The C-Reactive Protein (Latex) assay is a particle enhanced turbidimetric assay. Human CRP agglutinates with latex particle coated with monoclonal anti-CRP antibodies. The precipitate is determined turbidimetrically at 552 nm (546 nm on cobas c 501 and c 311 analyzers).

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

Based on the provided text, the "acceptance criteria" are implied by the performance characteristics presented for the modified device, and in comparison to the predicate device. The submission focuses on demonstrating that the modified device's performance is either "Same" as the predicate or improved/updated without compromising safety or effectiveness.

Feature	Predicate Device (K981897) Performance	Modified Device (C-Reactive Protein (Latex)) Performance	Comparison / Acceptance Implication
Precision	Level 1: CV within-run 1.8%, CV Total 2.9%Level 2: CV within-run 1.5%, CV Total 2.7%	Same as Predicate	The modified device maintains the same precision as the predicate, indicating it continues to meet the established performance standard for precision.
Lower Detection Limit	0.25 mg/L	1.00 mg/L* (`*Performance has not changed. The specification is now stated as the claim`)	This is a clarification/re-statement of the specification, not a change in performance. The acceptance criterion is effectively "performance has not changed from the predicate's 0.25 mg/L, but it is now claimed as 1.00 mg/L". This implies the device still meets the previous performance level even with a different stated claim.
Method Comparison (K981897 vs. K951595)	n=244r=0.993Lin. Regression: y=1.07x - 6.2 mg/LP/B Regression: y=1.00x - 2.7 mg/LValues: 0.62 to 421 mg/L	-	This section describes the predicate's original method comparison. The current submission's comparison (see next row) would be the new acceptance criteria for method comparison for the modified device.
Method Comparison (Modified Device vs. Predicate)	-	n=150r=0.999Lin. Regression: y=0.996x - 0.60 mg/LP/B Regression: y=0.992x - 0.16 mg/LValues: 0.62 to 362 mg/L	The acceptance criteria here would be indicated by the strong correlation coefficient (r=0.999) and regression equations close to y=x, demonstrating substantial equivalence to the predicate device. This shows the modified device provides comparable results to the predicate across the tested range.
Lipemia (L-index) Interference	Turbid samples exceeding 0.1 Absorbance recognized by "High Activity" check. Effective results after post-dilution. Triglyceride levels above 7.5 g/L decrease apparent CRP value significantly.	COBAS INTEGRA 400/400 plus: No significant interference up to L index of 1500 (lower concentration) and 623 (higher concentration).COBAS INTEGRA 700/800: No significant interference up to L index of 1094 (lower concentration) and 797 (higher concentration).Poor correlation between L index and triglycerides. Turbid samples exceeding 0.1 Absorbance recognized by "High Activity" check; effective results after post-dilution.	The modified device provides more specific and quantitative data on Lipemia interference using Intralipid. The acceptance criteria are that, up to specified L-index values at different concentration ranges on different instruments, there is "No significant interference." This demonstrates improved characterization (and thus understanding of limitations) for interference. The overall performance (turbid sample recognition and post-dilution) is "Same."
Measuring Range	0-160 mg/L (0-1600 mg/L with postdilution, factor 10)	Integra 700, 800, 400, 400 plus, cobas c 111: 1-200 mg/L (1:10 dilution for higher)cobas c 501 / c 311: 1-250 mg/L (1:3 dilution for higher)	The acceptance criteria are the expanded measuring ranges (up to 200 mg/L or 250 mg/L depending on the instrument) and the demonstrated efficacy of the specified post-dilution protocols (1:10 or 1:3). This shows an improvement in the device's capabilities without compromising accuracy within the extended range.
Calibrator	CRP T Standard (K954992)	Cfas Proteins (K012393)	The acceptance criteria for the new calibrator (Cfas Proteins) would be that its use does not adversely affect the fundamental performance characteristics (precision, accuracy, range) of the assay, implicitly demonstrated by the other performance studies.
Quality Control	CRP T Control (K954992), CRP T Control N (K003400)	CRP T Control N, Precinorm Protein (K012371), Precipath Protein (K012371)	Similar to the calibrator, the acceptance criteria for the new quality controls (Precinorm Protein, Precipath Protein) would be that they enable effective quality monitoring without negatively impacting assay performance.
Reagent Stability (On-board)	12 weeks	12 weeks (Note: On-board stability on cobas c 111, 5 weeks)	For most platforms, the on-board stability remains "Same," meeting the previous acceptance standard. For the cobas c 111, the acceptance criterion is 5 weeks, presumably established through specific testing for that platform.

2. Sample Sizes and Data Provenance

Test Set Sample Sizes:
- Method Comparison (Modified Device vs. Predicate): n=150
- Predicate Method Comparison (old data): n=244
- Lipemia Interference: The text provides L-index values, implying samples were tested, but does not list specific sample numbers.
- Precision: Not explicitly stated for the "test set" but generally relies on replicates of samples across different levels.
Data Provenance: The text does not explicitly state the country of origin of the data or whether it was retrospective or prospective. Given it is a modification of an existing device by Roche Diagnostics (headquartered in Indianapolis, IN, USA, but a global company), and it involves specific instrumentation (COBAS Integra, Roche/Hitachi cobas c), it is likely prospective testing conducted in a laboratory setting, potentially at multiple sites, to validate the modifications. Without further details, specific provenance cannot be determined.

3. Number of Experts and Qualifications for Ground Truth

This device is an in vitro diagnostic (IVD) device for quantitative determination of C-reactive protein. For such devices, "ground truth" is typically established by:
- Reference Methods: Comparison against established, well-characterized reference methods or highly accurate existing assays.
- Trueness/Accuracy to Certified Reference Materials: Using materials with assigned values traceable to international standards (e.g., IFCC/BCR/CAP reference preparation CRM 470 as mentioned for traceability).
The concept of "number of experts" and "qualifications of experts" (like radiologists) for ground truth is generally not applicable to this type of IVD device. The ground truth is determined by the analytical performance against known standards and other validated methods, not by human interpretation of images or observations.

4. Adjudication Method

Not applicable. Adjudication methods (e.g., 2+1, 3+1) are typically used in studies where human interpretation of data (like medical images in AI studies) requires consensus or tie-breaking. For an IVD device like C-Reactive Protein (Latex), the results are quantitative numerical values, and the comparison is statistical against reference methods or the predicate, not through expert adjudication of results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. An MRMC study is not relevant for this type of IVD device. MRMC studies are used for evaluating diagnostic imaging systems or AI systems where human readers interpret cases, and the study assesses how AI assistance impacts human reader performance. This device is an automated biochemical assay, not an imaging interpretation tool.

6. Standalone Performance (Algorithm Only without Human-in-the-Loop)

Yes, this is a standalone device. The C-Reactive Protein (Latex) assay, as an automated turbidimetric assay, operates independently to produce a quantitative result. There is no human "in the loop" during the measurement process itself, beyond loading samples and reagents and interpreting the final numerical result. The performance characteristics (precision, linearity, method comparison, interference) represent the standalone performance of the assay on the specified instruments.

7. Type of Ground Truth Used

Reference Methods and Traceability to Certified Reference Materials: The "Method Comparison" section compares the device to a predicate device (K981897), which itself was likely validated against a reference method (the predicate's comparison was against "non-latex CRP (K951595)"). The device also states traceability to the IFCC/BCR/CAP reference preparation CRM 470 for 14 serum proteins. This indicates that the "ground truth" for calibrating and validating the assay's accuracy is tied to established international reference materials and methods.

8. Sample Size for the Training Set

Not explicitly stated in the provided text, and likely not applicable in the typical "training set" sense for AI/machine learning. This is a chemical assay, not an AI/machine learning algorithm that requires a "training set" in that context. The development process includes formulation, optimization, and extensive validation with numerous samples, but these are generally considered part of the R&D and validation phases, rather than a distinct "training set" as understood in AI.

9. How the Ground Truth for the Training Set Was Established

Not applicable in the typical AI sense. Since the device is a chemical assay rather than an AI model requiring a training phase, there isn't a "training set" with ground truth established in the same way. The accuracy and performance of the assay are intrinsically linked to the chemical design, reagent quality, instrument parameters, and calibration against reference materials (like CRM 470), which are developed and optimized through standard laboratory practices and analytical validation.

Summary

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K073277

MAR – 6 2008

510(k) Summary -- C-Reactive Protein (Latex)

Introduction	According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence.
Submittername, address,contact	Roche Diagnostics9115 Hague RdIndianapolis IN 46250(317) 521-7637
	Contact person: Kerwin Kaufman
	Date prepared: November 21, 2007
SubmissionPurpose	Roche Diagnostics hereby submits this Special 510(k): Device Modificationto provide notification of modifications to our C-Reactive Protein (Latex)assay. This assay was originally cleared for use in K981897 on the COBASIntegra 700 (analyzer cleared in K951595). Submission history for additionalapplications to the COBAS Integra family and to Roche/Hitachi cobas csystems are summarized in the following Submission History section.
	Since the K981897 filing, several modifications to the C-Reactive Protein(Latex) application on the COBAS Integra platform include:
	• change of calibrator and controls,
	• validation of the high end of the measuring range of the assay up to 200mg/L, and
	• more specific Lipemia interference (L-Index) data provided based ontesting with Intralipid instead of triglycerides.
	The Limitations-interference section of the COBAS Integra labeling was alsomodified to include information about HAMA, monoclonal gammopathy,and additional testing of a common drug panel. This information is not adevice modification but was provided for more safe and effective use of theassay.
	A further device modification was validated in C-Reactive Protein (Latex)applications to the Roche/Hitachi cobas c 501 and cobas c 311:• The high end of the measuring range was validated up to 250 mg/L
	Continued on next page
SubmissionHistory	Applications of the K981897 CRP Latex modified reagent were applied toadditional analyzers within the COBAS Integra family including Integra 400-800, 400 Plus and cobas c 111, as well as Roche/Hitachi family cobas c 501and c 311 analyzers via Letters to File or Internal Documentation per theReagent Replacement policy:■ Integra 400, K951595/A003■ Integra 800, K951595/A008■ Integra 400 plus, K951595/A009■ cobas c 111, Internal Documentation, K981897/A003■ cobas c 501, Internal Documentation, K060373/A001 (referencingK981897)■ cobas c 311, Internal Documentation, K981897/A005
Device Name	Proprietary name: C-Reactive Protein (Latex)Common name: C-Reactive ProteinClassification name: C-reactive protein immunological test system
EstablishmentRegistration	The establishment registration number for Roche Diagnostics GmbHPenzberg is 9610126.
Classification	The FDA has classified the C-reactive protein immunological test system inClass II.

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510(k) Summary – C-Reactive Protein (Latex), Continued

Panel	ClassificationNumber	ClassificationName	RegulationCitation
82 Immunology	DCN	C-reactive proteinimmunological testsystem	21 CFR 866.5270

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510(k) Summary – C-Reactive Protein (Latex), Continued

DeviceDescription	The C-Reactive Protein (Latex) assay is a particle enhanced turbidimetricassay. Human CRP agglutinates with latex particle coated with monoclonalanti-CRP antibodies. The precipitate is determined turbidimetrically at 552nm (546 nm on cobas c 501 and c 311 analyzers).
Intended use	In vitro test for the quantitative immunological determination of C-reactiveprotein in human serum and plasma on COBAS INTEGRA systems.In vitro test for the quantitative determination of C-reactive protein in human
PredicateDevice	We claim substantial equivalence to the COBAS INTEGRA C-ReactiveProtein (Latex) cleared as K981897.
Substantialequivalency –Similarities	The table below indicates the similarities between the modified C-ReactiveProtein (Latex) test and its predicate device (original COBAS INTEGRA C-Reactive Protein (Latex), K981897).

Feature	Predicate: COBAS INTEGRA C-Reactive Protein (Latex) (K981897)	Modified device: C-ReactiveProtein (Latex)
General
Intended Use	The cassette COBAS INTEGRA C-Reactive Protein (Latex), (CRPLX)contains an in vitro diagnostic reagentsystem intended for use on COBASINTEGRA 700 for the quantitativeimmunological determination ofhuman C-reactive protein in serumand plasma.	In vitro test for the quantitativeimmunological determination of C-reactive protein in human serum andplasma on COBAS INTEGRAsystems.In vitro test for the quantitativedetermination of C-reactive proteinin human serum and plasma onRoche/Hitachi cobas c systems.
Indications forUse	Measurements of C-reactive proteinaids in evaluation of the amount ofinjury to body tissues.	Same
Feature	Predicate: COBAS INTEGRA C- Reactive Protein (Latex) (K981897)	Modified device: C-Reactive Protein (Latex)
Specimen type	Serum and Plasma. Acceptableanticoagulants include heparin,EDTA, fluoride and citrate.	Same
Instrumentplatform	Integra 700 analyzer.	Integra family including Integra 700,800, 400, 400 plus, and cobas c111.Also Roche/Hitachi family of cobasc systems including cobas c501 andcobas c311.
Test principle
Determinationof C-reactiveprotein	Particle enhanced turbidimetric assay.Human CRP agglutinates with latexparticle coated with monoclonal anti-CRP antibodies. The precipitate isdetermined turbidimetrically at 552nm.	SameDetermined turbidimetrically at 546nm on Roche/Hitachi cobas csystems
Reagent information
Antibody	Mouse monoclonal anti-CRPantibodies	Same
Traceability	Traceable to the IFCC/BCR/CAPreference preparation CRM 470(RPPHS 91/0619) for 14 serumproteins	Same
R1	TRIS buffer with bovine serumalbumin and immunoglobulins(mouse) stabilized with 0.09% sodiumazide (liquid)	Same
R2 = SR	Latex particles coated with anti-CRP(mouse) in glycine buffer stabilizedwith 0.09% sodium azide (liquid)	Same
Reagentstability	2-8 °C until expiration dateOn-board: 12 weeks	SameNote: On-board stability on cobas c111, 5 weeks
Feature	Predicate: COBAS INTEGRA C-Reactive Protein (Latex) (K981897)	Modified device: C-ReactiveProtein (Latex)
Performance characteristics
Precision	Level 1, 6.2 mg/LCV within-run, 1.8%CV Total, 2.9%Level 2, 142 mg/LCV within-run, 1.5%CV Total, 2.7%	Same
Lower detectionlimit	0.25 mg/L	1.00 mg/L** Performance has not changed.The specification is now stated asthe claim
MethodComparison	COBAS Integra 700 CRP Latex (withCRP T Standard) versus COBAS Integra700 with non-latex CRP (K951595):n=244r=0.993$Lin. Regression, y = 1.07x - 6.2 mg/L$$P/B Regression, y = 1.00x - 2.7 mg/L$Values ranged from 0.62 to 421 mg/L	COBAS Integra 700 CRP Latex (withCRP T Standard) versus COBASIntegra 700 CRP Latex (with CfasProtein)n=150r=0.999$Lin. Regression, y = 0.996x - 0.60 mg/L$$P/B Regression, y = 0.992x - 0.16 mg/L$Values ranged from 0.62 to 362 mg/L

Continued on next page

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Substantial equivalency -- Similarities (continued)

、

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510(k) Summary -- C-Reactive Protein (Latex), Continued

Substantial equivalency – Similarities (continued)

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510(k) Summary -- C-Reactive Protein (Latex), Continued

The table below indicates the differences between the modified C-Reactive Substantial equivalency -Protein (Latex) test and its predicate device (original COBAS INTEGRA C-Differences Reactive Protein (Latex), K981897).

Feature	Predicate: COBAS INTEGRA C-Reactive Protein (Latex) (K981897)	Modified device: C-ReactiveProtein (Latex)

Calibrator	CRP T Standard (K954992)	Cfas Proteins (K012393)
Quality control	CRP T Control (K954992)CRP T Control N (K003400)	CRP T Control NPrecinorm Protein (K012371)Precipath Protein (K012371)
Lipemia(L-index)Interference	Lipemia: Triglyceride levels higherthan 7.5 g/L decrease the apparentCRP value significantly. Turbidsamples exceeding 0.1 Absorbance arerecognized by the "High Activity"check. Correct results can be obtainedafter post-dilution.	Lipemia: (Intralipid)COBAS INTEGRA 400/400 plus analyzers:No significant interference up to an L indexof 1500 in the lower concentration range(3 mg/L or 28.6 nmol/L).No significant interference up to an L indexof 623 in the higher concentration range(80 mg/L or 762 nmol/L).COBAS INTEGRA 700/800 analyzers:No significant interference up to an L indexof 1094 in the lower concentration range(3 mg/L or 28.6 nmol/L).No significant interference up to an L indexof 797 in the higher concentration range(80 mg/L or 762 nmol/L).There is poor correlation between theL index (corresponds to turbidity) andtriglycerides concentration.Turbid samples exceeding 0.1 Absorbanceare recognized by the "High Activity"check. Correct results can be obtained afterpostdilution.

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Feature	Predicate: COBAS INTEGRA C-Reactive Protein (Latex) (K981897)	Modified device: C-ReactiveProtein (Latex)
MeasuringRange	0-160 mg/L0-1600 mg/L with postdilutionPostdilution factor of 10recommended	Integra 700, 800, 400, 400 plus, andcobas c 111:1-200 mg/LDetermine samples having higherconcentrations via the rerunfunction. Dilution of samples viathe rerun function is a 1:10 dilution.Results from samples diluted by thererun function are automaticallymultiplied by a factor of 10.cobas c 501 / c 311:1-250 mg/LDetermine samples having higherconcentrations via the rerunfunction. Dilution of samples viathe rerun function is a 1:3 dilution.Results from samples diluted by thererun function are automaticallymultiplied by a factor of 3.

Substantial equivalency - Differences (continued)

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized graphic of an abstract human figure with three horizontal lines extending from its back, all in black. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" is arranged in a circular fashion around the graphic.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Roche Diagnostics Corp. c/o Mr. Kerwin L. Kaufman Regulatory Affairs Principal 9115 Hague Rd. Indianapolis, IN 46250

Re: K073277

Trade/Device Name: Roche C-Reactive Protein (Latex) Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCN Dated: February 13, 2008 Received: February 19, 2008

Dear Mr. Kaufman:

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.

MAR - 6 2008

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The

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Page 2 –

FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Robert Becker/

Robert L. Becker, Jr., M.D., PH.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):

(013277

Device Name: Roche C-Reactive Protein (Latex)

Indications For Use:

In vitro test for the quantitative immunological determination of C-reactive protein in human serum and plasma on COBAS INTEGRA systems.

In vitro test for the quantitative determination of C-reactive protein in human serum and plasma on Roche/Hitachi cobas c systems.

Measurements of C-reactive protein aids in evaluation of the amount of injury to body tissues.

Prescription Use XXX (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Maria M. Han

Page 1 of ____________________________________________________________________________________________________________________________________________________________________

Division Slan-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K073277

Regulation Number and Section

§ 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).