(251 days)
No reference devices were used in this submission.
No
The document describes a standard chromogenic assay for quantitative determination of heparin and apixaban activity/concentration. There is no mention of AI, ML, or any computational methods beyond standard data analysis for quantification and comparison to reference curves.
No
Explanation: This device is an in-vitro diagnostic assay used to quantify UFH, LMWH, and apixaban activity/concentration in human plasma, which is for diagnostic purposes, not therapeutic intervention.
Yes
This device is an "In-vitro diagnostic automated chromogenic assay" for the quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity, and apixaban concentration, in human plasma. This directly indicates its use for diagnostic purposes.
No
The device is an in-vitro diagnostic assay kit consisting of reagents (Xa and a chromogenic substrate). While it is used with automated coagulation analyzers which contain software, the device itself is a physical reagent kit, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The document explicitly states "In-vitro diagnostic automated chromogenic assay" and describes its use for quantitative determination of substances (heparin and apixaban) in human plasma samples. This is a core characteristic of IVDs.
- Device Description: The description details the assay's mechanism, which involves chemical reactions with patient samples in vitro (outside the body) to produce a measurable result.
- Intended User/Care Setting: It specifies "For in-vitro diagnostic use only" and "For laboratory professional use," further confirming its IVD status.
- Performance Studies: The document describes performance studies like precision, reproducibility, LoB, LoD, LoQ, linearity, and interference studies, which are standard for demonstrating the analytical performance of an IVD.
- Predicate Device(s): The mention of predicate devices with K numbers (which are associated with FDA clearances for medical devices, including IVDs) indicates that this device is being compared to other legally marketed IVDs.
All these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
INNOVANCE Anti-Xa assay in combination with INNOVANCE Heparin Calibrator is an In-vitro diagnostic automated chromogenic assay for the quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity in human plasma collected from venous blood samples in 3.2 % sodium citrated tubes in the clinical laboratory. The quantitative determination of UFH and LMWH can be performed on the BCS XP System, CS-2500 System, CS-5100 System and the CA-660 System. For use with plasma from patients undergoing anticoagulant therapy with either UFH or LMWH.
INNOVANCE Anti-Xa assay in combination with INNOVANCE Apixaban Standards provides quantitative determination of the concentration of apixaban in human plasma collected from venous blood samples in 3.2 % sodium citrated tubes in the clinical laboratory. The quantitative determination of apixaban can be performed on CS-2500 System. For use with plasma from patients undergoing anticoagulant therapy with apixaban in situations where quantification of apixaban levels may be indicated:
- Patient with bleeding
- Patient with risk for bleeding (e.g. during perioperative management) .
- Patient with conditions affecting pharmacokinetics (e.g. deteriorating renal function, extremes of . body weight, treatment with other drugs known to affect pharmacokinetics of apixaban).
The performance of this device has not been established in neonate and pediatric patient populations.
Product codes (comma separated list FDA assigned to the subject device)
QLU
Device Description
INNOVANCE Anti-Xa assay is a one stage chromogenic assay. The reagent kit consists of two components. One component (Reagent) contains Xa. the other (Substrate) a chromogenic substrate specific for Xa. Upon mixing of INNOVANCE Anti-Xa Reagent and INNOVANCE Anti-Xa Substrate, Xa converts the chromogenic substrate into two products, one of them is paranitroaniline. The formation of paranitroaniline can be quantified by the coaqulation analyzer employing light absorption at a specific wavelength (405 nm).
In the presence of a heparin containing sample the formation of paranitroaniline will be reduced in a time dependent manner. This is due to inhibition of Xa by the heparin/AT complex is formed in the patient's plasma and competes with the substrate conversion by Xa. The concentration of the complex is not only dependent on the concentration of heparin but also on the availability of the patient's endogenous antithrombin. By comparison to a reference curve the heparin activity of the sample can be quantified.
To reduce the influence from heparin antagonists, such as platelet factor 4 (PF4), dextran sulfate is included in the reaction mixture.
In the presence of an apixaban containing sample factor Xa is inhibited directly by this inhibitor. Comparison to an inhibitor specific reference curve allows quantification of the inhibitor concentration in the sample.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
The performance of this device has not been established in neonate and pediatric patient populations. For use in adult population according to the predicate device information.
Intended User / Care Setting
For in-vitro diagnostic use only.
For laboratory professional use.
For prescription use only.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision: Precision studies were conducted with the CS-2500 System as described in the CLSI document EP05-A3, using INNOVANCE Apixaban Control 1, INNOVANCE Apixaban Control 2 and 4 plasma pools.
Results:
Plasma pool 1 (n=240, Mean=31.4 ng/mL): Repeatability SDh=0.9 ng/mL, Within-Device/Lab Precision SDh=2.0 ng/mL
Plasma Pool 2 (n=240, Mean=50.1 ng/mL): Repeatability SDh=0.7 ng/mL, Within-Device/Lab Precision SDh=1.1 ng/mL
INNOVANCE Apixaban Control 1 (n=240, Mean=74.9 ng/mL): Repeatability CVi=1.58%, Within-Device/Lab Precision CVi=2.48%
Plasma pool 3 (n=240, Mean=95.8 ng/mL): Repeatability CVi=1.25%, Within-Device/Lab Precision CVi=2.03%
INNOVANCE Apixaban Control 2 (n=240, Mean=277.6 ng/mL): Repeatability CVi=2.20%, Within-Device/Lab Precision CVi=2.57%
Plasma pool 3 (n=240, Mean=320.5 ng/mL): Repeatability CVi=1.24%, Within-Device/Lab Precision CVi=2.09%
Reproducibility: Assessed based on internally conducted studies, including site, laboratory, operator and lot variability factors.
Results:
Sample concentration
§ 864.7295 Heparin and direct oral factor Xa inhibitor drug test system.
(a)
Identification. A heparin and direct oral factor Xa inhibitor drug test system is intended for the detection of heparin and direct oral factor Xa inhibitors in human specimens collected from patients taking heparin or direct oral factor Xa inhibitors. This device is intended to aid in the management of therapy in conjunction with other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include the following:
(i) Detailed documentation of analytical device performance studies and results demonstrating acceptable analytical performance with a sufficient number of specimens tested in order to obtain unbiased estimates of analytical performance. This documentation shall include the following as appropriate to the technology, specimen types tested, and intended use of the device:
(A) Studies and results for that demonstrate device precision including repeatability and reproducibility, using quality controls and clinical samples, when appropriate. Precision studies must assess specimens for each indicated drug at concentrations throughout the measuring range of the device including near clinically relevant levels, as appropriate. The study must evaluate different sources of variability including, as appropriate, between-run, between-operator, between-lot, between-instrument, between-day, and between-site;
(B) Studies and results that demonstrate that the device is free from clinically significant interference, from endogenous and exogenous interferents associated with the target population(s), and interferents that are specific for, or related to, the technology or methodology of the device;
(C) Data to demonstrate appropriate specimen stability for the intended sample matrices under the intended conditions for specimen collection, handling, and storage described in the device labeling;
(D) Studies and results that demonstrate the linear range, limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ), as applicable to the technology of the device; and
(E) For any devices intended for use for near patient testing, studies and results that demonstrate the robustness of the device in the hands of the intended user, including the entire testing procedure, pre-analytical specimen processing steps, and results interpretation.
(ii) Detailed documentation of clinical performance testing in which the performance is analyzed relative to a comparator that FDA has determined is appropriate. Specimens must be representative of the intended use population(s) and must cover the full range of the device output and any clinically relevant decision points as appropriate.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) Identification of any known interferents, including all endogenous, exogenous, technology-specific, and patient population-specific interferents, specific to the test outputs. The information must include the concentration(s) or level(s) of the interferent at which clinically significant interference was found to occur, and the concentration range or levels at which interference was not found to occur;
(ii) A prominent statement that the device is not intended for use in monitoring patients taking heparin or direct oral factor Xa inhibitors; and
(iii) Limiting statements indicating, as applicable:
(A) That the device should only be used in conjunction with information available from clinical evaluations and other diagnostic procedures; and
(B) That the device is not specific to the direct oral factor Xa inhibitor that has been evaluated and may detect the presence of other direct factor Xa inhibitors that have not been evaluated.
0
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October 10, 2024
Siemens Healthcare Diagnostics Products GmbH Anja Wilhelm Manager Regulatory Affairs Emil-von-Behring-Strasse 76 Marburg, HE 35041 Germany
Re: K240315
Trade/Device Name: INNOVANCE Anti-Xa Regulation Number: 21 CFR 864.7295 Regulation Name: Heparin And Direct Oral Factor Xa Inhibitor Drug Test System Regulatory Class: Class II Product Code: QLU Dated: September 10, 2024 Received: September 10, 2024
Dear Anja Wilhelm:
We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"
1
(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rue"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
2
Sincerely,
Image /page/2/Picture/3 description: The image contains the text "Min Wu-S) A". The text is written in a simple, sans-serif font. The letters are black, and the background is white. The text appears to be a name or a title, with the "-S) A" possibly indicating a suffix or abbreviation.
Min Wu, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
3
Indications for Use
510(k) Number (if known) K240315
Device Name INNOVANCE Anti-Xa
Indications for Use (Describe)
INNOVANCE Anti-Xa assay in combination with INNOVANCE Heparin Calibrator is an In-vitro diagnostic automated chromogenic assay for the quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity in human plasma collected from venous blood samples in 3.2 % sodium citrated tubes in the clinical laboratory. The quantitative determination of UFH and LMWH can be performed on the BCS XP System, CS-2500 System, CS-5100 System and the CA-660 System. For use with plasma from patients undergoing anticoagulant therapy with either UFH or LMWH.
INNOVANCE Anti-Xa assay in combination with INNOVANCE Apixaban Standard provides quantitative determination of the concentration of apixaban in human plasma collected from venous blood samples in 3.2 % sodium citrated tubes in the clinical laboratory. The quantitative determination of apixaban can be performed on CS-2500 System. For use with plasma from patients undergoing anticoagulant therapy with apixaban in situations where quantification of apixaban levels may be indicated:
· Patient with bleeding,
· Patient with risk for bleeding (e.g. during perioperative management),
· Patient with conditions affecting pharmacokinetics (e.g. deteriorating renal function, extremes of body weight, treatment with other drugs known to affect pharmacokinetics of apixaban).
The performance of this device has not been established in neonate and pediatric patient populations.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) Summary
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of 21 CFR §807.92, the Safe Medical Act of 1990, and follows the FDA quidance 'The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]', issued July 28, 2014.
1. Applicant
| Siemens Healthcare Diagnostics Products GmbH | |
|---|---|
| Emil-von-Behring-Str. 76 | |
| 35041 Marburg, Germany | |
| Contact Person: | Anja Wilhelm |
| Email: | anja.wilhelm@siemens-healthineers.com |
| Phone: | +49 172 3428316 |
| 2. Device | |
| Name of Device: | INNOVANCE Anti-Xa |
| Regulation Number: | 21 CFR 864.7295 |
| Regulation Description: | Heparin And Direct Oral Factor Xa Inhibitor Drug Test System |
| Product Code: | QLU |
| Device Classification Name: | Anti-Factor Xa Activity Test System, Apixaban |
| Regulatory Class: | Class II |
| 510(k) Review Panel | Hematology (81) |
| 3. Predicate Device | |
| Name of Device / 510(k): | HemosIL Liquid Anti-Xa / DEN190032, K213464, K223187 |
| Regulation Number: | 21 CFR 864.7295 |
| Regulation Description: | Heparin And Direct Oral Factor Xa Inhibitor Drug Test System |
| Product Code: | QLU |
| Device Classification Name: | Anti-Factor Xa Activity Test System, Apixaban |
| Regulatory Class: | Class II |
| 510(k) Review Panel | Hematology (81) |
A Class 2 Device Recall HemosIL Liquid Anti-Xa was issued on October 19, 2021. The recall topic was related to labeled On-board instrument stability issue for current and future lots, reduced On-board Instrument Stability from 7 days. Furthermore, in K213464 Instrumentation Laboratory Company cleared the reduced on-board stability claims of 4 days for the ACL TOP Family/ACL TOP Family 50 Series.
5
No reference devices were used in this submission.
4. Device Description / Test Principle
INNOVANCE Anti-Xa assay is a one stage chromogenic assay. The reagent kit consists of two components. One component (Reagent) contains Xa. the other (Substrate) a chromogenic substrate specific for Xa. Upon mixing of INNOVANCE Anti-Xa Reagent and INNOVANCE Anti-Xa Substrate, Xa converts the chromogenic substrate into two products, one of them is paranitroaniline. The formation of paranitroaniline can be quantified by the coaqulation analyzer employing light absorption at a specific wavelength (405 nm).
In the presence of a heparin containing sample the formation of paranitroaniline will be reduced in a time dependent manner. This is due to inhibition of Xa by the heparin/AT complex is formed in the patient's plasma and competes with the substrate conversion by Xa. The concentration of the complex is not only dependent on the concentration of heparin but also on the availability of the patient's endogenous antithrombin. By comparison to a reference curve the heparin activity of the sample can be quantified.
To reduce the influence from heparin antagonists, such as platelet factor 4 (PF4), dextran sulfate is included in the reaction mixture.
In the presence of an apixaban containing sample factor Xa is inhibited directly by this inhibitor. Comparison to an inhibitor specific reference curve allows quantification of the inhibitor concentration in the sample.
5. Intended Use / Indications for Use
INNOVANCE Anti-Xa assay in combination with INNOVANCE Heparin Calibrator is an In-vitro diagnostic automated chromogenic assay for the quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity in human plasma collected from venous blood samples in 3.2 % sodium citrated tubes in the clinical laboratory. The quantitative determination of UFH and LMWH can be performed on the BCS XP System, CS-5100 System, CS-5100 System and the CA-660 System. For use with plasma from patients undergoing anticoagulant therapy with either UFH or LMWH.
INNOVANCE Anti-Xa assay in combination with INNOVANCE Apixaban Standards provides quantitative determination of the concentration of apixaban in human plasma collected from venous blood samples in 3.2 % sodium citrated tubes in the clinical laboratory. The quantitative determination of apixaban can be performed on CS-2500 System. For use with plasma from patients undergoing anticoagulant therapy with apixaban in situations where quantification of apixaban levels may be indicated:
- . Patient with bleeding
- Patient with risk for bleeding (e.g. during perioperative management) .
- Patient with conditions affecting pharmacokinetics (e.g. deteriorating renal function, extremes of . body weight, treatment with other drugs known to affect pharmacokinetics of apixaban).
The performance of this device has not been established in neonate and pediatric patient populations.
6. Special Conditions for Use Statements
For in-vitro diagnostic use only.
For laboratory professional use.
For prescription use only.
6
7. Special instrument requirements:
When used with INNOVANCE Heparin Calibrator:
- BCS XP System •
- . Automated Blood Coagulation Analyzer CA-600 series (CA-600 series)
- AUTOMATED BLOOD COAGULATION ANALYZER CS-2500 (CS-2500 System)
- . AUTOMATED BLOOD COAGULATION ANALYZER CS-5100 (CS-5100 System)
When used with INNOVANCE Apixaban Standards:
- . AUTOMATED BLOOD COAGULATION ANALYZER CS-2500 (CS-2500 System)
8. Comparison of Technological Characteristics with the Predicate Device
The following table presents a comparison of the similarities and differences between the proposed device INNOVANCE Anti-Xa and the predicate device HemosIL Liquid Anti-Xa including their dedicated calibrator and control materials.
| Item | Predicate Device
HemosIL Liquid Anti-Xa | Subject Device
INNOVANCE Anti-Xa |
|--------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use /
Indication for Use | HemosIL Liquid Anti-Xa is an automated chromogenic assay for in vitro diagnostic use by laboratory professionals in clinical laboratories. The assay provides quantitative results on 3.2% citrated human plasma for the following analytes based on the calibrators used:
• When used with HemosIL Heparin Calibrators:
Quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity on the ACL TOP Family and ACL TOP Family 50 Series.
• When used with HemosIL Apixaban Calibrators:
Quantitative determination of apixaban on the ACL TOP Family and ACL TOP Family 50 Series through measurement of factor Xa activity, which is inversely proportional to the apixaban level. With HemosIL Apixaban Calibrators, the assay is intended to measure apixaban concentrations in patients on apixaban | INNOVANCE Anti-Xa assay in combination with INNOVANCE Heparin Calibrator is an In-vitro diagnostic automated chromogenic assay for the quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity in human plasma collected from venous blood samples in 3.2 % sodium citrated tubes in the clinical laboratory. The quantitative determination of UFH and LMWH can be performed on the BCS XP System, CS-2500 System, CS-5100 System and the CA-660 System. For use with plasma from patients undergoing anticoagulant therapy with either UFH or LMWH.
INNOVANCE Anti-Xa assay in combination with INNOVANCE Apixaban Standards provides quantitative determination of the concentration of apixaban in human plasma collected from venous blood samples in 3.2 % sodium citrated tubes in the clinical laboratory. The quantitative determination of apixaban can be performed on CS-2500 System. For use |
| Item | Predicate Device | Subject Device |
| | HemosIL Liquid Anti-Xa | INNOVANCE Anti-Xa |
| | therapy in the following situations where
measurement of apixaban levels could
be useful to have as additional
information:
-
Patients at risk for major bleeding
-
Patients experiencing a bleeding
episode
When used with HemosIL
Rivaroxaban Calibrators:
Quantitative determination of
rivaroxaban on the ACL TOP Family and
ACL TOP Family 50 Series through
measurement of factor Xa activity, which
is inversely proportional to the
rivaroxaban level. With HemosIL
Rivaroxaban Calibrators, the assay is
intended to measure rivaroxaban
concentrations in patients on
rivaroxaban therapy in the following
situations where measurement of
rivaroxaban levels could be useful to
have as additional information:
-
Patients at risk for major bleeding
-
Patients experiencing a bleeding
episode
The assay is not a stand-alone test and
the results should be used in conjunction
with other clinical and laboratory
findings.
For use in adult population. For
prescription use only | with plasma from patients undergoing
anticoagulant therapy with apixaban in
situations where quantification of
apixaban levels may be indicated:
- Patient with bleeding
- Patient with risk for bleeding
(e.g. during perioperative
management) - Patient with conditions affecting
pharmacokinetics (e.g.
deteriorating renal function,
extremes of body weight,
treatment with other drugs
known to affect
pharmacokinetics of apixaban).
The performance of this device has not
been established in neonate and
pediatric patient populations. |
| Sample Type | 3.2% citrated human plasma | Same |
| Measurement | Quantitative | Same |
| Testing
Methodology | Chromogenic | Same |
| Reporting Unit | ng/mL | Same |
| Item | Predicate Device
HemosIL Liquid Anti-Xa | Subject Device
INNOVANCE Anti-Xa |
| Instrument type | Automated Coagulation analyzer | Same |
Similarities of the Reagents
7
8
Similarities of the Calibrator Material
| Item | Predicate Device
HemosIL Apixaban Calibrators | Subject Device
INNOVANCE Apixaban Standards |
|-------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | HemosIL Apixaban Calibrators are
intended for the calibration of the
HemosIL Liquid Anti-Xa assay when
testing for apixaban on the ACL TOP
Family and ACL TOP Family 50 Series. | For calibration of the INNOVANCE Anti-
Xa
assay for the quantitative
determination of the concentration of
apixaban in citrated human plasma. |
| | used by the instrument to automatically
prepare a calibration curve | used to establish a reference curve
(calibration curve) |
| Matrix | human citrated plasma | human plasma, citrated |
| Physical status | lyophilized | lyophilized |
| Concentration
levels | 2
Calibrator 1: no apixaban Calibrator 2:
lot-specific | 2
Standard 0: no apixaban Standard 1: lot-
specific |
Similarities of the Control Material
| Item | Predicate Device | Subject Device |
|---|---|---|
| HemosIL Apixaban Controls | INNOVANCE Apixaban Controls | |
| Intended Use | HemosIL Apixaban Controls are for the quality control of the HemosIL Liquid Anti-Xa assay when testing for apixaban on the ACL TOP Family and ACL TOP Family 50 Series. | |
| Apixaban Low Control: Assayed control intended for the assessment of precision and accuracy of the assay at the low concentration of apixaban. | ||
| Apixaban High Control: Assayed control intended for the assessment of precision and accuracy of the assay at the high concentration of apixaban. | For quality control of the INNOVANCE Anti-Xa assay for the quantitative determination of apixaban in citrated human plasma. | |
| Matrix | human citrated plasma | human plasma, citrated |
| Physical status | lyophilized | lyophilized |
9
| Item | Predicate Device
HemosIL Apixaban Controls | Subject Device
INNOVANCE Apixaban Controls |
|-------------------------|-----------------------------------------------|-----------------------------------------------|
| Concentration
levels | 2 (concentrations lot-specific) | 2 (concentrations lot-specific) |
Differences of the Reagents
| Item | Predicate Device
HemosIL Liquid Anti-Xa | Subject Device
INNOVANCE Anti-Xa |
|-------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Instrumentation | ACL TOP Family (K160276)
ACL TOP Family 50 Series (K150877) | AUTOMATED BLOOD COAGULATION
ANALYZER CS-2500 (CS-2500
System) (K172286) |
| On-board
Stability | 4 days | 72 hours |
| Open Reagent
Stability | 1 month | 8 weeks |
| Composition | The HemosIL Anti-Xa kit includes the
following components: | The INNOVANCE Anti-Xa kit includes
the following components: |
| | Factor Xa reagent: Liquid preparation
containing purified bovine Factor Xa
(approximately 5.5 nkat/mL),
Tris-Buffer, EDTA, dextran
sulfate, sodium chloride and
bovine serum albumin.
Chromogenic substrate: liquid
chromogenic substrate S-2732
(approximately 1.2 mg/mL) and
bulking agent. | Ready to use liquid containing:
FXa, bovine (~0.7 IU/mL)
buffers/stabilizers, preservatives
pH 8
Ready to use liquid containing:
Suc-lle-Glu(piperidin-1-yl)-Gly-Arg-
pNA.HCl (1.25 mg/mL)
buffers/stabilizers, preservatives
pH 5 |
| Limit of Detection | 9 ng/mL for apixaban | 3.3 ng/mL for apixaban |
| Linearity | 20 to 1000 ng/mL for apixaban | 20 to 700 ng/mL for apixaban |
| Kit
Size
Configurations | 4 mL Kit Vial Size (Size 1):
Factor Xa reagent (Cat. No.
0020302612): 5 x 2.5 mL vial of a
liquid preparation containing purified
bovine Factor Xa (approximately 5.5
nkat/mL), Tris- Buffer, EDTA, dextran
sulfate, sodium chloride and bovine
serum albumin. | INNOVANCE Anti-Xa (Only 1 Size):
INNOVANCE Anti-Xa Reagent:
5 x 3.2 mL vial of a liquid preparation.
INNOVANCE Anti-Xa Substrate:
5 x 4.0 mL vial of liquid chromogenic
substrate. |
10
| Item | Predicate Device
HemosIL Liquid Anti-Xa | Subject Device
INNOVANCE Anti-Xa |
|----------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------|
| | Chromogenic substrate (Cat. No.
0020302622): 5 x 3 mL vial of liquid
chromogenic substrate S-2732
(approximately 1.2 mg/mL) and
bulking agent.
10 mL Kit Vial Size (Size 2): | |
| | Factor Xa reagent (Cat. No.
0020303610): 5 x 5 mL vial of a liquid
preparation containing purified
bovine Factor Xa (approximately 5.5
nkat/mL), Tris-Buffer, EDTA, dextran
sulfate, sodium chloride and bovine
serum albumin.
Chromogenic substrate (Cat. No.
0020303620): 5 x 6 mL vial of liquid
chromogenic substrate S-2732
(approximately 1.2 mg/mL) and bulking
agent | |
| Calibrators (Sold
Separately) | HemosIL Apixaban Calibrators Target
Levels: 0 and ~500 ng/mL | INNOVANCE Apixaban Standards
Target Levels: 0 and ~420 ng/mL |
| Controls (Sold
Separately) | HemosIL Apixaban Controls
Target Levels: ~75 and ~300 ng/mL | INNOVANCE Apixaban Controls
Target Levels: ~70 and ~260 ng/mL |
Differences of the Calibrator Material
| Item | Predicate Device | Subject Device |
|---|---|---|
| HemosIL Apixaban Calibrators | INNOVANCE Apixaban Standards | |
| Stability | ||
| after | ||
| reconstitution | 7 days at 2-8°C in the closed original | |
| vial, | 2-8 °C: reconstituted, 40 hours (closed original vial) | |
| 8 hours at 15-25°C on-board the ACL | ||
| TOP Family/ACL TOP Family 50 Series | ||
| or | 15-25 °C: reconstituted, 12 hours (closed original vial) | |
| 60 days at -20°C in the closed original | ||
| vial (single thaw only). | ||
| Traceability | There are no international standards for apixaban. Calibrator value assignments are traceable to apixaban supplied by the manufacturer and quantitated in plasmas assayed by Liquid Chromatography - tandem Mass Spectrometry (LC-MS/MS). | There are no international standards for apixaban. The concentration of apixaban is calibrated against an internal reference preparation and is lot specific. |
11
Differences of the Control Material
| Item | Predicate Device
HemosIL Apixaban Controls | Subject Device
INNOVANCE Apixaban Controls |
|--------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Stability
after
reconstitution | 7 days at 2-8°C in the closed original
vial
8 hours at 15-25°C on-board the ACL
TOP Family/ACL TOP Family 50 Series
60 days at -20°C in the closed original
vial (single thaw only). | 2-8 °C: reconstituted, 48 hours (closed
original vial)
15-25 °C: reconstituted, 20 hours
(closed original vial)
≤-18 °C: reconstituted, 4 weeks
(closed original vial) |
| Traceability | There are no international standards for
apixaban. Control value assignments
are traceable to apixaban supplied by
the manufacturer and quantitated in
plasmas assayed by Liquid
Chromatography – tandem Mass
Spectrometry (LC-MS/MS). | There are no international standards for
apixaban. The concentration
of
apixaban is calibrated against an
internal reference preparation |
The differences between the predicate device and proposed device do not result in a change to the intended use of apixaban method, the indications for use, or to safety and efficacy when used according to the product labeling.
9. Performance Data
The following performance data were provided in support of the substantial equivalence determination.
Precision
Precision studies were conducted with the CS-2500 System as described in the CLSI document EP05-A3, using INNOVANCE Apixaban Control 1, INNOVANCE Apixaban Control 2 and 4 plasma pools.
| | | | Repeatability | | Within-Device/Lab
Precision | |
|------------------------------|-----|---------------|---------------|----------|--------------------------------|----------|
| Sample | n | Mean
ng/mL | SDh
ng/mL | CVi
% | SDh
ng/mL | CVi
% |
| Plasma pool 1 | 240 | 31.4 | 0.9 | - | 2.0 | - |
| Plasma Pool 2 | 240 | 50.1 | 0.7 | - | 1.1 | - |
| INNOVANCE Apixaban Control 1 | 240 | 74.9 | - | 1.58 | - | 2.48 |
| Plasma pool 3 | 240 | 95.8 | - | 1.25 | - | 2.03 |
| INNOVANCE Apixaban Control 2 | 240 | 277.6 | - | 2.20 | - | 2.57 |
| Plasma pool 3 | 240 | 320.5 | - | 1.24 | - | 2.09 |
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Reproducibility
Reproducibility was assessed based on internally conducted studies, including site, laboratory, operator and lot variability factors.
| Combined sites | Combined assay lots | |||
|---|---|---|---|---|
| Sample concentration | SDh | |||
| ng/mL | CVi | |||
| % | SDh | |||
| ng/mL | CVi | |||
| % | ||||