PT-Multi Calibrator is intended as a calibrator set for local PT/INR calibration and/or local verification of the INR system for plasma based procedures with designated Siemens thromboplastins Dade® Innovin® or Thromborel® S on the BCS® / BCS® XP Systems.

Device Description

PT-Multi Calibrator is a set of certified plasmas for local PT/INR calibration and/or local verification of the INR system for plasma based procedures using Siemens Dade® Innovin® or Thromborel® S reagents on Siemens BCS® Coaguiation Systems.

The calibrator levels are manufactured using a combination of normal and depleted human plasma.

AI/ML Overview

Here's a summary of the acceptance criteria and the study details for the PT-Multi Calibrator, based on the provided document:

This device is an in-vitro diagnostic (IVD) calibrator, not an AI/ML powered device, therefore some of the requested information (e.g., number of experts, adjudication method, MRMC studies, standalone performance, training set details) are not applicable. I will provide information relevant to IVD calibrator performance evaluation.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a quantitative manner as typically seen for novel medical devices. Instead, it presents performance data from "Method Comparison studies" and "Precision studies," implying that the suitability of the device is demonstrated by these results, generally expected to align with established clinical performance for such calibrators. For the purpose of this response, I will interpret the presented study results as demonstrating the device meets the implicit performance standards for a calibrator.

Implicit Performance Criteria (Demonstrated by Study Results)

Performance Metric	Description	Reported Device Performance (Summary)
Method Comparison (INR Calibration Accuracy)	Demonstrated through linear regression analysis comparing the PT-Multi Calibrator to conventional local ISI/MNPT calibration methods. The regression equations (y = mx + b) are typically expected to have a slope (m) close to 1 and an intercept (b) close to 0, indicating good agreement between methods.	Thromborel S:- Individual Sites: Slopes (y=mx+b) ranged from 0.92 to 1.03; Intercepts ranged from -0.02 to +0.05. - All Sites Combined: y=0.93x + 0.03 (without extrapolation), y=0.94x + 0.03 (with extrapolation).Innovin:- Individual Sites: Slopes ranged from 0.92 to 1.10; Intercepts ranged from -0.20 to +0.06.- All Sites Combined: y=0.97x - 0.04. These results suggest good linearity and agreement with existing methods.
Precision (Reproducibility & Repeatability)	Evaluated by coefficients of variation (CV%) for assays (e.g., Within-day CV%, Between-run CV%, Between-day CV%, Within-device CV%) across different calibrator levels (CPP, C2, NPP, PPP) and reagent lots. Lower CV% values indicate higher precision.	General Trend Across Sites, Reagents, and Calibrator Lots:- Repeatability %: Generally ranged from ~1% to ~2.5% for most calibrator levels, with some instances slightly higher (e.g., up to 4.7%).- Within-day-CV %: Typically ranged from ~1% to ~3%, with some values up to ~6%.- Between-run-CV %: Often around or below 1%, with some values up to ~4%.- Between-day-CV %: Generally ranged from ~1% to ~3%, with some values up to ~5%.- Within-device-CV %: Generally ranged from ~1% to ~3%, with some values up to ~5%. These values are typical for high-quality IVD calibrators, indicating good precision.

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

Method Comparison Studies (Test Set):
- Sample Size (n):
  - For Thromborel S (without extrapolation): Individual sites had 'n' values ranging from 118 to 138.
  - For Thromborel S (with extrapolation): Individual sites had 'n' values ranging from 119 to 139.
  - For Innovin: Individual sites had 'n' values ranging from 102 to 136.
  - Total for Thromborel S: 738 (without extrapolation) and 768 (with extrapolation) samples.
  - Total for Innovin: 693 samples.
- Data Provenance: The studies were conducted at three different sites: Denver (presumably USA), Munich (Germany), and Marburg (Germany). The data is prospective as these are controlled validation studies for regulatory submission.
Precision Studies (Test Set):
- Sample Size: The tables indicate 20-day ANOVA precision studies. While specific 'n' values per measurement are not explicitly stated for individual data points, the nature of ANOVA precision studies typically involves multiple measurements over multiple days, runs, and replicates for each calibrator level. The tables report mean INR values and various CV% metrics, derived from this systematic measurement process. The number of independent measurements is substantial given the 20-day duration and multiple types of CVs.
- Data Provenance: The studies were conducted at the same three sites: Denver, Munich, and Marburg. The data is prospective as these are controlled validation studies for regulatory submission.

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

Not Applicable (N/A) for this device.

This device is an in vitro diagnostic calibrator. Its "ground truth" is established by its intrinsic chemical properties and its ability to accurately calibrate an instrument to a known standard (e.g., International Normalized Ratio - INR). The ground truth for calibrators is typically established through:

Traceability: Ensuring the calibrator's assigned values are traceable to recognized international reference materials or methods (e.g., WHO international standards for PT/INR).
Manufacturing Control: Strict quality control during manufacturing to ensure consistency and accuracy of the calibrator's analyte concentrations.
Method Comparison: Comparison against established, conventional calibration methods (as presented in the documentation).

Therefore, "experts" in the sense of clinical decision-makers (like radiologists) are not used to establish the ground truth for this type of calibrator.

4. Adjudication Method for the Test Set

Not Applicable (N/A) for this device.

Adjudication methods (like 2+1, 3+1) are typically used in studies involving human interpretation of data where consensus is needed to define a ground truth (e.g., image interpretation). For an IVD calibrator, the results are quantitative measurements, and the accuracy and precision are determined by statistical analysis of these measurements against a known reference or by internal consistency, not by human adjudicators.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not Applicable (N/A) for this device.

This device is an in vitro diagnostic calibrator, not an AI-powered diagnostic tool used by human readers. Therefore, MRMC studies and "improvement with AI vs without AI assistance" are not relevant to its evaluation.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

Not Applicable (N/A) for this device.

This device is a "standalone" product in the sense that it is a physical calibrator kit. Its performance is evaluated intrinsically (precision) and in comparison to other calibration methods (accuracy) when used with an instrument, not as an algorithm separate from human interaction. The concept of "human-in-the-loop performance" or an "algorithm only" study does not apply to a physical calibrator.

7. The type of Ground Truth Used

For an in vitro diagnostic calibrator, the "ground truth" is intrinsically linked to:

Reference Methods/Materials: The calibrator's values are ultimately traceable to established reference methods and/or internationally recognized reference materials for the specific analyte (in this case, Prothrombin Time/INR).
Conventional Local Calibration Methods: In the method comparison studies, the PT-Multi Calibrator's performance is compared against "conventional local ISI/MNPT" (International Sensitivity Index / Mean Normal Prothrombin Time). This conventional method serves as the established "truth" or reference for evaluating the new calibrator's accuracy.

8. The Sample Size for the Training Set

Not Applicable (N/A) for this device in the context of machine learning.

The concept of a "training set" typically applies to machine learning algorithms. As a physical IVD calibrator, the device itself does not undergo machine learning training. Its development involves chemical and manufacturing processes, and its specifications are derived from extensive R&D and validation studies. The method comparison and precision studies described above represent the validation/test sets for demonstrating the device's performance.

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

Not Applicable (N/A) for this device.

As explained in point 8, there is no "training set" in the machine learning sense for this product. The ground truth for calibrators is established through traceability to international standards, rigorous manufacturing controls, and analytical validation against existing, validated methods.

Summary

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510(k) Premarket Notification K093848 PT-Multi Calibrator Additional Information November 2010 Page 56 of 60

Attachment 5

DEC 2 0 2010 510(k) Summary of Safety and Effectiveness PT-Multi Calibrator

The device name, including both the trade or proprietary name and the common or usual (a) name and the classification name of the device.

Trade or proprietary name:	PT-Multi Calibrator
Common or usual name:	Calibrators
Classification name:	Multipurpose System for In Vitro Coagulation Studies (21CFR 864.5425)

(b) The establishment registration number, if applicable, of the owner or operator submitting the premarket notification submission.

Establishment Registration Numbers:	Site Activity
9610806	Manufacturer:Siemens Healthcare Diagnostics Marburg GmbHEmil-von-Behring Str. 7635041 Marburg, Germany
2517506	Distributor/Applicant:Siemens Healthcare Diagnostics Inc.Glasgow SiteBldg. 500, M.S. 514P.O. Box 6101Newark, Delaware 19714-6101

The class in which the device has been put under Section 513 of the Act and, if known. its (c) appropriate panel: or, if the owner or operator determines that the device has not been classified under such section, a statement of the determination and the basis for the person's determination that the device is not so classified.

Class: II Panel: Hematology Product Code: GGN

Action taken by the person required to register to comply with the requirements of the Act (d) under Section 514 for performance standards.

To date, no performance standards have been finalized for this device.

Device Description (e)

The calibrator levels are manufactured using a combination of normal and depleted human plasma.

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510(k) Premarket Notification K093848 PT-Multi Calibrator Additional Information November 2010 Page 57 of 60

(f) Device Intended Use

PT-Multi Calibrator is intended as a calibrator set for local PT/NR calibration and/or local verification of the INR system for plasma based procedures with designated Siemens thromboplastins Dade® Innovin® or Thromborel® S on the BCS® / BCS® XP Systems.

A statement indicating the device is similar to and/or different from other products of (g) comparable type in commercial distribution, accompanied by data to support the statement. This information may include an identification of similar products, materials, design considerations, energy expected to be used or delivered by the device, and a description of the operational principles of the device.

The PT-Multi Calibrator is substantially equivalent in intended use to HemoslL INR Validate®, HemosIL®-ISI Calibrate, ISI web Software (K090563), Instrumentation Laboratories Co., Lexington, MA 02421. Both devices are intended as calibrators for monitoring the accuracy and control of oral anticoagulant therapy.

Suitability of this Device is supported by the data provided below (e)

Method Comparison studies were conducted at three different sites using at least two lots of PT-Multi Calibrator and the conventional local ISI/MNPT. Precision was evaluated at three different sites with at least two lots of PT-Multi Calibrator. Results of the studies are summarized in the tables below.

	BCS System
					without extrapolation		with extrapolation(factor 1.2)
	Local Test System	MNPT	ISI	PT Multi Calibrator (lot #)Local INR Calibration	n	Regression Analysis	n	Regression Analysis
Denver	Thromborel Slot 545197	10,9	1,12	37591	138	$y=0.95x -0.00$	139	$y=0.95x -0.00$
	Innovinlot 536999	8,4	0,92	37592	136	$y=0.92x +0.06$	139	$y=0.92x+0.06$
				37591	136	$y=0.97x -0.10$	N/A	N/A
				37592	130	$y=0.97x -0.03$	N/A	N/A
Munich	Thromborel Slot 545116	11,5	1,12	37591	118	$y= 0.97x -0.02$	123	$y= 0.97x -0.02$
				37592	118	$y= 0.93x +0.06$	123	$y= 0.93x +0.05$
	Innovinlot 536997	8,7	0,92	37591	106	$y= 1.10x -0.20$	N/A	N/A
				37592	102	$y= 1.09x -0.13$	N/A	N/A
Marburg	Thromborel Slot 545248	12,2	1,05	37591	118	$y=0.92x +0.05$	122	$y=0.92x +0.05$
				38585	110	$y=1.02x + 0.01$	121	$y=1.03x + 0.00$
	Innovinlot 539126	8,4	0,93	37591	112	$y=0.94x -0.02$	N/A	N/A
				38585	107	$y=0.98x -0.02$	N/A	N/A
all sites	Thromborel S			37591, 37592,38585	738	$y=0.93x+0.03$	768	$y=0.94x+0.03$
	Innovin			37591, 37592,38585	693	$y=0.97x-0.04$	N/A	N/A

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510(k) Premarket Notification K093848 PT-Multi Calibrator
Additional Information November 2010 Page 58 of 60

20 Day ANOVA Precision Studies on the BCS System
Denver	Local Test System	PATMUTH 36 by of B7591	Par Mith Calbrator Dr 37592
	Innovin lot 536999 Thromborel S lot 545197	Innovin lot 536999 Thromborel S lot 545197	Sinnovin lot 536999 Thromborel S lot 545197
	CPP C2 NPP PPP CPP CPP C2 NPPLPPP	CPP C2 NPB PPP CPP C2 NPP PPP	CRRIC2 NPB PPP CPP CPP C22 NPR PPP
Mean (INR)	12:11 3.0 21 0 4.0 2.4 3.7 1.0 3.6	2:0 2.8 2.8 2.4 2.4 -3.6 -11.0 3.6	22 13 12 3 8 3 8 2 3 6 1 0 1 3 6 11 0 1 3 5
Repeatability %	17781113 32 108837 1131-2 0.9	18 11 2 10 8 1 37 1 1 3 1 1 2 0.9	1.8. 11.11 1 2 - 2 10.8 3.6 13.6 1.0 1.0.9
Within-day-CV %	17 18 5 5 2 2 2 3 7 1 1 61.7 1.5	118 81.5 5 5 5 8 8 8 6 1 6 1 1 6 1 1 .6 1 1 5	1.8 1.5 11.5 11:51 3.8 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5
Between-run-CV %	0.0 - 0.0 0.0 1 3 0.0 5 0.0 5 0.0 01.2 1412	0.0 80.9 8.3 31:31 0.5 0.9 1.0 1.2	10.0 10.0 8 2 2 2 1 13 1 10.0 11 12 131
Between-day CV %	10.5 10.7 10.0 10.70 115 10.3 1.0.6 10.0	10.5 10.7 10.73 10.73 11.5 10.3 1.0.6 10.01	20.5 10.7 12 3 10.72 1.4 120.4 10.4 10.4 10.4 10.5
	Within-device-CV % 11:81 215 11:12 1 31:63 14:0 161:6 1:1.8 151:57	19 9 1 1 7 1 8 - 2 1 5 7 7 - 1 6 1 1 . 7 - 1 5 ]	18 11 8 12 9 12 9 21 8 1 6 1 6 1 6 8 1 6 1 6 8 15

Munich	Local Test System	Prividen Childre ter leit somers 1	े कि में सेविकारियां दिए ने कहाने
	Innovin lot 536967 Thromborel S lot 545116	Innovin lot 536967 Thromborel S lot 545116	Innovin lot 536967 Thromborel S lot 5451.16
	CPP 2C2 NEP PRP CPP C2 NEP PP	CPP RC21 NPF PPP1 CREBICC23 NPR PPP	CRR (C2) NEB PRB CPP (CPP) C23) NPP PPP
Mean (INR)	22313 228 210 183 41 22 5 1 3.7 1 11 13 13 4	222 22 3 1 0 1 3 6 1 2 . 4 3 5 5 1 8 1 0 1 3 .3	222 229 120 13:61 22:41 3:51 31:0 13:2
Repeatability %	21.2 10.5 10.5 120.5 120.6 10.9 120.6	113 10.6 10.51 10.5 120.5 12.7 10.6 14.12 10.6	12.03 10.6 110.2 10.2 13.0 20.8 120.0
Within-day-CV %	31 8110 71 0 7 10 8 1 5 0 1 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1	119 8078 108 80.8 85.0 84.11 161.5 3:01	10.0 20 20.8 10.8 11.4 8 1 4.0 1 4.0 1 1.0 1 1.0 1
Between-run-CV %	1.31 0.5 10.61 10.61 10.61 13.3 11.4.0 131.41 13.0	174112015110.6 120.6 1 40.6 1 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1	12 10 4 10 6 10 6 10 6 1 3 9 1 3 9 1 1 1 1 12 9
	Between-day CV % 150:0110.831515131313131313131.0.0: 181.51 2.3.	10.01 20.81 41.22 121.91 19.0 119.0 1121.58 12.31	10.01 10.9 12 152 1511 12.1 10.01 10.00 11 3 1 12:3
	Within-device-CV % 18118131312207 5.03112.07 5.0 12413192.11] 13:8,	19 181241515211 5.0 14.17 22 13.8	19 13 13 13 13 12 13 13 13 13 13 13 13 13 7
		Previous and Brotant Productions of	Calling of the land of 38585
Marburg	(oca Test System)
	Innovin lot 539126 Thromborel S lot 545248	Innovin'lot 539126 Thrombore IS lot 545248	Innovin lot 539126 Thrombore IS lot 545248
	CPP C2 Non B BPP CPP C2 NRP PPP	CPP 2C2 NEB PRP CPP CPP CPP RC2 NPP PPG	ICPE ICO21 NRE EPP CERECO NAS I PER
Mean (INR)	222 23.0 110 113.84 227 11:38 141.0 143.3	2 41 82 81 81 0 18 61 2 6 2 8 15 15 10 33 16	12-21133.0118110 13.71 22.71 23.91 11.01 13.3181 07 10 7410 41 14 7 100 51 1039 1037
Repeatability %	813 10 61 20 73 10 41 4 7 4 7 1 20 5 10 9 130.7	113 120 74 10 74 10 74 20 44 7 2 80 5 2 61 0 1 10 6 8
Within-day-CV %	21:41 60.8 10.73 2018 11.0 81 8 121.4 1.1.0 121.3 1	11.41 10.91 10:72 2019 11.4 88 111 11.0 1 11:3810:51 20:74 10:24 18 00 8 1 80 8 1 2 12 1 1 1 1	1741 101 20.73 10:00 80.73 10.03 121 11.03 103 11.310.51 80.78 10.01 10.8 11 131 10.31 10.31 10.32 10.31
Between-run-CV %	10:48 10.7 10.0 1 80.88 110 1 11:33 10.5 121 1610.91 813110.67 10.6 17.1 12.3 12.2 10.38 10.3	312 13 13 1 1 1 1 12 3 32 2 1 1 0 10 3 3	10.8 13 13 10.6 1310 12.3 13.2 2 1510 10.4
Between-day CV %	Within-device-CV % [21:6] 51:67 0.9 ] 81:49 [5.4 1.2.7 ] 11:4 01:3	1.7.1. 1. 1.0.99.2.6.2. 1.4.1.5.3.132.8.1.1.4.1.3	116 116 10.9 131.41 5.4 152.7 121.4 1813

Sample legend:	CPP Control Plasma P	below lowest calibrator
	C2ICi-Trol 2
	NPP(normal plasma pool
	ppppathological plasma pool

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird symbol on the right side. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the bird symbol.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

Siemens Healthcare Diagnostics Inc. c/o Mr. Radames Riesgo Regulatory Affairs & Compliance Manager Glasgow Business Community (GBC) PO Box 6101 MS 514 Newark, DE 19702

DEC 2 0 2010

Re: K093848

Trade/Device Name: PT-Multi Calibrator Regulation Number: 21 CFR §864.5425 Regulation Name: Multipurpose System for In Vitro Coagulation Studies Regulatory Class: Class II Product Code: GGN, JIS Dated: November 29, 2010 Received: November 30, 2010

Dear Mr. Riesgo:

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 class II (Special Controls), 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and 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 FDA finding of substantial equivalence of your device to a legally marketed

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Page 2 - Mr. Radames Riesgo

predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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

http://www.fda.gov/MedicalDevices/Safety/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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 (301) 796-7100 or at its Internet address . http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Thara McLen

Maria M. Chan, 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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Attachment 4

Indications for Use Statement

510(k) Number (if known): K093848

Device Name: PT-Multi Calibrator DEC 2 0 2010

Indications for Use:

Intended Use: PT-Multi Calibrator is intended as a calibrator set for local PT/INR calibration and/or local verification of the INR system for plasma based procedures with designated Siemens thromboplastins Dade® Innovin® or Thromborel® S on the BCS® / BCS® XP Systems.

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801)

(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

Page 1 of 1

Office of In Vitro Diagnostic
Device Evaluation and Safety

510(k) K093848

Regulation Number and Section

§ 864.5425 Multipurpose system for in vitro coagulation studies.

(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.