©2007 Wortham Laboratories, Inc. Training Coagulation Training Presentation v1.1 – 7.2007 ©2007 Wortham Laboratories, Inc.

Wortham Training This presentation is intended to inform our sales network and professional medical practitioners about the next generation of coagulation products. This presentation is made available with the following important conditions inherent to the delivery of product information to the medical community and our sales network: While the information prepared herein is presented in good faith, changes may occur which affect the intended result of this presentation. Please understand that literature and training regarding the proper utilization of Wortham products may be updated at any time. Material changes in product information will be made available as changes are made. This presentation was prepared in June 2007. Each WLI Presentation is dated. The use of any medical product requires specific instruction which may exceed the scope of this presentation. Please consult Wortham Laboratories product inserts, your distributor and/or our support desk with any product questions. We are devoted to your satisfaction and success. While this presentation represents Wortham products as suitable for a particular purpose, the presentation alone cannot act as a sole source of information for introducing this product into your laboratory or other setting. We will provide a full complement of supporting tools and documentation to assist you. The contents of this presentation are Copyright ©2007 Wortham Laboratories. This presentation contains internationally recognized trademark of Wortham Laboratories, Incorporated. Other trademarks referenced herein are the property of their specific owners, and are incorporated throughout for the exclusive purpose of information, education and training. THIS PRESENTATION IS FORMATTED FOR NARRATIVE HOSTING, and cannot serve as a sole product insert or instructional reference document. WELCOME TO WORTHAM LABORATORIES – TOMORROW’S TECHNOLOGY TODAY

Indications for Use

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Stasis 1 Coagulation Control (Normal) 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.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Stasis 2 Coagulation Control (Abnormal) Indications For Use: Wortham Laboratories 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.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Stasis 3 Coagulation Control (Abnormal) Indications For Use: Wortham Laboratories 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.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Serathan-A PT Reagent Indications For Use: Wortham Laboratories 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.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Serathan-B PT Reagent Indications For Use: Wortham Laboratories 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.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Intrin-SI APTT Reagent Indications For Use: Wortham Laboratories 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.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Intrin-EA APTT Reagent Indications For Use: Wortham Laboratories 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.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Fibrinogen Control Plasma Normal Indications For Use: Wortham Laboratories Fibrinogen Control Normal, a quantitative control plasma, is intended for use in the quality control of fibrinogen assays.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Fibrinogen Control Plasma Low Indications For Use: Wortham Laboratories Fibrinogen Control Low, a quantitative control plasma, is intended for use in the quality control of fibrinogen assays.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Heparin Control Plasma Level 1 Indications For Use: Wortham Laboratories Heparin Control Level 1, is intended as a quality control of the Activated Partial Thromboplastin Time (APTT) during heparin monitoring.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Heparin Control Plasma Level 2 Indications For Use: Wortham Laboratories Heparin Control Level 2, is intended as a quality control of the Activated Partial Thromboplastin Time (APTT) during heparin monitoring.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Fibrinogen Assay Set Indications For Use: Wortham Laboratories 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.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Fibrinogen Buffer Indications For Use: Wortham Laboratories Fibrinogen Buffer is designed as a diluent for fibrinogen studies.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Thrombin Reagent Indications For Use: Wortham Laboratories Thrombin Reagent is intended for thrombin to convert fibrinogen in the quantitative determination of fibrinogen in plasma samples.

Indications for Use 510(k) Number (if known): K060968 Device Name: Wortham Laboratories Calcium Chloride Solution 0.02 M Indications For Use: Wortham Laboratories Calcium Chloride Solution 0.02 M (CaCl2) is intended for quantitative use with ellagic acid (Intrin-EA) or silicon particulate activators (Intrin-SI) in performing the activated partial thromboplastin time (APTT) on citrated plasma.

Product Inserts: Stasis I

Product Inserts: Stasis 1 Coagulation Control Plasma Level 1 (Normal) Intended Use Review 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.

Product Inserts: Stasis 1 Coagulation Control Plasma Level 1 (Normal) Summary and Principle The use of plasma controls is essential for assuring quality in coagulation testing. Normal and abnormal controls should be run with each group of assays, with every 40 samples, reagent changes, instrument modification, and with a change in personnel. Stasis 1 and at least one abnormal control such as Stasis 2 or Stasis 3, are an integral part of a complete quality assurance program.

Product Inserts: Stasis 1 Coagulation Control Plasma Level 1 (Normal) Expected Values When Stasis 1 was evaluated on 60 samples on the BBL Fibrometer, the following results were obtained: Serathan-B (ISI=1.58) Serathan-A (ISI=1.20) Mean ±2SD PT 11.7 sec 11.5-11.9 sec. 12.6 sec. 12.4-12.8 sec. Intrin - SI Intrin - EA APTT 29.5 sec 29.3-29.7 sec 29.0 sec 28.6-29.4 sec Fibrinogen - Normal Fibrinogen 301 mg/dl 299-303 mg/dl

Product Inserts: Stasis 1 Coagulation Control Plasma Level 1 (Normal) Regarding Expected Values These values should only be used as a guideline. Each laboratory should establish a Normal Reference Range (NRR) using instrumentation, blood collection methods, and testing techniques used in that laboratory. The NRR should be reestablished or at least verified when changing lot numbers of the same control. A new NRR should be established with any change in reagents, instrumentation, blood collection techniques or anticoagulant.

Product Inserts: Stasis 1 Coagulation Control Plasma Level 1 (Normal) Performance Characteristics 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) singlicate assays, produced a coefficient of variations of < 1% for the PT, < 1% for the APTT, and < 1% for Fibrinogen assays on the BBL Fibrometer. Actual values recorded depend on the instrument and reagent used.

Product Inserts: Stasis II

Product Inserts: Stasis 2 Coagulation Control Plasma Level 2 (Abnormal) Intended Use Wortham Laboratories 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.

Product Inserts: Stasis 2 Coagulation Control Plasma Level 2 (Abnormal) Summary and Principle The use of plasma controls is essential for assuring quality in coagulation testing. Normal and abnormal controls should be run with each group of assays, with every 40 samples, reagent changes, instrument modification, and with a change in personnel. Stasis 2 and a normal control, such as Stasis 1, are an integral part of a complete quality assurance program.

Product Inserts: Stasis 2 Coagulation Control Plasma Level 2 (Abnormal) Expected Values When Stasis 2 was evaluated on 60 samples on the BBL Fibrometer, the following results were obtained: Serathan-B (ISI=1.58) Serathan-A (ISI=1.20) Mean ±2SD PT 21.2 sec. 20.4-22.0 sec. 36.4 sec. 35.6-37.2 sec. Intrin - SI Intrin - EA APTT 55.8 sec. 55.0-56.6 sec. 46.5 sec. 46.0-47.0 sec.

Performance Characteristics Product Inserts: Stasis 2 Coagulation Control Plasma Level 2 (Abnormal) Performance Characteristics 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) singlicate assays, produced a coefficient of variations of < 1% for the PT, < 1.5% for the APTT assays on the BBL Fibrometer. Actual values recorded depend on the instrument and reagent used.

Product Inserts: Stasis III

Product Inserts: Stasis 3 Coagulation Control Plasma Level 3 (Abnormal) Intended Use Wortham Laboratories 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.

Product Inserts: Stasis 3 Coagulation Control Plasma Level 3 (Abnormal) Summary and Principle The use of plasma controls is essential for assuring quality in coagulation testing. Normal and abnormal controls should be run with each group of assays, with every 40 samples, reagent changes, instrument modification, and with a change in personnel. Stasis 3 and a normal control, such as Stasis 1, are an integral part of a complete quality assurance program.

Product Inserts: Stasis 3 Coagulation Control Plasma Level 3 (Abnormal) Expected Values When Stasis 3 was evaluated on 60 samples on the BBL Fibrometer, the following results were obtained: Serathan-B (ISI=1.58) Serathan-A (ISI=1.20) Mean ±2SD PT 32.5 sec. 31.6-33.4 sec. 61.5 sec. 60.7-62.3 sec. Intrin - SI Intrin - EA APTT 70.5 sec. 69.4-71.6 sec. 64.8 sec. 63.8-65.8 sec.

Performance Characteristics Product Inserts: Stasis 3 Coagulation Control Plasma Level 3 (Abnormal) Performance Characteristics 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 < 1% for the PT, < 1.6% for the APTT assays on the BBL Fibrometer. Actual values recorded depend on the instrument and reagent used.

Product Inserts: Serathan A

Product Inserts: Serathan-A Thromboplastin Reagent Intended Use Wortham Laboratories 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.

Product Inserts: Serathan-A Thromboplastin Reagent Summary and Principle 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 Factor I (fibrinogen), II (Prothrombin), V (Proaccelerin), VII (Stable) and X (Stuart) will be prolonged in this test. The PT is widely used to monitor oral anticoagulation therapy. 1,2 Oral anticoagulants reduce the activity of Vitamin K dependent clotting factors (II,VII,IX,X, Protein C, and Protein S), and the PT is prolonged as a result. The one step PT measures the clotting time of plasma after adding a source thrombplastin and calcium. The recalcification of plasma with thromboplastin generates activated FXa. FXa in turn activates Prothombin to thrombin, which converts fibrinogen to an insoluble fibrin clot.

Product Inserts: Serathan-A Thromboplastin Reagent Expected Values In an outside laboratory, when 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 These values are intended as a guideline only. Each laboratory should establish a Normal Reference Range (NRR) using instrumentation, blood collection methods, and testing techniques used in that laboratory. The NRR should be reestablished or at least verified when changing lot numbers of the same reagent. A new NRR should be established with any change in reagents, instrumentation, blood collection techniques, or anticoagulant. The clotting time of abnormal plasmas will depend on the ISI of the reagent lot in use.

Product Inserts: Serathan-A Thromboplastin Reagent Performance Characteristics / Precisions Precisions: Precision of Prothrombin Time results is dependent on many factors, such as the instrument technique and the reagent in use. Serathan-A was assayed by testing the reagent against three lots each of a normal and abnormal control plasma, in singlicate assays, on the BBL Fibrometer. A summary of the results follow: Level 1 Level 2 Level 3 n run(sec) % CV within-run 60 12.66 0.89% 36.45 1.09% 61.60 1.25% run-run 12.67 0.88% 36.47 1.08% 61.13 1.28%

Product Inserts: Serathan-A Thromboplastin Reagent Performance Characteristics / Sensitivity Sensitivity: Serathan-A detects deficiencies in the extrinsic pathway as determined by the Prothrombin Time test. Factor sensitivity testing was performed by diluting pool normal plasma, with factor deficient plasmas such that the final factor concentration ranged from 10-100%. Pt testing of those samples was performed on the BBL Fibrometer instrument: Prothrombin Time (Mean sec) n = 20 % Factor Factor II Factor V Factor VII Factor X 100 11.79 11.99 11.90 50 11.80 13.41 12.79 13.11 40 12.02 14.20 12.98 13.60 30 12.38 15.20 13.82 14.52 20 12.99 16.29 14.11 15.21 10 14.31 18.66 15.51 17.52

Product Inserts: Serathan-A Thromboplastin Reagent Reportable Range/Linearity The linearity of Serathan-A to warfarin (n=40), measured on the BBL Fibrometer, was 0-13.5 mg/dl. Each laboratory should establish their own linearity, using instrumentation, blood collection methods, and testing techniques used in the laboratory.

Product Inserts: Serathan-A Thromboplastin Reagent Determination of INR An undesirable consequence of oral anticoagulant therapy may be a tendency to bleed unnecessarily. To maximize the desired therapeutic effects and minimize bleeding, the World Health Organization (WHO) has recommended a procedure to standardize testing and treatments. This procedure is based on the International Normalized Ratio (INR).

Product Inserts: Serathan-A Thromboplastin Reagent Determination of INR The INR is calculated using the ratio of the patient PT to the mean of the NRR (mean NRR) according to the following mathematical relationship:

Product Inserts: Serathan-A Thromboplastin Reagent Determination of INR For example only: With an ISI of 1.20 and a mean normal of 12.2 seconds, the INR for a PT of 28.2 seconds is calculated as follows:

Product Inserts: Serathan-A Thromboplastin Reagent International Sensitivity Index (ISI) The International Sensitivity Index (ISI) is a measure of the thromboplastin/instrument sensitivity to coagulation factors. ISI values are assigned by comparison to a primary reference material. By preparing a range of warfarin plasma samples, Serathan-A reagent is measured against a European Reference Material (ERM), using a thromboplastin standard. High sensitivity reagents have low ISI values. According to WHO recommendations, INR values above 5.5 place the patient at unnecessarily risk for bleeding complications. It is generally advised that patients on stabilized oral anticoagulant therapy should be maintained at an INR of 2.0 – 3.5, depending on the clinical indication. The lot specific ISI value for Serathan-A can be found on the box label.

Product Inserts: Serathan-A Thromboplastin Reagent Correlation Studies Correlation studies were performed against another thromboplastin reagent by performing PT testing on 120 adult normal and coumadin patient samples, in singlicate assays. Testing was performed on the BBL Fibrometer instrument. Reference PT Clotting Time (sec) R = 0.999 y = 0.948 x+ 0.62

Product Inserts: Serathan-A Thromboplastin Reagent Correlation Studies Reference PT Clotting Time (sec) R = 0.999 y = 0.982 x- 0.180

Product Inserts: Serathan B

Product Inserts: Serathan-B Thromboplastin Reagent Intended Use Wortham Laboratories 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.

Product Inserts: Serathan-B Thromboplastin Reagent Summary and Principle 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 Factor I (fibrinogen), II (Prothrombin), V (Proaccelerin), VII (Stable) and X (Stuart) will be prolonged in this test. The PT is widely used to monitor oral anticoagulation therapy. 1,2 Oral anticoagulants reduce the activity of Vitamin K dependent clotting factors (II,VII,IX,X, Protein C, and Protein S), and the PT is prolonged as a result. The one step PT measures the clotting time of plasma after adding a source thrombplastin and calcium. The recalcification of plasma with thromboplastin generates activated FXa. FXa in turn activates Prothombin to thrombin, which converts fibrinogen to an insoluble fibrin clot.

Product Inserts: Serathan-B Thromboplastin Reagent Expected Values In an outside laboratory, when 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 These values are intended as a guideline only. Each laboratory should establish a Normal Reference Range (NRR) using instrumentation, blood collection methods, and testing techniques used in that laboratory. The NRR should be reestablished or at least verified when changing lot numbers of the same reagent. A new NRR should be established with any change in reagents, instrumentation, blood collection techniques, or anticoagulant. The clotting time of abnormal plasmas will depend on the ISI of the reagent lot in use.

Product Inserts: Serathan-B Thromboplastin Reagent Performance Characteristics / Precisions Precisions: Precision of Prothrombin Time results is dependent on many factors, such as the instrument technique and the reagent in use. Serathan-B was assayed by testing the reagent against three lots each of a normal and abnormal control plasma, in singlicate assays, on the BBL Fibrometer. A summary of the results follow: Level 1 Level 2 Level 3 n run(sec) % CV within-run 60 11.57 0.80% 21.17 1.27% 32.51 1.42% run-run 11.56 0.75% 21.13 1.22% 1.44%

Product Inserts: Serathan-B Thromboplastin Reagent Performance Characteristics / Sensitivity Sensitivity: Serathan-B detects deficiencies in the extrinsic pathway as determined by the Prothrombin Time test. Factor sensitivity testing was performed by diluting pool normal plasma, with factor deficient plasmas such that the final factor concentration ranged from 10-100%. Pt testing of those samples was performed on the BBL Fibrometer instrument: Prothrombin Time (Mean sec) n = 20 % Factor Factor II Factor V Factor VII Factor X 100 11. 00 11.49 11.40 11.60 50 11.01 11.89 12.41 13.39 40 13.09 13.82 30 11.79 13.19 13.90 14.91 20 12.30 14.70 14.79 16.32 10 13.71 17.12 16.48 20.02

Product Inserts: Serathan-B Thromboplastin Reagent Reportable Range/Linearity The linearity of Serathan-B to warfarin (n=40), measured on the BBL Fibrometer, was 0-12.8 mg/dl. Each laboratory should establish their own linearity, using instrumentation, blood collection methods, and testing techniques used in the laboratory.

Product Inserts: Serathan-B Thromboplastin Reagent Determination of INR An undesirable consequence of oral anticoagulant therapy may be a tendency to bleed unnecessarily. To maximize the desired therapeutic effects and minimize bleeding, the World Health Organization (WHO) has recommended a procedure to standardize testing and treatments. This procedure is based on the International Normalized Ratio (INR).

Product Inserts: Serathan-B Thromboplastin Reagent Determination of INR The INR is calculated using the ratio of the patient PT to the mean of the NRR (mean NRR) according to the following mathematical relationship:

Product Inserts: Serathan-B Thromboplastin Reagent Determination of INR For example only: With an ISI of 1.55 and a mean normal of 11.4 seconds, the INR for a PT of 26.9 seconds is calculated as follows:

Product Inserts: Serathan-B Thromboplastin Reagent International Sensitivity Index (ISI) The International Sensitivity Index (ISI) is a measure of the thromboplastin/instrument sensitivity to coagulation factors. ISI values are assigned by comparison to a primary reference material. By preparing a range of warfarin plasma samples, Serathan-B reagent is measured against a European Reference Material (ERM), using a thromboplastin standard. High sensitivity reagents have low ISI values. According to WHO recommendations, INR values above 5.5 place the patient at unnecessarily risk for bleeding complications. It is generally advised that patients on stabilized oral anticoagulant therapy should be maintained at an INR of 2.0 – 3.5, depending on the clinical indication. The lot specific ISI value for Serathan-B can be found on the box label.

Product Inserts: Serathan-B Thromboplastin Reagent Correlation Studies Correlation studies were performed against another thromboplastin reagent by performing PT testing on 120 adult normal and coumadin patient samples, in singlicate assays. Testing was performed on the BBL Fibrometer instrument. Reference PT Clotting Time (sec) R = 0.996 y = 0.989 x+ 0.039

Product Inserts: Serathan-B Thromboplastin Reagent Correlation Studies Reference PT Clotting Time (sec) R = 0.999 y = 0.982 x- 0.180

Lupus Sensitivity Study to Serathan and Intrin Reagents Objective: Perform a Lupus sensitivity comparative study of Intrin-SI and Intrin-EA to Pacific Hemostasis’ Kontact and APTT-LS reagents.

Lupus Sensitivity Study Materials & Equipment Lupus Plasma Samples Serathan-A Reagent Serathan-B Reagent Pacific Hemostasis DS Reagent Pacific Hemostasis D Reagent Intrin-SI Reagent Intrin-EA Reagent Pacific Hemostasis Kontact Reagent Pacific Hemostasis APTT-LS Reagent 0.02 M CaCl2 Fibrometer 0.1, 0.2 Pipetter 0.1-1ml Volumetric Pipetter

Lupus Sensitivity Study Procedure: Twenty samples of positive anticoagulant Lupus samples from George King Biological (Lot GK5003-214g1) were measured by performing a PT on Wortham Laboratories Serathan-A (ISI=1.20) and Serathan-B (ISI=1.52) and Intrin reagents and comparing them to the predicate device Pacific Hemostasis Thromboplastin-DS (ISI=1.20) and Thromboplastin-D (ISI=1.54). APTT reagents Intrin-SI and Intrin-EA were measured against the Predicate Kontact and APTT-LS, a Kaolin and ellagic acid activator, respectively.

Lupus Sensitivity Study: Results Sample Serathan-A Serathan-B Thrombo-DS Thrombo-D Level 1 12.4 11.4 10.6 Level 2 36.0 22.4 35.2 21.7 Level 3 68.3 32.9 66.9 31.2 1 13.8 12.9 11.9 2 13.9 13.4 3 13.5 4 5 12.5 6 7 8 9 10 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 6 13.9 12.4 13.4 11.9 7 13.8 12.4 13.9 11.9 8 13.8 12.4 13.4 11.9 9 13.8 12.4 13.4 11.9 10 13.8 12.5 13.4 12.4 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 40.4 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 32.4 28.9 3 57.5 58.9 30.7 28.4 4 52.8 47.9 31.2 27.4 5 50.3 38.5 30.7 25.9 6 49.7 43.9 32.4 27.9 7 51.4 44.4 35.1 28.4 8 57.2 66.9 34.6 33.9 9 55.8 46.9 32.3 28.4 10 56.5 48.9 32.7 27.9 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81

Lupus Sensitivity Study: Results Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 28.9 3 57.5 58.9 30.7 4 52.8 47.9 31.2 5 50.3 38.5 25.9 6 49.7 43.9 7 44.4 35.1 8 57.2 66.9 34.6 33.9 9 46.9 32.3 10 56.5 48.9 32.7 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81 6 13.9 12.4 13.4 11.9 7 13.8 12.4 13.9 11.9 8 13.8 12.4 13.4 11.9 9 13.8 12.4 13.4 11.9 10 13.8 12.5 13.4 12.4 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 40.4 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 32.4 28.9 3 57.5 58.9 30.7 28.4 4 52.8 47.9 31.2 27.4 5 50.3 38.5 30.7 25.9 6 49.7 43.9 32.4 27.9 7 51.4 44.4 35.1 28.4 8 57.2 66.9 34.6 33.9 9 55.8 46.9 32.3 28.4 10 56.5 48.9 32.7 27.9 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81

Lupus Sensitivity Study: Conclusions Although Lupus has little effect on the extrinsic system, clearly, only the PT reagents with a 1.20 ISI detected its anticoagulant effect. The silicone activator in both of the APTT reagents was sensitive to positive Lupus anticoagulant plasma, while the thromboplastin reagent with a 1.52-1.54 ISI and the ellagic acid activator remained unresponsive. The stabilizers in the Wortham Laboratories reagents gave a more consistent reproducible result of the PT reagents Serathan-A and Serathan-B 0.040 standard deviation to Thromboplastin-DS 0.273 and Thromboplastin-D 0.200 SD. Likewise, the stability of Intrin-SI and Intrin-EA produced a 3.321 and 1.428 SD, respectively, compared to the predicates Kontacts 8.651 SD and APTT-LS 2.263 SD. 6 13.9 12.4 13.4 11.9 7 13.8 12.4 13.9 11.9 8 13.8 12.4 13.4 11.9 9 13.8 12.4 13.4 11.9 10 13.8 12.5 13.4 12.4 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 40.4 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 32.4 28.9 3 57.5 58.9 30.7 28.4 4 52.8 47.9 31.2 27.4 5 50.3 38.5 30.7 25.9 6 49.7 43.9 32.4 27.9 7 51.4 44.4 35.1 28.4 8 57.2 66.9 34.6 33.9 9 55.8 46.9 32.3 28.4 10 56.5 48.9 32.7 27.9 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81

Serathan Reagent Linearity Study Objective: This study was to measure the linearity of Serathan-A and Serathan-B reagents.

Serathan Reagent Linearity Study Materials & Equipment Serathan-A (1 Serathan Reagent Linearity Study Materials & Equipment Serathan-A (1.20 ISI) Reagent Serathan-B (1.52 ISI) Reagent Stasis 1 Control Warfarin Fibrometer 1-10 μl Pipetter 0.1, 0.2 Pipetter 0.1-1 ml Volumetric Pipetter

Serathan Reagent Linearity Study: Procedure Eighteen samples of warfarin plasma were prepared from 0.2g warfarin/ml H2O, by adding the following volumes to normal plasma: 6 13.9 12.4 13.4 11.9 7 13.8 12.4 13.9 11.9 8 13.8 12.4 13.4 11.9 9 13.8 12.4 13.4 11.9 10 13.8 12.5 13.4 12.4 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 40.4 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 32.4 28.9 3 57.5 58.9 30.7 28.4 4 52.8 47.9 31.2 27.4 5 50.3 38.5 30.7 25.9 6 49.7 43.9 32.4 27.9 7 51.4 44.4 35.1 28.4 8 57.2 66.9 34.6 33.9 9 55.8 46.9 32.3 28.4 10 56.5 48.9 32.7 27.9 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81 Each sample was run in singlicate, assayed using standard PT procedures on the BBL Fibrometer.

Serathan Reagent Linearity Study: RESULTS Serathan-A 6 13.9 12.4 13.4 11.9 7 13.8 12.4 13.9 11.9 8 13.8 12.4 13.4 11.9 9 13.8 12.4 13.4 11.9 10 13.8 12.5 13.4 12.4 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 40.4 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 32.4 28.9 3 57.5 58.9 30.7 28.4 4 52.8 47.9 31.2 27.4 5 50.3 38.5 30.7 25.9 6 49.7 43.9 32.4 27.9 7 51.4 44.4 35.1 28.4 8 57.2 66.9 34.6 33.9 9 55.8 46.9 32.3 28.4 10 56.5 48.9 32.7 27.9 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81

Serathan Reagent Linearity Study: RESULTS Thromboplastin-DS 6 13.9 12.4 13.4 11.9 7 13.8 12.4 13.9 11.9 8 13.8 12.4 13.4 11.9 9 13.8 12.4 13.4 11.9 10 13.8 12.5 13.4 12.4 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 40.4 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 32.4 28.9 3 57.5 58.9 30.7 28.4 4 52.8 47.9 31.2 27.4 5 50.3 38.5 30.7 25.9 6 49.7 43.9 32.4 27.9 7 51.4 44.4 35.1 28.4 8 57.2 66.9 34.6 33.9 9 55.8 46.9 32.3 28.4 10 56.5 48.9 32.7 27.9 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81

Serathan Reagent Linearity Study: RESULTS Serathan-B 6 13.9 12.4 13.4 11.9 7 13.8 12.4 13.9 11.9 8 13.8 12.4 13.4 11.9 9 13.8 12.4 13.4 11.9 10 13.8 12.5 13.4 12.4 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 40.4 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 32.4 28.9 3 57.5 58.9 30.7 28.4 4 52.8 47.9 31.2 27.4 5 50.3 38.5 30.7 25.9 6 49.7 43.9 32.4 27.9 7 51.4 44.4 35.1 28.4 8 57.2 66.9 34.6 33.9 9 55.8 46.9 32.3 28.4 10 56.5 48.9 32.7 27.9 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81

Serathan Reagent Linearity Study: RESULTS Thromboplastin-D

Product Inserts: Intrin-SI

Product Inserts: Intrin-SI Activated PTT Reagent Intended Use Wortham Laboratories 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.

Product Inserts: Intrin-SI Activated PTT Reagent Summary and Principle The Activated Partial Thromboplastin Time (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, XII. The APTT is also used in the monitoring of heparin therapy, where the clotting time is prolonged in proportion to the level of heparin. The APTT is performed by adding reagent containing a plasma activator and phospholipid to the test specimen. The mixture is incubated for 3 minutes at 37°C for optimum activation. Calcium chloride is added and clot formation is timed.

Product Inserts: Intrin-SI Activated PTT Reagent Expected Values When Intrin-SI was evaluated on 60 normal adult patients on the BBL Fibrometer, the following results were obtained: PT Mean (sec) Range (± 2SD) N Photo-optical 29.5 29.3-29.6 60 Mechanical These values should only be used as a guideline. Each laboratory should establish a Normal Reference Range (NRR) using instrumentation, blood collection methods, and testing techniques used in that laboratory. The NRR should be reestablished or at least verified when changing lot numbers of the same control. A new NRR should be established with any change in reagents, instrumentation, blood collection techniques or anticoagulant.

Product Inserts: Intrin-SI Activated PTT Reagent Performance Characteristics / Precision Precision of the Activated Partial Thromboplastin Time result is dependent on many factors, such as the instrument technique and the reagent in use. 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 within-run 60 29.51 0.29% 55.75 0.74% 70.49 0.75% run-run

Product Inserts: Intrin-SI Activated PTT Reagent Performance: Heparin Sensitivity Intrin-SI sensitivity to heparin was measured by comparison testing. The mean of 60 heparin patient samples on the BBL Fibrometer was 90.54 for Intrin-SI and 85.64 for the Reference APTT reagent, yielding a 4.90 mean difference. Regression analysis demonstrated a correlation coefficient of 0.995. Intrin-SI APTT Clotting Time (sec) R = 0.995 y = 1.026 x+ 1.354 Each laboratory should establish its own heparin sensitivity curve using the same heparin source used for therapy in that institution. Variations can result from different brands of heparin, tissue origin, and salt forms.

Product Inserts: Intrin-SI Activated PTT Reagent Performance Characteristics / Sensitivity Intrin-SI detects deficiencies in the intrinsic pathway as determined by the APTT. Factor sensitivity testing was performed by diluting pool normal plasma, with factor deficient plasmas such that the final factor concentration range was from 10-100%. Testing of the sample was performed on the BBL Fibrometer instrument: Activated Partial Thromboplastin Time (Mean sec) n = 20 % Factor Factor VIII Factor IX Factor XI Factor XII 100 28.52 29.59 29.17 28.56 50 34.77 32.78 30.35 40 38.02 35.80 34.23 30 42.31 42.61 39.57 37.83 20 49.91 50.22 46.00 41.59 10 57.21 56.14 53.68 48.83

Product Inserts: Intrin-SI Activated PTT Reagent 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. Each laboratory should establish their own linearity, using instrumentation, blood collection methods, and testing techniques used in the laboratory.

Product Inserts: Intrin-SI Activated PTT Reagent Correlation Studies Correlation 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. Reference APPT Clotting Time (sec) R = 0.998 y = 1.032 x+ 0.15

Product Inserts: Intrin-SI Activated PTT Reagent Correlation Studies Reference APPT Clotting Time (sec) R = 0.844 y = 1.033 x- 4.76

Product Inserts: Intrin-EA

Product Inserts: Intrin-EA Activated PTT Reagent Intended Use Wortham Laboratories 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.

Product Inserts: Intrin-EA Activated PTT Reagent Summary and Principle The Activated Partial Thromboplastin Time (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, XII. The APTT is also used in the monitoring of heparin therapy, where the clotting time is prolonged in proportion to the level of heparin. The APTT is performed by adding reagent containing a plasma activator and phospholipid to the test specimen. The mixture is incubated for 3 minutes at 37°C for optimum activation. Calcium chloride is added and clot formation is timed.

Product Inserts: Intrin-EA Activated PTT Reagent Expected Values When Intrin-EA was evaluated on 60 normal adult patients on the BBL Fibrometer, the following results were obtained: PT Mean (sec) Range (± 2SD) N Photo-optical 29.0 28.7 – 29.3 60 Mechanical 28.5 – 29.5 These values should only be used as a guideline. Each laboratory should establish a Normal Reference Range (NRR) using instrumentation, blood collection methods, and testing techniques used in that laboratory. The NRR should be reestablished or at least verified when changing lot numbers of the same control. A new NRR should be established with any change in reagents, instrumentation, blood collection techniques or anticoagulant.

Product Inserts: Intrin-EA Activated PTT Reagent Performance Characteristics / Precision Precision of the Activated Partial Thromboplastin Time result is dependent on many factors, such as the instrument technique and the reagent in use. 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 within-run 60 29.01 0.51% 48.03 0.41% 67.74 0.73% run-run 29.03 0.60% 47.52 0.44% 0.71%

Product Inserts: Intrin-EA Activated PTT Reagent Performance: Heparin Sensitivity Intrin-EA sensitivity to heparin was measured by comparison testing. The mean of 60 heparin patient samples on the BBL Fibrometer was 70.59 for Intrin-EA and 66.87 for the Reference APTT reagent, yielding a 3.72 mean difference. Regression analysis demonstrated a correlation coefficient of 0.996. Intrin-EA APTT Clotting Time (sec) R = 0.996 y = 1.021 x+ 1.346 Each laboratory should establish its own heparin sensitivity curve using the same heparin source used for therapy in that institution. Variations can result from different brands of heparin, tissue origin, and salt forms.

Product Inserts: Intrin-EA Activated PTT Reagent Performance Characteristics / Sensitivity Intrin-EA detects deficiencies in the intrinsic pathway as determined by the APTT. Factor sensitivity testing was performed by diluting pool normal plasma, with factor deficient plasmas such that the final factor concentration range was from 10-100%. Testing of the sample was performed on the BBL Fibrometer instrument: Activated Partial Thromboplastin Time (Mean sec) n = 20 % Factor Factor VIII Factor IX Factor XI Factor XII 100 29.36 28.54 29.47 26.82 50 33.86 32.38 34.74 29.89 40 35.08 34.03 36.26 31.14 30 37.33 36.34 38.61 32.23 20 40.47 38.64 41.35 33.33 10 45.10 40.89 46.84 35.04

Product Inserts: Intrin-EA Activated PTT Reagent Reportable Range/Linearity A 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. Each laboratory should establish their own linearity, using instrumentation, blood collection methods, and testing techniques used in the laboratory.

Product Inserts: Intrin-EA Activated PTT Reagent Correlation Studies Correlation 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. Reference APPT-LS Clotting Time (sec) R = 0.996 y = 1.022 x+ 1.293

Product Inserts: Intrin-EA Activated PTT Reagent Correlation Studies Reference APPT-LS Clotting Time (sec) R = 0.979 y = 1.037 x- 4.363

Lupus Sensitivity Study to Serathan and Intrin Reagents Objective: Perform a Lupus sensitivity comparative study of Intrin-SI and Intrin-EA to Pacific Hemostasis’ Kontact and APTT-LS reagents.

Lupus Sensitivity Study Materials & Equipment Lupus Plasma Samples Serathan-A Reagent Serathan-B Reagent Pacific Hemostasis DS Reagent Pacific Hemostasis D Reagent Intrin-SI Reagent Intrin-EA Reagent Pacific Hemostasis Kontact Reagent Pacific Hemostasis APTT-LS Reagent 0.02 M CaCl2 Fibrometer 0.1, 0.2 Pipetter 0.1-1ml Volumetric Pipetter

Lupus Sensitivity Study Procedure: Twenty samples of positive anticoagulant Lupus samples from George King Biological (Lot GK5003-214g1) were measured by performing a PT on Wortham Laboratories Serathan-A (ISI=1.20) and Serathan-B (ISI=1.52) and Intrin reagents and comparing them to the predicate device Pacific Hemostasis Thromboplastin-DS (ISI=1.20) and Thromboplastin-D (ISI=1.54). APTT reagents Intrin-SI and Intrin-EA were measured against the Predicate Kontact and APTT-LS, a Kaolin and ellagic acid activator, respectively.

Lupus Sensitivity Study: Results Sample Serathan-A Serathan-B Thrombo-DS Thrombo-D Level 1 12.4 11.4 10.6 Level 2 36.0 22.4 35.2 21.7 Level 3 68.3 32.9 66.9 31.2 1 13.8 12.9 11.9 2 13.9 13.4 3 13.5 4 5 12.5 6 7 8 9 10 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 6 13.9 12.4 13.4 11.9 7 13.8 12.4 13.9 11.9 8 13.8 12.4 13.4 11.9 9 13.8 12.4 13.4 11.9 10 13.8 12.5 13.4 12.4 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 40.4 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 32.4 28.9 3 57.5 58.9 30.7 28.4 4 52.8 47.9 31.2 27.4 5 50.3 38.5 30.7 25.9 6 49.7 43.9 32.4 27.9 7 51.4 44.4 35.1 28.4 8 57.2 66.9 34.6 33.9 9 55.8 46.9 32.3 28.4 10 56.5 48.9 32.7 27.9 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81

Lupus Sensitivity Study: Results Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 28.9 3 57.5 58.9 30.7 4 52.8 47.9 31.2 5 50.3 38.5 25.9 6 49.7 43.9 7 44.4 35.1 8 57.2 66.9 34.6 33.9 9 46.9 32.3 10 56.5 48.9 32.7 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81 6 13.9 12.4 13.4 11.9 7 13.8 12.4 13.9 11.9 8 13.8 12.4 13.4 11.9 9 13.8 12.4 13.4 11.9 10 13.8 12.5 13.4 12.4 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 40.4 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 32.4 28.9 3 57.5 58.9 30.7 28.4 4 52.8 47.9 31.2 27.4 5 50.3 38.5 30.7 25.9 6 49.7 43.9 32.4 27.9 7 51.4 44.4 35.1 28.4 8 57.2 66.9 34.6 33.9 9 55.8 46.9 32.3 28.4 10 56.5 48.9 32.7 27.9 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81

Lupus Sensitivity Study: Conclusions Although Lupus has little effect on the extrinsic system, clearly, only the PT reagents with a 1.20 ISI detected its anticoagulant effect. The silicone activator in both of the APTT reagents was sensitive to positive Lupus anticoagulant plasma, while the thromboplastin reagent with a 1.52-1.54 ISI and the ellagic acid activator remained unresponsive. The stabilizers in the Wortham Laboratories reagents gave a more consistent reproducible result of the PT reagents Serathan-A and Serathan-B 0.040 standard deviation to Thromboplastin-DS 0.273 and Thromboplastin-D 0.200 SD. Likewise, the stability of Intrin-SI and Intrin-EA produced a 3.321 and 1.428 SD, respectively, compared to the predicates Kontacts 8.651 SD and APTT-LS 2.263 SD.

Intrin-SI / Intrin-EA Linearity Study Objective: This study is to measure the linearity of Intrin-SI and Intrin-EA reagents.

Intrin-SI / Intrin-EA Linearity Study Materials & Equipment Stasis 1 Coagulation Control Sodium Heparin Intrin-SI Reagent Intrin-EA Reagent 0.02 M CaCl2 Pacific Hemostasis Kontact Pacific Hemostasis APTT-LS Fibrometer 0.1, 0.2 Pipetter 0.1-1 ml Volumetric Pipetter

Intrin-SI / Intrin-EA Linearity Study : Procedure A base heparin concentrate was prepared by adding 10 mg of Sigma Chemicals Sodium Heparin (H3393-1MU), lot 045K1819, to 182 ml Stasis 1 control. Test samples were prepared by pipetting 10, 20, 30, 40 and 50 μl to 0.99, 0.98, 0.97, 0.96, 0.95 ml Stasis control, respectively, to produce 0.1, 0.2, 0.3, 0.4, and 0.5 U/ml heparin samples. This process was repeated 3 times for each APTT reagent. Heparin linearity was measured by performing and APTT assay for each reagent. 6 13.9 12.4 13.4 11.9 7 13.8 12.4 13.9 11.9 8 13.8 12.4 13.4 11.9 9 13.8 12.4 13.4 11.9 10 13.8 12.5 13.4 12.4 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 40.4 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 32.4 28.9 3 57.5 58.9 30.7 28.4 4 52.8 47.9 31.2 27.4 5 50.3 38.5 30.7 25.9 6 49.7 43.9 32.4 27.9 7 51.4 44.4 35.1 28.4 8 57.2 66.9 34.6 33.9 9 55.8 46.9 32.3 28.4 10 56.5 48.9 32.7 27.9 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81

Intrin-SI / Intrin-EA Linearity Study : RESULTS 6 13.9 12.4 13.4 11.9 7 13.8 12.4 13.9 11.9 8 13.8 12.4 13.4 11.9 9 13.8 12.4 13.4 11.9 10 13.8 12.5 13.4 12.4 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 40.4 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 32.4 28.9 3 57.5 58.9 30.7 28.4 4 52.8 47.9 31.2 27.4 5 50.3 38.5 30.7 25.9 6 49.7 43.9 32.4 27.9 7 51.4 44.4 35.1 28.4 8 57.2 66.9 34.6 33.9 9 55.8 46.9 32.3 28.4 10 56.5 48.9 32.7 27.9 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81

Intrin-SI / Intrin-EA Linearity Study : RESULTS 6 13.9 12.4 13.4 11.9 7 13.8 12.4 13.9 11.9 8 13.8 12.4 13.4 11.9 9 13.8 12.4 13.4 11.9 10 13.8 12.5 13.4 12.4 Mean 13.82 12.42 13.36 12.00 SD 0.040 0.040 0.273 0.200 %CV 0.29 0.32 2.04 1.67 Sample Intrin-SI Kontact Intrin-EA APTT-LS Level 1 28.0 27.4 28.4 27.9 Level 2 40.4 39.4 41.3 40.4 Level 3 55.8 51.4 62.6 60.4 1 58.3 61.9 33.5 32.4 2 59.2 57.0 32.4 28.9 3 57.5 58.9 30.7 28.4 4 52.8 47.9 31.2 27.4 5 50.3 38.5 30.7 25.9 6 49.7 43.9 32.4 27.9 7 51.4 44.4 35.1 28.4 8 57.2 66.9 34.6 33.9 9 55.8 46.9 32.3 28.4 10 56.5 48.9 32.7 27.9 Mean 55.07 51.52 32.56 28.95 SD 3.51 8.65 1.43 2.26 %CV 6.37 16.80 4.39 7.81

Intrin-SI / Intrin-EA Linearity Study Conclusions: Both Intrin-SI and Intrin-EA demonstrated linearity of 0-5 U/ml of heparin.

Product Inserts: Fibrinogen Control, Normal

Product Inserts: Fibrinogen Control, Normal Intended Use Wortham Laboratories Fibrinogen Control (Normal), a quantitative control plasma, is intended for use in the quality control of fibrinogen assays.

Product Inserts: Fibrinogen Control, Normal Summary and Principle The thrombin clotting time fibrinogen assay is based on the method described by Clauss. In the presence of high concentrations of thrombin, the time required for clot formation in dilute plasma is inversely proportional to the fibrinogen concentrations.

Product Inserts: Fibrinogen Control, Normal Expected Values Values were assayed using thrombin clotting time (Clauss) methodology. Three lots of Wortham Laboratories Normal Fibrinogen Control was 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. Recovery values may vary with other procedures. Actual values recovered depend on the instrument and reagent used.

Product Inserts: Fibrinogen Control, Normal Performance Characteristics Wortham Laboratories Normal Fibrinogen Control 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.

Product Inserts: Fibrinogen Control, Low

Product Inserts: Fibrinogen Control, Low Intended Use Wortham Laboratories Fibrinogen Control (Low), a quantitative control plasma, is intended for use in the quality control of fibrinogen assays.

Product Inserts: Fibrinogen Control, Low Summary and Principle The thrombin clotting time fibrinogen assay is based on the method described by Clauss. In the presence of high concentrations of thrombin, the time required for clot formation in dilute plasma is inversely proportional to the fibrinogen concentrations.

Product Inserts: Fibrinogen Control, Low Expected Values Values were assayed using thrombin clotting time (Clauss) methodology. Three lots of Wortham Laboratories Low Fibrinogen Control was 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. Recovery values may vary with other procedures. Actual values recovered depend on the instrument and reagent used.

Product Inserts: Fibrinogen Control, Low Performance Characteristics Wortham Laboratories Low Fibrinogen Control 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.

Product Inserts: Heparin Control Level 1 (0.25 U/ml)

Product Inserts: Heparin Control Level 1 (0.25 U/ml) Intended Use Wortham Laboratories Heparin Control Level 1 is intended as a quality control of the Activated Partial Thromboplastin Time (APTT) during heparin monitoring.

Product Inserts: Heparin Control Level 1 (0.25 U/ml) Summary and Principle 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, such as Wortham Laboratories Heparin Control Plasma Level 1 and 2. Heparin affects the intrinsic coagulation pathway, prolonging the Activated Partial Thromboplastin Time (APTT) test. The APTT is a common screening test performed in the clinical laboratory. It is primarily used to detect certain factor deficiencies, however, it also can be used to monitor heparin therapy.

Product Inserts: Heparin Control Level 1 (0.25 U/ml) Expected Values Wortham Laboratories Heparin Control Plasma is dependent on the overall test system, which includes factors such as reagent, instrument, protocol and individual technique. However, the Heparin Control 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.

Product Inserts: Heparin Control Level 1 (0.25 U/ml) Performance Characteristics When using Heparin Control Level 1 Plasma as abnormal APTT control, within-run precision studies performed on the BBL Fibrometer using Wortham Laboratories Intrin-SI reagent yielded CV’s of 1.82 %, and a 1.77% CV for run-run assays.

Product Inserts: Heparin Control Level 2 (0.35 U/ml)

Product Inserts: Heparin Control Level 2 (0.35 U/ml) Intended Use Wortham Laboratories Heparin Control Level 2, is intended as a quality control of the Activated Partial Thromboplastin Time (APTT) during heparin monitoring.

Product Inserts: Heparin Control Level 2 (0.35 U/ml) Summary and Principle 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, such as Wortham Laboratories Heparin Control Plasma Level 1 and 2. Heparin affects the intrinsic coagulation pathway, prolonging the Activated Partial Thromboplastin Time (APTT) test. The APTT is a common screening test performed in the clinical laboratory. It is primarily used to detect certain factor deficiencies, however, it also can be used to monitor heparin therapy.

Product Inserts: Heparin Control Level 2 (0.35 U/ml) Expected Values Wortham Laboratories Heparin Control Plasma is dependent on the overall test system, which includes factors such as reagent, instrument, protocol and individual technique. However, the Heparin Control 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.

Product Inserts: Heparin Control Level 2 (0.35 U/ml) Performance Characteristics When using Heparin Control Level 2 Plasma as abnormal APTT control, within-run precision studies performed on the BBL Fibrometer using Wortham Laboratories Intrin-SI reagent yielded CV’s of 1.92 %, and a 1.81% CV for run-run assays.

Product Inserts: Fibrinogen Assay Set (250 Determinations)

Product Inserts: Fibrinogen Assay Set Intended Use Wortham Laboratories 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.

Product Inserts: Fibrinogen Assay Set Summary and Principle The thrombin clotting time fibrinogen assay is based on the method described by Clauss. In the presence of high concentrations of thrombin, the time required for clot formation in dilute plasma is inversely proportional to the fibrinogen concentrations.

Product Inserts: Fibrinogen Assay Set Expected Values Laboratories should establish a normal control interval for fibrinogen measurement. Generally, the normal control is 200-400 mg/dl.

Product Inserts: Fibrinogen Assay Set Performance Characteristics Accuracy Three lots of normal and low fibrinogen plasmas were tested in singlicate with Wortham Laboratories reagents on the BBL Fibrometer. A summary of the results follows: Control Dilution n Mean (sec) SD Normal 1:6 180 15.08 0.087 Low 1:3 15.18 0.088

Product Inserts: Fibrinogen Assay Set Performance Characteristics Precision 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 dilution 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 run-run Normal 60 0.56% CV 180 0.57% CV Low 0.60% CV 0.58% CV

Product Inserts: Fibrinogen Buffer

Product Inserts: Fibrinogen Buffer Intended Use Wortham Laboratories Fibrinogen Buffer is designed as a diluent for fibrinogen studies.

Product Inserts: Thrombin Reagent

Product Inserts: Thrombin Reagent Intended Use Wortham Laboratories Thrombin Reagent is intended for thrombin to convert fibrinogen in the quantitative determination of fibrinogen in plasma samples.

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

Product Inserts: Thrombin Reagent Expected Values Laboratories should establish a normal control interval for fibrinogen measurement. Generally, the normal control is 200-400 mg/dl.

Product Inserts: Thrombin Reagent Performance Characteristics Accuracy Three lots of normal and low fibrinogen plasmas were tested in singlicate with Wortham Laboratories reagents on the BBL Fibrometer. A summary of the results follows: Control Dilution n Mean (sec) SD Normal 1:6 180 15.08 0.087 Low 1:3 15.18 0.088

Product Inserts: Thrombin Reagent Performance Characteristics Precision 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 dilution 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 run-run Normal 60 0.56% CV 180 0.57% CV Low 0.60% CV 0.58% CV

Product Inserts: Thrombin Reagent Reportable Range/Linearity The Thrombin Reagent (100IU/ml) when diluted 10-100%, demonstrated linearity from 100 IU/ml to 10 IU/ml. Each laboratory should establish their own linearity using instrumentation, blood collection methods, and testing techniques used in the laboratory.

Product Inserts: Calcium Chloride 0.02M

Product Inserts: Calcium Chloride Intended Use Wortham Laboratories Calcium Chloride Solution 0.02 M (CaCl2) is intended for quantitative use with ellagic acid (Intrin-EA) or silicon particulate activators (Intrin-SI) in performing the activated partial thromboplastin time (APTT) on citrated plasma.

Coagulation Controls and Reagents: Real Time Stability Study

Real Time Stability Study Objective A real time stability study of the coagulation controls and reagents: StasisTM 1, 2 and 3, SerathanTM- A and B, IntrinTM – SI and EA, Fibrinogen, Thrombin, Heparin, when stored at -2°C and 4°C, is being conducted.

Real Time Stability Study Materials and Methods Coagulation Control Level I Thromboplastin-D Thromboplastin-DS Kontact APTT-LS 0.02 M CaCl2 Fibrinogen Assay Set Heparin Control, Level I WHO 2nd International Thrombin Standard, lot K. 12 x 75 tubes 15 ml polypropylene screw cap bottles parafilm 37°C water bath 25°C incubator 2-4°C refrigerator -10°C freezer

Real Time Stability Study Procedures The coagulation controls and reagents prepared from the accelerated stability studies, which were stored at -10°C, were used in this real time stability study. Testing was done one lot of each product and assayed on the BBL Fibrometer. Samples of the coagulation products were tested daily for the first 30 days, one product at its study temperature at a time. All coagulation products stored at -2°C were thawed and refrozen for each test day, thereby, evaluating the product’s repetitive freeze-thaw capacity. Freshly prepared Pacific Hemostasis controls and reagents were used to measure the activity of the stressed samples. StasisTM controls were assayed for PT and APTT. Both SerathanTM and IntrinTM reagents were measured against a Level I coagulation control. The Fibrinogen Assay Set and Heparin Control were used to test the Low Fibrinogen and Level 1 Heparin stressed samples, respectively. The WHO 2nd International Thrombin Standard was used to measure the thrombin activity of the Thrombin Reagent stressed samples.

Real Time Stability Study Conclusions The first 30 days of the revised stability study, where the frozen storage has been changes from -10°C to -2°C, show no loss of activity. Real time studies will be ongoing.

510(k) Summary: Stasis 1 Coagulation Control

510(k): Stasis 1 Coagulation Control Device Name: Wortham Laboratories Stasis 1 Coagulation Control (Normal) #K060968 Common Name: Normal Coagulation Control Classification Name: Plasma Coagulation Control, a Class II device as per 21 CFR Section 864.5425 (Product Code GGC). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis Coagulation Control Level I (K984129)

510(k): Stasis 1 Coagulation Control Description Wortham Laboratories Stasis 1 Coagulation Control (Normal) is a liquid stable citrated plasma obtained from healthy donors. Stabilizers and buffers have been added to the plasma. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found to be non-reactive for HBsAg and negative for antibodies to HIV and HCV.

510(k): Stasis 1 Coagulation Control Intended 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.

510(k): Stasis 1 / Substantial Equivalence Characteristics Intended Use New Device Routine coagulation for PT, PTT, fibrinogen assays in the normal range Predicate Control Composition Liquid Human citrated plasma Lypholyzed human citrated plasma Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 35 months @ 2-8° C, lypholyzed 8 hours @ 2-8° C, rehydrated Reference Values PT CV% within-run (ISI=1.54) 0.75% 0.90% within-run (ISI=1.20) 0.88% 1.40% run-run (ISI=1.54) 0.67% 0.85% run-run (ISI=1.20) 0.89% 1.38% APTT within-run (Kaolin) 0.63% 1.54% within-run (Ellagic-Acid) 0.62% run-run (Kaolin) 0.61% 1.20% run-run (Ellagic Acid) 0.60%

510(k): Stasis 1 / Substantial Equivalence Fibrinogen CV% within-run 0.56% 0.59% run-run 0.57% 0.60% Expected Range Mechanical Mean ± 2SD PT 11.67 11.5-11.8 sec 11.66 11.4-11.9 sec APTT: 29.51 29.3-29.7 sec 28.38 28.0-28.8 sec Fibrinogen: 306.3 301-313 g/dl 297-315 g/dl Storage ≤ -2° C 2 - 8° C Assay Factors PT, APTT, Fibrinogen

510(k): Stasis 1 - Conclusions Wortham Laboratories Stasis 1 and Pacific Hemostasis Coagulation Control Level I have the same intended use, as normal controls for the quantitative measurement of the Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and fibrinogen levels. Both are preparations of citrated plasma obtained from normal donors with added stabilizers and buffers. Mechanical assays of Stasis 1 to the predicate normal plasma control with two different sensitive thromboplastin reagents, with an ISI of 1.20 and 1.58, yielded a within-run standard deviation of 0.0809 and 0.0922 for Stasis 1 respectively, compared to a 0.1714 and a 0.1050 SD for the predicate control from the same reagents. A run-run precision of Stasis 1 produced a 0.1026 and 0.0784 SD with the two thromboplastin reagents, compared to 0.1733 and 0.0987 SD of Pacific Hemostasis Control. Mechanical measurements of the APTT in both Stasis 1 and Pacific Hemostasis Level I Control with two different activator reagents, Kaolin and ellagic acid, produced a within-run 0.0863 and a 0.1792 standard deviation, respectively, while the predicate control yielded a 0.1989 and a 0.2455 SD. A run-run precision of the Stasis 1 Control measured at 0.1705 and 0.1749 SD to the two APTT activators, contrasted to Pacific Hemostasis Level I Controls 0.3339 and 0.2453 SD.

510(k): Stasis 1 - Conclusions The processing of the Fibrinogen levels in both study graphs on the fibrometer instrument produced a within-run 0.0850 and a 0.0858 run-run standard deviation for Stasis 1, which a within-run 0.089 SD and run-run 0.0900 SD was observed in the Pacific Hemostasis Level 1 Control. Reproducibility of the two controls yielded a 0.86% within-run coefficient of variation and a run-run 0.89% CV for Stasis 1, compared respectively to the predicate control of 1.36% CV and 1.38% CV. The performance data presented here, as well as the undistinguishable intended use and technological characteristics support the substantial equivalence claim for Wortham Laboratories Stasis 1 Coagulation Control to Pacific Hemostasis Coagulation Control Level I. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

510(k) Summary: Stasis 2 Coagulation Control

510(k): Stasis 2 Coagulation Control Device Name: Wortham Laboratories Stasis 2 Coagulation Control (Abnormal) #K060968 Common Name: Abnormal Coagulation Control Classification Name: Plasma Coagulation Control, a Class II device as per 21 CFR Section 864.5425 (Product Code GGC). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis Coagulation Control Level II (K984130)

510(k): Stasis 2 Coagulation Control Description Wortham Laboratories Stasis 2 Coagulation Control (Abnormal) is a liquid stable citrated plasma obtained from healthy donors. Stabilizers and buffers have been added to the plasma. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found to be non-reactive for HBsAg and negative for antibodies to HIV and HCV.

510(k): Stasis 2 Coagulation Control Intended Use Wortham Laboratories 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.

510(k): Stasis 2 / Substantial Equivalence Characteristics Intended Use New Device Routine coagulation for PT, PTT, assays in the moderately abnormal range Predicate Routine coagulation for PT, PTT, assays in the moderately abnormal range Control Composition Liquid Human citrated plasma Lypholyzed human citrated plasma Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 34 months @ 2-8° C, lypholyzed 8 hours @ 2-8° C, rehydrated Reference Values PT CV% within-run (ISI=1.54) 1.01% 1.41% within-run (ISI=1.20) 1.10% 1.28% run-run (ISI=1.54) 0.98% 1.30% run-run (ISI=1.20) 1.19%

510(k): Stasis 2 / Substantial Equivalence APTT CV% within-run (Kaolin) 0.76% 1.00% within-run (Ellagic-Acid) 0.50% 0.91% run-run (Kaolin) 1.06% run-run (Ellagic Acid) 0.48% 0.90% Expected Range Mechanical Mean ± 2SD PT 20.14 19.9-20.3 sec 20.25 19.7-20.8 sec APTT: 55.75 54.9-56.6 sec 55.01 53.9-56.2 sec Storage ≤ -2° C 2 - 8° C Assay Factors PT, APTT

510(k): Stasis 2 - Conclusions Wortham Laboratories Stasis 2 and Pacific Hemostasis Coagulation Control Level II have the same intended use, as normal controls for the quantitative measurement of the Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT). Both are preparations of citrated plasma obtained from normal donors with added stabilizers and buffers. Mechanical assays of Stasis 2 to the predicate moderately abnormal plasma control with two different sensitive thromboplastin reagents, 1.20 ISI and 1.58 ISI, yielded a standard deviation of 0.5992 and 0.2023 for Stasis 2 respectively, compared to a 0.4638 SD and a 0.2856 SD for the predicate control from the same reagents. A run-run precision of Stasis 2 produced a 0.3664 and 0.1984 SD with the two thromboplastin reagents, compared to 0.4296 and 0.2644 SD of Pacific Hemostasis Control. Mechanical measurements of the APTT in both Stasis 2 and Pacific Hemostasis Level II Control with two different activator reagents, Kaolin and ellagic acid, produced a 0.4135 and a 0.2341 standard deviation, respectively, while the predicate control yielded a 0.5721 and a 0.4045 SD. A run-run precision of the Stasis 2 Control measured at 0.4136 and 0.2233 SD to the two APTT activators, contrasted to Pacific Hemostasis Level II Controls 0.5628 and 0.4043 SD.

510(k): Stasis 2 - Conclusions Reproducibility of the two controls yielded a 1.10% within-run coefficient of variation and a run-run 1.01% CV for Stasis 2, compared respectively to the predicate control of 1.28% CV and 1.19% CV. The performance data presented here, as well as the undistinguishable intended use and technological characteristics support the substantial equivalence claim for Wortham Laboratories Stasis 2 Coagulation Control to Pacific Hemostasis Coagulation Control Level II. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

510(k) Summary: Stasis 3 Coagulation Control

510(k): Stasis 3 Coagulation Control Device Name: Wortham Laboratories Stasis 3 Coagulation Control (Abnormal) #K060968 Common Name: Abnormal Coagulation Control Classification Name: Plasma Coagulation Control, a Class II device as per 21 CFR Section 864.5425 (Product Code GGC). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis Coagulation Control Level III (K984131)

510(k): Stasis 3 Coagulation Control Description Wortham Laboratories Stasis 3 Coagulation Control (Abnormal) is a liquid stable citrated plasma obtained from healthy donors. Stabilizers and buffers have been added to the plasma. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found to be non-reactive for HBsAg and negative for antibodies to HIV and HCV.

510(k): Stasis 3 Coagulation Control Intended Use Wortham Laboratories 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.

510(k): Stasis 3 / Substantial Equivalence Characteristics Intended Use New Device Routine coagulation for PT, PTT, assays in the high abnormal range Predicate Routine coagulation for PT, PTT, assays in the high abnormal range Control Composition Liquid Human citrated plasma Lypholyzed human citrated plasma Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 35 months @ 2-8° C, lypholyzed 8 hours @ 2-8° C, rehydrated Reference Values PT CV% within-run (ISI=1.54) 1.45% 1.68% within-run (ISI=1.20) 1.36% 1.52% run-run (ISI=1.54) 1.46% 1.70% run-run (ISI=1.20) 1.44% 1.34%

510(k): Stasis 3 / Substantial Equivalence APTT CV% within-run (Kaolin) 0.80% 1.12% within-run (Ellagic-Acid) 0.76% run-run (Kaolin) 0.75% 1.15% run-run (Ellagic Acid) 1.11% Expected Range Mechanical Mean ± 2SD PT 32.50 32.0-33.0 sec 32.49 31.4-33.6 sec APTT: 70.49 69.4-71.5 sec 70.13 68.8-71.4 sec Storage ≤ -2° C 2 - 8° C Assay Factors PT, APTT

510(k): Stasis 3 - Conclusions Wortham Laboratories Stasis 3 and Pacific Hemostasis Coagulation Control Level III have the same intended use, as normal controls for the quantitative measurement of the Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT). Both are preparations of citrated plasma obtained from normal donors with added stabilizers and buffers. Mechanical assays of Stasis 3 to the predicate moderately abnormal plasma control with two different sensitive thromboplastin reagents, 1.20 ISI and 1.58 ISI, yielded a standard deviation of 0.8385 and 0.4721 for Stasis 3 respectively, compared to a 0.9333 and a 0.5467 for the predicate control from the same reagents. A run-run precision of Stasis 3 produced a 0.841 and 0.4712 SD with the two thromboplastin reagents, compared to 0.9696 and 0.5512 SD of Pacific Hemostasis Control.

510(k): Stasis 3 - Conclusions Mechanical measurements of the APTT in both Stasis 3 and Pacific Hemostasis Level III Control with two different activator reagents, Kaolin and ellagic acid, produced a 0.5278 and a 0.4928 standard deviation, respectively, while the predicate control yielded a 0.6465 and a 0.7160 SD. A run-run precision of the Stasis 3 Control measured at 0.5273 and 0.4860 SD to the two APTT activators, contrasted to Pacific Hemostasis Level III Controls 0.8029 and 0.7133 SD. Reproducibility of the two controls yielded a 1.35% within-run coefficient of variation and a run-run 1.36% CV for Stasis 3, compared respectively to the predicate control of 1.52% CV and 1.58% CV. The performance data presented here, as well as the undistinguishable intended use and technological characteristics support the substantial equivalence claim for Wortham Laboratories Stasis 3 Coagulation Control to Pacific Hemostasis Coagulation Control Level III. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

510(k) Summary: Serathan-A PT Reagant

510(k): Serathan-A PT Reagant Device Name: Wortham Laboratories Serathan-A PT Reagant #K060968 Common Name: Prothrombin Time Classification Name: Prothrombin Time Test, is a Class II device, as per 21 CFR 864.7750 (Product Code GJS). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis Thromboplastin DS (K940082)

510(k): Serathan-A PT Reagant Description Wortham Laboratories Serathan-A PT Reagent is a liquid stable extract of rabbit thromboplastin containing calcium, stabilizer and buffer. Serathan-A is an in-vitro diagnostic reagent intended for use for the performance of Prothrombin Time (PT) testing and quantitative PT-based factor assays for Factors II, V. VII and X.

510(k): Serathan-A PT Reagant Intended Use Wortham Laboratories 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.

510(k): Serathan-A / Substantial Equivalence Characteristics Intended Use New Device Performance of Prothrombin Time (PT) testing for the detection of coagulation abnormalities in the extrinsic pathway Predicate Reagent Composition Liquid Rabbit Thromboplastin Lypholyzed Rabbit Thromboplastin Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 30 months @ 2-8° C, lypholyzed 7 days @ 2-8° C, rehydrated Reference Values within-run CV% Level 1 0.89% 1.36% Level 2 1.09% 1.28% Level 3 1.25% 1.52% run-run 0.88% 1.38% 1.08% 1.19% 1.58%

510(k): Serathan-A / Substantial Equivalence Lupus Sensitivity CV% 0.29% 2.04% Factor Assay Factor II 1.25% 0.42% Factor V 0.25% 0.37% Factor VII 0.38% Factor X 0.18% 0.32%

510(k): Serathan-A / Substantial Equivalence Expected Range Mean (sec) % II V VII X 100 11.79 11.99 11.90 11.69 11.67 11.80 50 13.41 12.79 13.11 11.72 13.31 12.70 12.98 40 12.02 14.20 13.60 11.92 14.09 12.92 13.51 30 12.38 15.20 13.82 14.52 12.30 15.13 13.72 14.38 20 12.99 16.29 14.11 15.21 12.80 16.22 14.02 15.10 10 14.31 18.66 15.51 17.52 18.48 15.38 17.30 Linearity 12.1 – 41.9 sec 11.9 – 41.1 sec Storage ≤ -2° C 2 - 8° C Assay Factors PT, Fibrinogen, Factors II, V, VII, X

510(k): Serathan-A Conclusions Wortham Laboratories Serathan-A and Pacific Hemostasis Thromboplastin-DS reagents have the same intended use, as for the quantitative measurement of the Prothrombin Time (PT), and Factors II, V, VII, X. Both reagents are preparations of rabbit thromboplastin and calcium chloride, with an International Sensitivity Index of 1.0 – 1.2. All assays were measured on the fibrometer yielding a PT standard deviation of 0.1135, 0.3977 and 0.7746 for Serathan-A on Level 1, Level 2, Level 3 plasma controls, respectively, compared to Pacific Hemostasis Thromboplastin-DS of 0.1694, 0.4320, 0.8556 standard deviation on the same controls. Comparing the precision of the two reagents in the factor assays produced a standard deviation of 0.030, 0.030, 0.030 and 0.022 for Factors II, V, VII, X, respectively for Serathan-A, contrasted to 0.0497, 0.043, 0.045, and 0.038 for Thromboplastin-DS.

510(k): Serathan-A Conclusions Reproducibility of the two reagents yielded a 1.09% within-run coefficient of variation and a run-run 0.97% CV for Serathan-A, compared respectively to the predicate control of 1.18% CV and 1.21% CV. The performance data presented here, as well as the undistinguishable intended use and technological characteristics support the substantial equivalence claim for Wortham Laboratories Serathan-A to Pacific Hemostasis Thromboplastin-DS. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

510(k) Summary: Serathan-B PT Reagant

510(k): Serathan-B PT Reagant Device Name: Wortham Laboratories Serathan-B PT Reagant #K060968 Common Name: Prothrombin Time Classification Name: Prothrombin Time Test, is a Class II device, as per 21 CFR 864.7750 (Product Code GJS). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis Thromboplastin D (K994100)

510(k): Serathan-B PT Reagant Description Wortham Laboratories Serathan-B PT Reagent is a liquid stable extract of rabbit thromboplastin containing calcium, stabilizer and buffer. Serathan-B is an in-vitro diagnostic reagent intended for use for the performance of Prothrombin Time (PT) testing and quantitative PT-based factor assays for Factors II, V. VII and X.

510(k): Serathan-B PT Reagant Intended Use Wortham Laboratories 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.

510(k): Serathan-B / Substantial Equivalence Characteristics Intended Use New Device Performance of Prothrombin Time (PT) testing for the detection of coagulation abnormalities in the extrinsic pathway Predicate Reagent Composition Liquid Rabbit Thromboplastin Lypholyzed Rabbit Thromboplastin Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 30 months @ 2-8° C, lypholyzed 7 days @ 2-8° C, rehydrated

510(k): Serathan-B / Substantial Equivalence Reference Values within-run CV% Level 1 0.80% 0.90% Level 2 1.27% 1.41% Level 3 1.42% 1.68% run-run 0.75% 0.85% 1.22% 1.30% 1.44% 1.70% Lupus Sensitivity 0.32% 1.67% Factor Assay Factor II 0.00% 0.39% Factor V 0.26% Factor VII 0.19% Factor X 0.31%

510(k): Serathan-B / Substantial Equivalence Expected Range Mean (sec) % II V VII X 100 11.00 11.49 11.40 11.60 10.88 11.38 11.28 11.48 50 11.01 11.89 12.41 11.39 11.80 12.32 13.13 40 13.09 13.82 11.41 12.29 12.92 13.56 30 11.79 13.19 13.90 14.91 11.70 13.00 13.71 14.73 20 12.30 14.70 14.79 16.32 12.22 14.50 16.08 10 17.12 16.48 20.02 13.63 16.93 16.17 19.81 Linearity 11.6 – 36.2 sec 11.1 – 35.6 sec Storage ≤ -2° C 2 - 8° C Assay Factors PT, Fibrinogen, Factors II, V, VII, X

510(k): Serathan-B Conclusions Wortham Laboratories Serathan-B and Pacific Hemostasis Thromboplastin-D reagents have the same intended use, as for the quantitative measurement of the Prothrombin Time (PT), and Factors II, V, VII, X. Both reagents are preparations of rabbit thromboplastin and calcium chloride, with an International Sensitivity Index of 1.5 – 1.7. All assays were measured on the fibrometer yielding a PT standard deviation of 0.0869, 0.2033 and 0.4721 for Serathan-B on Level 1, Level 2, Level 3 plasma controls, respectively, compared to Pacific Hemostasis Thromboplastin-D of 0.1050, 0.2856, 0.5467 standard deviation on the same controls. Comparing the precision of the two reagents in the factor assays produced a standard deviation of 0.03, 0.03, 0.022 and 0.022 for Factors II, V, VII, X, respectively for Serathan-B, contrasted to 0.043, 0.036, 0.036, and 0.036 for Thromboplastin-D.

510(k): Serathan-B Conclusions Reproducibility of the two reagents yielded a 0.80% within-run coefficient of variation and a run-run 0.75% CV for Serathan-B, compared respectively to the predicate control of 0.91% CV and 0.89% CV. The performance data presented here, as well as the undistinguishable intended use and technological characteristics support the substantial equivalence claim for Wortham Laboratories Serathan-B to Pacific Hemostasis Thromboplastin-D. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

510(k) Summary: Intrin-SI APTT Reagent

510(k): Intrin-SI APTT Reagent Device Name: Wortham Laboratories Intrin-SI APTT Reagant #K060968 Common Name: Activated Partial Thromboplastin Time (APTT) Classification Name: Activated Partial Thromboplastin is a Class II device, as per 21 CFR 864.7925 (Product Code GFO). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis Kontact (K023362)

510(k): Intrin-SI APTT Reagent Description Wortham Laboratories Intrin-SI APTT reagent is intended for use in determining activated partial thromboplastin time (APTT) and coagulation factor assays that are based on a modified APTT. The capacity of blood to form a fibrin clot by way of the intrinsic hemostatic pathway requires coagulation factors XII, XI, IX, VIII, platelet lipids and calcium. The assay is performed by the addition of a suspension of rabbit cephalin with the surface activator Kaolin.

510(k): Intrin-SI APTT Reagent Intended Use Wortham Laboratories 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.

510(k): Intrin-SI / Substantial Equivalence Characteristics Intended Use New Device Performance of Activated Partial Thromboplastin Time (APTT) testing for the detection of coagulation abnormalities in the intrinsic pathway Predicate Reagent Composition Liquid Rabbit Thromboplastin with a silicon activator Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 12 months @ 2-8° C 30 days @ 2-8° C, open

510(k): Intrin-SI / Substantial Equivalence Reference Values within-run CV% Level 1 0.29% 1.54% Level 2 0.74% 1.00% Level 3 0.75% 1.16% run-run 1.20% 1.01% 1.15% Heparin Sensitivity 0.25 U/ml 1.57% 2.30% 0.35 U/ml 1.53% 2.02% Lupus Sensitivity 6.37% 16.80% Factor Assay Factor VIII 0.13% 0.31% Factor IX 0.10% 0.32% Factor XI 0.16% 0.26% Factor XII 0.18% 0.34%

510(k): Intrin-SI / Substantial Equivalence Expected Range Mean (sec) % VIII IX XI XII 100 28.52 29.59 29.17 28.56 27.85 28.12 28.05 27.78 50 34.77 32.78 30.35 33.75 34.08 31.38 29.26 40 38.02 35.80 34.23 36.14 37.21 34.80 33.13 30 42.31 42.61 39.57 37.83 40.90 41.74 38.52 36.64 20 49.91 50.22 46.00 41.59 47.22 49.16 45.15 40.31 10 57.21 56.14 53.68 48.83 54.18 55.12 52.32 47.67 Storage ≤ -2° C 2 - 8° C Assay Factors APTT, Heparin, Factors VIII, IX, XI, XII

510(k): Intrin-SI Conclusions Wortham Laboratories Intrin-SI and Pacific Hemostasis Kontact reagents have the same intended use, as for the quantitative measurement of the Activated Partial Thromboplastin Time (APTT), Heparin, and Factors VIII, IX, XI, XII. Both reagents are preparations of rabbit thromboplastin and a silicon activator from kaolin. All assays were measured on the fibrometer yielding an APTT standard deviation of 0.0863, 0.4135 and 0.5278 for Intrin-SI on Level 1, Level 2, Level 3 plasma controls, respectively, compared to Pacific Hemostasis Kontact of 0.1989, 0.5721, 0.6465 standard deviation on the same controls. Intrin-SI sensitivity to heparin at 0.25 U/ml and 0.35 U/ml, yielded a 0.2236 standard deviation to both levels of heparin compared to 0.3078 and 0.3664 standard deviation, respectively, in the predicate product.

510(k): Intrin-SI Conclusions Comparing the precision of the two reagents in the factor assays produced a standard deviation of 0.036, 0.030, 0.046, and 0.050 SD for Factors VIII, IX, XI, XII, respectively for Intrin-SI, to 0.087, 0.089, 0.074, and 0.096 SD for Kontact. Reproducibility of the two reagents yielded a 0.67% coefficient of variation at 0.25 U/ml and 0.48% CV at 0.35 U/ml heparin, compared to Kontact 0.94% CV and 0.72% CV, respectively. The performance data presented here, as well as the undistinguishable intended use and technological characteristics support the substantial equivalence claim for Wortham Laboratories Intrin-SI to Pacific Hemostasis Kontact. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

510(k) Summary: Intrin-EA APTT Reagent

510(k): Intrin-EA APTT Reagent Device Name: Wortham Laboratories Intrin-SI APTT Reagant #K060968 Common Name: Activated Partial Thromboplastin Time (APTT) Classification Name: Activated Partial Thromboplastin is a Class II device, as per 21 CFR 864.7925 (Product Code GFO). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis APTT-LS (K891337)

510(k): Intrin-EA APTT Reagent Description Wortham Laboratories Intrin-EA APTT reagent is intended for use in determining activated partial thromboplastin time (APTT) and coagulation factor assays that are based on a modified APTT. The capacity of blood to form a fibrin clot by way of the intrinsic hemostatic pathway requires coagulation factors XII, XI, IX, VIII, platelet lipids and calcium. The assay is performed by the addition of a suspension of rabbit cephalin with the surface activator ellagic acid.

510(k): Intrin-EA APTT Reagent Intended Use Wortham Laboratories 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.

510(k): Intrin-EA / Substantial Equivalence Characteristics Intended Use New Device Performance of Activated Partial Thromboplastin Time (APTT) testing for the detection of coagulation abnormalities in the intrinsic pathway Predicate Reagent Composition Liquid Rabbit Thromboplastin with ellagic acid activator Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 22 months @ 2-8° C, lypholyzed 30 days @ 2-8° C, rehydrated

510(k): Intrin-EA / Substantial Equivalence Reference Values within-run CV% Level 1 0.51% 0.85% Level 2 0.41% 0.91% Level 3 0.73% 1.12% run-run 0.44% 0.90% 0.71% 1.11% Heparin Sensitivity 0.25 U/ml 1.03% 0.35 U/ml 0.54% Lupus Sensitivity 4.39% 7.81% Factor Assay Factor VIII 0.17% 0.23% Factor IX 0.24% Factor XI 0.14% 0.29% Factor XII 0.13% 0.26%

510(k): Intrin-EA / Substantial Equivalence Expected Range Mean (sec) % VIII IX XI XII 100 29.36 28.54 29.47 26.82 28.23 27.48 28.32 25.78 50 33.86 32.38 34.74 29.89 32.57 31.26 33.36 28.65 40 35.08 34.03 36.26 31.14 33.83 33.02 35.03 29.78 30 37.33 36.34 38.61 32.23 36.13 35.12 37.30 31.09 20 40.47 38.64 41.35 33.33 39.20 37.40 40.14 32.04 10 45.10 40.89 46.84 35.04 43.78 39.86 45.70 33.21 Linearity 29.0 – 70.7 sec 28.5 – 69.6 sec Storage ≤ -2° C 2 - 8° C Assay Factors APTT, Heparin, Factors VIII, IX, XI, XII

510(k): Intrin-EA Conclusions Wortham Laboratories Intrin-EA and Pacific Hemostasis APTT-LS reagents have the same intended use, as for the quantitative measurement of the Activated Partial Thromboplastin Time (APTT), Heparin, and Factors VIII, IX, XI, XII. Both reagents are preparations of rabbit thromboplastin and ellagic acid as an activator. All assays were measured on the fibrometer yielding an APTT standard deviation of 0.1483, 0.1968 and 0.4961 for Intrin-EA on Level 1, Level 2, Level 3 plasma controls, respectively, compared to Pacific Hemostasis APTT-LS of 0.1908, 0.4030, 0.8900 standard deviation on the same controls. Intrin-EA sensitivity to heparin at 0.25 U/ml and 0.35 U/ml, yielded a 0.2236 standard deviation to both levels of heparin compared to 0.3078 and 0.3664 standard deviation, respectively, in the predicate product.

510(k): Intrin-EA Conclusions Comparing the precision of the two reagents in the factor assays produced a standard deviation of 0.049, 0.048, 0.043, and 0.036 SD for Factors VIII, IX, XI, XII, respectively for Intrin-EA, to 0.064, 0.065, 0.083, and 0.068 SD for APTT-LS. Reproducibility of the two reagents yielded a 0.71% coefficient of variation at 0.25 U/ml and 0.54% CV at 0.35 U/ml heparin, compared to APTT-LS 1.03% CV and 0.91% CV, respectively. The performance data presented here, as well as the undistinguishable intended use and technological characteristics support the substantial equivalence claim for Wortham Laboratories Intrin-EA to Pacific Hemostasis APTT-LS. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

510(k) Summary: Fibrinogen Control Plasma (Normal)

510(k): Fibrinogen Control Plasma (Normal) Device Name: Wortham Laboratories Fibrinogen Control Plasma (Normal) #K060968 Common Name: Fibrinogen Control Plasma Classification Name: Plasma, Coagulation Control, is a Class II device as per 21 CFR 864.5425 (Product Code GHH). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis Fibrinogen Assay (K800826)

510(k): Fibrinogen Control Plasma Description Wortham Laboratories Fibrinogen Normal Control is a liquid stable preparation of citrated plasma obtained from healthy donors, which contains stabilizers and buffers. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found non-reactive for HBsAg and negative for antibodies to HIV and HCV.

510(k): Fibrinogen Control Plasma Intended Use Wortham Laboratories Fibrinogen Control Normal, a quantitative control plasma, is intended for use in the quality control of fibrinogen assays.

510(k): FCP / Substantial Equivalence Characteristics Intended Use New Device To determine quantitative level of fibrinogen in plasma sample, and for quality control in monitoring heparin therapy with APTT testing Predicate Control Composition Liquid Human citrated plasma Lypholyzed Human citrated plasma Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 24 months @ 2-8° C, lypholyzed 16 hours @ 2-8° C, rehydrated

510(k): FCP / Substantial Equivalence Reference Values within-run CV% Normal 0.56% 0.59% Low 0.60% 0.63% run-run 0.57% 0.58% 0.67% Expected Range Mechanical Mean ± 2SD 306.3 301-313 g/dl 297-315 g/dl 99.1 97-103 g/dl 99.8 97-104 g/dl Storage ≤ -2° C 2 - 8° C Assay Factors Fibrinogen

510(k): Fibrinogen Control Plasma - Normal Conclusions Wortham Laboratories Normal Fibrinogen Control and Pacific Hemostasis Normal Fibrinogen Control have the same intended use, as for the quantitative measurement of fibrinogen levels in human plasma. Both are preparations of citrated human plasma, obtained from normal donors with added stabilizers and buffers. Mechanical assays produced a standard deviation of 0.085 for Wortham Laboratories Fibrinogen Control, compared to a 0.089 standard deviation for Pacific Hemostasis Fibrinogen Control. Reproducibility of the two controls yielded a 0.56% within-run coefficient of variation and a run-run 0.53% CV for Wortham Laboratories Fibrinogen Control compared respectively to the predicate control of 0.59% CV and 0.60% CV. The performance data presented here, as well as the undistinguishable intended use and technological characteristics support the substantial equivalence claim for Wortham Laboratories Normal Fibrinogen Control to Pacific Hemostasis Normal Fibrinogen Control. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

510(k) Summary: Fibrinogen Control Plasma (Low)

510(k): Fibrinogen Control Plasma (Low) Device Name: Wortham Laboratories Fibrinogen Control Plasma (Low) #K060968 Common Name: Fibrinogen Control Plasma Classification Name: Plasma, Coagulation Control, is a Class II device as per 21 CFR 864.5425 (Product Code GHH). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis Fibrinogen Assay (K800826)

510(k): Fibrinogen Control Plasma Description Wortham Laboratories Fibrinogen Low Control is a liquid stable preparation of citrated plasma obtained from healthy donors, which contains stabilizers and buffers. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found non-reactive for HBsAg and negative for antibodies to HIV and HCV.

510(k): Fibrinogen Control Plasma (Low) Intended Use Wortham Laboratories Fibrinogen Control Low, a quantitative control plasma, is intended for use in the quality control of fibrinogen assays.

510(k): FCP / Substantial Equivalence Characteristics Intended Use New Device To determine quantitative level of fibrinogen in plasma sample, and for quality control in monitoring heparin therapy with APTT testing Predicate Control Composition Liquid Human citrated plasma Lypholyzed Human citrated plasma Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 24 months @ 2-8° C, lypholyzed 16 hours @ 2-8° C, rehydrated

510(k): FCP / Substantial Equivalence Reference Values within-run CV% Normal 0.56% 0.59% Low 0.60% 0.63% run-run 0.57% 0.58% 0.67% Expected Range Mechanical Mean ± 2SD 306.3 301-313 g/dl 297-315 g/dl 99.1 97-103 g/dl 99.8 97-104 g/dl Storage ≤ -2° C 2 - 8° C Assay Factors Fibrinogen

510(k): Fibrinogen Control Plasma - Low Conclusions Wortham Laboratories Low Fibrinogen Control and Pacific Hemostasis Low Fibrinogen Control have the same intended use, as for the quantitative measurement of fibrinogen levels in human plasma. Both are preparations of citrated human plasma, obtained from normal donors with added stabilizers and buffers. Mechanical assays produced a standard deviation of 0.092 for Wortham Laboratories Fibrinogen Control, compared to a 0.095 standard deviation for Pacific Hemostasis Fibrinogen Control. Reproducibility of the two controls yielded a 0.60% within-run coefficient of variation and a run-run 0.58% CV for Wortham Laboratories Fibrinogen Control compared respectively to the predicate control of 0.63% CV and 0.67% CV. The performance data presented here, as well as the undistinguishable intended use and technological characteristics support the substantial equivalence claim for Wortham Laboratories Low Fibrinogen Control to Pacific Hemostasis Low Fibrinogen Control. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

510(k) Summary: Heparin Control Plasma Level 1

510(k): Heparin Control Plasma 1 Device Name: Wortham Laboratories Heparin Control Plasma (Level 1) #K060968 Common Name: Heparin Control Plasma Level 1 Classification Name: Plasma, Coagulation Control, is a Class II device as per 21 CFR 864.5425 (Product Code GGN). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis Heparin Control Level 1 (K992278)

510(k): Heparin Control Plasma 1 Description Wortham Laboratories Heparin Control Level 1 is a liquid stable preparation of citrated plasma obtained from healthy donors, which contains sodium heparin, stabilizers and buffers. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found non-reactive for HBsAg and negative for antibodies to HIV and HCV.

510(k): Heparin Control Plasma 1 Intended Use Wortham Laboratories Heparin Control Level 1, is intended as a quality control of the Activated Partial Thromboplastin Time (APTT) during heparin monitoring.

510(k): Heparin Control Plasma 1 Substantial Equivalence Characteristics Intended Use New Device Used in heparin assay for quality control in monitoring heparin therapy with APTT testing, yielding slightly abnormal range for Level 1 (0.25 U/ml) and marked abnormal range for Level 2 (0.35 U/ml) Predicate Control Composition Liquid Human citrated plasma with heparin Lypholyzed Human citrated plasma with heparin Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 36 months @ 2-8° C, lypholyzed 8 hours @ 2-8° C, rehydrated

510(k): Heparin Control Plasma 1 Substantial Equivalence Reference Values within-run CV% 0.25 U/ml 1.82% 2.14% 0.35 U/ml 1.77% 2.04% run-run 1.92% 2.27% 1.81% 2.07% Expected Range Mechanical Mean ± 2SD Level 1 46.82 45.2-48.5 sec 46.94 44.8-49.1 sec Level 2 63.49 62.4-64.6 sec 62.64 60.1-65.2 sec Storage ≤ -2° C 2 - 8° C Assay Factors Heparin

510(k): Heparin Control Plasma 1 Conclusions Wortham Laboratories Heparin Control Level 1 and Pacific Hemostasis Heparin Control Level 1 have the same intended use, as for quality control in monitoring heparin therapy with APTT testing. Both are prepared from porcine heparin in normal human citrated plasma. The APTT value will be in the slightly abnormal range for Level 1 Heparin Control. Mechanical assays produced a within-run standard deviation of 0.8296 and a 0.8930 run-run standard deviation for Wortham Laboratories Level 1 Heparin Control, compared to the predicate control of 1.0640 and 1.0859 standard deviation, respectively.

510(k): Heparin Control Plasma 1 Conclusions Reproducibility of the two controls yielded a 1.33% within-run coefficient of variation and a run-run 1.92% CV for Wortham Laboratories Heparin Control Level 1, compared respectively to the predicate control of 2.15% CV and 2.27% CV. The performance data presented here, as well as the undistinguishable intended use and technological characteristics support the substantial equivalence claim for Wortham Laboratories Heparin Control Level 1 to Pacific Hemostasis Heparin Control Level 1. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

510(k) Summary: Heparin Control Plasma Level 2

510(k): Heparin Control Plasma 2 Device Name: Wortham Laboratories Heparin Control Plasma (Level 2) (0.35 U/ml). #K060968 Common Name: Heparin Control Plasma Level 2 Classification Name: Plasma, Coagulation Control, is a Class II device as per 21 CFR 864.5425 (Product Code GGN). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis Heparin Control Level II (K992279)

510(k): Heparin Control Plasma 2 Description Wortham Laboratories Heparin Control Level 2 is a liquid stable preparation of citrated plasma obtained from healthy donors, which contains sodium heparin, stabilizers and buffers. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found non-reactive for HBsAg and negative for antibodies to HIV and HCV.

510(k): Heparin Control Plasma 2 Intended Use Wortham Laboratories Heparin Control Level 2, is intended as a quality control of the Activated Partial Thromboplastin Time (APTT) during heparin monitoring.

510(k): Heparin Control Plasma 2 Substantial Equivalence Characteristics Intended Use New Device Used in heparin assay for quality control in monitoring heparin therapy with APTT testing, yielding slightly abnormal range for Level 1 (0.25 U/ml) and marked abnormal range for Level 2 (0.35 U/ml) Predicate Control Composition Liquid Human citrated plasma with heparin Lypholyzed Human citrated plasma with heparin Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 36 months @ 2-8° C, lypholyzed 8 hours @ 2-8° C, rehydrated

510(k): Heparin Control Plasma 2 Substantial Equivalence Reference Values within-run CV% 0.25 U/ml 1.82% 2.14% 0.35 U/ml 1.77% 2.04% run-run 1.92% 2.27% 1.81% 2.07% Expected Range Mechanical Mean ± 2SD Level 1 46.82 45.2-48.5 sec 46.94 44.8-49.1 sec Level 2 63.49 62.4-64.6 sec 62.64 60.1-65.2 sec Storage ≤ -2° C 2 - 8° C Assay Factors Heparin

510(k): Heparin Control Plasma 2 Conclusions Wortham Laboratories Heparin Control Level 2 and Pacific Hemostasis Heparin Control Level 2 have the same intended use, as for quality control in monitoring heparin therapy with APTT testing. Both are prepared from porcine heparin in normal human citrated plasma. The APTT value will be in the slightly abnormal range for Level 2 Heparin Control. Mechanical assays produced a within-run standard deviation of 1.1205 and a 1.1496 run-run standard deviation for Wortham Laboratories Level 2 Heparin Control, compared to the predicate control of 1.2775 and 1.2975 standard deviation, respectively.

510(k): Heparin Control Plasma 2 Conclusions Reproducibility of the two controls yielded a 1.77% within-run coefficient of variation and a run-run 1.81% CV for Wortham Laboratories Heparin Control Level 2, compared respectively to the predicate control of 2.047% CV and 2.07% CV. The performance data presented here, as well as the undistinguishable intended use and technological characteristics support the substantial equivalence claim for Wortham Laboratories Heparin Control Level 2 to Pacific Hemostasis Heparin Control Level 2. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

510(k) Summary: Fibrinogen Assay Set

510(k): Fibrinogen Assay Set Device Name: Wortham Laboratories Fibrinogen Assay Set #K060968 Common Name: Fibrinogen Control Plasma Classification Name: Plasma, Coagulation Control, is a Class II device as per 21 CFR 864.5425 (Product Code GHH). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis Fibrinogen Assay (K800826)

510(k): Fibrinogen Assay Set Description Wortham Laboratories Fibrinogen Assay Set contains a liquid stable preparation of citrated plasma obtained from healthy donors, which contains stabilizers, buffers, and a bovine reagent and buffer solution which are also provided in the set. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found non-reactive for HBsAg and negative for antibodies to HIV and HCV.

510(k): Fibrinogen Assay Set Intended Use Wortham Laboratories 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.

510(k): Fibrinogen Assay Set Substantial Equivalence Characteristics Intended Use New Device To determine quantitative level of fibrinogen in plasma sample, and for quality control in monitoring heparin therapy with APTT testing Predicate Reagent Composition Liquid Bovine Thrombin Lypholyzed Bovine Thrombin Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 24 months @ 2-8° C, lypholyzed 16 hours @ 2-8° C, rehydrated

510(k): Fibrinogen Assay Set Substantial Equivalence Reference Values within-run CV% Normal 0.56% 0.59% Low 0.60% 0.63% run-run 0.57% 0.58% 0.67% Expected Range Mechanical Mean ± 2SD 306.3 301-313 g/dl 297-315 g/dl 99.1 97-103 g/dl 99.8 97-104 g/dl Storage ≤ - 2° C 2 - 8° C Assay Factors Fibrinogen

510(k): Fibrinogen Assay Set Conclusions Wortham Laboratories Fibrinogen Assay Set and Pacific Hemostasis Fibrinogen Assay Set have the same intended use, as for the quantitative measurement of fibrinogen levels in human plasma. Both are preparations of citrated human plasma, obtained from normal donors with added stabilizers and buffers, and using bovine thrombin as the activating reagent. Mechanical assays produced a standard deviation of 0.085 for Wortham Laboratories Fibrinogen Control, compared to a 0.089 standard deviation for Pacific Hemostasis Fibrinogen Control.

510(k): Fibrinogen Assay Set Conclusions Reproducibility of the two controls yielded a 0.56% within-run coefficient of variation and a run-run 0.53% CV for Wortham Laboratories Fibrinogen Control compared respectively to the predicate control of 0.59% CV and 0.60% CV. The performance data presented here, as well as the undistinguishable intended use and technological characteristics support the substantial equivalence claim for Wortham Laboratories Fibrinogen Assay Set to Pacific Hemostasis Fibrinogen Assay Set. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

510(k) Summary: Thrombin Reagent

510(k): Thrombin Reagent Device Name: Common Name: Wortham Laboratories Thrombin Reagent #K060968 Common Name: Thrombin Time Test Classification Name: Fibrinogen Determination System, Class II, 21 CFR 864.7340 (Product Code GJA and KQJ). This device is intended for clinical use in conjunction with an analyzer to measure clot formation. Predicate: Pacific Hemostasis Thrombin Reagent (K970645)

510(k): Thrombin Reagent Description Wortham Laboratories Thrombin Reagent is a liquid stable preparation of activated bovine prothrombin proteins (Factor IIa). Intended Use Wortham Laboratories Thrombin Reagent is intended for thrombin to convert fibrinogen in the quantitative determination of fibrinogen in plasma samples.

510(k): Thrombin Reagent Substantial Equivalence Characteristics Intended Use New Device To determine quantitative level of fibrinogen in plasma sample. Predicate Reagent Composition Liquid bovine thrombin Lypholyzed bovine thrombin Stability 12 months @ ≤ -2° C 30 days @ 2-4° C 28 months @ 2-8° C, lypholyzed 1 day @ 2-8° C, rehydrated

510(k): Thrombin Reagent Substantial Equivalence Reference Values CV% within-run 0.67% 0.68% run-run 0.71% Expected Range Mechanical Mean ± 2SD 119 118-120 IU/ml Storage ≤ -2° C 2 - 8° C Assay Factors Fibrinogen

510(k): Thrombin Reagent Conclusions Wortham Laboratories Thrombin Reagent and Pacific Hemostasis Thrombin Reagent have the same intended use, as normal reagents for reactive coagulation assays. Both are preparations of activated bovine prothrombin protein (Factor IIa). The performance data presented here, as well as the indistinguishable intended use and technological characteristics, support the substantial equivalence claim for Wortham Laboratories Thrombin Reagent to Pacific Hemostasis Thrombin Reagent. Based on the data provided, it is our conclusion that these two products are substantially equivalent.

Wortham Labels and Cartons

StasisTM Labeling

SerathanTM Labeling

IntrinTM + Others:

Required Carton Labeling

Required Carton Labeling Wortham Laboratories, Inc. Composition: Stasis 1 Control, a frozen liquid preparation, is processed from human plasma collected with 3.2% sodium citrate anticoagulant, with stabilizers and buffers added for a liquid control. Caution: Human source plasma used in the product was tested by FDA approved methods and found to be negative for immunodeficiency virus (HIV) 1 and 2, hepatitis B virus (HBV), and hepatitis C (HCV). Since no test method can offer complete assurance that infectious agents are absent, extreme care should be taken. Intended 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. For in vitro diagnostic use Cat No: 4002-01-1 IVD

Marketing Success and Strategy Wortham Marketing Success and Strategy

Product Contrast: A D V A N T A G E S All liquid system 1 year shelf life Ready to use; no downtime No waste Low product coefficient of variation (%CV) Repetitive freeze-thaw stability Less storage space Sensitivity to coagulation therapy

Sales Strategy: T A R G E T The market consists of two groups. A. Laboratories with existing reagent contract B. Laboratories without a reagent contract in place Laboratory most likely to have a reagent contract: A. Large to medium sized hospitals. B. Large to medium sized reference laboratories Laboratory most likely not to have a reagent contract: A. Small hospitals and medical / surgical clinics B. Private medical laboratories / Private practice C. Veterinary hospitals

Sales Strategy: T A R G E T Laboratories WITH reagent contracts. It is necessary to have our products evaluated one year before their contract expires. Determine the responsible party: Locate the decision maker with signing authority. Local: Laboratory Director or Laboratory Manager Corporate: VP of New Products / Purchasing Officer

Service Excellence: Reagent Contract Wortham Laboratories will offer a unique Reagent Contract to our customers. What makes our Reagent Contract different? Any type or model of coagulation instrument can be acquired Not limited only to the competitor’s instrument No need to switch to an inferior coagulation product line or a product line that cost more, in order to obtain a specific instrument

Service Excellence: Maintenance A Service Maintenance Contract covering limits beyond the instrument warranty can be added to the Reagent Contract. Market Leading Customer Service In time, a pool of Customer Service staff members will be able to speak to our customers in the following languages: English Arabic Spanish Hebrew Portugese Mandarin German Japanese French Korean Italian Tagalong

Presentation is Complete. T h a n k Y o u Wortham Wortham Laboratories, Inc. www.worthamlabs.com ©2007 Wortham Laboratories, Inc. All Rights Reserved International Office: USA 1+423.296.0090