Clinical Chemistry - The Sentinel Plasmaproteins Cal 3x is a device intended for medical purposes for use in Ceruloplasmin, Kappa light chains, Lambda light chains, Transferrin, Alpha 1-Acid Glycoprotein, Alpha 1-Antitrypsin, Haptoglobin, Immunoglobulin A, Immunoglobulin G and Immunoglobulin M assays, to establish points of reference that are used in the determination of values in the measurement of Ceruloplasmin, Kappa light chains, Lambda light chains, Transferrin, Alpha 1-Acid 1 - Antitrypsin, Glycoprotein, Alpha Haptoglobin, Immunoglobulin A, Immunoglobulin G and Immunoglobulin M in human serum and plasma.
Sentinel Plasmaproteins Cal 3x must only be used for the calibration of plasmaprotein tests with the immunoturbidimetric methods.

Device Description

The Sentinel Plasmaproteins Cal 3x is a liquid, ready-to-use calibrator prepared from plasmatic plasmaproteins in human-based serum. It consists of 4 x 1 mL bottles of aqueous material containing Ceruloplasmin, Kappa light chains, Lambda light chains, Transferrin, Alpha 1-Acid Glycoprotein, Alpha 1-Antitypsin, Haptoglobin, Immunoglobulin A, Immunoglobulin G and Immunoglobulin M in a human serum matrix. This material, when stored as directed, is stable until the date printed on the label. Calibrator traceability was stated as certificated to CRM 470 (Certified Reference Material), renamed ERM-DA 470 (European Reference Materials).

AI/ML Overview

This looks like a submission for an In Vitro Diagnostic (IVD) device, specifically a calibrator for plasmaprotein assays. The provided text describes the device and its modifications, not a study evaluating an AI-powered diagnostic device in the traditional sense (e.g., image-based diagnosis). Therefore, many of the requested elements for an AI study (like sample size for test set, number of experts, adjudication method, MRMC study, standalone performance, ground truth for training set, etc.) are not applicable to this type of submission.

However, I can extract the relevant information regarding the acceptance criteria and the "study" (validation process) for this calibrator to demonstrate its substantial equivalence.

Here's the information based on the provided text, with clarifications where the requested AI study elements do not apply:

Acceptance Criteria and Device Performance for Sentinel Plasmaproteins Cal 3X

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Sentinel Plasmaproteins Cal 3x calibrator relate to the expected range for the target values of each analyte when calibrated. The "reported device performance" is essentially the determination that the calibrated values fall within these specified ranges after the validation process.

Analyte	Acceptance Criteria (Target Value Range) (mg/dL)	Reported Device Performance (Implied: Within Range)
alpha 1-Acid Glycoprotein	From 176 to 254	Within Range
Albumin	From 9344 to 14016	Within Range
Alpha 1-Antitrypsin	From 334 to 454	Within Range
Ceruloplasmin	From 66 to 124	Within Range
Haptoglobin	From 272 to 366	Within Range
Immunoglobulin A	From 478 to 718	Within Range
Immunoglobulin G	From 2264 to 3396	Within Range
Immunoglobulin M	From 204 to 3396	Within Range
Kappa	From 508 to 762	Within Range
Lambda	From 306 to 458	Within Range
Transferrin	From 580 to 872	Within Range

Additional Performance Criteria for Accepting a Single Run:

Results of normal and abnormal approved control materials are within the expected ranges.
The % recovery of Internal Calibrator Master Lot is within 97% - 103%.

Criteria for Target Value Determination:

Absence of outliers (single data - Mean > 3SD).
Imprecision less than 5%.
The obtained mean must be the Target value.

2. Sample Size Used for the Test Set and Data Provenance

This is an IVD calibrator, not an AI diagnostic device that uses a "test set" of patient data in the typical sense.

Sample Size for Testing: For the validation of the calibrator, aliquots of the Plasmaproteins Cal 3x to be tested were analyzed in triplicate during each testing run. For each analyte, three (3) analytical runs were performed on at least two (2) different days.
Data Provenance: The calibrator is prepared from plasmatic plasmaproteins in human-based serum. The exact country of origin for the human serum is not specified, but the submission is from Milan, Italy. The testing described is prospective, as it involves laboratory analysis of the manufactured calibrator.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

This is not applicable as this is an IVD calibrator. "Ground truth" for this device refers to the certified reference materials and established laboratory methods used to assign values to the calibrator, not expert consensus on medical images or patient outcomes. The traceability of the calibrator was stated as certificated to CRM 470 (Certified Reference Material), renamed ERM-DA 470 (European Reference Materials), which represents a highly standardized "ground truth" for analytical measurements.

4. Adjudication Method for the Test Set

Not applicable for an IVD calibrator. The "adjudication" is based on adherence to established quality control ranges, % recovery of internal calibrators, and statistical checks for outliers and imprecision as described in point 1.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. This type of study is not relevant for an IVD calibrator. The submission focuses on demonstrating substantial equivalence to predicate calibrators and validating the assigned values through laboratory testing.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done

While the device itself operates without human intervention once the assays are set up, the concept of "standalone performance" as typically applied to AI algorithms (i.e., algorithm only without human interaction) is not applicable here. The device is a calibrator, which is a component in a larger analytical process; its performance is intrinsically linked to the assays and instruments it calibrates. The "standalone" aspect would be its ability to consistently provide accurate reference points.

7. The Type of Ground Truth Used

The ground truth for the analyte values in the calibrator is established by traceability to certificated reference materials (CRM 470 / ERM-DA 470), which provides highly accurate and internationally recognized standards for the quantification of these plasma proteins. This is complemented by an "Internal Calibrator Master Lot" used in the calibration process.

8. The Sample Size for the Training Set

Not applicable. This is an IVD calibrator, not an AI algorithm that undergoes "training." The "training" of the analytical process would involve setting up and validating the immunoturbidimetric assays on specific instruments according to manufacturer protocols, using the reference materials.

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

Not applicable. As above, this is an IVD calibrator. The "ground truth" for the overall analytical process (which the calibrator is a part of) is established through certified reference materials and validated immunoassay methodologies. The target value assignment procedure for the calibrator itself is described as being in internal SOPs and under defined conditions, utilizing the mentioned CRMs and an Internal Calibrator Master Lot.

Summary

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K081533

JUN 2 5 2008

510(k) Summary

Submitter's Name/Address SENTINEL CH. SpA Via Robert Koch, 2

20152 Milano - Italy

Contact Person Fabio Rota Technical Director Regulatory Affairs Tel. +39 02 34551448 Fax: +39 02 34551464

Date of Preparation of this Summary:	May 30Th, 2008
Device Trade or Proprietary Name:	Sentinel Plasmaproteins Cal 3X
Device Common/Usual Name orClassification Name:	Plasmaproteins Cal 3X
Classification Number/Class:	JIX/Class II

This summary of 510(k) safety and cffectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is:

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Device Description:

Original (Plasmaproteins Cal 3x, K051457).

The Sentinel Plasmaproteins Cal 3x is a liquid, ready-to-use calibrator prepared from plasmatic plasmaproteins in human-based serum. It consists of 4 x 1 mL bottles of aqueous material containing Ceruloplasmin, Kappa light chains and Lambda light chains in a human serum matrix. This material, when stored as directed, is stable until the date printed on the label. Calibrator traceability was stated as certificated to CRM 470 (Certified Reference Material).

Modified Plasmaproteins Cal 3x

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Description of modifications:

The modified Plasmaproteins Cal 3x is substantially equivalent to the previous cleared Sentinel Plasmaproteins 3x (K051457) and to the predicate device Roche Calibrator for Automated Systems (C.f.a.s.) Proteins (K011226).

The modification with respect to K051457 consists of certification in the following new analytes:

Alpha 1-Acid Glycoprotein a )
b) Alpha 1-Antitrypsin
c) Haptoglobin
d) Immunoglobulin A
Immunoglobulin G c)
f) Immunoglobulin M
Transferrin g)

All the above listed analytes arc already contained in the original Plasmaproteins Cal 3x. Thus neither modification of the chemical's compositions nor of its production procedures have been made to the original Plasmaproteins Cal 3x (K051457).

These modifications did not significantly change the safety and effectiveness of the device as demonstrated in the Performance Characteristics Summary.

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Intended Use:

Sentinel Plasmaproteins Cal 3x must only be used for the calibration of plasmaprotein tests with the immunoturbidimetric methods.

Description of the Calibrator Material:

Sentinel Plasmaproteins Cal 3x contains analytes (plasmaproteins) in human serum based matrix. The analytes consist of:

Alpha 1-Acid Glycoprotein દા )
Alpha 1-Antitrypsin b)
ে) Haptoglobin
Immunoglobulin A d)
e) Immunoglobulin G
f) Immunoglobulin M
Transferrin பூ)

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Assigned Values and Value Assignment Process:

Target value assignment procedure is described in internal SOP and under defined conditions.

Immunoturbidimetric assays are calibrated against an Internal Calibrator Master Lot on a specific automatic analyzer as shown in the table below:

Analyte/assays	Instrument
Alpha 1-Acid Glycoprotein	Roche Hitachi 911
Alpha 1-Antitrypsin	Roche Hitachi 911
Ceruloplasmin	Abbott c8000 ARCHITECT®
Haptoglobin	Roche Hitachi 911
Immunoglobulin A	Roche Hitachi 911
Immunoglobulin G	Roche Hitachi 911
Immunoglobulin M	Roche Hitachi 911
Kappa	Abbott c8000 ARCHITECT®
Lambda	Abbott c8000 ARCHITECT®
Transferrin	Roche Hitachi 911

During each testing run the following samples are tested:

Two levels (normal and abnormal) of approved control materials in 1. triplicate to cnsure the effectiveness of the measurements.
1. Aliquots of Internal Calibrator Master lot in triplicate
1. Aliquots of Plasmaproteins Cal 3x to be tested in triplicate

For each analyte, three (3) analytical runs on at least two (2) different days are performed.

Single run is accepted if:

The results of level normal and abnormal approved control materials are within 1. the expected ranges.

1. The % recovery of Internal Calibrator Master Lot is within 97% - 103%.

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The mean and Standard Deviation and %CV of the all measurements are calculated. Data is inspected for outliers detection (single data-Mean > 3SD) and for imprecision of the measurements according to predefined criteria.

In case of abscncc of outliers and of imprecision >= 5 %, the obtained mean is the Target value.

The obtained Target value has to be within the range indicated in the following table:

Analyte	Plasmaproteins 3x (mg/dL)
alpha 1-Acid Glycoprotein	From 176 to 254
Albumin	From 9344 to 14016
Alpha 1-Antitrypsin	From 334 to 454
Ceruloplasmin	From 66 to 124
Haptoglobin	From 272 to 366
Immunoglobulin A	From 478 to 718
Immunoglobulin G	From 2264 to 3396
Immunoglobulin M	From 204 to 3396
Kappa	From 508 to 762
Lambda	From 306 to 458
Transferrin	From 580 to 872

Directions for Use:

Refer to Draft Package Insert and Draft Labelling on Section IV and Section V.

Performance Characteristics:

Please refer to Section III.

Conclusion:

The modified Plasmaproteins Cal 3x is substantially equivalent to the Predicate Device and to the previous Cleared Plasmaproteins Cal 3x as demonstrated by results obtained in the studies.

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Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized depiction of an eagle with its wings spread, symbolizing protection and care. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle, indicating the department's name and national affiliation. The logo is presented in black and white, giving it a formal and official appearance.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 2 5 2008

Sentinel CH. SPA c/o Mr. Fabio Rota via Robert Koch, 2 Milano, Italy 20152

Re: K081533

Trade/Device Name: Sentinel Plasmaproteins Cal 3x Regulation Number: 21 CFR 862.1150 Regulation Name: Claibrator Regulatory Class: Class II Product Code: JIX Dated: May 30, 2008 Received: June 02, 2008

Dear Mr. Rota:

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.

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The 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) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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 at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Jean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology 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):

Device Name: Plasmaproteins Cal 3x

Indications for Use

Prescription Use_X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 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)

Division Sign-Off

e of In Vitro Diagn

510(k) K081533

Regulation Number and Section

§ 862.1150 Calibrator.

(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.