Optilite Rheumatoid Factor Kit

K162263 · The Binding Site Group , Ltd. · DHR · May 3, 2017 · Immunology

Device Facts

• Record ID: K162263
• Device Name: Optilite Rheumatoid Factor Kit
• Applicant: The Binding Site Group , Ltd.
• Product Code: DHR · Immunology
• Decision Date: May 3, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5775
• Device Class: Class 2

Intended Use

The Optilite Rheumatoid Factor (RF) Kit is intended for the quantitative in vitro measurement of rheumatoid factor in serum using the Binding Site Optilite analyser. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. This test should be used in conjunction with other laboratory and clinical findings.

Device Story

The Optilite Rheumatoid Factor Kit is an in vitro diagnostic reagent set used on the Binding Site Optilite analyser. It utilizes immunoturbidimetry to measure rheumatoid factor concentration in serum samples. The assay involves a reaction between the rheumatoid factor in the patient sample and human IgG adsorbed onto latex particles, forming insoluble complexes. As light passes through the suspension, the amount of transmitted light is measured by a photodiode; this transmission is inversely proportional to the protein concentration. The analyser automatically calculates concentrations using a stored calibration curve. The device is intended for use in clinical laboratory settings by trained personnel. Results assist clinicians in diagnosing rheumatoid arthritis when interpreted alongside other clinical and laboratory findings.

Clinical Evidence

Bench testing only. Performance evaluated per CLSI guidelines (EP05-A2, EP6-A, EP17-A, EP07-A2). Precision studies (n=84 replicates) showed total CVs between 3.8% and 6.9%. Linearity confirmed across 7–100 IU/mL. Method comparison with 103 clinical samples yielded a Pearson correlation of 0.984 and Passing Bablok regression y = 0.90x + 2.51. Positive percent agreement was 95.8% and negative percent agreement was 71.4%. Reference range verified using 50 normal serum samples.

Technological Characteristics

Quantitative immunoturbidimetric assay. Reagents include glycine buffer, latex particles adsorbed with human IgG, and sodium azide. Measuring range: 7–100 IU/mL (standard) and 70–1000 IU/mL (diluted). Operates on the Binding Site Optilite analyzer using photodiode detection. Traceable to WHO Standard 64/2. Stability: 12 months unopened, 3 months open-vial, 30 days on-board.

Indications for Use

Indicated for the quantitative measurement of rheumatoid factor in serum to aid in the diagnosis of rheumatoid arthritis in patients. Prescription use only.

Regulatory Classification

Identification

A rheumatoid factor immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis.

Predicate Devices

• Rheumatoid Factor (RF) Kit for use on SPAPLUS (K160070)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which features a staff with a snake winding around it, and three human profiles facing right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the symbol.

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

May 3, 2017

The Binding Site Group Ltd. Mr. Jon Lauder Regulatory Affairs Specialist 8 Calthorpe Road Edgbaston Birmingham, West Midlands B15 1QT UK

Re: K162263

Trade/Device Name: Optilite® Rheumatoid Factor Kit Regulation Number: 21 CFR 866.5775 Regulation Name: Rheumatoid factor immunological test system Regulatory Class: II Product Code: DHR Dated: April 6, 2017 Received: April 7, 2017

Dear Mr. Lauder:

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

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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 [phone] or [phone] 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 [phone] or [phone] or at its Internet address

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

Sincerely yours,

Kelly Oliner -S

For

Leonthena Carrington, MBA, MS, MT(ASCP) Director Division of Immunology and Hematology 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)

Device Name Optilite Rheumatoid Factor Kit

### Indications for Use (Describe)

The Optilite Rheumatoid Factor (RF) Kit is intended for the quantitative in vitro measurement of rheumatoid factor in serum using the Binding Site Optilite analyser. Measurement of rheumatoid factor may aid in the diagnosis of theumatoid arthritis. This test should be used in conjunction with other laboratory and clinical findings.

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

| <span style="font-family: Arial, sans-serif;">☒</span> Prescription Use (Part 21 CFR 801 Subpart D) | <span style="font-family: Arial, sans-serif;">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C) |
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# Optilite Rheumatoid Factor Kit 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

Jon Lauder Regulatory Affairs Specialist The Binding Site Group Ltd. 8 Calthorpe Road Edgbaston Birmingham, West Midlands, B15 1QT, UK Telephone: [phone] Email: [e-mail] or [e-mail]

## A. 510(k) Number:

K162263

## B. Purpose for Submission:

New device

### C. Measurand:

Rheumatoid Factor

### D. Type of Test:

Quantitative immunoturbidimetry

# E. Applicant:

The Binding Site

### F. Proprietary and Established Names:

Optilite Rheumatoid Factor Kit

### G. Regulatory Information:

- 1. Regulation section: 21 CFR 866.5775, Rheumatoid factor immunological test system
- 2. Classification: Class II
- 3. Product code: DHR - system, test, rheumatoid factor
- 4. Panel: Immunology (82)

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## H. Intended use:

# 1. Intended use(s):

The Optilite Rheumatoid Factor (RF) Kit is intended for the quantitative in vitro measurement of rheumatoid factor in serum using the Binding Site Optilite analyser. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. This test should be used in conjunction with other laboratory and clinical findings.

## 2. Indication(s) for use:

Same as Intended use.

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

Prescription use only

### 4. Special instrument requirements:

The Binding Site Optilite turbidimetric analyser (K110035)

### l. Device Description:

The Optilite Rheumatoid Factor Kit comprises the following reagents:

Reaction Buffer: Containing Glycine Buffer pH 8.3, Sodium Chloride, Sodium Ethylenediamine tetra acetic acid disodium salt dehydrate, Bovine serum albumin, Sodium Azide 0.09% w/v

Latex Reagent: Containing Glycine Buffer pH 7.3, Sodium Chloride, Latex particle adsorbed human IqG. Sodium Azide 0.09% w/v.

RF Controls: Supplied at 2 levels, Low and High. Target values and ranges are supplied in the Quality Control certificate. Supplied ready for use.

RF Calibrator: Calibration has been carried out and value has been assigned using an immunoturbidimetric method standardised to the International Reference Preparation, WHO Standard 64/2. Supplied ready for use.

### J. Substantial equivalence information:

- 1. Predicate device name(s) and 510(k) number(s):
Rheumatoid Factor (RF) Kit for use on SPAPLUS; K160070

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| Similarities | | |
|---------------------|---------------------------------------------------------------|-------------------------|
| Item | Test device | Predicate |
| Assay type | Quantitative | Same |
| Specimen Type | Serum | Same |
| Antibody | Human IgG anti-human-IgM | Same |
| Intended use | Turbidimetric in vitro quantification<br>of rheumatoid factor | Same |
| Calibration | WHO 64/2 | Same |
| Reference Interval | 12.5 IU/mL | Same |
| Open Vial Stability | 3 months | 3 months |
| On-board stability | 30 days | 30 days |
| Differences | | |
| Item | Test device | Predicate |
| Measuring range | 7 - 100 IU/mL (1+0) | 10 - 104 IU/mL (1/1) |
| | 70 - 1000 IU/mL (1+9) | 70 - 1040 IU/mL (1/100) |
| Instrument | Binding Site Optilite | Binding Site SPAPLUS |

#### 2. Comparison with predicate:

# K. Standards and Guidance documents referenced:

CLSI EP17-A Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline

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-A2 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Second Edition

# L. Test Principle:

The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum 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-A2, where 5 sample preparations were tested in 2 runs per day (each of the 2 runs in duplicate) over 21 days using 3 analysers. Acceptance criteria were total precision (%CV<10%), within-run precision (%CV<5%), between-run precision (%CV<8%), and between-day precision (%CV<8%). A summary of the results is shown below. All results are in IU/mL.

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| Level | | 1 | 2 | 3 | 4 | 5 |
|--------------|-----|------|------|------|------|------|
| N | | 84 | 84 | 84 | 84 | 84 |
| Mean (IU/mL) | | 12.3 | 19.4 | 38.1 | 75.7 | 191 |
| Within | SD | 0.3 | 0.13 | 0.22 | 1.26 | 2.79 |
| Run | %CV | 2.5 | 0.7 | 0.6 | 1.7 | 1.5 |
| Between | SD | 0.26 | 0.29 | 0.5 | 0.95 | 2.82 |
| run | %CV | 2.2 | 1.5 | 1.3 | 1.3 | 1.5 |
| Between | SD | 0.74 | 0.71 | 1.49 | 2.83 | 6.11 |
| day | %CV | 6 | 3.7 | 3.9 | 3.7 | 3.2 |
| Total | SD | 0.84 | 0.78 | 1.59 | 3.24 | 7.28 |
| | %CV | 6.9 | 4 | 4.2 | 4.3 | 3.8 |

### Results:

### 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 ±10% or 10% of the medical decision point.

A dilution series comprising a high pool and low pool was tested in 3 replicates.

Weighted Linear Regression analysis was performed by plotting the % High Pool against the observed concentration, from which a weighted linear fit was generated for each point in the dilution series. This was then compared with the observed result and the difference calculated. Observed nonlinearity was less than 10%, or 10% of the medical decision point.

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

### i) Traceability:

The calibration of the assay is traceable to the International Reference Preparation of Rheumatoid Arthritis Serum WHO 64/2.

### ii) Kit Stability:

Real-time stability - Reagents are identical to those in the predicate device (K972220). Additional real time stability was therefore not assessed. The shelf life of the reagents is 12 months.

Open-vial stability - The RF Reagent, Calibrator and Controls can be stored, opened at 2-8°C for up to 3 months.

On-board stability - The RF Reagent can be stored on-board the Optilite Analyser for up to 30 days.

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# d. Detection limit.

The analytical sensitivity was determined in accordance with CLSI EP17-A. The Limit of Blank (LoB) was based on 60 determinations of a blank sample and was estimated as the 95% percentile of the distribution. The Limit of Detection (LoD) was calculated according to the equation LoB + 1.645 x SDs where SDs, the standard deviation, was based on 6 determinations of 4 samples with analyte levels near the lower limit of the reportable range. Total error at LoQ was within the maximum allowable total error.

The limit of quantitation (LoQ) for this assay is defined as the bottom of the measuring range, 7 IU/mL. The LoQ validation study was based on CLSI EP17-A Protocols for Determination of Limits of Detection and Limits of Quantitation.

e. Analytical specificity:

Interferences were assessed according to CLSI EP7-A2 by testing samples at different RF concentrations. Each sample was spiked with interfering substances and tested. For noninterference to be claimed, the mean results from the spiked samples must be within 10% of the mean of the control samples. The data demonstrated that the assay was not affected by the following substances at the concentrations given below.

### Results:

| Interferent | Concentration | Interferent | Concentration |
|----------------------|---------------|----------------------|---------------|
| Ascorbic Acid | 342µmol/L | Acetylsalicylic Acid | 3.63mmol/L |
| Conjugated Bilirubin | 200mg/L | Penicillin | 75mg/L |
| Haemoglobin | 2.5g/L | Caffeine | 308µmol/L |
| Intralipid | 250mg/dL | Prednisolone | 100µg/mL |
| Triglyceride | 500mg/dL | Digoxin | 7.8nmol/L |
| Acetaminophen | 1324µmol/L | Cimetidine | 79.2µmol/L |
| Ibuprofen | 2425µmol/L | Theophylline | 222µmol/L |
| Methotrexate | 2mmol | Phenytoin | 198µmol/L |

f. Assay cut-off:

Not determined

#### 2. Comparison studies:

a. Method comparison with predicate device:

103 samples were tested using the Optilite Kit and an alternative commercially available assay. Samples were tested in singlicate.

| Passing Bablok | Slope 95% CI | Intercept 95% CI |
|------------------------|--------------|------------------|
| y = 0.90x + 2.51 IU/mL | 0.87 to 0.97 | 0.76 to 3.88 |

| Pearson's r |
|-------------|
| 0.984 |

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### b. Matrix comparison:

None

- 3. Clinical studies:
a. Clinical Sensitivity: None determined

b. Clinical specificity: None determined

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

#### 4. Clinical cut-off:

None determined

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

The reference range of <12.5 IU/mL was transferred from the predicate device.

#### N. Proposed Labelling:

The labelling 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.