunction with other laboratory and clinical findings.

The Optilite C-Reactive Protein Calibrator is intended for the calibration of the Optilite C-Reactive Protein Reagent on the Optilite analyser.

The Optilite C-Reactive Protein Controls are intended for use in quality control by monitoring accuracy and precision for the Optilite C-Reactive Protein Reagent.

2. Indication(s) for use:

Same as Intended use(s).

1. Special conditions for use statement(s):
  Prescription use only
1. Special instrument requirements:
  The Binding Site Optilite analyser

I. Device Description:

The Optilite C-Reactive Protein Reagent is comprised of a dual wedge containing the following:

Antiserum: Supplied in stabilised liquid form. Preservatives: 0.099% sodium azide, TRIS pH 8.0.

Reaction Buffer: Containing 0.099% sodium azide, TRIS pH 7.5 as preservatives.

The Optilite C-Reactive Protein Calibrator is comprised of the following: Pooled human serum, supplied in stabilised liquid form. Containing 0.099% sodium azide, as preservative.

The Optilite C-Reactive Protein Controls are comprised of the following: Pooled human serum, supplied in stabilised liquid form. Containing 0.099% sodium azide, as preservative.

J. Substantial equivalence information:

1. Predicate device name(s) and 510(k) number(s):
  Roche Diagnostics Tina-Quant C-Reactive Protein Gen. 3 (K083444)

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2. Comparison with predicate:

Similarities

ltem	Device	Predicate
Intended use	Quantitative in vitro determination ofC-reactive protein (CRP).	Same.
Method	Turbidimetry	Same.
Reference Interval	<5mg/L	Same.
Sample type	Serum	Serum (also Li-heparin and EDTAplasma)

Differences

Item	Device	Predicate
Measuring Range	5-285mg/L (neat)25-1425mg/L (1/5 dilution)	0.3-350mg/L (neat)0.6-700mg/L (1/2 dilution)
Analyser	Optilite	Hitachi 912, 917, Modular P
Antibody	anti- human CRP (goat)	anti-human CRP (mouse)
Open vial stability	Three months at 2 to 8°C	Not stated.
On board stability	30 days.	84 days opened and refrigeratedon the analyser.
Reagent	Antiserum	Latex particles coated with anti-CRP(mouse)
Calibration	6 point, single calibrator diluted onanalyser	5 point, single calibrator diluted onanalyser
Wavelength	340nm	570nm/800nm
Traceability	DA474	CRM470

K. Standards and Guidance documents referenced:

Guidance for Industry - Review Criteria for Assessment of C - Reactive Protein (CRP), High Sensitivity C-Reactive Protein (hsCRP) and Cardiac C-Reactive Protein (cCRP) Assays Guidance for Industry and FDA Staff

CLSI EP17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition

CLSI EP7-A2 Interference Testing in Clinical Chemistry, Approved Guideline - Second Edition

CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach

CLSI EP5-A3 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Third Edition

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L. Test Principle:

The determination of soluble antigen (CRP) concentration by turbidimetric methods involves the reaction with specific antiserum (anti-CRP) to form insoluble complexes. When light is passed through the suspension formed a portion of the light is transmitted and focused onto a photodiode by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

Precision/Reproducibility: a.

The studies were based on CLSI EP5-A3, where 4 sera samples (targeted to 6.8mg/L, 9.5mg/L, 21.5mg/L and 65.4mg/L) were tested in 2 runs per day (each of the 2 runs in duplicate) over 21 days using 1 reagent lot on 3 analysers. Results met the acceptance criteria for total precision (%CV<10%), within-run precision (%CV<5%), between-run precision (%CV<8%), and between-day precision (%CV<8%).

Sample	1	2	3	4
Mean concentration (mg/L)	6.8	9.5	21.5	65.4
Total precision	SD	0.42	0.41	0.55	2.03
	%CV	6.2	4.3	2.6	3.1
Within-run precision	SD	0.18	0.12	0.22	0.49
	%CV	2.7	1.2	1.0	0.7
Between-run precision	SD	0.09	0.12	0.18	0.52
	%CV	1.4	1.3	0.8	0.8
Between-day precision	SD	0.37	0.37	0.47	1.90
	%CV	5.4	3.9	2.2	2.9
Between-batch precision	SD	0.06	0.41	1.67	4.24
	%CV	0.6	1.9	2.6	2.9
Between-instrument precision	SD	0.20	0.06	0.17	1.64
	%CV	3.0	0.7	0.8	2.5

b. Linearity/assay reportable range:

The studies followed CLSI EP6-A, whereby linearity was assessed across the curve width at the standard sample dilution (1+0).

The acceptance criteria were that the %CV for each sample should be ≤8% and the allowable nonlinearity was 0.5mg/L up to 5mg/L, and ± 10% above 5mg/L.

In order to maintain matrix integrity, any spiking with pure protein was no greater than 30% of the total volume.

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A series of 14 samples was tested in 3 replicates. Results met the Acceptance criteria for CV<8%.

% High pool	MeanResult	SD	%CV
100.0%	316.03	0.231	0.1%
90.0%	274.87	1.041	0.4%
80.0%	254.07	1.595	0.6%
70.0%	224.27	1.457	0.6%
60.0%	193.40	1.706	0.9%
50.0%	163.53	0.451	0.3%
40.0%	138.37	0.764	0.6%
30.0%	108.87	0.643	0.6%
20.0%	73.37	0.321	0.4%
10.0%	35.80	0.608	1.7%
2.5%	9.97	0.058	0.6%
1.5%	6.27	0.058	0.9%
1.0%	4.93	0.058	1.2%
0.5%	2.70	0.100	3.7%

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

i) Traceability:

The calibration of the assay is traceable to the international reference standard ERM-DA474.

ii) Kit Stability:

Real-time stability - A study to establish shelf-life stability (from the date of manufacture when stored at recommended temperature 2-8°C) of the Optilite CRP Kit is on-going. Currently available data supports a 5-month stability claim.

Open-vial stability - The Optilite CRP Kit reagents can be stored, opened at 2 - 8°C for up to 3 months.

On-board stability - The Optilite CRP Kit reagents can be stored on-board the Optilite Analyser for at least 30 days.

d. Detection limit.

The analytical sensitivity was determined in accordance with CLSI EP17-A2. The Limit of Blank (LoB) was based on 4 serum samples run 5 times per day, over 3 days, on 2 reagent lots to give a total of 60 results per lot. The LoB was estimated for each lot as the 95% percentile of the distribution.

The Limit of Detection (LoD) was based on 4 serum samples run 5 times per day, over 3 days, on 2 reagent lots to give a total of 60 results per lot. The LoD calculation followed parametric analysis.

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The LoQ was determined from 4 serum samples targeted to be close to the bottom of the measuring range, tested 5 times per day over 3 days on 2 reagent lots.

For LoB and LoD, the highest result obtained from the two lots tested was the final result (see below):

LoB	LoD	LoQ
1.35mg/L	2.66mg/L	5.0mg/L

e. Analytical specificity:

Interferences were assessed according to CLSI EP7-A2 by testing serum samples with CRP concentrations falling at approximately 9mg/L, 60mg/L and 150mg/L. Each sample was spiked with interfering substances and tested in replicates of 3. For non-interference to be claimed, the mean results from the spiked samples must be within 10% of the mean of the control samples.

Haemoglobin and Bilirubin results: The data demonstrated that the assay was not affected by high levels of the following substances: haemoglobin (5g/L) and bilirubin (200mg/L).

Intralipid and Triglyceride results: The data demonstrated that the assay was not affected by triglyceride (500mg/dL), and intralipid (250mg/dL).

Rheumatoid Factor results: The data demonstrated that the assay was not affected by rheumatoid factor (2417IU/mL).

Drug Interference results: The data demonstrated that the assay was not affected by the 14 therapeutic drugs tested at the concentrations given below.

Drug	Concentration tested
Acetaminophen	1324µmol/L
Acetylsalicylic Acid	3.63mmol/L
Amoxicillin	206µmol/L
Ascorbic Acid	342µmol/L
Caffeine	308µmol/L
Cefotaxime	673µmol/L
Theophylline	222µmol/L
Chloramphenicol	155µmol/L
Cimetidine	79.2µmol/L
Digoxin	7.8nmol/L
Fluconazole	245µmol/L
Ibuprofen	1212.5µmol/L
Penicillin	75mg/L
Phenytoin	198µmol/L

f. Assay cut-off:

Not applicable

1. Comparison studies:
  a. Method comparison with predicate device:

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A total of 193 serum samples spanning the dynamic range were assayed in singlicate by both the Optilite C-Reactive Protein Kit and the Tina-Quant C-Reactive Protein Gen. 3 assay for use on the Modular P analyser. The samples included 83 normal donors and 110 clinical samples.

Regression statistics are based on the balance of the paired results.

Regressionfit	RegressionEquation	Slope(95% CI)	Intercept( 95% CI)
WeightedLinear	Y = 1.07x + 1.16	1.05 to 1.09	0.84 to 1.48
Passing-Bablok	Y = 1.00x + 5.56	0.98 to 1.03	4.10 to 6.87
WeightedDeming	Y = 1.07x + 1.04	1.05 to 1.09	0.45 to 1.64

98.4% of samples tested gave clinically concordant results on both analysers.

b. Matrix comparison:
None
1. Clinical studies:
- a. Clinical Sensitivity:

Not applicable

b. Clinical specificity:
Not applicable

c. Other clinical supportive data (when a. and b. are not applicable):

Not applicable

1. Clinical cut-off:
  Not applicable
1. Expected values/Reference range:
  The reference interval was verified by testing 50 adult donor samples.

Consensus reference interval for adults: <5 mg/L Reference: Dati F, Schumann G, Thomas L et al. Consensus of a group of professional societies and diagnostic companies on guidelines for interim reference ranges for 14 proteins in serum based on the standardization against the IFCC/BCR/CAP reference material (CRM 470). Eur J. Clin Chem Clin Biochem 1996;34:517-520.

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N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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Image /page/9/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

February 28, 2018

The Binding Site Group Ltd. Kirsty Samuels Regulatory Affairs Officer 8 Calthorpe Road, Edgbaston Birmingham, B15 1QT Gb

Re: K172868

Trade/Device Name: Optilite C-Reactive Protein Reagent.Optilite C-Reactive Protein Calibrator, Optilite C-Reactive Protein Controls Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCN Dated: September 18, 2017 Received: September 20, 2017

Dear Kirsty Samuels:

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

Regulation Number and Section

§ 866.5270 C-reactive protein immunological test system.

(a)
Identification. A C-reactive protein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.(b)
Classification. Class II (performance standards).