HemosIL Calibration plasma is intended for the calibration of coagulation assays on IL and ELECTRA Coagulation Systems. The calibration plasma is prepared using citrated plasma plasmapheresed from healthy donors to maintain the characteristics of a normal plasma pool.

Device Description

AI/ML Overview

Acceptance Criteria and Study for HemosIL Calibration Plasma

This device, HemosIL Calibration Plasma, is a calibrator for coagulation assays. The performance data presented focuses on its precision in various coagulation analytes. Due to the nature of a calibrator, the acceptance criteria are implicitly tied to the precision requirements for each analyte as demonstrated by the predicate devices or established laboratory practice for calibration quality.

Here's an analysis based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state numerical acceptance criteria. However, typical acceptance criteria for calibrators revolve around established precision limits (e.g., %CV) that ensure the calibrator is stable and reliable for its intended use. The reported "Within Run %CV" values would be compared against these unstated, but generally understood, acceptable precision ranges for each analyte.

Analyte	Reagent	Reported Mean	Reported Within Run %CV	Implicit Acceptance Criteria (Example)
APTT (Seconds)	HemosIL APTT-SP	30.5	1.15	e.g., < 5% CV
Antithrombin (%)	HemosIL Liquid Antithrombin	104	2.04	e.g., < 5% CV
Factor V (%)	HemosIL FV Deficient Plasma	117	2.09	e.g., < 5% CV
Factor VIII (%)	HemosIL FVIII Deficient Plasma	83.2	4.28	e.g., < 10% CV
Fibrinogen - Clauss (mg/dL)	HemosIL Fibrinogen-C	295	2.30	e.g., < 5% CV
Fibrinogen - PT-Based (mg/dL)	HemosIL PT-Fib Recombinant	288	5.12	e.g., < 10% CV
Plasmin Inhibitor (%)	HemosIL Plasmin Inhibitor	97.7	2.02	e.g., < 5% CV
Plasminogen (%)	HemosIL Plasminogen	84.6	1.59	e.g., < 5% CV
Protein C (%)	HemosIL ProClot	96.8	4.73	e.g., < 10% CV
Protein S (%)	HemosIL Protein S	70.9	3.39	e.g., < 5% CV
PT (Seconds)	HemosIL PT-Fib Recombinant	11.0	1.45	e.g., < 5% CV
Thrombin Time (Seconds)	HemosIL Thrombin Time (2 mL)	7.59	1.84	e.g., < 5% CV
Thrombin Time (Seconds)	HemosIL Thrombin Time (5 mL)	16.9	2.13	e.g., < 5% CV
Thrombin Time (Seconds)	HemosIL Thrombin Time (8 mL)	24.5	1.27	e.g., < 5% CV
von Willebrand Factor (%)	HemosIL VWF Antigen	104	1.13	e.g., < 5% CV

Note: The "Implicit Acceptance Criteria (Example)" column contains typical precision thresholds for similar analytes in laboratory settings, as the document does not explicitly state acceptance criteria. The reported performance shows all %CV values are well within typically accepted ranges for laboratory calibrators, indicating the device meets the implicit precision requirements.

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

Sample Size: The precision testing involved running the HemosIL Calibration plasma in replicates of eight (n=8) for each analyte. This was performed across four ACL 9000 coagulation analyzers, resulting in a total of N=32 data points for each analyte (8 replicates * 4 analyzers).
Data Provenance: The document does not explicitly state the country of origin for the data or whether it was retrospective or prospective. However, given the context of a 510(k) submission to the FDA (USA) by a US-based company (Instrumentation Laboratory Company, Lexington, MA), it is highly probable that the study was conducted in the United States and was prospectively designed for the purpose of this submission.

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

This section is not applicable to this device. As a laboratory calibrator, its "ground truth" is not established by human expert consensus or interpretation of images/data. Instead, the "ground truth" for a calibrator refers to its assigned target values and the demonstration of its precision and consistency around those values. These values are determined through rigorous analytical methods and reference to primary standards or established methodologies, not expert opinions.

4. Adjudication Method for the Test Set

This section is not applicable to this device for the same reasons stated in point 3. Adjudication methods like 2+1 or 3+1 are used when human interpretation is involved and there's a need to resolve discrepancies. For a calibrator, the performance is assessed objectively through quantitative measurements of precision and accuracy against established analytical methods.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that involve human interpretation (e.g., radiologists reading images) and assesses the impact of AI assistance on human performance. The HemosIL Calibration Plasma is a laboratory calibrator, not an AI-assisted diagnostic tool.

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

This is implicitly analogous to standalone performance of the calibrator itself. The precision testing directly measures the performance of the calibrator (and the reagents/analyzers it calibrates) without human interpretation affecting the result. The study shows the inherent performance characteristics of the calibrator and its interaction with the coagulation systems and reagents.

7. The Type of Ground Truth Used

The "ground truth" for the HemosIL Calibration plasma is established through:

Analytical measurement: The reported "Mean" values for each analyte represent the established concentration or activity of that analyte in the calibrator plasma. These values are determined using highly accurate and precise laboratory methods.
Reference to established standards: While not explicitly detailed, calibrators like HemosIL are typically traceable to international reference materials or highly characterized primary standards to ensure accuracy and comparability across different laboratories.
Consistency and precision: The "Within Run %CV" demonstrates the calibrator's ability to consistently produce the same result when measured repeatedly, which is a critical aspect of its "truthfulness" as a calibrator.
Plasma source: The text mentions it's "prepared using citrated plasma plasmapheresed from healthy donors to maintain the characteristics of a normal plasma pool," which defines its biological "ground truth" as a normal human plasma matrix.

8. The Sample Size for the Training Set

This section is not applicable to this device. The HemosIL Calibration plasma is a biological product used for calibration; it is not an algorithm or AI model that requires a "training set" in the computational sense. Its "development" involves formulation, characterization, and value assignment, not machine learning.

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

This section is not applicable for the same reasons explained in point 8.

Summary

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SEP 2 8 2004

K041905

Section 3 HemosIL Calibration plasma - 510(k) Summary (Summary of Safety and Effectiveness)

Submitted by:

Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, MA 02421 Phone: 781-861-4467 781-861-4207 Fax:

Contact Person:

Carol Marble, Regulatory Affairs Director Phone: 781-861-4467 / Fax: 781-861-4207

Summary Prepared:

July 14, 2004

Name of the Device(s):

HemosIL Calibration plasma

Classification Name(s):

862.1150	Calibrator	Class II
JIX	Calibrator, Multi-Analyte Mixture

Identification of Predicate Device(s):

K905203	HemosIL Assayed Reference Plasma-Normal (for ELECTRA Series Analyzers)
K002400	Assess Calibration Plasma (for ACL Family of Analyzers)NOTE: FDA cleared as part of the individual ACL Coagulation Analyzers510(k) submissions; for example, the ACL Advance (K002400).

Description of the Device/Intended Use(s):

Statement of Technological Characteristics of the Device Compared to Predicate Device:

Hemos L Calibration plasma is substantially equivalent in performance, intended use and safety and effectiveness to the predicate devices: Assess Calibration Plasma on the ACL Family of Coagulation Analyzers and HemosIL Assayed Reference Plasma-Normal on the ELECTRA Series of Coagulation Analyzers.

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Section 3 (Cont.) HemosIL Calibration plasma - 510(k) Summary (Summary of Safety and Effectiveness)

Summary of Performance Data:

Precision testing was performed as part of the value assignment process by running Hemos L Calibration plasma in replicates of eight on four ACL 9000 coagulation analyzers (n=32) with the IL reagents listed below:

Analyte	Reagent	Mean	Within Run%CV
APTT (Seconds)	HemosIL APTT-SP	30.5	1.15
Antithrombin (%)	HemosIL Liquid Antithrombin	104	2.04
Factor V (%)	HemosIL FV Deficient Plasma	117	2.09
Factor VIII (%)	HemosIL FVIII Deficient Plasma	83.2	4.28
Fibrinogen - Clauss (mg/dL)	HemosIL Fibrinogen-C	295	2.30
Fibrinogen - PT-Based (mg/dL)	HemosIL PT-Fib Recombinant	288	5.12
Plasmin Inhibitor (%)	HemosIL Plasmin Inhibitor	97.7	2.02
Plasminogen (%)	HemosIL Plasminogen	84.6	1.59
Protein C (%)	HemosIL ProClot	96.8	4.73
Protein S (%)	HemosIL Protein S	70.9	3.39
PT (Seconds)	HemosIL PT-Fib Recombinant	11.0	1.45
Thrombin Time (Seconds)	HemosIL Thrombin Time (2 mL)	7.59	1.84
	HemosIL Thrombin Time (5 mL)	16.9	2.13
	HemosIL Thrombin Time (8 mL)	24.5	1.27
von Willebrand Factor (%)	HemosIL VWF Antigen	104	1.13

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features an abstract eagle design with three stylized wing strokes. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular pattern around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 2 8 2004

Ms. Carol Marble Regulatory Affairs Director Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, Massachusetts 02421

Re: K041905

Trade/Device Name: HemosIL Calibration Plasma Regulation Number: 21 CFR § 862.1150 Regulation Name: Calibrator, Multi-Analyte Mixture Regulatory Class: II Product Code: JIX Dated: September 17, 2004 Received: September 20, 2004

Dear Ms. Marble:

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). 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.

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Page 2

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 or questions on the proce Evaluation and Safety at (301) 594-3084. 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 Four may other of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Robert L. Becker Jr.

Robert L. Becker, Jr., M.D., Ph. 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 Statement

510(k) Number (if known): K041905

HemosIL Calibration plasma Device Names:

Indications for Use:

HemosIL Calibration plasma is intended for the calibration of coagulation assays on IL and TremosiL Canoration plasma is interest calibration plasma is prepared using citrated plasma ELECTIVE Cougarator "Dystems" to maintain the characteristics of a normal plasma pool.

र Prescription Use __ (Part 21 CFR 801 Subpart D) 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)

Josephine Bautista
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K041905

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.