← Product Code [GGN](/submissions/HE/subpart-f%E2%80%94automated-and-semi-automated-hematology-devices/GGN) · K161316

# George King Coumadin Plasma (K161316)

_George King Bio-Medical, Inc. · GGN · Feb 23, 2017 · Hematology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/HE/subpart-f%E2%80%94automated-and-semi-automated-hematology-devices/GGN/K161316

## Device Facts

- **Applicant:** George King Bio-Medical, Inc.
- **Product Code:** [GGN](/submissions/HE/subpart-f%E2%80%94automated-and-semi-automated-hematology-devices/GGN.md)
- **Decision Date:** Feb 23, 2017
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 864.5425
- **Device Class:** Class 2
- **Review Panel:** Hematology

## Indications for Use

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

## Device Story

George King Coumadin® Plasma is an assayed control plasma derived from single human donors stabilized on Coumadin® therapy. It serves as a quality control material for monitoring the accuracy of coagulation analyzers and thromboplastin reagents. The device is used by trained laboratory personnel in clinical laboratories. The plasma is thawed and placed on an optical coagulation analyzer (specifically the ACL TOP 500). The analyzer performs a quantitative clottable prothrombin time (PT) assay using RecombiPlastin 2G reagent. The device output is a PT value, which is converted to an International Normalized Ratio (INR) using the formula INR = [PT / MNPT]^ISI. These INR values are compared against assigned control ranges (Level I: 1.5–2.8; Level II: 2.9–4.0; Level III: >4.0) to verify the performance of the laboratory's coagulation testing system. This ensures the accuracy of patient anticoagulant therapy monitoring.

## Clinical Evidence

Bench testing only. Precision and reproducibility were evaluated following CLSI EP05-A3 guidelines across three clinical sites using the ACL TOP 500 and ACL TOP 700 analyzers. Total precision (CV%) for INR ranged from 1.54% to 4.26% across three levels. Stability studies (on-board and 6-month real-time) confirmed performance within acceptable ranges. No clinical patient data was required or provided.

## Technological Characteristics

Human fresh frozen citrated plasma; no additives. Principle: Prothrombin time/INR monitoring. Form factor: Individual frozen vials. Connectivity: None (standalone control material). Storage: -70°C. No software or electronic components.

## Regulatory 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.

## Special Controls

*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.

## Predicate Devices

- CryoCheck INR Validation Set ([K971219](/device/K971219.md))

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
> Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/).

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM

A. 510(k) Number:
K161316

B. Purpose for Submission:
Clearance of a new device

C. Measurand:
Prothrombin Time (PT) and International Normalized Ratio (INR)

D. Type of Test:
Quantitative clotting assay

E. Applicant:
George King Bio-Medical, Inc.

F. Proprietary and Established Names:
George King Coumadin® Plasma

G. Regulatory Information:

1. Regulation section:
21 CFR § 864.5425, Multipurpose system for in vitro coagulation studies

2. Classification:
Class II

3. Product code:
GGN, Plasma, coagulation control

4. Panel:
Hematology (81)

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H. Intended Use:

1. Intended use(s):

The George King Coumadin® Plasma is 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.

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

2. Indication(s) for use:

Same as the Intended Use

3. Special conditions for use statement(s):

For prescription use only

4. Special instrument requirements:

Instrumentation Laboratory ACL TOP 500 coagulation analyzer

I. Device Description:

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

The INR value of the donor plasma is determined using the ACL TOP 500 with RecombiPlastin 2G reagent 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:

$$
\mathrm{INR} = \left[\mathrm{PT} / \mathrm{MNPT}\right]^{\mathrm{ISI}}
$$

Level I: INR Control: 1.5 – 2.8

Level II: INR Control: 2.9 – 4.0

Level III: INR Control: > 4.0

J. Substantial Equivalence Information:

1. Predicate device name(s):

CryoCheck INR Validation Set

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2. Predicate 510(k) number(s):

K971219

3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device
George King Coumadin® Plasma | Predicate
CryoCheck INR Validation Set  |
|  Intended use | The George King Coumadin® Plasma is 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.

The intended users of the George King Coumadin® Plasma are trained laboratory personnel working in clinical laboratories. | CryoCheck INR Validation Set is recommended for use in monitoring the accuracy and control of oral anticoagulant therapy using the International Normalized Ratio (INR) on a variety of prothrombin time systems. CryoCheck INR Validation Set in not intended for use as calibration or reference plasma and should not be used for calibrating the local International Sensitivity Index (ISI) of commercial thromboplastins.  |
|  Differences  |   |   |
| --- | --- | --- |
|  Item | Device
George King Coumadin® Plasma | Predicate
CryoCheck INR Validation Set  |
|  On Board stability | 6 hours | 24 hours at 2–8°C  |
|  Shelf-life stability | 6 months | NA  |
|  Reagent format | Frozen citrated plasma | Same  |
|  Storage | –70°C | –20°C to –80°C  |

K. Standard/Guidance Document Referenced (if applicable):

CLSI EP05-A3, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Third Edition

CLSI EP15-A3, User Verification of Precision and Estimation of Bias

CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents

L. Test Principle:

Tri-level George King Coumadin® Plasma was designed to monitor the accuracy of the

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coagulation analyzer and thromboplastin and evaluate new lots of thromboplastin reagent or new coagulation analyzer. It will be used the same manner as the patient's plasma sample in quantitative clottable prothrombin time assay with RecombiPlastin 2G

## M. Performance Characteristics:

### 1. Analytical performance:

#### a. Precision/Repeatability

A precision (repeatability) study was assessed in-house on three lots of George King Coumadin® Plasma on the ACL TOP 500 and the test was performed with two runs per day and two replicates per run for 20 days using a specific lot of RecombiPlasTin 2G according to the CLSI EP05-A3 guideline. Plasma was first thawed in a water bath at 37°C for 2–5 minutes prior to the test. The data for within-run, between-run, between-day, and total precision of the International Normalized Ratio (INR) and Prothrombin time (PT) were calculated for each lot and summarized in the table below.

Level 1: INR range: 1.5 – 2.8

|  Lot | Mean | N | Within-run |   | Between-run |   | Between-day |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | CV% | SD | CV% | SD | CV% | SD | CV%  |
|  1 | 2.32 | 80 | 0.04 | 1.82 | 0.00 | 0.00 | 0.03 | 1.54 | 0.05 | 2.38  |
|  2 | 2.27 | 80 | 0.03 | 1.75 | 0.00 | 0.00 | 0.03 | 1.30 | 0.05 | 2.15  |
|  3 | 2.31 | 80 | 0.04 | 1.98 | 0.00 | 0.00 | 0.03 | 1.32 | 0.06 | 2.38  |

Level 1: Prothrombin Time

|  Lot | Mean (Sec) | N | Within-run |   | Between-run |   | Between-day |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | CV% | SD | CV% | SD | CV% | SD | CV%  |
|  1 | 28.2 | 80 | 0.51 | 1.81 | 0.00 | 0.00 | 0.44 | 1.56 | 0.67 | 2.39  |
|  2 | 27.5 | 80 | 0.48 | 1.76 | 0.00 | 0.00 | 0.36 | 1.33 | 0.61 | 2.21  |
|  3 | 27.9 | 80 | 0.55 | 1.98 | 0.00 | 0.00 | 0.37 | 1.34 | 0.67 | 2.39  |

Level 2: INR range: 2.9 – 4.0

|  Lot | Mean | N | Within-run |   | Between-run |   | Between-day |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | CV% | SD | CV% | SD | CV% | SD | CV%  |
|  1 | 3.25 | 80 | 0.04 | 1.53 | 0.00 | 0.00 | 0.04 | 1.39 | 0.06 | 2.07  |
|  2 | 3.03 | 80 | 0.04 | 1.53 | 0.00 | 0.00 | 0.03 | 1.17 | 0.05 | 1.93  |
|  3 | 2.83 | 80 | 0.03 | 1.28 | 0.00 | 0.00 | 0.03 | 1.05 | 0.04 | 1.66  |

Level 2: Prothrombin Time

|  Lot | Mean (Sec) | N | Within-run |   | Between-run |   | Between-day |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | CV% | SD | CV% | SD | CV% | SD | CV%  |
|  1 | 39.3 | 80 | 0.61 | 1.55 | 0.00 | 0.00 | 0.56 | 1.41 | 0.83 | 2.10  |
|  2 | 36.9 | 80 | 0.58 | 1.57 | 0.00 | 0.00 | 0.44 | 1.19 | 0.73 | 1.97  |

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|  Lot | Mean (Sec) | N | Within-run |   | Between-run |   | Between-day |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | CV% | SD | CV% | SD | CV% | SD | CV%  |
|  3 | 34.5 | 80 | 0.45 | 1.32 | 0.00 | 0.00 | 0.37 | 1.08 | 0.59 | 1.70  |

Level 3: INR range: > 4.0

|  Lot | Mean | N | Within-run |   | Between-run |   | Between-day |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | CV% | SD | CV% | SD | CV% | SD | CV%  |
|  1 | 4.66 | 80 | 0.05 | 1.14 | 0.00 | 0.00 | 0.04 | 1.03 | 0.07 | 1.54  |
|  2 | 6.95 | 80 | 0.10 | 1.46 | 0.00 | 0.00 | 0.05 | 0.79 | 0.11 | 1.66  |
|  3 | 4.74 | 80 | 0.06 | 1.45 | 0.00 | 0.00 | 0.03 | 1.75 | 0.07 | 1.64  |

Level 3: Prothrombin Time

|  Lot | Mean (Sec) | N | Within-run |   | Between-run |   | Between-day |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | CV% | SD | CV% | SD | CV% | SD | CV%  |
|  1 | 57.2 | 80 | 0.66 | 1.16 | 0.00 | 0.00 | 0.61 | 1.07 | 0.90 | 1.58  |
|  2 | 86.0 | 80 | 1.28 | 1.49 | 0.00 | 0.00 | 0.69 | 0.80 | 1.46 | 1.69  |
|  3 | 58.3 | 80 | 0.85 | 1.46 | 0.00 | 0.00 | 0.44 | 0.76 | 0.96 | 1.64  |

## b. Precision/Reproducibility:

A reproducibility study was conducted at three clinical laboratories using the ACL TOP 500 and ACL TOP 700 with multiple operators. Samples from each lot were assayed for 5 days, one run per day and five replicates per run for a total of 25 replicates per site. The data of within-run (repeatability), between-day, between-site and total precision (reproducibility) at each level were calculated following CLSI EP05-A3 guidelines for all sites and are summarized in the tables below.

Level 1: INR range: 1.5 – 2.8

|  Lot | Mean | N | Within-run |   | Between-day |   | Between-site |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  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  |

Level 1: Prothrombin Time

|  Lot | Mean | N | Within-run |   | Between-day |   | Between-site |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | CV% | SD | CV% | SD | CV% | SD | CV%  |
|  3603 | 2.32 | 75 | 0.24 | 0.86 | 0.70 | 2.51 | 0.12 | 0.44 | 0.75 | 2.70  |
|  3747 | 2.27 | 75 | 0.30 | 1.10 | 0.76 | 2.79 | 0.00 | 0.00 | 0.82 | 3.01  |
|  3746 | 2.30 | 75 | 0.39 | 1.41 | 0.81 | 2.92 | 0.00 | 0.00 | 0.89 | 3.24  |

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Level 2:INR range: 2.9 - 4.0

|  Lot | Mean | N | Within-run |   | Between-day |   | Between-site |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  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  |

Level 2: Prothrombin Time

|  Lot | Mean | N | Within-run |   | Between-day |   | Between-site |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  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  |

Level 3: INR range:  $>4.0$

|  Lot | Mean | N | Within-run |   | Between-day |   | Between-site |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  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  |

Level 3: Prothrombin Time

|  Lot | Mean | N | Within-run |   | Between-day |   | Between-site |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  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  |

c. Linearity/assay reportable range:

Not applicable

d. Traceability, Stability, Expected values (controls, calibrators, or methods):

Value Assignment:

The INR value of the George King Coumadin® Plasma was assigned by testing one manufactured lot per INR level of plasma. The value assignment test was performed on ACL TOP 500 coagulation analyzer using RecombinplasTin 2 G with five vials per day over 4 days. The final dataset of each lot resulted in a total of 20 measurements per INR level. Standard deviation was used to determine the range of INR values for each George King Coumadin® Plasma lot and the mean INR values were assigned to each lot.

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# On Board stability:

For each INR level, three George King Coumadin® Plasma lots were tested to determine on-board stability. The plasma was thawed in a water bath at 37°C for 2–5 minutes. The thawed plasma was poured into labeled vials and kept on-board the ACL TOP 500 analyzer for testing. The samples were tested in duplicate at time 0 (baseline) and 2, 4, 6 and 7 hour increments using a quantitative clottable prothrombin time assay with RecombiPlastin 2G. INR values were calculated from the PT values. The initial baseline (0 hour) INR was used as the comparison value for acceptability.

Stability performance of each George King Coumadin® Plasma lot was assessed in terms of percentage change over time and INR values for each level of George King Coumadin® Plasma at each time point were within the acceptable range, supportive of a 6-hour on-board stability claim.

# Shelf-life stability

A 6-month real-time stability test was performed on the ACL TOP 500 coagulation analyzer using one lot of George King Coumadin® Plasma per INR level were tested at each testing interval (~30 days) for this study (using one vial of plasma from each lot). The real-time stability study is ongoing with a 3-year study plan. Data was collected at 0, 32, 62, 94, 121, 154, 188 days and day 0 data is used as the baseline value for stability comparison.

Stability performance of each George King Coumadin® Plasma lot was assessed in terms of percentage change over time and INR values for each level of George King Coumadin® Plasma at each time point were within the acceptable range, supportive of a 6-month real-time stability claim.

d. Detection limit:

Not applicable

e. Analytical specificity:

Not applicable

f. Assay cut-off:

Not applicable

g. Interference Study:

Not applicable

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2. Comparison studies:
a. Method comparison:
Not applicable
b. Matrix comparison:
Not applicable
c. Clinical cut-off:
Not applicable

5. Expected values:
The expected values are included with each package insert based on the control value assignment of each lot.

N. Proposed Labeling:
The labeling is complete and satisfies the requirements of 21 CFR Part 809.10.

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

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**Source:** [https://fda.innolitics.com/submissions/HE/subpart-f%E2%80%94automated-and-semi-automated-hematology-devices/GGN/K161316](https://fda.innolitics.com/submissions/HE/subpart-f%E2%80%94automated-and-semi-automated-hematology-devices/GGN/K161316)

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