(490 days)
No
The device description and performance studies focus on a standard immunoassay technique (particle enhanced immunonephelometry) and do not mention any AI or ML components for data analysis or interpretation.
No.
This device is an in-vitro diagnostic reagent used to quantitatively measure C-reactive protein in human samples, which falls under diagnostics, not therapeutic treatment of diseases or conditions.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states that the device is an "in-vitro diagnostic reagent" for the quantitative determination of C-reactive protein, which is used for the "detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases" and as an "independent risk marker for the identification of individuals at risk for future cardiovascular disease." These are all functions of a diagnostic device.
No
The device is an in-vitro diagnostic reagent, which is a chemical substance used in a laboratory test, not a software program. It is used with specific hardware systems (BN II and BN ProSpec System) to perform the test.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "CardioPhase® hsCRP is an in-vitro diagnostic reagent for the quantitative determination of C-reactive protein (CRP) in human serum, and heparin and EDTA plasma..."
The "Device Description" also describes it as an "in vitro diagnostic reagent".
Furthermore, the "Intended User / Care Setting" indicates "Prescription Use (Part 21 CFR 801 Subpart D)", which is consistent with the regulatory classification of many IVD devices.
N/A
Intended Use / Indications for Use
CardioPhase® hsCRP is an in-vitro diagnostic reagent for the quantitative determination of C-reactive protein (CRP) in human serum, and heparin and EDTA plasma by means of particle enhanced immunonephelometry using the BN II and BN ProSpec® System. In acute phase response, increased levels of plasma proteins, including C-reactive protein, is observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases. High sensitivity CRP (hsCRP) measurements may be used as an independent risk marker for the identification of individuals at risk for future cardiovascular disease. Measurements of hsCRP, when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, may be useful as an independent marker of prognosis for recurrent events, in patients with stable coronary disease or acute coronary syndromes.
Product codes
NQD
Device Description
The CardioPhase hsCRP assay is an in vitro diagnostic reagent for the quantitative determination C-reactive protein, in human serum, and heparinized and EDTA plasma by means of particle-enhanced immunoassay determination.
Polystyrene particles coated with monoclonal antibodies specific to human CRP are aggregated when mixed with samples containing CRP. These aggregates scatter a beam of light passed through the sample. The intensity of the scattered light is proportional to the concentration of the relevant protein in the sample. The result is evaluated by comparison with a standard of known concentration.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Prescription Use
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
9.3.1 Detection Capabilities
The limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) were determined according to the CLSI document EP17-A2:2012, Evaluation of Detection Capability for Clinical CLSI Laboratory Measurement Procedures: Approved Guideline— Second Edition. The LoB and LoD estimates were evaluated separately for each reagent lot on each BN System and the reagent lot and analyzer combination yielding the highest value was used for the LoB, LoD and LoQ claims.
The LoB study was performed with five (5) independent analyte-free samples. The LoB study was carried out with one (1) BN ProSpec System, one (1) BNII System, three (3) different reagent lots, one (1) calibrator lot, five (5) analyte-free samples, one (1) single determination of five (5) individual aliquots of each sample on three (3) days and with one (1) trained operator. This protocol results in 75 measurements per reagent lot, a total of 450 measurements (including the two workflows) on each of the two (2) analyzers resulting in 900 measurements overall.
All results measured on blank samples for the LoB study yielded results below the respective LoQ.
To determine the limit of the detection (LoD) and Limit of Quantitation (LoQ), serum samples with concentrations ranging from approximately 0.05 mg/L to 0.26 mg/L CRP were prepared. Five replicates of six patient samples were run once per day for five days using three hsCRP Reagent lots on one BNProSpec and one BN II totaling 1080 determinations. The Limit of Detection (LoD) was calculated parametrically following the recommendations in the CLSI guideline. The LoD is greater than Limit of Blank and equal or below Limit of Quantitation.
The Limit of Quantitation (LoQ) was calculated using the data generated for the LoD study and was based on an imprecision goal of less than 20% CV. The LoQ was set to 0.094 mg/L based on the sample/instrument/reagent lot combination with the highest imprecision observed in the study (
§ 866.5270 C-reactive protein immunological test system.
(a)
Identification. A C-reactive protein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.(b)
Classification. Class II (performance standards).
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December 16, 2022
Siemens Healthcare Diagnostics Products GmbH Martina Pfeiff Regulatory Affairs Manager Emil-von-Behring Str. 76 Marburg, 35041 Germany
Re: K212559
Trade/Device Name: CardioPhase® hsCRP Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: NQD Dated: June 22, 2022 Received: June 23, 2022
Dear Martina Pfeiff:
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/cfpmp/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 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
1
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 medical devices and radiation-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,
Digitally signed by Paula Paula Caposino -S Caposino -S Date: 2022.12.16 10:44:12 -05'00'
Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known)
Device Name CardioPhase® hsCRP
Indications for Use (Describe)
CardioPhase® hsCRP is an in-vitro diagnostic reagent for the quantitative determination of C-reactive protein (CRP) in human serum, and heparin and EDTA plasma by means of particle enhanced immunonephelometry using the BN II and BN ProSpec® System. In acute phase response, increased levels of plasma proteins, including C-reactive protein, is observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases. High sensitivity CRP (hsCRP) measurements may be used as an independent risk marker for the identification of individuals at risk for future cardiovascular disease. Measurements of hsCRP, when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, may be useful as an independent marker of prognosis for recurrent events, in patients with stable coronary disease or acute coronary syndromes.
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) Summary per 21 CFR 807.92 Type of 510(k): Special 510(k)
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K212559
1. Submitter
Siemens Healthcare Diagnostics Products GmbH Emil-von-Behring-Str. 76 35041 Marburg, Germany
| Contact Person : | Martina Pfeiff |
|---|---|
| Email : | martina.pfeiff@siemens-healthineers.com |
| Phone: | +49 (174) 3319336 |
| Fax: | +49 (6421) 394977 |
| Date of Preparation: | June 23, 2022 |
2. Device Information
| Proprietary Name: | CardioPhase® hsCRP |
|---|---|
| Common or Usual Name: | C-reactive protein immunological test system |
| Product Code: | NQD |
| Classification Name: | system, test, C-Reactive Protein per 21CFR |
| 866.5270 | |
| Regulatory Class: | II |
| 510(k) Review Panel: | Immunology (82) |
4
Special 510(k) CardioPhase hsCRP Change in Reference Standard Material
3. Legally Marketed Unmodified / Predicate Devices
Cleared for use on Siemens' BN Systems under K033908 on January 22, 2004 as an invitro diagnostic reagent for the quantitative determination of C-reactive protein (CRP) in human serum, and heparin and EDTA plasma by means of particle enhanced immunonephelometry using the BN Systems.
| Trade Name | Common/Usual
Name | Classification | Product
Code | Panel | FDA
clearance |
|------------------------------|----------------------------------------------------|-----------------------------------|-----------------|--------------------|--------------------------------|
| Cardio Phase
hsCRP | C-reactive protein
immunological test
system | Class II per
21CFR
866.5270 | NQD | Immunology
(82) | K964527*
K991385
K033908 |
- Clearance of N Rheumatology Standard SL (calibrator used with above mentioned reagent)
4. Device Description / Test Principle
The CardioPhase hsCRP assay is an in vitro diagnostic reagent for the quantitative determination C-reactive protein, in human serum, and heparinized and EDTA plasma by means of particle-enhanced immunoassay determination.
Polystyrene particles coated with monoclonal antibodies specific to human CRP are aggregated when mixed with samples containing CRP. These aggregates scatter a beam of light passed through the sample. The intensity of the scattered light is proportional to the concentration of the relevant protein in the sample. The result is evaluated by comparison with a standard of known concentration.
5
5. Intended Use / Indications for Use
CardioPhase hsCRP assay
CardioPhase hsCRP is an in-vitro diagnostic reagent for the quantitative determination of C-reactive protein (CRP) in human serum, and heparin and EDTA plasma by means of particle enhanced immunonephelometry using the BN II and BN ProSpec System. In acute phase response, increased levels of a number of plasma proteins, including Creactive protein, is observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases. High sensitivity CRP (hsCRP) measurements may be used as an independent risk marker for the identification of individuals at risk for future cardiovascular disease. Measurements of hsCRP, when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, may be useful as an independent marker of prognosis for recurrent events, in patients with stable coronary disease or acute coronary syndromes.
CardioPhase hsCRP consists of a suspension of polystyrene particles coated with mouse monoclonal antibodies ( 10 mg/L) after repeated testing should be evaluated for noncardiovascular etiologies.
The expert panel recommends against screening of the entire adult population for hsCRP as a public health measure.
Patients with evidence of active infection, systemic inflammatory processes or trauma should not be tested for cardiovascular disease risk assessment until these conditions have abated.
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Application of secondary prevention measures should not depend on hsCRP determination, but rather an array of risk factors (global risk assessment). Serial measurements of CRP should not be used to monitor effects of treatment. Two separate CRP measurements (optimally two weeks apart) should be obtained before performing risk assessment, due to within-subject CRP variability. Measurement of hsCRP is an independent marker of risk.
hsCRP levels may be useful in motivating patients to improve lifestyle behaviors.
7. Special instrument requirements:
BN II System (K943997) BN ProSpec System(K001647) BN Systems (nephelometry)
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8. Technological characteristics
Similarities and Differences to the predicate:
The following is a table with a comparison of the similarities and differences between the proposed ERM-DA474/IFCC standardized CardioPhase hsCRP assay to the predicate device ERM-DA470 standardized CardioPhase hsCRP assay.
Table 8.-1: Similarities and Differences between proposed ERM-DA474/IFCC standardized and predicate ERM-DA470 standardized CardioPhase hsCRP
| Predicate | Proposed Device | |
|---|---|---|
| Siemens Healthcare | ||
| CardioPhase hsCRP | ||
| ERM-DA470 standardized | ||
| (K033908) | Siemens Healthcare | |
| CardioPhase hsCRP | ||
| ERM-DA474/IFCC | ||
| standardized | ||
| Indications for Use | cardiac risk assessment and | |
| injury/inflammation | Same | |
| Sample Type | Human serum, heparin and EDTA | |
| plasma | Same | |
| Reagent Packaging | 3 x 1 mL | Same |
| Units | mg/L | Same |
| Detection Method | Nephelometry | Same |
| Measurement | Quantitative | Same |
| Detection Antibody | Mouse monoclonal antibodies | Same |
| Reagent Composition | Polystyrene particles coated with | |
| monoclonal antibodies | Same | |
| Calibrator | N Rheumatology Standard SL | Same |
| Traceability/Standardization | ERM-DA470 | ERM-DA474/IFCC |
| Calibrator Levels | One level | Same |
| Analytical Measuring Range | CRP sensitive (CRP2) = 0.16 - 10 mg/L | |
| CRP (CRP1)= 3.1 – 200 mg/L | CRP sensitive (CRP2) = 0.16 - 10 mg/L | |
| CRP (CRP1)= 3.1 – 100 mg/L | ||
| Expected Values | Healthy Individuals ≤ 3 mg/L | Same |
| Cardiac Risk Stratification according | ||
| to AHA/CDC Scientific Statement: |
Relative Risk &p> | |
8
The differences between the predicate device and proposed device do not result in a change to the intended use, the indications for use, or to safety and efficacy when used according to the product labeling.
9
9. Summary of Design Control Activities
A risk analysis was performed with risks identified. Mitigation of risk to acceptable levels was achieved through verification activities summarized below.
9.1 Risk Analysis
Risk analysis was performed according to the ISO14971:2019 standard, Medical Devices - Application of Risk Management to Medical Devices. The change to the standard reference material for the CardioPhase hsCRP assay is the only change made to the test system. The reagents, packaging and instruments used for analysis remain unchanged. The labeling of the package insert for N Rheumatology Standard SL was updated including the reference to the new reference material ERM-DA474.
Each difference was analyzed, and its effect identified. Severity and probability were estimated by risk class. Risks were mitigated to the degree acceptable.
9.2. Verification Activities
Based on the results of the risk analysis, verification activities were identified, pertinent studies were determined and acceptance criteria established. The following studies were necessary to determine substantial equivalence:
9.3. Performance Studies
9.3.1 Detection Capabilities
The limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) were determined according to the CLSI document EP17-A2:2012, Evaluation of Detection Capability for Clinical CLSI Laboratory Measurement Procedures: Approved Guideline— Second Edition. The LoB and LoD estimates were evaluated separately for each reagent lot on each BN System and the reagent lot and analyzer combination yielding the highest value was used for the LoB, LoD and LoQ claims.
The LoB study was performed with five (5) independent analyte-free samples. The LoB study was carried out with one (1) BN ProSpec System, one (1) BNII System, three (3) different reagent lots, one (1) calibrator lot, five (5) analyte-free samples, one (1) single determination of five (5) individual aliquots of each sample on three (3) days and with one (1) trained operator. This protocol results in 75 measurements per reagent lot, a total of 450 measurements (including the two workflows) on each of the two (2) analyzers resulting in 900 measurements overall.
All results measured on blank samples for the LoB study yielded results below the respective LoQ.
10
To determine the limit of the detection (LoD) and Limit of Quantitation (LoQ), serum samples with concentrations ranging from approximately 0.05 mg/L to 0.26 mg/L CRP were prepared. Five replicates of six patient samples were run once per day for five days using three hsCRP Reagent lots on one BNProSpec and one BN II totaling 1080 determinations. The Limit of Detection (LoD) was calculated parametrically following the recommendations in the CLSI guideline. The LoD is greater than Limit of Blank and equal or below Limit of Quantitation
The Limit of Quantitation (LoQ) was calculated using the data generated for the LoD study and was based on an imprecision goal of less than 20% CV. The LoQ was set to 0.094 mg/L based on the sample/instrument/reagent lot combination with the highest imprecision observed in the study (