The George King Coumadin® Plasma is an assayed control plasma derived from a single donor on Coumadin® therapy and is intended for in vitro diagnostic use in monitoring the accuracy of the coagulation analyzer and thromboplastin using the clottable prothrombin time/INR on an optical instrument with appropriate commercial reagents. George King Coumadin® Plasma may be used when evaluating a new lot of thromboplastin reagent or new coagulation analyzer.

Device Description

Each lot of George King Coumadin® Plasma is from a single human donor stabilized on at least 6-weeks of Coumadin® therapy. The donor plasma is obtained via plasmapheresis using 4.0% sodium citrate and frozen immediately at -70°C.

The INR of the donor plasma is determined using the ACL Top 500 using RecombiPlastin 2G and each plasma is then categorized into one of the three INR levels of control material based on the testing results obtained using the following INR calculation: INR = (Patient PT / Mean of normal range) ISI.

Level 1 - INR Control: 1.5-2.8
Level 2 - INR Control: 2.9-4.0
Level 3 - INR Control: >4.0

AI/ML Overview

The George King Coumadin® Plasma is an assayed control plasma for in vitro diagnostic use in monitoring the accuracy of coagulation analyzers and thromboplastin using the clottable prothrombin time/INR.

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

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria	Reported Device Performance
Precision (INR)	Total CV < 10%	INR Range 1.5-2.8: Total CVs 1.30%-2.38% (met)
		INR Range 2.9-4.0: Total CVs 1.66%-2.07% (met)
		INR Range >4.1: Total CVs 1.54%-1.66% (met)
Precision (Protime)	Total CV < 10%	Protime Range 1.5-2.8: Total CVs 2.21%-2.39% (met)
		Protime Range 2.9-4.0: Total CVs 1.70%-2.10% (met)
		Protime Range >4.1: Total CVs 1.58%-1.69% (met)
Reproducibility (INR)	Total CV < 10%	INR Range 1.5-2.8: Reproducibility CVs 2.74%-3.14% (met)
		INR Range 2.9-4.0: Reproducibility CVs 2.41%-4.13% (met)
		INR Range >4.0: Reproducibility CVs 2.68%-4.26% (met)
Reproducibility (Protime)	Total CV < 10%	Protime Range 1.5-2.8: Reproducibility CVs 2.70%-3.24% (met)
		Protime Range 2.9-4.0: Reproducibility CVs 2.47%-4.23% (met)
		Protime Range >4.0: Reproducibility CVs 2.73%-4.30% (met)
Open Vial Stability	Pre-determined acceptance criteria (not specified numerically)	Stable for 6 hours at 19-22°C (met)
Shelf-Life Stability	Real-time testing on-going to update shelf-life	Current claim of 6 months at -70°C

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

Precision Study: For each of the three INR ranges, three different lots of GK Coumadin® Plasma were tested. For each lot, 80 replicates (n=80) were analyzed (20 days with 2 runs per day and 2 replicates per run). The study was conducted in-house. Data provenance is therefore in-house, prospective testing.
Reproducibility Study: For each of the three INR ranges, three different lots were tested. For each lot, samples were assayed for 5 days, one run per day, for a total of N=75 samples. This study was performed across three different clinical laboratories, implying prospective, external data, presumably from the US.
Stability Studies: Three lots of GK Coumadin® Plasma were used for both open vial and shelf-life stability studies. Data provenance is in-house, prospective testing.

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

This information is not provided in the document. The studies conducted are analytical performance studies (precision, reproducibility, stability) for a control plasma, not diagnostic accuracy studies that rely on expert ground truth. The "ground truth" here is the measured INR or Prothrombin Time value.

4. Adjudication Method for the Test Set

This information is not applicable as the studies are analytical performance studies of a control material and do not involve human diagnostic interpretation or adjudication of results.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for diagnostic devices where human readers interpret medical images or data. The George King Coumadin® Plasma is a control material for laboratory instruments.

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

Yes, the studies presented (precision, reproducibility, stability) evaluate the performance of the device (George King Coumadin® Plasma) in a standalone manner, as measured by laboratory instruments (ACL TOP series) using specified reagents (RecombiPlastin 2G). There is no "human-in-the-loop" component being evaluated for the performance of the device itself; rather, it is a control used to monitor the accuracy of an instrument.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the performance studies is the measured INR and Prothrombin Time values obtained from the specified laboratory instruments and reagents. For the initial categorization of donor plasma into INR levels, the INR was determined using the ACL Top 500 and RecombiPlastin 2G.

8. The Sample Size for the Training Set

There is no explicit mention of a separate "training set" in the provided document. The development of a control plasma does not typically involve a machine learning algorithm that is trained on a dataset. The document describes the manufacturing and analytical validation of a control material.

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

As there is no explicit training set mentioned for an algorithm, the concept of "ground truth for the training set" is not applicable in the context of this device. The INR of the donor plasma is determined by standard laboratory methods using a calibrated instrument for categorization into control levels.

Summary

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Image /page/0/Picture/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an abstract image of three faces in profile, stacked on top of each other. The faces are stylized and appear to be connected.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

February 23, 2017

George King Bio-Medical, Inc. Ms. Barbara Young Director of Scientific Affairs 11771 W.112" Street Overland Park, KS 66210

Re: K161316

Trade/Device Name: George King Coumadin® Plasma Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: Class II Product Code: GGN Dated: January 20, 2017 Received: January 24, 2017

Dear Ms. Young:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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 Parts 801 and 809); medical device reporting (reporting of

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medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800)638-2041 or (301)796-7100 or at its Internet addresshttp://www.fda.gov/MedicalDevicesforYou /Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/ReportaProblem/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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/ Industrv/default.htm.

Sincerely,

Leonthena R. Carrington -S

Lea Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K161316

Device Name George King Coumadin® Plasma

Indications for Use (Describe)

The intended users of the George King Coumadin® Plasma are trained laboratory personnel working in clinical laboratories.

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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Image /page/3/Picture/0 description: The image shows the logo for George King Bio-Medical, Inc. The logo features a stylized letter "K" formed by a red and blue blood vessel. The text "GEORGE KING BIO-MEDICAL, INC." is in blue, with the tagline "Since 1973" and "SETTING THE PACE IN CLINICAL HEMATOLOGY" below.

510(k) Summary (21 CFR 807.92) Coumadin® Plasma

A. Submitter George King Bio-Medical, Inc. 11771 W. 112th St Overland Park, KS 66210 Telephone: (913) 469-5464 Fax: (913) 469-0871
B. Contact Person Barbara Young Director of Laboratory Operations Telephone: (913) 469-5464 Fax: (913) 469-0871
C. Date prepared: 2-10-17
D. Device Identification

Common Name: Coumadin® Plasma Product Trade Name: George King Coumadin® Plasma

Classification Regulation: Plasma, Coagulation

E. Substantial Equivalence Information
Predicate device name: CryoCheck INR Validation Set Predicate 510(k) number: K971219 Precision BioLogic Inc. 140 Eileen Stubbs Ave, Dartmouth, NS B3B 0A9 Canada Telephone: (902) 468-6482

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F. Device Description

Image /page/4/Figure/3 description: This image shows the formula for calculating INR (International Normalized Ratio). The formula is INR = (Patient PT / Mean of normal range) ISI. The formula is presented in a clear and concise manner, with each component labeled appropriately. The image is likely intended for use in a medical or laboratory setting.

Level 1 - INR Control: 1.5-2.8 Level 2 - INR Control: 2.9-4.0 Level 3 - INR Control: >4.0

G. Intended Use
The George King Coumadin® Plasma is an assayed control plasma derived from a single donor on Coumadin® therapy and is intended for use in monitoring the accuracy and control of oral anticoagulant therapy using the INR on an optical instrument with appropriate commercial reagents.

The intended users of the George King Coumadin® Plasma are trained laboratory personnel working in clinical laboratories and research centers.

H. Technical Comparison with Predicate

Similarities

ITEM	DEVICE	PREDICATE
Indications for use	George KingCoumadin® PlasmaThe George King Coumadin® Plasma is anassayed control plasma derived from a singledonor on Coumadin® therapy and is intendedfor in vitro diagnostic use in monitoring theaccuracy of the coagulation analyzer andthromboplastin using the clottableprothrombin time/INR on an opticalinstrument with appropriate commercialreagents. George King Coumadin® Plasmamay be used when evaluating a new lot ofthromboplastin reagent or new coagulationanalyzer.The intended users of the George KingCoumadin® Plasma are trained laboratorypersonnel working in clinical laboratories.	Precision BioLogic CryoCheck INRValidation Set (K971219)The Prothrombin Time (PT) was first describedby Quick and is a common method ofmonitoring oral anticoagulant treatment inpatients receiving warfarin and related drugs.In 1983 the World Health Organization (WHO)described a scheme for PT standardizationbased on the Internal Normalized Ratio (INR).Indicated for use in monitoring the accuracyand control of oral anticoagulant therapy usingthe INR.Not intended for use as calibration or referenceplasma and should not be used for calibratingthe local International Sensitivity Index (ISI) ofcommercial thromboplastins.Designed to enhance the effective monitoringof oral anticoagulant therapy

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ITEM	DEVICE	PREDICATE
	George KingCoumadin® Plasma	Precision BioLogic CryoCheck INRValidation Set (K971219)
Product Code	GGN- Plasma, Coagulation Control	GGN- Plasma, Coagulation Control
TestPrinciple	$INR = \left(\frac{\text{Patient PT}}{\text{Mean of normal range}}\right)^{\text{ISI}}$	Same
Composition	Human fresh frozen citrated plasma withno additives	Assumed frozen citrated plasma sincemost controls sold by P.B are frozen innature.

Differences

ITEM	DEVICE	PREDICATE
Preparation	Collected via plasmapheresisfrom individual human donorsstabilized on Coumadin® therapy.	Well characterized warfarinized plasmas(could not find preparation method)
How Sold	Purchased by individual vials, notas a “set”.	Packaged as a “set” with varying INR ranges

Has the same indications for use
Same test principle and composition
Demonstrates that the device is as safe and effective as a legally marketed device, and does not raise different questions of safety and effectiveness than the predicate device.

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I. Summary of Performance Characteristics

1. Analytical performance

a. Precision

Precision was assessed in-house on 3 different lots of each of 3 INR ranges of GK Coumadin® Plasma on the ACL TOP 500. Precision was evaluated in accordance with CLSI EP05-A2, for 20 days with 2 runs per day and 2 replicates per run for each sample (n=80) using a specific lot of RecombiplasTin 2G.

INR Range: 1.5 – 2.8

Sample Description	Mean Value	n	Within-Run		Between-Run		Between-Day		Total
			SD	CV%	SD	CV%	SD	CV%	SD	CV%
Lot 1	2.33	80	0.04	1.82	0.00	0.00	0.03	1.54	0.05	2.38
Lot 2	2.27	80	0.03	1.75	0.00	0.00	0.03	1.30	0.02	1.30
Lot 3	2.31	80	0.04	1.98	0.00	0.00	0.03	1.32	0.03	1.32

Protime

Sample Description	MeanValue	n	Within-Run		Between-Run		Between-Day		Total
			SD	CV%	SD	CV%	SD	CV%	SD	CV%
Lot 1	28.2	80	0.51 / 1.81		0.00 / 0.00		0.44 / 1.56		0.67 / 2.39
Lot 2	27.5	80	0.48 / 1.76		0.00 / 0.00		0.36 / 1.33		0.61 / 2.21
Lot 3	27.9	80	0.55 / 1.98		0.00 / 0.00		0.37 / 1.34		0.67 / 2.39

INR Range: 2.9 – 4.0

Sample Description	MeanValue	n	Within-Run		Between-Run		Between-Day		Total
			SD	CV%	SD	CV%	SD	CV%	SD	CV%
Lot 1	3.25	80	0.04	1.53	0.00	0.00	0.04	1.39	0.06	2.07
Lot 2	3.03	80	0.04	1.53	0.00	0.00	0.03	1.17	0.05	1.93
Lot 3	2.83	80	0.03	1.28	0.00	0.00	0.03	1.05	0.04	1.66

Protime

Sample Description	MeanValue	n	Within-Run		Between-Run		Between-Day		Total
			SD	CV%	SD	CV%	SD	CV%	SD	CV%
Lot 1	39.3	80	0.61 / 1.55		0.00 / 0.00		0.56 / 1.41		0.83 / 2.10
Lot 2	36.9	80	0.58 / 1.57		0.00 / 0.00		0.44 / 1.19		0.73 / 1.97
Lot 3	34.5	80	0.45 / 1.32		0.00 / 0.00		0.37 / 1.08		0.59 / 1.70

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INR Range: > 4.1

Sample Description	Mean Value	n	Within-Run		Between-Run		Between-Day		Total
			SD	CV%	SD	CV%	SD	CV%	SD	CV%
Lot 1	4.66	80	0.05	1.14	0.00	0.00	0.04	1.03	0.07	1.54
Lot 2	6.95	80	0.10	1.46	0.00	0.00	0.05	0.79	0.11	1.66
Lot 3	4.74	80	0.06	1.45	0.00	0.00	0.03	0.75	0.07	1.64

Protime

Sample Description	MeanValue	n	Within-Run		Between-Run		Between-Day		Total
			SD	CV%	SD	CV%	SD	CV%	SD	CV%
Lot 1	57.2	80	0.66 / 1.16		0.00 / 0.00		0.61 / 1.07		0.90 / 1.58
Lot 2	86.0	80	1.28 / 1.49		0.00 / 0.00		0.69 / 0.80		1.46 / 1.69
Lot 3	58.3	80	0.85 / 1.46		0.00 / 0.00		0.44 / 0.76		0.96 / 1.64

. The results met pre-specified acceptance criteria of CV < 10%

b. Reproducibility

A reproducibility study was performed at three (3) different clinical laboratories, all using an ACL TOP series instruments and RecombiplasTin 2G (Site 1: ACL TOP 500, Site 2: ACL TOP 700, Site 3: ACL TOP 500) and multiple operators. Samples from each lot were assayed for 5 days, one run per day ,for a total of (N=75)

The tables below include the between site data for the reproducibility site evaluation. INR values are followed by the Protime values for each lot number.

INR Range: 1.5 – 2.8

			Repeatability		Between Day		Between Site		Reproducibility
Lot	Mean	n	SD	CV	SD	CV	SD	CV	SD	CV
3603	2.32	75	0.02	0.85	0.05	2.44	0.02	0.92	0.06	2.74
3747	2.27	75	0.02	1.07	0.06	2.69	0.00	0.00	0.06	2.90
3746	2.30	75	0.03	1.40	0.06	2.81	0.00	0.00	0.07	3.14

Protime

			Repeatability		Between Day		Between Site		Reproducibility
Lot	Mean	n	SD	CV	SD	CV	SD	CV	SD	CV
3630	27.9	75	0.24	0.86	0.70	2.51	0.12	0.44	0.75	2.70
3747	27.3	75	0.30	1.10	0.76	2.79	0.00	0.00	0.82	3.01
3746	27.6	75	0.39	1.41	0.81	2.92	0.00	0.00	0.89	3.24

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INR Range: 2.9-4.0

Lot	Mean	n	Repeatability		Between Day		Between Site		Reproducibility
			SD	CV	SD	CV	SD	CV	SD	CV
3748	3.27	75	0.03	1.14	0.12	3.83	0.00	0.00	0.13	3.99
3749	3.06	75	0.09	3.18	0.08	2.63	0.00	0.00	0.12	4.13
3751	2.86	75	0.04	1.38	0.05	1.98	0.00	0.05	0.06	2.41

Protime

Lot	Mean	n	Repeatability		Between Day		Between Site		Reproducibility
Lot	Mean	n	SD	CV	SD	CV	SD	CV	SD	CV
3748	39.7	75	0.46	1.17	1.54	3.90	0.00	0.00	1.61	4.07
3749	37.0	75	1.21	3.27	0.99	2.68	0.00	0.00	1.56	4.23
3751	34.6	75	0.48	1.39	0.70	2.04	0.00	0.00	0.85	2.47

INR Range: >4.0

Lot	Mean	n	Repeatability		Between Day		Between Site		Reproducibility
Lot	Mean	n	SD	CV	SD	CV	SD	CV	SD	CV
3750	4.66	75	0.04	0.97	0.11	2.50	0.00	0.00	0.12	2.68
3752	6.94	75	0.08	1.16	0.28	4.09	0.00	0.00	0.29	4.26
3753	4.74	75	0.05	1.10	0.16	3.44	0.00	0.00	0.17	3.61

Protime

			Repeatability		Between Day		Between Site		Reproducibility
Lot	Mean	n	SD	CV	SD	CV	SD	CV	SD	CV
3750	56.9	75	0.55	0.98	1.45	2.55	0.00	0.00	1.56	2.73
3752	85.2	75	0.97	1.14	3.49	4.10	0.52	0.61	3.66	4.30
3755	57.9	75	0.63	1.10	2.04	3.52	0.00	0.00	2.13	3.68

The results met pre-specified acceptance criteria of CV < 1 .

c. Stability Studies

Open Vial Stability Study: The open vial stability study was conducted on-board the ACL TOP instrument using three lots of GK Coumadin® plasma. The study demonstrated the GK Coumadin® Plasma is stable for 6 hours at 19-22°C. The study met the pre-determined acceptance criteria.

Shelf-Life Stability Study: The closed vial stability study is being conducted at the storage temperature of -70°C using three lots of GK Coumadin® plasma. The current stability claim is 6 months from the date of manufacture. Real time stability testing is on-going and will be used to update the shelf life as more data becomes available.

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d. Interference Study: Not applicable
e. Detection limit: Not applicable
f. Analytical Specificity: Not applicable
g. Assay cut-off: Not applicable
1. Comparison Studies:
- a. Method comparison with predicate device Not applicable
- b. Matrix comparison Not applicable
1. Clinical Studies
- a. Clinical Sensitivity Not Applicable
- b. Clinical Specificity Not Applicable
1. Clinical Cut-off Not applicable

Expected Values – A lot specific Certificate of Analysis with an assigned reference value is provided in the package insert accompanying the product.

J. Proposed Labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10

K. Conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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.