K Number

Device Name

HEMOSIL READIPLAS TIN

Manufacturer

INSTRUMENTATION LABORATORY CO.

Date Cleared

2013-03-24

(212 days)

Product Code

GJS GIS

Regulation Number

864.7750

Intended Use

HemosIL ReadiPlasTin is an in vitro diagnostic thromboplastin reagent, based on recombinant human tissue factor, for the quantitative determination, in human citrated plasma, of Prothrombin Time (PT) and Fibrinogen, on the ACL TOP Family of analyzers. The product is intended to be used for the evaluation of the extrinsic coagulation pathway and the monitoring of Oral Vitamin K Antagonist Therapy.

Device Description

The thromboplastin reagent included in the ReadiPlasTin kit is a liquid liposomal preparation that contains recombinant human tissue factor (RTF) in a synthetic phospholipid blend combined with calcium chloride, buffer and a preservative. In the PT test, the addition of tissue thromboplastin to the patient plasma, in the presence of calcium ions, initiates the activation of the extrinsic pathway. This results in the conversion of fibrinogen to fibrin, with the formation of a solid gel. The fibrinogen is then quantitated by relating the absorbance to a calibrator. ReadiPlasTin can be used with II's Normal control, Routine controls 1-3, Low abnormal control, high abnormal control, ISI calibrate and INR validate.

More Information

Contact

Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

K070005

Reference Devices

ACL TOP 700, ACL TOP 500 CTS

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a reagent and its performance characteristics for a standard in vitro diagnostic test (Prothrombin Time and Fibrinogen). There is no mention of AI, ML, or any computational algorithms beyond standard data analysis for performance evaluation.

Therapeutic

No.
This device is an in vitro diagnostic (IVD) reagent used for quantitative determination of Prothrombin Time (PT) and Fibrinogen in human plasma, which falls under diagnostic purposes rather than therapeutic treatment.

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states "HemosIL ReadiPlasTin is an in vitro diagnostic thromboplastin reagent...". The entire document describes the reagent's use for quantitative determination of Prothrombin Time (PT) and Fibrinogen, which are diagnostic tests for evaluating the extrinsic coagulation pathway.

SaMD (Software as a Medical Device)

The device is a reagent (a chemical substance used in a chemical reaction) for in vitro diagnostic testing, not a software-only medical device.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The very first sentence of the "Intended Use / Indications for Use" section explicitly states: "HemosIL ReadiPlasTin is an in vitro diagnostic thromboplastin reagent..."

Furthermore, the "Intended User / Care Setting" section states: "For in-vitro diagnostic use only."

These statements clearly indicate that the device is intended to be used outside of the body to examine specimens (in this case, human citrated plasma) for diagnostic purposes.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Product codes

GJS, GIS

Device Description

ReadiPlasTin can be used with II's Normal control, Routine controls 1-3, Low abnormal control, high abnormal control, ISI calibrate and INR validate.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

For in-vitro diagnostic use only. For prescription use.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies

Analytical performance:
a. Precision/Reproducibility: Precision and Reproducibility was assessed utilizing 3 lots of reagent on 3 representative members of the ACL TOP Family (2 ACL TOP 700 and an ACL TOP 500 CTS) by 3 independent operators. 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 level (n=80/ instrument/ lot).
b. Linearity/assay reportable range: A fibrinogen linearity study was performed in accordance with CLSI EP6-A. Results met the acceptance criteria of r≥0.95, supporting the device's insert claim of a Fibrinogen Analytical Range of 60-700mg/dL.
c. Traceability, Stability, Expected values (controls, calibrators, or methods): Each batch of ReadiPlasTin reagent is calibrated against an ISI certified House Standard which in turn is calibrated against the corresponding international reference preparation according to the WHO recommendations. The reported INR Reference values were determined over multiple runs on IL coagulation systems running a specific lots of PT reagent against a House Standard ISI Calibrate, which is traceable to the current WHO International Standard identified in the INR Reference table of the product insert and consensus values from > 200 laboratories. Unopened reagent and diluent are stable until the expiration date shown on the vial, when stored at 2-8°C. Once prepared for use, the reagent is stable for 10 days at 2-8°C in closed original vial, or for 10 days at 15°C on the ACL TOP Family in the original vial with no stirring. For optimal stability remove the reagent from the system and store it closed at 2-8°C in the original vial. Do not freeze.
d. Detection limit: Extrinsic factor linearity studies were performed on factors II, V, VII and X. Results met the acceptance criteria at r≥0.95.
e. Analytical Specificity: Testing for interfering substances was performed according to CLSI EP7-A. The assay was insensitive to Heparin, Hemoglobin, Triglycerides, and Bilirubin up to certain levels.
f. Assay cut-off: Not Applicable
Comparison studies:
a. Method Comparison with predicate device: An in-house method comparison was performed in accordance with EP09-A2 on 100+ samples (Normal & Abnormal), comparing HemosIL ReadiPlasTin on representative members of the ACL TOP Family (ACL TOP 700 & ACL TOP 500 CTS), against HemosIL RecombiPlasTin 2G.
b. Matrix comparison: A fresh versus frozen sample study was performed (n=245) on both normal (n=140) and abnormal (n=105) patient samples. The results demonstrated comparable performance on fresh and once-thawed samples.
Clinical studies: NA
Clinical cut-off: NA
Expected values/Reference range: A normal range study (n=199), was performed in accordance with CLSI C28-A3, testing healthy subjects who were not coagulated, with ReadiPlasTin reagent, on a representative member of the ACL TOP Family (ACL TOP 700).

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found (Performance metrics are listed as slopes, intercepts, and correlation coefficients for method comparisons and %CV for precision, not standard sensitivity/specificity/PPV/NPV.)

Predicate Device(s)

K070005

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

Regulation Number and Section

§ 864.7750 Prothrombin time test.

(a)
Identification. A prothrombin time test is a device used as a general screening procedure for the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin therapy (the administration of one of the coumarin anticoagulants in the treatment of venous thrombosis or pulmonary embolism).(b)
Classification. Class II (performance standards).

Summary

K122584

MAR 2 4 2013

510K SUMMARY

ASSAY ONLY TEMPLATE

A. 510(k) Number

TBD

New Assay (ReadiPlasTin only)

Instrumentation Laboratory Co.

Absorbance clot detection

HemosIL ReadiPlasTin

Prothrombin Time (PT) and Fibrinogen

Purpose for Submission B.
C. Measurand
D. Type of Test
E. Applicant
F. Proprietary Name
G. Regulatory Information

Product Name	HemosIL ReadiPlasTin
Regulation section:	21 CFR 864.7750	21CFR 864.7340
Classification:	Class II	Class II
Product code:	GJS	GIS
Common Name	Prothrombin Time Test	Fibrinogen Test
Classification name:	Test, Time, Prothrombin	Test, Fibrinogen
Panel:	Hematology	Hematology

H. Intended Use

Intended use(s): 1.
HemosIL ReadiPlasTin is an in vitro diagnostic thromboplastin reagent, based on recombinant human tissue factor, for the guantitative determination, in human citrated plasma, of Prothrombin Time (PT) and Fibrinogen, on the ACL TOP Family of analyzers. The product is intended to be used for the evaluation of the extrinsic coagulation pathway and the monitoring of Oral Vitamin K Antagonist Therapy.
1. Indication(s) for use:
  Same as intended use(s).
Special conditions for use statement(s): 3.
For in-vitro diagnostic use only. For prescription use.
Special instrument requirements: 4.
ACL TOP Family analyzers

I. Device Description

ReadiPlasTin can be used with II's Normal control, Routine controls 1-3, Low abnormal control, high abnormal control, ISI calibrate and INR validate.

J. Substantial Equivalence Information:

Predicate device name(s): 1.
HemosIL RecombiPlasTin 2G K070005

1. Predicate 510(k) #: Comparison with predicate: 3.
  Table of similarities:

Characteristic	Predicate	Applicant
Company	Instrumentation Laboratory (self)	Same
Device Name	HemosIL RecombiPlasTin 2G	HemosIL ReadiPlasTin
K#	K070005	TBD
Intended Use	HemosIL RecombiPlasTin 2G is a
high sensitivity thromboplastin
reagent, which is based on
recombinant human tissue factor
(RTF), for the quantitative
determination, in human citrated
plasma, of Prothrombin Time
(PT) on IL Coagulation and
ELECTRA Systems and Fibrinogen
on IL Coagulation Systems only.
The product is used for the
evaluation of the extrinsic
coagulation pathway, and the
monitoring of Oral Anticoagulant
Therapy (OAT).	HemosIL ReadiPlasTin is an
in vitro diagnostic
thromboplastin reagent,
based on recombinant
human tissue factor (RTF),
for the quantitative
determination, in human
citrated plasma, of
Prothrombin Time (PT) and
Fibrinogen, on the ACL TOP
Family of analyzers. The
product is intended to be
used for the evaluation of
the extrinsic coagulation
pathway and the
monitoring of Oral Vitamin
K Antagonist Therapy.
Mode of	Prothrombin Measurement
In the PT test, the addition of the
tissue thromboplastin to the
patient sample, in the presence
of calcium, initiates the
activation of the extrinsic
pathway. This results in the
conversion of fibrinogen to fibrin,
with the formation of a solid gel.
PT derived Fibrinogen
Fibrinogen is quantitated (PT
based method) by relating the
absorbance or light scatter
during clotting to a calibrator.	Same
Operation
Sample Type	Citrated Plasma	Same

Table of differences

Characteristic	Predicate	Applicant
Device Name	HemosIL RecombiPlasTin 2G	HemosIL ReadiPlasTin
Delivery	Lyophilized	Liquid

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

No FDA performance standard or FDA guidance has been established.

L. Test Principle

The thromboplastin reagent included in the ReadiPlasTin kit, after mixing with the ReadiPlasTin Diluent, is a liposomal preparation that contains recombinant human tissue factor (RTF), re-lipidated in a synthetic phospholipid blend.

In the PT test, the addition of the tissue thromboplastin (ReadiPlasTin reagent) to the patient plasma in the presence of calcium ions initiates the activation of the extrinsic pathway. This results ultimately in the conversion of fibrin, with formation of a solid gel.

The Fibrinogen is quantitated (PT-based method) by relating the absorbance or lightscatter during clotting to a calibrator.

M. Performance Characteristics

1. Analytical performance:

Precision/Reproducibility a.
Precision and Reproducibility was assessed utilizing 3 lots of reagent on 3 representative members of the ACL TOP Family (2 ACL TOP 700 and an ACL TOP 500 CTS) by 3 independent operators. 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 level (n=80/ instrument/ lot).

Prothrombin Time (seconds)

| System | | HemosIL
ReadiPlasTin | | | Mean PT | | | | | |
|-------------------|--|-------------------------|-----|-----|-------------------|------|------|-------------|-----|-----|
| ACL TOP
Family | | Normal Control | | | 11.4 | 11.7 | 12.1 | | | |
| | | Low Abnormal | | | 21.6 | 21.6 | 22.1 | | | |
| | | High Abnormal | | | 36.2 | 35.5 | 34.8 | | | |
| | | | | | | | | | | |
| Controls | | Within Run (%CV) | | | Between Run (%CV) | | | Total (%CV) | | |
| Normal | | 0.6 | 0.6 | 0.6 | 0.1 | 0.1 | 0.1 | 1.2 | 1.4 | 1.1 |
| Low Abnormal | | 0.7 | 0.6 | 1.1 | 0.6 | 0.3 | 0.0 | 2.9 | 1.5 | 1.2 |
| High Abnormal | | 0.5 | 0.7 | 0.9 | 0.5 | 0.6 | 0.3 | 1.7 | 1.9 | 1.4 |

Fibrinogen (mq/dL)

		Mean Fibrinogen
System	Controls	Lot 1 Lot2 Lot3
ACL TOP Family	Normal ·	297.5 284.6 287.9
	Low Abnormal.	121.8 114.9 117.2
	Low Fibrinogen	135.4 135.7 135.8

	Within Run (%CV)	Between Run (%CV)	Total (%CV)
Controls	Lot1 Lot2 Lot3	Lot1 Lot2 Lot3	Lot1 Lot2 Lot3
Normal	1.2
1.1
1.2	1.4
1.4
1.8	2.0
2.2
2.0
Low Abnormal	1.5
1.4
1.8	1.6
1.0
1.3	2.2
2.4
1.8
Low Fibrinogen	2.9
3.2
3.4	0.0
0.0
0.0	3.5
3.1
3.5

b. Linearity/assay reportable range:

Fibrinogen:

A fibrinogen linearity study was performed in accordance with CLSI EP6-A. Results met the acceptance criteria of r≥0.95, supporting the device's insert claim of a Fibrinogen Analytical Range of 60-700mg/dL.

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

Traceability

Each batch of ReadiPlasTin reagent is calibrated against an ISI certified House Standard which in turn is calibrated against the corresponding international reference preparation according to the WHO recommendations.

The reported INR Reference values were determined over multiple runs on IL coagulation systems running a specific lots of PT reagent against a House Standard ISI Calibrate, which is traceable to the current WHO International Standard identified in the INR Reference table of the product insert and consensus values from > 200 laboratories.

Stability

Unopened reagent and diluent are stable until the expiration date shown on the vial, when stored at 2-8°C. Once prepared for use, the reagent is stable for 10 days at 2-8°C in closed original vial, or for 10 days at 15°C on the ACL TOP Family in the original vial with no stirring. For optimal stability remove the reagent from the system and store it closed at 2-8°C in the original vial. Do not freeze.

d. Detection limit:

Extrinsic Factor Linearity:

Extrinsic factor linearity studies were performed on factors II, V, VII and X. Results met the acceptance criteria at r≥0.95.

Analytical Specificity: e.

Testing for interfering substances was performed according to CLSI EP7-A. The assay was insensitive to Heparin, Hemoglobin, Triglycerides, and Bilirubin up to the following levels:

	Heparin
Parameter	UFH	LMW	Hemoglobin	Triglycerides	Bilirubin
PT (sec)	1.0 IU/mL	1.4 IU/mL	500 mg/dL	1000 mg/dL	50 mg/dL
Fibrinogen	1.5 IU/mL	1.7 IU/mL	500 mg/dL	600 mg/dL	50 mg/dL

f. Assay cut-off: Not Applicable

2. Comparison studies:

Method Comparison with predicate device: a.

An in-house method comparison was performed in accordance with EP09-A2 on 100+ samples (Normal & Abnormal), comparing HemosIL ReadiPlasTin on representative members of the ACL TOP Family (ACL TOP 700 & ACL TOP 500 CTS), against HemosIL RecombiPlasTin 2G, with the following result(s)10.

Assay	Instrument	n	Slope (95% CI)	Intercept (95% CI)	r
'PT(sec)	ACL TOP	230	0.913 (0.907-0.919)	0.948 (0.835-1.062)	0.9989
PT (INR)	700	65	0.979 (0.961-0.996)	0.026 (-0.020-0.072)	0.9975
Fibrinogen		241	0.946 (0.935-0.958)	-4.3 (-9.1-0.5)	0.9955
PT(sec)	ACL	238	0.903 (0.896-0.910)	1.091(0.945-1.236)	0.9981
PT (INR)	TOP 500	65	0.937 (0.914-0.959)	0.016 (0.100-0.232)	0.9955
Fibrinogen	CTS	242	0.975 (0.962-0.988)	-7.6 (-12.9--2.2)	0.9945

In US field studies, the following data were obtained using a specific lot of ReadiPlasTin on the ACL TOP:

Parameter	Site	n	Slope (95% CI)	Intercept (95% CI)	r
PT(sec)	Site 1	254	0.909 (0.900-0.918)	0.45 (0.24-0.66)	0.9966
	Site 2	312	0.970 (0.962-0.978)	0.51 (0.34-0.68)	0.9972
	Site 3	135	0.889 (0.874-0.903)	1.76 (1.40-2.12)	0.9955
PT (INR)	Site 1	76	0.938 (0.916-0.961)	0.138 (0.079-0.197)	0.9947
	Site 2	89	0.928 (0.892-0.963)	0.119 (0.033-0.205)	0.9838
	Site 3	71	0.914 (0.891-0.937)	0.120 (0.060-0.181)	0.9945
Fibrinogen	Site 1	237	0.947 (0.936-0.957)	4.5 (-0.3-9.3)	0.9964
	Site 2	284	0.971(0.961-0.982)	0.56 (-4.4-5.5)	0.9956
	Site 3	129	0.998 (0.978-1.019)	-4.2 (-13.6 to 5.2)	0.9931

b. Matrix comparison:
A fresh versus frozen sample study was performed (n=245) on both normal (n=140) and abnormal (n=105) patient samples. The results demonstrated comparable performance on fresh and once-thawed samples.

3. Clinical studies:

Clinical Sensitivity: NA a.
Clinical Specificity: NA b.
Other clinical supportive data (when a. and b. are not applicable): NA C.
Clinical cut-off: NA 4.

5. Expected values/Reference range *:

A normal range study (n=199), was performed in accordance with CLSI C28-A3, testing healthy subjects who were not coagulated, with ReadiPlasTin reagent, on a representative member of the ACL TOP Family (ACL TOP 700). The reference range was established as:

Assay	NR Reference Interval*	Lower Limit (95% CI)	Upper Limit (95% CI)
PT (sec)		10.2 (9.7-10.4)	12.9 (12.7-14.1)
Fibrinogen (mg/dL)		282 (274-332)	553 (531-562)

*These results were obtained using a specific lot of reagent. Due to many variables which may affect clotting times, each laboratory should verify its own normal range.

N. Proposed Labeling

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

0. Conclusion

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

P. Administrative Information

Applicant Contact Information

Name of applicant:	Instrumentation Laboratory Co.
Mailing address:	180 Hartwell Road
Bedford, MA 01730, USA
Phone #:	781-861-4350
Fax #:	781-861-4207
E-mail address:	jemery@ilww.com
Contact:	Jacqueline Emery, BSEE
Regulatory Affairs Manager

Date Prepared

August 21, 2012

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles an abstract human figure or a caduceus, which is a traditional symbol of medicine.

Public Health Service

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

March 24, 2013

Instrumentation Laboratory Co. c/o Ms. Jacqueline Emery Regulatory Affairs Manager 180 Hartwell Road Bedford, MA 01730

Re: K122584

Trade/Device Name: HemosIL® ReadiPlasTin Regulation Number: 21 CFR § 864.7750 Regulation Name: Prothrombin time test Regulatory Class: Class II Product Code: GJS, GIS Dated: March 15, 2013 Received: March 18, 2013

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 Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

Page 2 - Ms. Jacqueline Emery

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 go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Leonthena R. Carrington -S

for

Maria Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

Indications for Use Statement

510(k) Number (if known): _K122584

HemosIL ReadiPlasTin Device Name:

Indications for Use:

HemosIL ReadiPlasTin is an in vitro diagnostic thromboplastin reagent, based on recombinant human tissue factor, for the quantitative determination, in human citrated plasma, of Prothrombin Time (PT) and Fibrinogen, on the ACL TOP® Family of analyzers. The product is intended to be used for the evaluation of the extrinsic coagulation pathway and the monitoring of Oral Vitamin K Antagonist Therapy.

Prescription Use V (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 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)

Leonthena R. Carrington -S

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k)_K122584