Optilite IgM Kit

K191635 · The Binding Site Group , Ltd. · CFN · Jul 15, 2019 · Immunology

Device Facts

• Record ID: K191635
• Device Name: Optilite IgM Kit
• Applicant: The Binding Site Group , Ltd.
• Product Code: CFN · Immunology
• Decision Date: Jul 15, 2019
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.5510
• Device Class: Class 2

Intended Use

The Optilite IgM Kit is intended for the quantitative measurement of IgM in human serum and plasma by turbidimetry on the Optilite analyzer.

Device Story

Optilite IgM Kit is an in vitro diagnostic reagent system for quantitative measurement of IgM in human serum, lithium heparin, or EDTA plasma. Device operates on Binding Site Optilite analyser using immunoturbidimetric principle; specific antiserum reacts with IgM antigen to form insoluble complexes. Light transmission through suspension is measured by photodiode; transmitted light is inversely proportional to IgM concentration. Instrument automatically calculates concentration via stored calibration curve. Used in clinical laboratories by trained personnel. Output provides quantitative IgM levels to assist clinicians in diagnosing abnormal protein metabolism and immune system deficiencies. Results are interpreted alongside other clinical and laboratory findings.

Clinical Evidence

No clinical studies were performed. Evidence consists of analytical bench testing including precision (repeatability, within-lab, between-instrument, between-lot), linearity, and method comparison against the predicate. Method comparison (n=180 samples) showed a correlation coefficient of 0.999, a mean bias of -2.13%, and Passing-Bablok slope of 0.9775. Reference interval transfer was validated using 20 healthy donor samples. Stability was verified via accelerated and real-time studies per CLSI EP25-A.

Technological Characteristics

Turbidimetric immunoassay; reagent contains goat anti-IgM antisera; designed for use on Optilite analyzer; quantitative measurement principle.

Indications for Use

Indicated for the quantitative measurement of IgM in human serum and plasma to aid in the diagnosis and monitoring of various immunological disorders.

Regulatory Classification

Identification

An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

Predicate Devices

• Optilite IgM Kit (K082129)

Submission Summary (Full Text)

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July 15, 2019

The Binding Site Group Ltd. Natasha Verhaak Regulatory Affairs Officer 8 Calthorpe Road Edgbaston, B15 1QT Gb

Re: K191635

Trade/Device Name: Optilite IgM Kit Regulation Number: 21 CFR 866.5510 Regulation Name: Immunoglobulins A, G, M, D, And E Immunological Test System Regulatory Class: Class II Product Code: CFN Dated: June 13, 2019 Received: June 19, 2019

Dear Natasha Verhaak:

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 aware 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.

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

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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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); 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 (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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Douglas Jeffery, Ph.D. Branch Chief Immunology and Flow Cytometry Branch Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Ouality 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: 06/30/2020 See PRA Statement below.

510(k) Number (if known) K191635

Device Name Optilite IgM Kit

Indications for Use (Describe)

The Optilite IgM Kit is intended for the quantitative in vitro measurement of IgM in human serum, lithium heparin or EDTA plasma using the Binding Site Optilite analyser. Measurement of IgM aids in the diagnosis of abnomal protein metabolism and the body's lack of ability to resist infectious agents. The test results are to be used in conjunction with other clinical and laboratory findings.

| Type of Use (Select one or both, as applicable) | |
|-------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------|
| <div> <span> <span style="text-decoration: underline;"></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 IgM Kit Special 510(k) Submission Summary

# Submitter Details

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

### Date Prepared: 4th July 2019

### A. 510(k) Number:

K191635

### B. Purpose for Submission:

Modification to an existing device

- C. Measurand: lgM
- D. Type of Test: Quantitative immunoturbidimetry

# E. Applicant:

The Binding Site

#### F. Proprietary and Established Names:

Optilite IgM Kit

#### G. Regulatory Information:

- 1. Regulation section:
21 CFR 866.5510, Immunoglobulins A, G, M, D, and E immunological test system

- 2. Classification: Class II
- 3. Product code: CFN - method, nephelometric, immunoglobulins (G, A, M)
- 4. Panel: Immunology (82)

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# H. Intended use:

# 1. Intended use(s):

The Optilite IgM Kit is intended for the quantitative in vitro measurement of IgM in human serum, lithium heparin or EDTA plasma using the Binding Site Optilite analyser. Measurement of IgM aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test results are to be used in conjunction with other clinical and laboratory findings.

The intended use is the same as the cleared kit and has not been changed.

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

Same as Intended use.

- 3. Special conditions for use statement(s):
Prescription use only

### 3. Special instrument requirements:

The Binding Site Optilite analyser

#### l. Device Description:

The Optilite IgM Kit comprises the following reagents:

Antiserum: Goat anti IgM supplied in stabilised liquid form. Preservatives: 0.099% sodium azide, 0.1% E-amino-n-caproic acid (EACA), 0.5% BSA and 0.01% benzamidine.

Calibrator and Controls: Pooled human serum, supplied in stabilised liquid form. Contain 0.099% sodium azide, 0.1% EACA and 0.01% benzamidine as preservatives. The concentration given on the quality control certificate has been obtained by comparison with the DA470k international reference material.

Reaction Buffer: Containing 0.099% sodium azide as a preservative.

#### J. Substantial equivalence information:

- 1. Predicate device name(s) and 510(k) number(s): Optilite IgM Kit (K082129)

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# 2. Comparison with predicate:

| Similarities | | |
|-----------------------------|------------------------------------------------------------------------------|-------------------|
| Item | Modified device | Registered device |
| Intended Use | Quantitative in vitro measurement of<br>IgM | Same |
| Test Method | Turbidimetric | Same |
| Specimen Type | Serum, lithium heparin, EDTA plasma | Same |
| Assay type | Quantitative | Same |
| On-board Stability | 30 days | Same |
| Calibration traceability | DA470k | Same |
| Measuring Range | 1+9<br>0.1 – 3.8 g/L<br>1+19<br><b>0.2 – 7.5 g/L</b><br>1+399<br>4 – 150 g/L | Same |
| Adult Reference<br>Interval | 0.35 – 2.42 g/L | Same |
| Instrument | Optilite | Same |
| Antigen excess<br>capacity | 74.48 g/L | Same |
| Calibration method | Pooled human sera | Same |
| Controls | Pooled human sera | Same |
| Open vial stability | 3 months | Same |
| Antibody processing | Affinity purification, specificity<br>confirmed by IEP | Same |

| Differences | | |
|------------------------------|---------------------|-------------------|
| Item | Modified device | Registered device |
| Source of detection antibody | Goat antibody | Sheep antibody |
| Antibody resting buffer | GBS and PBS (50:50) | GBS |

# K. Standards and Guidance documents referenced:

CLSI EP17-A2 Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline

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

CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents- 1® 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.

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### M. Performance Characteristics (if/when applicable):

- 1. Analytical performance:
- Precision/Reproducibility: a.

The precision studies were based on CLSI EP5-A3 Evaluation of Precision Performance of Clinical Quantitative Measurement Methods as was agreed in pre-submission meeting Q171503.

The repeatability and within laboratory study was performed over 20 working days, with 2 runs per day and 2 reps per run. 5 different samples were assessed using 1 reagent lot on 1 analyser.

| Repeatability and Within Laboratory Summary | | | | | | | | | | |
|---------------------------------------------|----|------------|------------|------|-------------|------|-------------|------|-------|------|
| | N | Mean (g/L) | Within run | | Between run | | Between day | | Total | |
| | | | SD | CV % | SD | CV % | SD | CV % | SD | CV % |
| Level 1 | 80 | 0.217 | 0.003 | 1.3 | 0.002 | 1.1 | 0.010 | 4.6 | 0.011 | 4.9 |
| Level 2 | 84 | 0.457 | 0.034 | 7.4 | 0.000 | 0.0 | 0.020 | 4.4 | 0.039 | 8.6 |
| Level 3 | 80 | 1.823 | 0.011 | 0.6 | 0.013 | 0.7 | 0.032 | 1.8 | 0.037 | 2.0 |
| Level 4 | 80 | 3.008 | 0.022 | 0.7 | 0.018 | 0.6 | 0.049 | 1.6 | 0.057 | 1.9 |
| Level 5 | 80 | 10.415 | 0.325 | 3.1 | 0.586 | 5.6 | 0.299 | 2.9 | 0.734 | 7.0 |

Repeatability and Within Laboratory Results:

The between instrument precision study was performed over 6 working days with 2 runs per day and 2 reps per run. 5 different samples were assessed using 1 reagent lot on 3 different analysers.

Between Instrument Results:

| | N | Mean<br>(mg/L) | Between<br>Instrument | |
|---------|----|----------------|-----------------------|------|
| | | | SD | CV % |
| Level 1 | 24 | 0.218 | 0.011 | 5.2 |
| Level 2 | 24 | 0.456 | 0.027 | 5.9 |
| Level 3 | 24 | 1.875 | 0.062 | 3.3 |
| Level 4 | 24 | 3.145 | 0.112 | 3.5 |
| Level 5 | 24 | 11.240 | 0.778 | 6.9 |

The between lot precision study was performed over 6 working days with 2 runs per day and 2 reps per run. 5 different samples were assessed using 2 reagent lots on 1 analyser.

Between Lot Results:

| | N | Mean<br>(mg/L) | Between Lot | |
|---------|----|----------------|-------------|------|
| | | | SD | CV % |
| Level 1 | 24 | 0.215 | 0.002 | 0.7 |
| Level 2 | 24 | 0.457 | 0.009 | 1.9 |
| Level 3 | 24 | 1.801 | 0.015 | 0.8 |
| Level 4 | 24 | 2.985 | 0.019 | 0.6 |
| Level 5 | 24 | 10.265 | 0.151 | 1.5 |

The above results do not indicate any change in performance compared to the device cleared in K082129. The precision claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended.

b. Linearity/assay reportable range:

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A linearity study was carried out as per the original submission (K082129) where a dilution series was produced from a high pool with a known concentration of 8.44 g/L and a low pool concentration of 0.17 g/L. Each diluted sample was tested in 3 replicates and a linear regression analysis was carried out. The linear regression equation was shown to be y= 1.029 x – 0.1752 g/L, with an r value of 0.998

These results are comparable to those currently presented in the product insert and therefore do not indicate any change in performance compared to the device cleared in K082129. The

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linearity claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended.

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

- i) Traceability:
The calibration of the assay is traceable to ERM-DA470k/IFCC.

ii) Kit Stability:

Accelerated Stability

Accelerated stability studies were carried out to verify that the stability of the kit is unchanged in accordance with ISO 23640:2015. 6 replicates of controls, internal reference and samples were tested over a period equivalent to 13-months and analysed in line with EP25-A with a maximum allowable difference of ±15% in order to verify the stability claim of 12 months. Reagents were stored at 37℃ to accelerate the study by a factor of 10.

#### Accelerated Stability Results

| Parameter | IR | Control | | Sample | | |
|------------------------------------------|------|---------|------|--------|------|------|
| | | Low | High | 1 | 2 | 3 |
| Accelerated stability<br>achieved (days) | 51.5 | 54 | 89.2 | 57 | 57 | 57 |
| Equivalent at 4ºC (days) | 507 | 531 | 878 | 561 | 561 | 561 |
| Stability required at 4ºC<br>(days) | 365 | 365 | 365 | 365 | 365 | 365 |
| Decision | Pass | Pass | Pass | Pass | Pass | Pass |

Real Time Stability

To further support the results of the accelerated stability testing, a real time stability study is currently being carried out in accordance with EP25-A and as was agreed in pre-submission meeting Q171503.

# On Board Stability

On-board stability studies were carried out as per the original submission and showed no difference in the cleared on-board stability claim

#### d. Detection limit.

The limit of quantitation (LoQ) for this assay is defined as the bottom of the measuring range, 0.1 g/L. The LoQ validation study was based on CLSI EP17-A2 Evaluation of the Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - 2nd Edition in accordance with pre-submission meeting Q171503. Four samples were tested using two reagent lots. The LoQ claim was validated by all the samples reporting within the acceptance criteria of an allowable CV of 8%.

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The limit of detection (LoD) represents the lowest measurable analyte level that can be distinguished from zero, this was estimated as 0.01 g/L in the original submission and the limit of blank (LoB) was estimated to be 0.007g/L. Additional testing was carried out following the antisera change and no change in performance was observed.

The results generated do not indicate any change in performance compared to the device cleared in K082129. The LoB, LoD and LoQ claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended.

e. Analytical specificity:

As per original submission K082129

f. Assay cut-off:

Not determined

- 3. Comparison studies:
### a. Method comparison with predicate device:

A comparison study was performed by analysing 120 serum samples and 60 plasma samples using the modified Optilite IgM Kit and the unmodified K082129 kit which is already commercially available. The study was carried out in accordance with pre-submission meeting Q171503. Bland Altman and Passing Bablok regression analysis generated the following results:

| Bland Altman Mean Bias | 95% Limits of Agreement | |
|------------------------|-------------------------------|------------------|
| -2.13% | -9.63% to 5.36% | |
| Passing Bablok | Slope 95% CI Intercept 95% CI | |
| Passing Bablok | Slope 95% CI | Intercept 95% CI |
| $y= 0.9775x + 0.009$ | 0.971 to 0.983 | 0.001 to 0.016 |

| Correlation coefficient | |
|------------------------------|--------------------------|
| 0.999 | |
| Predicate Sample Range (g/L) | Test Samples Range (g/L) |
| 0.121 – 16.464 | 0.130 – 15.688 |

The above results do not indicate any change in performance compared to the device cleared in K082129. The comparison claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended.

#### b. Matrix comparison:

Serum and plasma matrices were included in the above method comparison study. As per the original submissionK082129, no difference between matrices were observed.

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### 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:

Following the protocol agreed in Q171503, 20 samples from apparently healthy US donors were tested using the modified assay. The acceptance criteria for the transfer is ≤2 samples falling outside of the limits of the reference interval to be transferred.

Of the 20 samples tested, 18 gave results within the reference interval, ranging from 0.480 to 1.522 g/L. Two samples were close to the lower boundary of the reference interval (0.35g/L) with results of 0.305 and 0.319 g/L. The results of this study therefore meet the acceptance criteria and indicate that the reference interval can be transferred from the originally cleared device.

#### N. Proposed Labelling:

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

The labelling is the same as the cleared kit and has not been changed.

#### O. Conclusion:

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