Behring Coagulation Timer is a photometric coagulation analyzer intended for clinical use to perform all coagulometric, chromogenic and immunologic coaqulation tests.

Device Description

Behring Coagulation Timer (BCT) is a fully automatic photo-optical coagulation instrument. The BCT is used in conjunction with the Behringwerke AG test kits for measurement of coagulation, fibrinolysis factors and inhibitors as well as to measure the function of the homeostatic system as a whole.

AI/ML Overview

This document describes the Behring Coagulation Timer (BCT), a new device, and compares its performance to a previously marketed device, the Behring Fibrintimer A (BFA), and in some cases, the Behring Chromotime System. The primary goal is to demonstrate substantial equivalence through correlation and precision studies.

Here's an analysis of the provided information concerning acceptance criteria and the study:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state formal "acceptance criteria" with numerical thresholds for correlation coefficients, y-intercepts, slopes, or %CV. Instead, it presents results and then a qualitative statement of "These studies support the substantial equivalence..." indicating that the observed performance was deemed acceptable.

However, we can infer implied acceptance criteria from the reported values and the claim of substantial equivalence. For comparative purposes, let's assume "acceptable" performance would be a high correlation (close to 1), a slope close to 1, and a y-intercept close to 0 for correlation studies, and low %CVs for precision studies.

Acceptance Criteria (Implied)	Reported Device Performance (BCT)
Correlation:
Correlation Coefficient (r) ~ 1	Thromborel S: r = 0.997
	Pathromtin: r = 0.99
	Berichrom Plasminogen: r = 0.96
	Berichrom Protein C: r = 0.99
Slope (m) ~ 1	Thromborel S: m = 0.97
	Pathromtin: m = 1.0
	Berichrom Plasminogen: m = 0.97
	Berichrom Protein C: m = 1.0
Y-intercept (b) ~ 0	Thromborel S: b = 0.72
	Pathromtin: b = -0.87
	Berichrom Plasminogen: b = 9.9
	Berichrom Protein C: b = -0.69
Precision: (%CV should be low)
	Thromborel S:
	Intra-Assay %CV: 0.50 to 0.81
	Inter-Assay %CV: 2.04 to 6.36
	Pathromtin:
	Intra-Assay %CV: 1.55 to 2.95
	Inter-Assay %CV: 1.75 to 2.51
	Berichrom Plasminogen:
	Intra-Assay %CV: 2.85 to 3.61
	Inter-Assay %CV: 2.19 to 3.95
	Berichrom Protein C:
	Intra-Assay %CV: 3.33 to 3.96
	Inter-Assay %CV: 1.90 to 2.54

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Correlation Studies:
- Thromborel S & Pathromtin: 83 samples were evaluated for both assays when comparing BCT vs BFA.
- Berichrom Plasminogen: 58 samples were evaluated when comparing BCT vs Behring Chromotime System.
- Berichrom Protein C: 74 samples were evaluated when comparing BCT vs Behring Chromotime System.
Precision Studies:
- For each of the four representative assays (Thromborel S, Pathromtin, Berichrom Plasminogen, Berichrom Protein C), 3 levels of control were run.
- Each level of control was run in replicates of 8 for five days, totaling n=40 measurements per level per assay (3 levels * 40 measurements = 120 measurements per assay).
- Intra-assay precision was calculated from either n=4 or n=8 precision values.
Data Provenance: The document does not specify the country of origin of the data samples or whether the studies were retrospective or prospective. Given the manufacturer's address in Germany, it's plausible the studies were conducted there. The nature of these lab-based tests (correlation and precision of an instrument) leans towards a prospective testing methodology where samples are run on both systems for comparison.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This study does not involve expert adjudication or interpretation for its ground truth. The "ground truth" for the correlation studies is the measurement obtained from the legally marketed equivalent device (BFA or Behring Chromotime System), which is also a lab instrument. For precision studies, the ground truth is the expected value of the control material, and the study assesses the device's ability to consistently reproduce measurements around that value. Therefore, no human experts are involved in establishing the "ground truth" in the way they would be in image interpretation or diagnostic performance studies.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. As explained in point 3, there is no need for expert adjudication in this type of instrument performance study. The comparison is between instrument readings.

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. This is a study evaluating the performance of a lab instrument (coagulation timer), not an AI-assisted diagnostic tool that involves human readers interpreting cases.

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

Yes, in essence, the entire study is a standalone performance evaluation of the BCT, compared to other standalone instruments (BFA, Behring Chromotime System). There is no "human-in-the-loop" component being evaluated in the context of diagnostic interpretation. The BCT itself is an automated instrument.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the correlation studies is the measurements obtained from the predicate devices (Behring Fibrintimer A and Behring Chromotime System). These devices are themselves calibrated lab instruments. For precision, the ground truth refers to the expected values of control materials used, and the goal is to demonstrate the BCT's ability to consistently measure these values. This is effectively a "reference standard" or "comparative device" ground truth.

8. The sample size for the training set

This document describes performance validation studies for a device, not a machine learning model. Therefore, there is no "training set" in the context of AI/ML. The device (BCT) operates based on pre-programmed algorithms and photometric principles, not through a learned model.

9. How the ground truth for the training set was established

Not applicable, as there is no training set for this type of device.

Summary

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Attachment 1

510(k) Summary of Safety and Effectiveness for Behring Coagulation Timer

Manufactures Name, Address, Telephone, and contact person, date of 1 . preparation:

Manufacturer	Behringwerke AG
	Postfach 1140
	35001 Marburg
	Germany

Distributor

Behring Diagnostics Inc. 151 University Avenue Westwood, MA 02090 617-320-3000 Attn: Kathleen Dray-Lyons

Preparation date: November 16, 1995

2 . Device Name/ Classification:

Behring Coagulation Timer: multipurpose system for in vitro coagulation studies Classification Number: class II (864.5425)

3 . Identification of the legally marketed device:

Behring Fibrintimer A

4 . Proposed Device Description:

5. Proposed Device Intended Use:

Behring Coagulation Timer is a photometric coagulation analyzer intended for clinical use to perform all coagulometric, chromogenic and immunologic coaqulation tests.

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Medical device to which equivalence is claimed and comparison 6. information:

The Behring Coagulation Timer (BCT) is substantially equivalent in intended use and results obtained to the Behring Fibrintimer A (BFA) which was the subject of 510(k) K926551 . The BCT like the BFA performs fully automatic, rapid quantitative measurement of coagulation time by optical detection. Both analyzers use photometric technology and offer continuous access operation. Both the BCT and the BFA process samples in the Random Access mode.

The BCT differs from the BFA in that the BCT can provide an Autostart with barcoded samples along with an integrated barcode scanner.

The BCT also differs from the BFA in that the BCT performs three basic types of assays clotting (fibrin clot), chromogenic (color development), and Immunologic (antibodies + latex) whereas the BFA can perform only clotting assays.

7. Proposed Device Performance Characteristics:

Correlation:

Performance characteristics of the Behring Coagulation System and the Behring Fibrintimer A were compared by evaluating several representative assays. The two clotting assays evaluated were Thromborel S and Pathromtin. For Thromborel S. 83 samples were evaluated on the BCT vs. the BFA. A correlation coefficient of 0.997 with a y-intercept of 0.72 and a slope of 0.97.

For Pathromtin, 83 samples were evaluated on the BCT vs the BFA. A correlation coefficient of 0.99 was obtained, with a y-intercept of -0.87 and a slope of 1.0.

The two colorometric assays which were evaluated were Berichrom Plasminogen and Berichrom Protein C. For the Berichrom Plasminogen. 58 samples were evaluated on the BCT vs the Behring Chromotime System (K901829). A correlation coefficient of 0.96 was obtained, with a y-intercept of 9.9 and a slope of 0.97.

For Berichrom Protein C, 74 samples were evaluated on the BCT vs the Behring Chromotime System. A correlation coefficient of 0.99 was obtained, with a v-intercept of -0.69 and a slope of 1.0.

These studies support the substantial equivalence of the BCT and the BFA.

Precision:

Precision of the BCT was evaluated using the above mentioned representative assays. Each level of control was run in replicates of 8 for five days. to total n=40. Intra-assay precision was calculated from either an n=4 or n=8 precision values over the 5 days. Precision data is summarized in the table below.

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Thromborel S:3 levels ranging from 11 to 59 secs		BCT
Intra-Assay %CV	0.50 to 0.81
Inter-Assay %CV	2.04 to 6.36
Pathromtin:3 levels ranging from 37 to 91 sec		BCT
Intra-Assay %CV	1.55 to 2.95
Inter-Assay %CV	1.75 to 2.51
Berichrom Plasminogen:3 levels ranging from 38.52 to 111.74 % norm		BCT
Intra-Assay %CV	2.85 to 3.61
Inter-Assay %CV	2.19 to 3.95
Berichrom Protein C:3 levels ranging from 77 to 104 % norm		BCT
Intra-Assay %CV	3.33 to 3.96
Inter-Assay %CV	1.90 to 2.54

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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.