← Product Code [GIZ](/submissions/HE/subpart-f%E2%80%94automated-and-semi-automated-hematology-devices/GIZ) · K060968

# STASIS - I, II AND III; SERATHAN - A, B; INTRIN - EA, SI CALCIUM CHLORIDE 0.02M; FIBRINOGEN CONTROL-NORMAL, LOW (K060968)

_Wortham Laboratories, Inc. · GIZ · May 15, 2007 · Hematology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/HE/subpart-f%E2%80%94automated-and-semi-automated-hematology-devices/GIZ/K060968

## Device Facts

- **Applicant:** Wortham Laboratories, Inc.
- **Product Code:** [GIZ](/submissions/HE/subpart-f%E2%80%94automated-and-semi-automated-hematology-devices/GIZ.md)
- **Decision Date:** May 15, 2007
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 864.5425
- **Device Class:** Class 2
- **Review Panel:** Hematology

## Indications for Use

Wortham Laboratories Stasis 1 Coagulation Control (Normal) is intended for use as a quality control to monitor the performance of Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and Fibrinogen assays. It will yield PT, APTT, and Fibrinogen values in the normal range.

## Device Story

Stasis 1 Coagulation Control is a liquid stable citrated plasma derived from healthy human donors, supplemented with stabilizers and buffers. It serves as a quality control material for clinical coagulation analyzers to monitor PT, APTT, and Fibrinogen assays. The device is intended for use by clinical laboratory professionals. By providing a standardized, stable control with known expected ranges, it allows laboratories to verify the accuracy and precision of their coagulation testing systems. This monitoring helps ensure reliable diagnostic results for patients undergoing coagulation studies, thereby supporting clinical decision-making regarding hemostasis and anticoagulant therapy.

## Clinical Evidence

Bench testing only. Precision studies (n=180 per control) showed CVs < 1.6% for PT/APTT/Fibrinogen. Linearity studies confirmed reportable ranges for warfarin and heparin monitoring. Method comparison against predicates using 120 patient samples (normal, coumadin, heparinized, lupus anticoagulant) showed high correlation (r=0.844 to 0.999).

## Technological Characteristics

Liquid stable citrated human plasma with added stabilizers and buffers. Storage: ≤ -2° C. Analyte factors: PT, APTT, Fibrinogen. 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

- Pacific Hemostasis Coagulation Control Level I ([K984129](/device/K984129.md))

## Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE

A. 510(k) Number:
K060968

B. Purpose for Submission:
New Device

C. Measurand:
Prothrombin Time (PT)
Activated Partial Thromboplastin Time (APTT)
Fibrinogen

D. Type of Test:
Quantitative, mechanical and photo-optical

E. Applicant:
Wortham Laboratories, Inc.

F. Proprietary and Established Names:
Stasis 1 Coagulation Control (Normal)
Stasis 2 Coagulation Control (Abnormal)
Stasis 3 Coagulation Control (Abnormal)

Serathan-A PT Reagent
Serathan-B PT Reagent

Intrin-SI APTT Reagent
Intrin-EA APTT Reagent
Calcium Chloride Solution 0.02 M

Fibrinogen Control Plasma Normal
Fibrinogen Control Plasma Low
Fibrinogen Buffer
Thrombin Reagent

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Fibrinogen Assay Set

Heparin Control Plasma Level 1

Heparin Control Plasma Level 2

## G. Regulatory Information:

1. Regulation section:
- 21 CFR 864.5425, Plasma, Coagulation Control
- 21 CFR 864.7750, Prothrombin Time Test
- 21 CFR 864.7925, Activated Partial Thromboplastin Time
- 21 CFR 864.7340, Fibrinogen Determination System

2. Classification:
- Class II

3. Product code:
- GIZ, Plasma, Control, Normal
- GGC, Plasma Control, Abnormal
- GGN, Plasma, Coagulation Control
- GJS, Test, Time, Prothrombin
- GFO, Activated, Test, Thromboplastin
- GIL Plasma, Fibrinogen Control
- KQJ, System, Fibrinogen Determination

4. Panel:
- 81 (Hematology)

## H. Intended Use:

1. Intended use(s):

Stasis 1 Coagulation Control (Normal) is intended for use as a quality control to monitor the performance of Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and Fibrinogen assays. It will yield PT, APTT, and Fibrinogen values in the normal range.

Stasis 2 Coagulation Control (Abnormal) is intended for use as a quality control to monitor the performance of Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT). It will yield PT, and APTT values in the moderate abnormal range.

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3

Stasis 3 Coagulation Control (Abnormal) is intended for use as a quality control to monitor the performance of Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT). It will yield PT, and APTT values in the strongly abnormal range.

Serathan-A PT reagent is an in-vitro diagnostic reagent intended in a clinical laboratory for the quantitative determination of Prothrombin Time (PT) testing for the detection of coagulation abnormalities in the extrinsic pathway. Serathan-A is a highly sensitive thromboplastin reagent.

Serathan-B PT reagent is an in-vitro diagnostic reagent intended in a clinical laboratory for the quantitative determination of Prothrombin Time (PT) testing for the detection of coagulation abnormalities in the extrinsic pathway. Serathan-B is a moderately sensitive thromboplastin reagent.

Intrin-EA APTT is an in-vitro diagnostic reagent used in the clinical laboratory for the quantitative determination of Activated Partial Thromboplastin Time (APTT) testing for the detection of coagulation abnormalities in the intrinsic pathway. Intrin-EA reagent is sensitive to mild coagulopathies.

Intrin-SI is an in-vitro diagnostic reagent used in the clinical laboratory for the quantitative determination of Activated Partial Thromboplastin Time (APTT) testing for the detection of coagulation abnormalities in the intrinsic pathway. Intrin-SI reagent is sensitive to heparin and lupus anticoagulant plasmas.

Calcium Chloride Solution 0.02 M (CaCl₂) is intended for quantitative use with ellagic acid (Intrin-EA) or silicone particulate activators (Intrin-SI) in performing the Activated Partial Thromboplastin Time (APTT) on citrated plasma.

Fibrinogen Plasma Controls Normal and Low are quantitative control plasma intended for use in the quality control of fibrinogen assays.

Fibrinogen Buffer is intended for use with fibrinogen controls for quantitative determine of fibrinogen in plasma.

Thrombin Reagent is intended for use in the quantitative determination of fibrinogen in plasma samples.

Fibrinogen Assay Set, containing a complete set of Normal Fibrinogen Control (200-400 mg/dl), Thrombin Reagent (100 IU/ml), and Fibrinogen Buffer, is intended for use in the quantitative determination of fibrinogen in plasma samples.

Heparin Control Level 1 and Level 2 are intended as a quality control of the Activated Partial Thromboplastin Time (APTT) during heparin monitoring.

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2. Indication(s) for use:
Same as above.

3. Special conditions for use statement(s):
Not applicable.

4. Special instrument requirements:
Not applicable.

I. Device Description:

Stasis 1, 2, and 3 are liquid controls processed from human plasma collected with 3.2% sodium citrate anticoagulant, with stabilizers and buffers added. The product is supplied in 10 ml bottles.

Serathan-A and Serathan-B reagents are liquid products prepared from rabbit brain tissue, calcium, sodium azide, salts and stabilizers. The reagents are supplied in 20 ml bottles.

Intrin-SI reagent is prepared from rabbit brain phospholipids, kaolin, sodium azide, salts and stabilizers. The reagent is supplied in 10 ml bottles.

Intrin-EA reagent is prepared from rabbit brain phospholipids, ellagic acid, sodium azide, salts, and stabilizers. The reagent is supplied in 10 ml bottles.

Calcium Chloride (CaCl₂) is composed of 0.222% calcium chloride and 0.1% sodium azide. This reagent is supplied in 10 ml bottles

Fibrinogen Plasma Controls Normal and Low are liquid controls prepared from human plasma collected with 3.2% sodium citrate anticoagulant, with stabilizers and buffers. This control is supplied in 10 ml bottles.

Fibrinogen Buffer consists of 1.3% TAPSO Buffer, 0.1% sodium chloride, 0.1% sodium azide, and stabilizers; pH 7.35±0.05. This buffer is supplied in 100 ml bottles

Thrombin reagent is a liquid bovine thrombin containing 100 IU/ml, 0.1% sodium azide, and stabilizers. This reagent is supplied in 10 ml bottles.

Fibrinogen Assay Set consists of: Normal Fibrinogen Control 200-400 mg/dl prepared from human plasma collected with 3.2% sodium citrate anticoagulant with stabilizers and buffers, Thrombin Reagent (100 IU/ml) which is liquid bovine thrombin, and Fibrinogen Buffer (TAPSO buffer in saline, pH 7.35±0.05, with 0.1% sodium azide as a preservative. This assay set contains 1 × 5 ml bottle of Normal

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Fibrinogen Control, 1 x 5 ml bottle of Thrombin Reagent and 4 x 100 ml bottles of Fibrinogen Buffer.

Heparin Control Level 1 is a liquid preparation of citrated human plasma containing, 0.25 U/ml sodium heparin (derived from porcine intestine), sodium azide, stabilizers and buffers. The product is supplied in 10 ml bottles.

Heparin Control Level 2 a liquid preparation of citrated human plasma containing, 0.35 U/ml sodium heparin (derived from porcine intestine), sodium azide, stabilizers and buffers. The product is supplied in 10 ml bottles.

## J. Substantial Equivalence Information:

1. Predicate device name(s):

Pacific Hemostasis Coagulation Control Level I, Pacific Hemostasis Coagulation Control Level II, Pacific Hemostasis Coagulation Control Level III

Pacific Hemostasis Thromboplastin-DS Reagent, Pacific Hemostasis Thromboplastin-D Reagent

Pacific Hemostasis APTT-LS, Pacific Hemostasis Kontact

Pacific Hemostasis Fibrinogen Normal and Low Control, Pacific Hemostasis, Thrombin Reagent, Pacific Hemostasis Heparin Control I

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

K984129, K984130, K984131

K940082, K994100

K891337, K023362

K832520, K800826

K992278, K992279

K970645

3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Stasis 1 | Pacific Hemostasis Level I  |
|  Intended Use | As a quality control to monitor performance of PT, APTT and Fibrinogen in the normal range. | Same  |
|  Expected Range (Mechanical) |  |   |
|  PT | 11.5-11.8 sec | 11.4-11.9 sec  |
|  APTT | 29.3-29.7 sec | 28.0-28.8 sec  |
|  Fibrinogen | 301-313 g/dl | 297-315 g/dl  |

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|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Stasis 1 | Pacific Hemostasis Level I  |
|  Differences  |   |   |
|  Composition | Liquid human citrated plasma | Lyophilized human citrated plasma  |
|  Stability | 12 months at ≥ -2°C, 30 days at 2-8°C | 35 months at 2-8°C, lyophilized, 8 hours at 2-8°C, rehydrated  |
|  Storage | ≥ -2°C | 2-8°C  |
|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Stasis 2 | Pacific Hemostasis Level II  |
|  Intended Use | As a quality control to monitor performance of PT and APTT in the moderate abnormal range. | Same  |
|  Expected Range (Mechanical) |  |   |
|  PT | 19.9-20.3 sec | 19.7-20.8 sec  |
|  APTT | 54.9-56.6 sec | 53.9-56.2 sec  |
|  Differences  |   |   |
|  Composition | Liquid human citrated plasma | Lyophilized human citrated plasma  |
|  Stability | 12 months at ≥ -2°C, 30 days at 2-8°C | 35 months at 2-8°C, lyophilized, 8 hours at 2-8°C, rehydrated  |
|  Storage | ≥ -2°C | 2-8°C  |
|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Stasis 3 | Pacific Hemostasis Level II  |
|  Intended Use | As a quality control to monitor performance of PT and APTT in the high abnormal range. | Same  |
|  Expected Range (Mechanical) |  |   |
|  PT | 32.0-33.0 sec | 31.4-33.6 sec  |
|  APTT | 69.4-71.5 sec | 68.8-71.4  |
|  Differences  |   |   |
|  Composition | Liquid human citrated plasma | Lyophilized human citrated plasma  |
|  Stability | 12 months at ≥ -2°C 30 days at 2-8°C | 35 months at 2-8°C, lyophilized 8 hours at 2-8°C, rehydrated  |
|  Storage | ≥ -2°C | 2-8°C  |

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|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Serathan-A PT | Pacific Hemostasis Thromboplastin-DS  |
|  Intended Use | For the quantitative determination of PT of coagulation abnormalities in the extrinsic pathway; highly sensitive | Same  |
|  Composition | Liquid Rabbit thromboplastin | Lyophilized Rabbit thromboplastin  |
|  International Sensitivity Index (ISI) | 1.0-1.2 | Same  |
|  Assay Factors | PT, Fibrinogen, Factors II, V, VII, X | Same  |
|  Differences  |   |   |
|  Stability | 12 months at ≥ -2°C 30 days at 2-8°C | 30 months at 2-8°C, lyophilized 7 days at 2-8°C, rehydrated  |
|  Storage | ≥ -2°C | 2-8°C  |
|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Serathan-B PT | Pacific Hemostasis Thromboplastin-D  |
|  Intended Use | For the quantitative determination of PT for coagulation abnormalities in the extrinsic pathway; moderately sensitive | Same  |
|  Composition | Liquid Rabbit thromboplastin | Lyophilized Rabbit thromboplastin  |
|  International Sensitivity Index (ISI) | 1.5-1.7 | Same  |
|  Assay Factors | PT, Fibrinogen, Factors II, V, VII, X | Same  |
|  Differences  |   |   |
|  Stability | 12 months at ≥ -2°C 30 days at 2-8°C | 30 months at 2-8°C, lyophilized 7 days at 2-8°C, rehydrated  |
|  Storage | ≥ -2°C | 2-8°C  |
|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Intrin-EA APTT Reagent | Pacific Hemostasis APTT-LS  |
|  Intended Use | For the quantitative determination of APTT for coagulation abnormalities in the intrinsic pathway; sensitive to mild coagulopathies. | Same  |
|  Composition | Liquid Rabbit thromboplastin with ellagic acid activator | Same  |
|  Assay Factors | APTT, Heparin, Factors VIII, IX,XI,XII | Same  |

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|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Intrin-EA APTT Reagent | Pacific Hemostasis APTT-LS  |
|  Differences  |   |   |
|  Stability | 12 months at ≥ -2°C 30 days at 2-8°C | 22 months at 2-8°C, lyophilized 30 days at 2-8°C, rehydrated  |
|  Storage | ≥ -2°C | 2-8°C  |
|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Intrin-SI APTT Reagent | Pacific Hemostasis Kontact  |
|  Intended Use | For the quantitative determination of APTT for coagulation abnormalities in the intrinsic pathway; sensitive to heparin and lupus anticoagulant plasmas. | Same  |
|  Composition | Liquid Rabbit thromboplastin with kaolin activator | Same  |
|  Assay Factors | APTT, Heparin, Factors VIII, IX,XI,XII | Same  |
|  Differences  |   |   |
|  Stability | 12 months at ≥ -2°C 30 days at 2-8°C | 12 months at 2-8°C, lyophilized 30 days at 2-8°C, rehydrated  |
|  Storage | ≥ -2°C | 2-8°C  |
|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Fibrinogen Control Plasma (Normal and Low) | Pacific Hemostasis Fibrinogen Assay  |
|  Intended Use | For use in the quality control of fibrinogen assays. | Same  |
|  Expected Range (Mechanical) |  |   |
|  Normal | 301-313 | 297-315  |
|  Low | 97-103 | 97-104  |
|  Differences  |   |   |
|  Composition | Liquid human citrated plasma | Lyophilized human citrated plasma  |
|  Stability | 12 months ≥ -2°C 30 days at 2-8°C | 24 months at 2-8°C, lyophilized 16 days at 2-8°C, rehydrated  |
|  Storage | ≥ -2°C | 2-8°C  |

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|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Thrombin Reagent) | Pacific Hemostasis Thrombin Reagent  |
|  Intended Use | For thrombin to convert fibrinogen in the quantitative determination of fibrinogen in plasma samples. | Same  |
|  Expected Range (Mechanical) |  |   |
|   | 118-120 IU/ml | 118-120 IU/ml  |
|  Differences  |   |   |
|  Composition | Liquid bovine thrombin | Lyophilized bovine thrombin  |
|  Stability | 12 months at ≥ -2°C
30 days at 2-8°C | 28 months at 2-8°C, lyophilized
1 day at 2-8°C, rehydrated  |
|  Storage | ≥ -2°C | 2-8°C  |
|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Heparin Control Plasma (Level 1 and Level 2) | Pacific Hemostasis Heparin (Control Level 1 and Level 2)  |
|  Intended Use | For use in the quality control of APTT during heparin monitoring, yielding slightly abnormal range for Level 1 (0.25 U/ml) and marked abnormal range for Level 2 (0.35 U/ml) | Same  |
|  Expected Range (Mechanical) |  |   |
|  Level 1 | 45.2-48.5 sec | 44.8-49.1 sec  |
|  Level 2 | 62.4-64.6 sec | 60.1-65.2 sec  |
|  Differences  |   |   |
|  Composition | Liquid human citrated plasma with heparin | Lyophilized human citrated plasma with heparin  |
|  Stability | 12 months at ≥ -2°C
30 days at 2-8°C | 36 months at 2-8°C, lyophilized
8 hours at 2-8°C, rehydrated  |
|  Storage | ≥ -2°C | 2-8°C  |

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

H47-A One Stage Prothrombin Time (PT) Test and Activated Partial Activated Thromboplastin (APTT) Test; Approved Guideline, NCCLS

H21-A3 Collection, Transport and Processing of Blood Specimens for Coagulation Testing and General Performance of Coagulation Assays; Approved Guideline; Third Edition, NCCLS

H30-A2 Procedure for the Determination of Fibrinogen in Plasma; Approved Guideline - Second Edition, NCCLS

WHO Expert Committee on Biological Standardization 28th Report: WHO Technical Series 610, World Health Organization, Geneva, pp. 14-15 and 45-51; 1977.

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L. Test Principle:

Stasis 1 (Normal), Stasis 2 (Moderate Abnormal), and Stasis 3 (High Abnormal):
The use of quality controls is essential for assuring quality in coagulation testing. Stasis 3 and a normal control, such as Stasis 1, are an integral part of a complete quality assurance program.

Serathan-A and Serathan-B reagents: The PT is used as a screen and quantitative test for coagulation factors in the extrinsic and common pathways. Patients with acquired or congenital disorders that reduce the activities of Fibrinogen and Factors II, V, VII, and X will be prolonged in this test. The PT is used to monitor oral anticoagulation therapy. The one step PT measures the clotting time of plasma after adding a source thromboplastin and calcium. The recalcification of plasma with thromboplastin generates activated FXa. FXa in turn activates Prothrombin, which converts fibrinogen to an insoluble fibrin clot.

Intrin-EA and Intrin-SI reagents: The APTT is an established tool as a quantitative test for the intrinsic coagulation factors. It is a simple versatile test which is sensitive to functional deficiencies of factors VIII, IX, XI, and XII. The APTT is performed by adding reagent containing a plasma activator and phospholipid to the test specimen.

Thrombin Control Normal and Low, Thrombin Reagent: The thrombin clotting time fibrinogen assay is based on the method described by Clauss. 1 In the presence of high concentrations of thrombin, the time required for clot formation in dilute plasma is inversely proportional to the fibrinogen concentrations.

Heparin Control Plasma Level 1 and 2: The anticoagulant heparin is used in the treatment of various thrombosis disorders, and for the prevention of thrombin formation during surgery. There are a number of assays available for the clinical laboratory to monitor heparin therapy. A critical component in these assays is the use of quality control plasmas.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Stasis 1 Control is formulated to have PT, APTT, and Fibrinogen values in the normal range. The reproducibility of three lots of the control, a run-run (n=180) singleize assays, produced a coefficient of variations of &lt; 1% for the PT, &lt; 1% for the APTT, and &lt; 1% for Fibrinogen assays. This study was performed on the BBL Fibrometer.

Stasis 2 Control is formulated to have PT, APTT values in the moderate abnormal range. The reproducibility of three lots of the control, a run-run (n=180) singleize assays, produced a coefficient of variations of &lt; 1% for the

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PT, $&lt; 1.5\%$ for the APTT assays. This study was performed on the BBL Fibrometer.

Stasis 3 Control is formulated to have PT, APTT values in the strongly abnormal range. The reproducibility of three lots of the control, a run-run (n=180) singlicate assays, produced a coefficient of variations of $&lt; 1\%$ for the PT, $&lt; 1.6\%$ for the APTT assays. This study was performed on the BBL Fibrometer.

Serathan-A and Serathan-B: Both reagents were assayed by testing the reagent against three lots each of normal and abnormal control plasma, in singlicate assays, on the BBL Fibrometer. A summary of the results follow:

Serathan-A

|   | Level 1 |   |   | Level 2 |   |   | Level 3  |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   | n | run(sec) | % CV | n | run(sec) | % CV | n | run(sec) | % CV  |
|  Within-run | 60 | 12.66 | 0.89% | 60 | 36.45 | 1.09% | 60 | 61.60 | 1.25%  |
|  Run-run | 60 | 12.67 | 0.88% | 60 | 36.47 | .08% | 60 | 61.13 | 1.28%  |

Serathan-B

|   | Level 1 |   |   | Level 2 |   |   | Level 3  |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   | n | run(sec) | % CV | n | run(sec) | % CV | n | run(sec) | % CV  |
|  Within-run | 60 | 11.57 | 0.80% | 60 | 21.17 | 1.27% | 60 | 32.51 | 1.42%  |
|  Run-run | 60 | 11.56 | 0.75% | 60 | 21.13 | 1.22% | 60 | 32.51 | 1.44%  |

Intrin-EA was assayed by testing the reagent against normal and abnormal control plasmas, in singlicate assays, on the BBL Fibrometer. A Summary of the results follows:

|   | Level 1 |   |   | Level 2 |   |   | Level 3  |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   | n | run(sec) | % CV | n | run(sec) | % CV | n | run(sec) | % CV  |
|  Within-run | 60 | 29.01 | 0.51% | 60 | 48.03 | 0.41% | 60 | 67.74 | 0.73%  |
|  Run-run | 60 | 29.03 | 0.60% | 60 | 47.52 | 0.44% | 60 | 67.74 | 0.71%  |

Intrin-SI was assayed by testing normal and abnormal plasmas on the BBL Fibrometer. A Summary of the results follows:

|  Level 1 |   |   |   | Level 2 |   |   | Level 3  |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  n | run(sec) | % CV | n | run(sec) | % CV | n | run(sec) | % CV |   |
|  Within-run | 60 | 29.51 | 0.29% | 60 | 55.75 | 0.74% | 60 | 70.49 | 0.75%  |
|  Run-run | 60 | 29.51 | 0.29% | 60 | 55.75 | 0.75% | 60 | 70.49 | 0.75%  |

Fibrinogen Control Low plasma samples were tested on the BBL Fibrometer, yielding a within-run and run-run precision of $0.60\%$ CV and $0.58\%$ CV, respectively.

Fibrinogen Control Normal plasma samples were tested on the BBL Fibrometer, yielding a within-run and run-run precision of $0.56\%$ CV and $0.57\%$ CV, respectively.

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Heparin Control Level 1 Plasma as abnormal APTT control, within-run precision studies performed on the BBL Fibrometer using Intrin-SI reagent yielded CV's of 1.82 %, and a 1.77% CV for run-run assays.

Heparin Control Level 2 Plasma as abnormal APTT control, within-run precision studies performed on the BBL Fibrometer using Intrin-SI reagent yielded CV's of 1.92 %, and a 1.81% CV for run-run assays.

Thrombin Reagent: Precision of the Normal and Low Fibrinogen Control result is dependent on many factors, such as the instrument, technique and the reagent used. A 1:6 and 1:8 dilutions of 3 lots of the Normal and Low Fibrinogen Control respectively, were made and assayed in singlicate on the BBL Fibrometer. A summary of the results follow:

|  Control | n | within-run | n | run-run  |
| --- | --- | --- | --- | --- |
|  Normal | 60 | 0.56% CV | 180 | 0.57% CV  |
|  Low | 60 | 0.60% CV | 180 | 0.58% CV  |

b. Linearity/assay reportable range:

Serathan-A Reportable Range/Linearity: A linearity study, assayed on the BBL Fibrometer, of Intrin-EA to measure warfarin in 18 plasma samples of 0-5 U/ml, yielded a linearity range of 12.1 -41.9 seconds.

Serathan-B reagents Reportable Range/Linearity: A linearity study, assayed on the BBL Fibrometer, to measure warfarin in 18 plasma samples of 0-5 U/ml, yielded a linearity range of 11.6 -36.2 seconds.

Intrin-EA A Reportable Range/Linearity: linearity study, assayed on the BBL Fibrometer, of Intrin-EA to measure heparin in 18 plasma samples of 0-5 U/ml, yielded a linearity range of 29.0 -70.7 seconds.

Intrin-SI Reportable Range/Linearity: A linearity study, assayed on the BBL Fibrometer, of Intrin-SI to measure heparin in 18 plasma samples of 0-5 U/ml, yielded a linearity range of 29.8 - 106.3 seconds.

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

Expected Values:

Stasis Control 1, 2, 3

When all levels of Stasis controls were evaluated on the BBL Fibrometer, the following results were obtained:

|   | Serathan-B (ISI=1.58) | Serathan-A (ISI=1.20)  |
| --- | --- | --- |
|  Stasis 1 | 11.5-11.9 | 12.4-12.8 sec  |
|  Stasis 2 | 20.4-22.0 | 31.6-33.4 sec  |
|  Stasis 3 | 31.6-33.4 sec | 60.7-62.3 sec  |

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|   | Intrin-SI | Intrin-EA  |
| --- | --- | --- |
|  Stasis 1 | 29.3-29.7 0 | 28.6-29.4 sec  |
|  Stasis 2 | 55.0-56.6 sec | 46.0-47.0 sec  |
|  Stasis 3 | 69.4-71.6 sec | 63.8-65.8 sec  |
|   | Fibrinogen, Normal |   |
|  Stasis 1 | 299-303 mg/dl |   |

## Fibrinogen Control Low

Three lots were evaluated in singlicate on the BBL Fibrometer (n=180), the run-run mean fibrinogen level of 99 mg/dl and a ± 2SD range of 98-100 mg/dl. Actual values recovered depend on the instrument and reagent used.

## Fibrinogen Control Normal

Three lots were evaluated in singlicate on the BBL Fibrometer (n=180), the run-run mean fibrinogen level was 301 mg/dl and at ± 2SD range of 300-302 mg/dl. Actual values recovered depend on the instrument and reagent used.

**Heparin Control Plasma Level 1** was assayed on the BBL Fibrometer produced a mean APTT clotting time of 46.9 seconds and a ± 2SD range of 45.1-48.7 seconds.

**Heparin Control Plasma Level 2** was assayed on the BBL Fibrometer produced a mean APTT clotting time of 63.5 seconds and a ± 2SD range of 61.2-65.8 seconds.

**Stability**: A Real Time Stability study for all coagulation controls and reagents was performed for 30 days at -2°C and 4°C. Results showed not loss of activity. Real time studies will be on going.

d. Detection limit:

Not Applicable.

e. Analytical specificity:

Not Applicable.

f. Assay cut-off:

Not Applicable.

2. Comparison studies:

a. Method comparison with predicate device:

**Serathan-A and Serathan-B** was tested against the predicate with 120 adult

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normal and coumadin patient samples, in singlicate assay.

Results:
Serathan A  r = 0.999  y = 0.948x + 0.620
Serathan-B  r = 0.996  y = 0.989x + 0.039

Intrin-EA and Intrin- SI: Studies were performed against another thromboplastin reagent by performing APTT testing on 120 adult normal and heparinized patient samples, and 10 lupus anticoagulant plasma samples in singlicate assay, on the BBL Fibrometer.

Results:
Intrin-EA  r = 0.996  y = 1.022x + 1.293
Lupus Study  r = 0.979  y = 1.037 x- 4.363
Intrin-SI  r = 0.998  y = 1.032x + 0.15
Lupus Study  r = 0.844  y = 1.033 x- 4.76

b. Matrix comparison:
Not Applicable.

3. Clinical studies:
a. Clinical Sensitivity:
Not Applicable.
b. Clinical specificity:
Not Applicable.
c. Other clinical supportive data (when a. and b. are not applicable):
Not Applicable.

4. Clinical cut-off:
Not Applicable.

5. Expected values/Reference range:

Serathan-B was evaluated on a normal population, the following results were obtained:
|  Instrument | PT Mean (sec) | Range (± 2SD) | N  |
| --- | --- | --- | --- |
|  ACL Advance | 11.5 | 10.9 –12.1 | 60  |

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Serathan-A was evaluated on a normal population, the following results were obtained:

|  Instrument | PT Mean (sec) | Range (± 2SD) | N  |
| --- | --- | --- | --- |
|  ACL Advance | 12.1 | 11.9 –12.3 | 60  |

Intrin-EA was evaluated on 60 normal adult patients using the BBL Fibrometer, the following results were obtained.

|   | PT Mean (sec) | Range (± 2SD) | N  |
| --- | --- | --- | --- |
|  Photo-optical | 29.0 | 28.7 –29.3 | 60  |
|  Mechanical | 29.0 | 28.5 –29.5 | 60  |

These values should only be used as a guideline. Each laboratory should establish a Normal Reference Range

Intrin-SI was evaluated on 60 normal adult patients, the following results were obtained.

|   | PT Mean (sec) | Range (± 2SD) | N  |
| --- | --- | --- | --- |
|  Photo-optical | 29.5 | 29.3 –29.6 | 60  |
|  Mechanical | 29.5 | 29.3 –29.6 | 60  |

## Thrombin Reagent

Laboratories should establish a normal control interval for fibrinogen measurement. The referenced normal control is 200-400 mg/dl.

## N. Proposed Labeling:

The labeling is sufficient and it 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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16

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**Source:** [https://fda.innolitics.com/submissions/HE/subpart-f%E2%80%94automated-and-semi-automated-hematology-devices/GIZ/K060968](https://fda.innolitics.com/submissions/HE/subpart-f%E2%80%94automated-and-semi-automated-hematology-devices/GIZ/K060968)

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