Optilite High Sensitivity C-Reactive Protein Kit

K180099 · The Binding Site Group , Ltd. · DCN · Oct 12, 2018 · Immunology

Device Facts

• Record ID: K180099
• Device Name: Optilite High Sensitivity C-Reactive Protein Kit
• Applicant: The Binding Site Group , Ltd.
• Product Code: DCN · Immunology
• Decision Date: Oct 12, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5270
• Device Class: Class 2

Intended Use

The Optilite High Sensitivity C-Reactive Protein Kit is intended for the quantitative in vitro measurement of C-Reactive Protein in serum using the Binding Site Optilite analyser for evaluation of conditions thought to be associated with inflammation, in otherwise healthy individuals. This test should be used in conjunction with other laboratory and clinical findings.

Device Story

The Optilite High Sensitivity C-Reactive Protein Kit is an in vitro diagnostic assay used on the Binding Site Optilite analyser. It measures C-Reactive Protein (CRP) in serum samples via latex-enhanced immunoturbidimetry. The device consists of latex reagent, calibrator, controls, and reaction buffer. In operation, the analyser mixes the sample with specific anti-CRP antibodies, forming insoluble complexes. Light transmission through the suspension is measured by a photodiode; the amount of transmitted light is inversely proportional to the CRP concentration. The analyser automatically calculates concentrations using a stored calibration curve. Used in clinical laboratory settings by trained personnel, the output provides quantitative CRP levels to assist clinicians in evaluating inflammatory conditions. The device benefits patients by providing standardized, high-sensitivity measurements to support clinical decision-making when used alongside other laboratory and clinical findings.

Clinical Evidence

Bench testing only. Performance validated via precision studies (CLSI EP5-A3) showing total precision %CV <10% across 5 samples (0.98-8.50 mg/L). Linearity confirmed (0.44-12.16 mg/L). Method comparison with predicate (n=391 samples, 302 within range) yielded Passing & Bablok regression y=0.99x+0.09 (95% CI slope 0.97-1.01). Analytical sensitivity: LoB 0.15 mg/L, LoD 0.17 mg/L, LoQ 0.5 mg/L. Interference testing (CLSI EP7-A2) showed no significant impact from hemoglobin, bilirubin, rheumatoid factor, lipids, or common therapeutic drugs.

Technological Characteristics

Latex-enhanced immunoturbidimetric assay. Reagents contain 0.099% sodium azide. Utilizes sheep anti-human CRP antibodies. Measuring range 0.5-10 mg/L. Calibration is 6-point, traceable to ERM-DA474. Designed for use on the Binding Site Optilite analyser. Standards referenced: CLSI EP17-A2, EP7-A2, EP6-A, EP5-A3.

Indications for Use

Indicated for the quantitative in vitro measurement of C-Reactive Protein in serum for the evaluation of conditions associated with inflammation in otherwise healthy individuals. Prescription use only.

Regulatory Classification

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.

Predicate Devices

• C-Reactive Protein High Sensitive Test System for Cobas Integra Instruments (k053603)

Submission Summary (Full Text)

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October 12, 2018

The Binding Site Group Ltd Andrea Thomas, Regulatory Affairs Manager 8 Calthorpe Road Edgbaston Birmingham B15 10T UK

Re: K180099

Trade/Device Name: Optilite High Sensitivity C-Reactive Protein Kit Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCN Dated: August 29, 2018 Received: September 4, 2018

Dear Andrea Thomas:

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. Although this letter refers to your product as a device, please be avare that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.

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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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions 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 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 ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

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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# Indications for Use

510(k) Number (if known) K180099

Device Name

Optilite High Sensitivity C-Reactive Protein Kit

Indications for Use (Describe)

The Optilite High Sensitivity C-Reactive Protein Kit is intended for the quantitative in vitro measurement of C-Reactive Protein in serum using the Binding Site Optilite analyser for evaluation thought to be associated with inflammation, in otherwise healthy individuals. This test should be used in conjunction with other laboratory and clinical findings.

| Type of Use (Select one or both, as applicable) | |
|----------------------------------------------------------------------------------|---------------------------------------------------------------------------------|
| <div> <span> Prescription Use (Part 21 CFR 801 Subpart D) </span> </div> | <div> <span> Over-The-Counter Use (21 CFR 801 Subpart C) </span> </div> |

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# Optilite High Sensitivity C-Reactive Protein Kit 510(k) Summary

Date prepared: 11th October 2018

# A. 510(k) Number:

K180099

# B. Purpose for Submission:

New device

### C. Measurand:

C-Reactive Protein

### D. Type of Test:

Quantitative immunoturbidimetry

### E. Applicant:

The Binding Site Group, Ltd. Contact person: Andrea Thomas Address: 8 Calthorpe Road, Birmingham, B15 1QT, United Kingdom Contact number: [phone]

### F. Proprietary and Established Names:

Optilite® High Sensitivity C-Reactive Protein Kit

### G. Regulatory Information:

- 1. Regulation section:
21 CFR 866.5270, C-reactive protein immunological test system.

- 2. Classification:
Class II

- 3. Product code:
DCN, System, Test, C-Reactive Protein

- 4. Panel:
Immunology (82)

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### H. Intended use:

### 1. Intended use(s):

The Optilite High Sensitivity C-Reactive Protein Kit is intended for the quantitative in vitro measurement of C-Reactive Protein in serum using the Binding Site Optilite analyser for evaluation of conditions thought to be associated with inflammation, in otherwise healthy individuals. This test should be used in conjunction with other laboratory and clinical findings.

### 2. Indication(s) for use:

Same as Intended use(s).

# 3. Special conditions for use statement(s):

Prescription use only

# 4. Special instrument requirements:

The Binding Site Optilite analyser

### l. Device Description:

The Optilite High Sensitivity C-Reactive Protein Kit is comprised of latex reagent, single calibrator, controls (high and low) and reaction buffer in liquid form. The reagents contain 0.099% sodium azide as preservative.

### J. Substantial equivalence information:

#### 1. Predicate device name(s) and 510(k) number(s):

C-Reactive Protein High Sensitive Test System for Cobas Integra Instruments (K053603)

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#### 2. Comparison with predicate:

#### Similarities

| ltem | Device | Predicate |
|---------------------|------------------------------------------------------------------|--------------------------------------------|
| Intended use | Quantitative in vitro measurement of<br>C-reactive protein (CRP) | Same |
| Reference Interval | <3mg/L | <5mg/L |
| Sample type | Serum | Serum (also Li-heparin and EDTA<br>plasma) |
| Reagent type | Latex enhanced | Same |
| Open vial stability | Three months at 2 to 8°C | 12 weeks (on-board) |
| Method | Turbidimetry | Same |

### Differences

| Item | Device | Predicate |
|--------------------|------------------------------------------------|---------------------------------------------|
| Measuring Range | 0.5-10mg/L (neat) | 0.1-20.0mg/L<br>1.5-300mg/L (1/15 dilution) |
| Analyser | Optilite | Integra |
| Antibody | anti- human CRP (sheep) | anti-human CRP (mouse) |
| On board stability | 30 days (refrigerated on analyser) | 12 weeks |
| Calibration | 6 point, single calibrator diluted on analyser | 5 point, calibrator set |
| Traceability | DA474 | ERM-DA470 (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 5 sera samples (targeted at 1mg/L, 1-3mg/L, 3mg/L, 5mg/L, and 9mg/L) were tested in 2 runs per day (each of the 2 runs in duplicate) over 21 days using 3 reagent lots 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 | 5 |
|------------------------------|-----|-------|-------|-------|-------|-------|
| Mean concentration (mg/L) | | 0.98 | 1.55 | 2.99 | 5.41 | 8.50 |
| Total precision | SD | 0.055 | 0.077 | 0.134 | 0.237 | 0.260 |
| | %CV | 5.6 | 5.0 | 4.5 | 4.4 | 3.1 |
| Within-run precision | SD | 0.029 | 0.024 | 0.047 | 0.115 | 0.168 |
| | %CV | 2.9 | 1.5 | 1.6 | 2.1 | 2.0 |
| Between-run precision | SD | 0.000 | 0.021 | 0.069 | 0.081 | 0.000 |
| | %CV | 0.0 | 1.4 | 2.3 | 1.5 | 0.0 |
| Between-day precision | SD | 0.047 | 0.070 | 0.104 | 0.191 | 0.199 |
| | %CV | 4.8 | 4.5 | 3.5 | 3.5 | 2.3 |
| Between-batch precision | SD | 0.011 | 0.022 | 0.057 | 0.131 | 0.137 |
| | %CV | 1.1 | 1.4 | 1.9 | 2.4 | 1.6 |
| Between-instrument precision | SD | 0.047 | 0.054 | 0.068 | 0.113 | 0.100 |
| | %CV | 4.7 | 3.5 | 2.3 | 2.1 | 1.2 |

### b. Linearity/assay reportable range:

A linearity study was performed following CLSI EP6-A. The linearity of the high sensitivity CRP assay has been confirmed using serially diluted serum samples to cover the standard measuring range of 0.5 – 10.0 mg/L. The results demonstrated that the high sensitivity CRP assay is linear over the ranges of 0.44 - 12.16 mg/L at 1+0 dilution with deviation from linearity ≤ 10%.

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- 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 High Sensitivity CRP Kit is on-going. Currently available data supports a 13 month stability claim.

Open-vial stability - The Optilite High Sensitivity CRP Kit can be stored, opened at 2 - 8℃ for up to 3 months.

On-board stability - The Optilite High Sensitivity CRP Kit 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 3 reagent lots to give a total of 60 results per lot. The LoB was estimated for each lot as the 95th percentile of the distribution.

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

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 |
|----------|----------|---------|
| 0.15mg/L | 0.17mg/L | 0.5mg/L |

### e. Analytical specificity:

Interferences were assessed according to CLSI EP7-A2 by testing serum samples with CRP concentrations targeted at <1mg/L, 1-3mg/L, 3mg/L and >3mg/L. Each sample was spiked with interfering substances and tested. 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), conjugated bilirubin (200mg/L) unconjugated bilirubin (200mg/L) and rheumatoid factor (25lU/mL).

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Intralipid and Triglyceride results: The data demonstrated that the assay was not affected by triglyceride (1000mg/dL), and intralipid (2000mg/dL).

Drug Interference results: The data demonstrated that the assay was not affected by the 6 therapeutic drugs tested at the concentrations given below.

| Drug | Concentration tested |
|----------------------|----------------------|
| Acetaminophen | 1324µmol/L |
| Acetylsalicylic Acid | 3.62mmol/L |
| Caffeine | 308µmol/L |
| Enalapril Maleate | 0.86µmol/L |
| Ibuprofen | 2425µmol/L |
| Warfarin | 32.5µmol/L |

f. Assay cut-off:

Refer to Expected Values.

#### 2. Comparison studies:

- a. Method comparison with predicate device:
A total of 391 serum samples, 302 of which reported results within the measuring range, were assayed in singlicate by both the Optilite High Sensitivity C-Reactive Protein Kit and the C-Reactive Protein High Sensitive Test System for Cobas Integra. The samples included 87 normal donors and 304 clinical samples.

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

| Results (n = 302) | | | | |
|-------------------|------------------|--------------|------------------|-----------|
| Analysis | Result | 95% CI Slope | 95% CI Intercept | Pass/Fail |
| Passing & Bablok | y = 0.99x + 0.09 | 0.97 to 1.01 | 0.05 to 0.11 | PASS |
| Weighted Deming | y = 0.97x + 0.10 | 0.94 to 0.99 | 0.07 to 0.13 | |
| Weighted Linear | y = 0.95x + 0.12 | 0.93 to 0.98 | 0.10 to 0.15 | |

b. Matrix comparison:

None

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### 3. 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

#### 4. Clinical cut-off:

Not applicable

#### 5. Expected values/Reference range:

The reference interval was verified by testing 50 adult donor samples.

Consensus reference interval for adults: <3 mg/L

Reference: Macy EM, Hayes TE, Tracy RP. Variability in the measurement of C-Reactive protein in healthy subjects; implications for reference intervals and epidemiological applications. Clin Chem 1997; 43: 52-8.

#### N. Proposed Labeling:

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

#### O. Conclusion:

The summary includes the conclusions drawn from the nonclinical and clinical tests (discussed above) that demonstrate that the device is as safe, as effective, and performs as well as or better than the predicate device