CRP Vario
Device Facts
| Record ID | K192118 |
|---|---|
| Device Name | CRP Vario |
| Applicant | SENTINEL CH. SpA |
| Product Code | DCK · Immunology |
| Decision Date | Nov 8, 2019 |
| Decision | SESE |
| Submission Type | Special |
| Regulation | 21 CFR 866.5270 |
| Device Class | Class 2 |
Intended Use
The CRP Vario assay [CRPVa] is for in vitro diagnostic use in the quantitative immunoturbidimetric determination of C-reactive protein in human serum and plasma (sodium and lithium heparin) using the ARCHITECT c Systems. Measurement of C-reactive protein is useful in the detection and evaluation of infection, tissue injury and inflammatory disorders. CRP Calibrators (including CRP Calibrator Set, CRP Calibrator HS and CRP Calibrator WR) are intended to be used for the calibration of the CRP Vario for the quantitative determination of C-reactive protein in human serum or plasma samples.
Device Story
The CRP Vario is an in vitro diagnostic assay for quantitative C-reactive protein (CRP) measurement in human serum and plasma. It utilizes an immunoturbidimetric principle where rabbit anti-CRP polyclonal antibodies adsorbed on latex particles react with CRP in the sample, causing turbidity proportional to CRP concentration. The assay is performed on ARCHITECT c Systems. Healthcare providers use the resulting quantitative values to detect and evaluate infection, tissue injury, and inflammatory disorders. The device is used in clinical laboratory settings by trained laboratory personnel. The primary modification in this submission is the traceability of the assay from CRM 470 to ERM-DA472/IFCC, alongside the removal of EDTA as an acceptable anticoagulant and updated specimen storage stability (1 year at -20°C).
Clinical Evidence
Bench testing only; no clinical data provided. Verification and validation activities were performed based on risk analysis to confirm the impact of the traceability modification.
Technological Characteristics
Immunoturbidimetric assay. Reagents: Glycine buffer (pH 7.0) and rabbit anti-CRP polyclonal antibodies on latex particles. Standardized to ERM-DA472/IFCC. Compatible with ARCHITECT c Systems. Specimen types: Serum, lithium heparin plasma, sodium heparin plasma. Storage: 1 year at -20°C.
Indications for Use
Indicated for quantitative immunoturbidimetric determination of C-reactive protein in human serum and plasma (sodium and lithium heparin) to aid in detection and evaluation of infection, tissue injury, and inflammatory disorders.
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
- CRP Vario (K050836)
Related Devices
- K242170 — K-ASSAY CRP (Ver.2) · Kamiya Biomedical Company, LLC · Apr 18, 2025
Submission Summary (Full Text)
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November 8, 2019
Sentinel CH, Spa Patricia Dupe Head of Quality System Via Robert Koch, 2 Milano, 20152 It
Re: K192118
Trade/Device Name: CRP Vario Regulation Number: 21 CFR 866.5270 Regulation Name: C-Reactive Protein Immunological Test System Regulatory Class: Class II Product Code: DCK Dated: August 1, 2019 Received: August 6, 2019
Dear Patricia Dupe:
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
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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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) 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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Douglas Jeffery, Ph.D. Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality 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) K192118
Device Name CRP Vario
#### Indications for Use (Describe)
CRP Vario
The CRP Vario assay [CRPVa] is for in vitro diagnostic use in the quantitative immunoturbidimetric determination of C-reactive protein in human serum and plasma (sodium and lithium heparin) using the ARCHITECT c Systems. Measurement of C-reactive protein is useful in the detection and evaluation of infection, tissue injury and inflammatory disorders.
CRP Calibrators (including CRP Calibrator Set, CRP Calibrator HS and CRP Calibrator WR): CRP Calibrators are intended to be used for the CRP Vario for the quantitative determination of C reactive protein in human serum or plasma samples.
| 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)
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## Section 15: 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807,92.
In accordance with 21 CFR 807.87, SENTINEL CH. hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification Special 510(k).
The purpose of this Special 510(k) Premarket Notification is to inform FDA of the proposed modifications to the CRP Vario labeling and provide sufficient detail to support a determination of substantial equivalence.
The primary change in the candidate device, CRP Vario, from the predicated device is the modification in the traceability of the assay from CRM 470 to ERM-DA472/IFCC.
Other changes that will also be addressed are the removal of the EDTA as tube type used for the specimen storage and the revision of the specimen from 3 years to 1 year when stored at -20°C.
Moreover, other changes to the device labeling implemented since the product initially cleared in 2005 were evaluated per the FDA Guidance document "Deciding When to Submit a 510(k)". Per the quidance document these changes required documentation only, and they did not present any new risks. The labeling changes are listed below:
- revision of the interference data for Bilirubin which was also separated into ● Conjugated and Unconjugated Bilirubin
- . revision of the High Sensitivity method precision
Note: There were no prior submissions for this device for which FDA provided feedback related to the data or information needed to support substantial equivalence.
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| Submitter Name | SENTINEL CH. SpA |
|-------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Address | Via Robert Koch,2<br>Milano (MI)<br>20152, Italy |
| Contact | Primary:<br>Patricia Dupé<br>+39 02 345 514 496<br>+39 02 345 514 64<br>patriciadupe@sentinel.it |
| Date prepared | November 08, 2019 |
| Proprietary Name | CRP Vario |
| Common name | C-Reactive Protein, Antigen, Antiserum, and Control |
| Classification Name | C-Reactive Protein, Antigen, Antiserum, and Control<br>Device, (21CFR 866.5270, Class 2 device) |
| Product Code | DCK |
| Predicate Devices | The candidate device is a modification of the predicate<br>device. The device name, CRP Vario, is unchanged from<br>how it was cleared in 510(k) k050836 on August 8th, 2005<br>and CLIA categorized on October 1st,2008 |
| Establishment<br>Registration | The Establishment Registration number for SENTINEL CH.<br>SpA is 9681753 |
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# 1. DEVICE DESCRIPTION
The CRP Vario assay is intended for the quantitative immunoturbidimetric determination of C-reactive protein in human serum and plasma.
It is supplied as a two-reagent kit which contains 2 reagents composed as follow:
| Reactive Ingredients | Concentration |
|-----------------------------------------------------------------------------------|---------------|
| Reagent 1: Glycine buffer (pH 7.0) | 1.28% |
| Reagent 2: Anti-CRP polyclonal antibodies<br>(rabbit) adsorbed on latex particles | 0.2% |
Inactive Ingredients:
Reagent 1: contains bovine albumin (≤ 1%) and sodium azide (< 0.1%). Reagent 2: contains bovine albumin (≤ 0.1%) and sodium azide (<0.1%).
Two different sizes of the product are available:
| REF | 6K26-30 | 6K26-41 |
|-----------|-----------|-----------|
| Reagent 1 | 2 x 37 mL | 3 x 86 mL |
| Reagent 2 | 2 x 37 mL | 3 x 86 mL |
A description of the CRP Calibrators, cleared under the same 510(k) k050836, are reported below:
### 1. CRP Calibrator Set
CRP Calibrator Set contains the following calibrator levels and it is prepared by diluting CRP with human serum and stabilized by adding sodium azide (< 0.1%).
The values assigned and the color of the caps corresponding to each level are indicated in the table below.
| Contents of Kit | Short Name | Cap Color | Concentration mg/dL | Concentration mg/L | Quantity |
|-----------------|------------|--------------|---------------------|--------------------|----------|
| Calibrator | CRP05 | White | 0.50 | 5.0 | 1 x 2 mL |
| Calibrator | CRP10 | Light yellow | 1.00 | 10.0 | 1 x 2 mL |
| Calibrator | CRP20 | Light green | 2.00 | 20.0 | 1 x 2 mL |
| Calibrator | CRP40 | Light blue | 4.00 | 40.0 | 1 x 2 mL |
| Calibrator | CRP80 | Pink | 8.00 | 80.0 | 1 x 2 mL |
| Calibrator | CRP160 | Magenta | 16.00 | 160.0 | 1 x 2 mL |
| Calibrator | CRP320 | Brown | 32.00 | 320.0 | 1 x 2 mL |
To convert results from mg/dL to mg/L, multiply by 10.
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# 2. CRP Calibrator HS
CRP Calibrator HS contains the following calibrator level and it is prepared by diluting CRP with human serum and stabilized by adding sodium azide (< 0.1%).
The value assigned and the color of the cap are indicated in the table below.
| Contents of<br>Kit | Short<br>Name | Cap<br>Color | Concentration<br>mg/dL | Concentration<br>mg/L | Quantity |
|--------------------|---------------|--------------|------------------------|-----------------------|----------|
| Calibrator | CRPHS | yellow | 0.25 | 2.50 | 1 x 2 mL |
To convert results from mg/dL to mg/L, multiply by 10.
## 3. CRP Calibrator WR
CRP Calibrator WR contains the following calibrator level and it is prepared by diluting CRP with human serum and stabilized by adding sodium azide (< 0.1%).
The value assigned and the color of the cap are indicated in the table below.
| Contents of<br>Kit | Short<br>Name | Cap<br>Color | Concentration<br>mg/dL | Concentration<br>mg/L | Quantity |
|--------------------|---------------|--------------|------------------------|-----------------------|----------|
| Calibrator | CRPWR | Green | 48.00 | 480.000 | 1 x 2 mL |
To convert results from mg/dL to mg/L, multiply by 10.
# 2. INDICATIONS FOR USE
The CRP Vario assay [CRPVa] is for in vitro diagnostic use in the quantitative immunoturbidimetric determination of C-reactive protein in human serum and plasma (sodium and lithium heparin) using the ARCHITECT c Systems. Measurement of Creactive protein is useful in the detection and evaluation of infection, tissue injury and inflammatory disorders.
CRP Calibrators (including CRP Calibrator Set, CRP Calibrator HS and CRP Calibrator WR) are intended to be used for the calibration of the CRP Vario for the quantitative determination of C-reactive protein in human serum or plasma samples.
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# 3. TECHNOLOGICAL CHARACTERISTICS
The primary change in the candidate device, CRP Vario, from the predicated device is the modification in the traceability of the assay from CRM 470 to ERM-DA472/IFCC.
Other changes that will also be addressed are the removal of the EDTA as tube type used for the specimen storage and the revision of the stability of the specimen from 3 years to 1 year when stored at -20°C.
Moreover, other changes to the device labeling implemented since the product initially cleared in 2005 were evaluated per the FDA Guidance document "Deciding When to Submit a 510(k)". Per the guidance document these changes required documentation only, and they did not present any new risks. The labeling changes are listed below:
- revision of the interference data for Bilirubin which was also separated into . Conjugated and Unconjugated Bilirubin
- . revision of the High Sensitivity method precision
The following Table 15-1 and Table 15-2 compare the CRP Vario with its predicate device, CRP Vario (k050836).
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| Table 15-1: Assay Comparison, General Assay Features | | | |
|------------------------------------------------------|--|--|--|
| Feature | Predicate Device CRP Vario (k050836) | Candidate Device CRP Vario | | | | | | | | | | | | | | | | |
|--------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|--|--|--|--|--|----------------------------------------------------------------------------------------|--|--|--|--|--|--|--|--|
| Reagent<br>Formulation | Reactive Ingredient Reagent 1: Glycine<br>buffer (pH 7.0) (1.28%)<br>Reactive Ingredient Reagent 2: Anti-<br>CRP polyclonal antibodies (rabbit)<br>adsorbed on latex particles (0.2%) | Same | | | | | | | | | | | | | | | | |
| Classification | Regulation name: C-Reactive Protein,<br>Antigen, Antiserum, and Control Device | Same | | | | | | | | | | | | | | | | |
| Test principle | Turbidimetric / Immunoturbidimetric | Same | | | | | | | | | | | | | | | | |
| Intended Use | The CRP Vario assay is used for the<br>quantitative immunoturbidimetric<br>determination of C-reactive protein in<br>human serum and plasma with variable<br>assay ranges [CRP16, CRP32, CRP48]<br>using the ARCHITECT c 8000® System,<br>the ARCHITECT c 16000™ System, and<br>the AEROSET System. | The CRP Vario assay [CRPVa] is for in<br>vitro diagnostic use in the quantitative<br>immunoturbidimetric determination of<br>C-reactive protein in human serum and<br>plasma (sodium and lithium heparin)<br>using the ARCHITECT c Systems.<br>Measurement of C-reactive protein is<br>useful in the detection and evaluation<br>of infection, tissue injury and<br>inflammatory disorders. | | | | | | | | | | | | | | | | |
| Specimen Type | Human serum, plasma | Same | | | | | | | | | | | | | | | | |
| Specimen tube type | · Serum<br>· Plasma with the following acceptable<br>anticoagulants:lithium heparin (with or<br>without gel barrier), sodium heparin, and<br>EDTA | · Serum<br>· Plasma with the following acceptable<br>anticoagulants: lithium heparin (with or<br>without gel barrier) and sodium heparin | | | | | | | | | | | | | | | | |
| Specimen storage | Temperature<br>Storage Maximum 20 to 25°C 15 days 2 to 8°C 2 months -20°C 3 years | | | | | | | | | Temperature<br>Storage Maximum 20 to 25°C 15 days 2 to 8°C 2 months -20°C 1 year | | | | | | | | |
| Standardization of<br>the calibrator | This method has been standardized<br>against CRM 470 | This method has been standardized<br>against ERM-DA472/IFCC | | | | | | | | | | | | | | | | |
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Table 15-2: Assay Comparison, Labeled Performance Characteristics
| Feature | Predicate Device CRP Vario (k050836) | Candidate Device CRP Vario | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
|---------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|
| Measuring<br>range | High Sensitivity Method 0.01 to 16.00 mg/dL (0.1 to 160 mg/L) Standard Method 0.02 to 32.00 mg/dL (0.2 to 320 mg/L) Wide Range 0.02 to 48.00 mg/dL (0.2 to 480 mg/L) | Same | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| Limit of<br>Quantitation | High Sensitivity Method 0.01 mg/dL (0.1 mg/L) Standard and Wide Range Methods 0.02 mg/dL (0.2 mg/L) | Same | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| Reference<br>range | Serum and plasma: ≤ 5 mg/L (0.5 mg/dL) | Same | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| Analytical<br>Specificity | The CRP Vario test is not affected by the presence of: Rheumatoid Factor up to 550 IU/MI conjugated and fetal bilirubin up to 30 mg/dL hemoglobin up to 0.5 g/dL and lipemia (< 5% intra-lipid approximating 1500 mg/dL of triglycerides). | Interefering<br>substance Interferent<br>Concentration Bilirubin, conjugated 66 mg/dL (1129 μmol/L) Bilirubin, cunonjugated 66 mg/dL (1129 μmol/L) Hemoglobin 500 mg/dL (5 g/L) Intralipid 1,500 mg/dL (15 g/L) Rheumatoid Factor 550 IU/MI (550 kU/L) | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| Precision | CRP High Sensitivity Method Level 1 Level 2 Level 3 Level 4 N 40 40 40 40 Mean (mg/L) 0.462 4.92 11.35 45.88 Within Run SD 0.019 0.035 0.148 0.298 %CV 4.00 0.72 1.30 0.65 Between Run SD 0.011 0.024 0.109 0.120 %CV 2.38 0.49 0.96 0.26 Total SD 0.022 0.043 0.183 0.389 %CV 4.66 0.87 1.62 0.85 NOTE: %CV was calculated prior to rounding Mean and SD.<br>CRP Standard Method Level 1 Level 2 Level 3 Level 4 N 40 40 40 40 Mean (mg/L) 5.10 18.30 73.30 319.40 Within Run SD 0.10 0.11 0.37 2.08 %CV 1.97 0.59 0.50 0.65 Between Run SD 0.04 0.12 0.14 1.12 %CV 0.78 0.65 0.19 0.35 Total SD 0.11 0.19 0.40 2.70 %CV 2.15 1.04 0.54 0.85 NOTE: %CV was calculated prior to rounding Mean and SD.<br>CRP Wide Range Method Level 1 Level 2 Level 3 Level 4 N 40 40 40 40 Mean (mg/L) 5.20 18.40 90.20 268.00 Within Run SD 0.06 0.18 0.69 3.32 %CV 1.16 0.99 0.77 1.24 Between Run SD 0.05 0.08 0.76 3.35 %CV 0.98 0.44 0.84 1.25 Total SD 0.1 0.22 1.25 4.92 %CV 1.91 1.17 1.39 1.83 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
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| Feature | Predicate Device CRP Vario (k050836) | | Candidate Device CRP Vario | |
|----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------|------|
| Method<br>comparison | CRP High Sensitivity Method<br>N<br>Y - Intercept (95% CI*)<br>Correlation Coefficient<br>Slope (95% CI*)<br>Standard Error of the Estimate<br>Range (mg/L)<br>* CI = Confidence Interval | AEROSET vs.<br>Nephelometer<br>45<br>-0.24 to 0.54<br>0.9994<br>0.985 to 1.006<br>0.96<br>1.0 to 104.0 | ARCHITECT vs.<br>AEROSET<br>45<br>-0.33 to 0.45<br>0.9994<br>0.975 to 0.996<br>0.96<br>1.1 to 103.3 | Same |
| | CRP High Sensitivity Method<br>(continued)<br>N<br>Y - Intercept (95% CI*)<br>Correlation Coefficient<br>Slope (95% CI*)<br>Standard Error of the Estimate<br>Range (mg/L)<br>* CI = Confidence Interval | AEROSET vs.<br>Turbidimetric<br>Method<br>55<br>-0.01 to 0.07<br>0.9995<br>0.992 to 1.009<br>0.10<br>0.2 to 13.6 | ARCHITECT vs.<br>Turbidimetric<br>Method<br>55<br>-0.02 to 0.10<br>0.9990<br>1.001 to 1.035<br>0.14<br>0.2 to 13.6 | |
| | CRP Standard Method<br>N<br>Y - Intercept (95% CI*)<br>Correlation Coefficient<br>Slope (95% CI*)<br>Standard Error of the Estimate<br>Range (mg/L)<br>* CI = Confidence Interval | AEROSET vs.<br>Nephelometer<br>54<br>-0.68 to 0.50<br>0.9996<br>1.004 to 1.020<br>1.64<br>1.0 to 219.0 | ARCHITECT vs.<br>AEROSET<br>54<br>-0.64 to 0.46<br>0.9997<br>0.977 to 0.991<br>1.58<br>0.6 to 223 | |
| | CRP Wide Range Method<br>N<br>Y - Intercept (95% CI*)<br>Correlation Coefficient<br>Slope (95% CI*)<br>Standard Error of the Estimate<br>Range (mg/L)<br>* Cl = Confidence Interval | AEROSET vs.<br>Nephelometer<br>59<br>-1.26 to 1.53<br>0.9989<br>1.023 to 1.051<br>4.10<br>1.0 to 286.0 | ARCHITECT vs.<br>AEROSET<br>59<br>-1.44 to 2.04<br>0.9982<br>0.968 to 0.999<br>5.28<br>0.7 to 301.2 | |
| Shelf Life | The shelf life for the CRP Vario is 18 months<br>from date of manufacture.<br>The shelf life for the CRP Calibrator Set, CRP<br>Calibrator WR and CRP Calibrator HS is 24<br>months from date of manufacture. | | | Same |
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# 4. SUMMARY OF PERFORMANCE EVALUATION
The risk analysis method used to assess the impact of the modifications was a Failure Modes and Effects Analysis (FMEA).
Based on the risk analysis, the modification to the CRP Vario standardization method did not introduce any new risk to the performance of the assay.
To address the modification, verification and validation activities, which are summarized below, demonstrated that all of the acceptance criteria were met.
## Linearity
Linearity evaluation followed the recommendations outlined in Clinical and Laboratory Standards Institute (CLSI) document EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: a Statistical Approach: Approved Guideline.
A high CRP serum pool was mixed with different proportions of a low serum pool to generate 12 concentrations with each concentration level tested in triplicate determinations.
Linear results were compared to 2nd and 3rd order polynomial fits against a pre-specified allowable error.
The linearity range was found to extend up to:
- 16.00 mg/dL for the High Sensitivity Method
- · 32.00 mg/dL for the Standard Method
- 48.00 mg/dL for the Wide Range Method
### Method Comparison
The primary change in the candidate device, CRP Vario, from the predicated device is the modification in the traceability of the assay from CRM 470 to ERM-DA472/IFCC. As this change was introduced in 2010, the Sentinel predicate device, which is the CRP Vario on market, is now traceable to ERM-DA472/IFCC and therefore this predicate device cannot be used for the Method comparison study. As such, the method comparison study has been conducted using Beckman Coulter CRP Latex REF. OSR6199, which is traceable to CRM 470 (cleared under 510(k) k051564) on AU5800 platform (cleared under 510(k) k112412).
The Method Comparison was tested using the recommendations of CLSI Protocol EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples. Human serum samples, spanning the measuring range, were tested with the candidate CRP Vario assay (traceable to ERM-DA472) on an ARCHITECT c8000 analyzer and compared to the predicate method (Beckman Coulter CRP Latex REF. OSR6199, traceable to CRM 470) on a Beckman AU5800 analyzer. The correlation between the assays for each method is summarized below.
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Representative results analyzed using the Passing-Bablok regression method are summarized in Table 15-3 below. Please note that the regression analysis was performed taking the mean value of the predicate method (Beckman) versus the 1® replicate of the candidate method (c8000).
| Method | Acceptance Criteria | Results | |
|----------------------------|---------------------|---------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| High Sensitivity<br>Method | Slope<br>R<br>n | 0.95 – 1.05<br>≥ 0.975<br>≥ 100 | <i>Mean Beckman vs 1st rep c8000</i><br>Slope 0.969 (0.964 – 0.974)<br>Intercept 0.019 (0.001 – 0.036) mg/dL<br>r 1.000<br>n 111<br>range: (0.01 – 15.71) mg/dL |
| Standard<br>Method | Slope<br>R<br>n | 0.95 – 1.05<br>≥ 0.975<br>≥ 100 | <i>Mean Beckman vs 1st rep c8000</i><br>Slope 0.956 (0.925 – 0.997)<br>Intercept -0.008 (-0.015 – -0.003) mg/dL<br>r 1.000<br>n 119<br>range: (0.01 – 27.74) mg/dL |
| Wide Range<br>Method | Slope<br>R<br>n | 0.95 – 1.05<br>≥ 0.975<br>≥ 100 | <i>Mean Beckman vs 1st rep c8000</i><br>Slope 0.976 (0.944 – 0.993)<br>Intercept -0.012 (-0.022 – -0.007) mg/dL<br>r 1.000<br>n 119<br>range: (0.02 – 43.31) mg/dL |
| Table 15-3: Results of the Method Comparison between the Candidate Sentinel device |
|------------------------------------------------------------------------------------|
| CRP Vario (LN. 6K26) and Beckman Coulter CRP Latex (REF. OSR6199). |
### Limit of Quantitation
A study was conducted to assess the sensitivity of CRP Vario High Sensitivity (HS), Standard (Std) and Wide Range (WR) methods.
The LoQ study was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP17-A2. The LOQ was determined using low-level analyte samples prepared at target levels concentrations of 0.08, 0.06, 0.05, 0.04. 0.03, 0.02, 0.01, and 0.005 mg/dL by diluting serum pool with SeraSub (a synthetic serum). Testing occurred over a minimum of 3 days, on 1 ARCHITECT c8000 System. Each sample was tested in a minimum of 10 replicates per run with 2 runs per day over 3 days, for a total of 60 replicates per sample.
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At a minimum the limit of quantitation shall be ≤ 0.03 mg/dL for hsCRP and ≤ 0.05 mg/dL for standard and Wide Range methods. The LOQ results are consistent with the original submission.
5. CONCLUSIONS
The differences between predicate and candidate do not impact the indications for use or technological characteristics.
The conclusions drawn from the nonclinical tests (discussed above) demonstrate the modified CRP Vario are as safe and effective as the predicate device.
The information submitted in the premarket notification is complete and supports a substantial equivalence decision.
