STA(R) - LIQUID ANTI-XA, MULTI HEP CALIBRATOR, QUALITY HNF / UFH, QUALITY HBPM / LMWH

K111822 · Diagnostica Stago, Inc. · KFF · Oct 26, 2011 · Hematology

Device Facts

• Record ID: K111822
• Device Name: STA(R) - LIQUID ANTI-XA, MULTI HEP CALIBRATOR, QUALITY HNF / UFH, QUALITY HBPM / LMWH
• Applicant: Diagnostica Stago, Inc.
• Product Code: KFF · Hematology
• Decision Date: Oct 26, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7525
• Device Class: Class 2

Intended Use

The STA® Liquid Anti-Xa kits are intended for use with STA-R®, STA Compact® and STA Satellite® analyzers, for the quantitative determination of the plasma levels of unfractionated (UFH) and low molecular weight (LMWH) heparins by measuring their anti-Xa activity on antithrombin in a competitive assay using a synthetic chromogenic substrate. The STA® Multi Hep Calibrator is a set of calibrator plasmas intended for use with STA-R®, STA Compact® and STA Satellite® analyzers, for the calibration of heparin (UFH and LMWH) activity assay by measuring the anti-Xa activity. The STA® Quality HNF/UFH kit is a set of two plasmas intended for the quality control of unfractionated heparin (UFH) activity assay by measuring the anti-Xa activity performed on STA-R®, STA Compact® and STA Satellite® analyzers. The STA® Quality HBPM/LMWH kit is a set of two plasmas intended for the quality control of low molecular weight heparin (LMWH) activity assay by measuring the anti-Xa activity performed on STA-R®, STA Compact® and STA Satellite® analyzers.

Device Story

STA® Liquid Anti-Xa is a chromogenic assay for quantitative measurement of UFH and LMWH in citrated human plasma. Input: patient plasma sample; Reagents: bovine factor Xa and chromogenic substrate. Principle: competitive assay where heparin-antithrombin complex inhibits factor Xa; residual factor Xa hydrolyzes substrate, releasing paranitroaniline; color intensity at 405 nm is inversely proportional to heparin concentration. Used in clinical laboratories on STA-R®, STA Compact®, and STA Satellite® analyzers. Output: heparin concentration (IU/mL). Results assist clinicians in monitoring anticoagulant therapy. Benefits: provides standardized, liquid-reagent-based monitoring of heparin activity to guide dosing decisions.

Clinical Evidence

Method comparison study conducted at 5 sites with 1017 patients (623 UFH, 394 LMWH). Compared subject device to predicate (STA-Rotachrom Heparin). Results: UFH slope 0.993 (95% CI 0.975-1.011), intercept -0.046, r=0.974; LMWH slope 1.004 (95% CI 0.995-1.014), intercept 0.008, r=0.995. Precision: repeatability %CV <7%, reproducibility %CV <10%. Linearity confirmed up to 1.10 IU/mL (UFH) and 2.0 IU/mL (LMWH).

Technological Characteristics

Chromogenic assay; lyophilized human plasma calibrators/controls; synthetic chromogenic substrate. Analyzers: STA-R®, STA Compact®, STA Satellite®. Connectivity: Integrated with Stago analyzers. Sterilization: Not applicable (reagents).

Indications for Use

Indicated for quantitative determination of unfractionated (UFH) and low molecular weight (LMWH) heparin levels in human plasma. Used for monitoring heparin activity in patients undergoing anticoagulant therapy. Contraindications not specified.

Regulatory Classification

Identification

A heparin assay is a device used to determine the level of the anticoagulant heparin in the patient's circulation. These assays are quantitative clotting time procedures using the effect of heparin on activated coagulation factor X (Stuart factor) or procedures based on the neutralization of heparin by protamine sulfate (a protein that neutralizes heparin).

Predicate Devices

• STA®-Rotachrom® Heparin (k010455)
• STA®-Calibrator HBPM/LMWH (k010350)
• STA®-Hepanorm H Calibrator Plasma Set (k854762)
• STA®-Heparin Control (k943520)
• STA®-Quality HBPM/LMWH (k010324)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows the word "Stago" in a stylized font, with a symbol above it that resembles three curved shapes forming a circular pattern. Below the word "Stago", there is the text "510(k) Summary" in a smaller, bold font. The text indicates that the image is likely related to a summary document for a medical device or product requiring 510(k) clearance.

1822

# OCT 2,6 2011

# Submitter's Information

Diagnostica Stago, Inc. Five Century Drive Parsippany, New Jersey 07054

Phone: [phone], x-4117 Facsimile: [phone]

Date Prepared: October 25, 2011

# Application Correspondent and Contact Person:

Carlo d'Alessandro, Director, IVD Quality and Regulatory DONAWA LIFESCIENCE CONSULTING Piazza Albania, 10 - 00153 Rome, Italy Phone: [phone] Facsimile:[phone]

### Device Names :

| Trade names<br>(products sold separately) | Common names | Classification name | Product<br>Code |
|-------------------------------------------|--------------------|------------------------------------------------|-----------------|
| STA® - Liquid Anti-Xa | Heparin Assay | Heparin Assay<br>21 CFR 864.7525 | KFF |
| STA® - Multi Hep Calibrator | Heparin Calibrator | Calibrator, secondary<br>21 CFR 862.1150 | JIT |
| STA® - Quality HNF/UFH | Heparin Control | Plasma, coagulation control<br>21 CFR 864.5425 | GGN |
| STA® - Quality HBPM/LMWH | Heparin Control | Plasma, coagulation control<br>21 CFR 864.5425 | GGN |

# Predicate Devices

| Predicate Device name | 510(k) number |
|---------------------------------------------------------------------------------|---------------|
| STA® - Rotachrom® Heparin | K010455 |
| STA® - Calibrator HBPM/LMWH | K010350 |
| STA® - Hepanorm® H<br>{formerly cleared as Hepanorm®<br>Calibration Plasma Set} | K854762 |
| STA® - Heparin Control | K943520 |
| STA® - Quality HBPM/LMWH | K010324 |

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Image /page/1/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in a serif font, with a stylized graphic above it. The graphic appears to be composed of three curved shapes arranged in a circular pattern, creating a sense of movement or rotation.

### Device Intended Use

- STA® Liquid Anti-Xa: The STA® Liquid Anti-Xa kits are intended for use with STA-R®, V STA Compact® and STA Satellite® analyzers, for the quantitative determination of the plasma levels of unfractionated (UFH) and low molecular weight (LMWH) heparins by measuring their anti-Xa activity on antithrombin in a competitive assay using a synthetic chromogenic substrate.
- ✔ STA® Multi Hep Calibrator: The STA® Multi Hep Calibrator is a set of calibrator plasmas intended for use with STA-R®, STA Compact®, and STA Satellite® analyzers, for the calibration of heparin (UFH and LMWH) activity assay by measuring the anti-Xa activity.
- STA® Quality HNF/UFH: The STA® Quality HNF/UFH kit is a set of two plasmas > intended for the quality control of unfractionated heparin (UFH) activity assay by measuring the anti-Xa activity performed on STA-R®, STA Compact®, and STA Satellite® analyzers.
- STA® Quality HBPM/LMWH: The STA® Quality HBPM/LMWH kit is a set of two > plasmas intended for the quality control of low molecular weight heparin (LMWH) activity assay by measuring the anti-Xa activity performed on STA-R®, STA Compact®, and STA Satellite®.

# Device descriptions

# ✓ STA® - Liquid Anti-Xa:

The STA® - Liguid Anti-Xa is a chromogenic assay technique used for determination of the level of UFH and LMWH that have high affinity for antithrombin by measuring their anti-Xa activity.

The normal function of a molecule of factor Xa, when present in plasma, is to cleave its natural substrate, prothrombin, to generate thrombin, the enzyme responsible for the formation of the fibrin clot. In the presence of heparin, competition occurs between this mechanism and the inhibitory mechanism exerted by the heparin-antithrombin complex, this inhibition being largely responsible for the anticoagulant action of heparin.

The proposed method is a one-step reaction based on a similar principle: as soon as factor Xa is added to the plasma-substrate mixture, two reactions take place simultaneously, namely,

- hydrolysis of the substrate by factor Xa
- inhibition of factor Xa by the heparin-antithrombin complex*.

After the necessary period of time for the competitive reaction to reach equilibrium, the quantity of paranitroaniline that is released is inversely proportional to the concentration of heparin present in the test medium.

* The heparin-antithrombin complex is made up from the heparin and the antithrombin (AT) peculiar to the patient.

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Image /page/2/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in a bold, sans-serif font, with a stylized graphic above it. The graphic appears to be an abstract shape, possibly representing a stylized leaf or a geometric design. The logo is simple and modern in appearance.

#### STA® - Multi Hep Calibrator >

The STA® - Multi Hep Calibrator reagents are lyophilized human plasmas at five different heparin concentrations. They are used to create the calibration curve on STA-R®, STA Compact®, and STA Satellite® analyzers performing the chromogenic method for heparin (UFH and LMWH) using STA® - Liquid Anti-Xa.

Three kinds of calibration are possible, depending on the type of molecule to be determined:

- a calibration with the Reagents 1, 2, 3, 4 and 5 for UFH and/or LMWH assays,

- a calibration with the Reagents 1, 2 and 4 dedicated to UFH assays,

- a calibration with the Reagents 1, 3 and 5 dedicated to LMWH assays.

# ✓ STA® - Quality HNF/UFH

The STA® - Quality HNF/UFH reagents are lyophilized human plasmas at two different UFH concentrations. They are used for the quality control of UFH activity assay by measuring the anti-Xa activity using the chromogenic method STA® - Liquid Anti-Xa performed on STA-R®, STA Compact®, and STA Satellite® analyzers.

#### > STA® - Quality HBPM/LMWH

The STA® - Quality HBPM/LMWH reagents are lyophilized human plasmas at two different LMWH concentrations. They are used for the quality control of LMWH activity assay by measuring the anti-Xa activity using the chromogenic methods, STA® - Liquid Anti-Xa and STA® - Rotachrom® Heparin, performed on STA-R®, STA Compact, and STA Satellite® analyzers.

# Statement of technological characteristics of the device compared to predicate devices

- STA® Liquid Anti-Xa is substantially equivalent to the predicate device, STA® V Rotachrom® Heparin (K010455) in indication/intended use, test principle, technology and performance thus yielding no new questions in safety and effectiveness.
- STA® Multi Hep Calibrator is substantially equivalent to the predicate devices, STA® -> Calibrator HBPM/LMWH Kit (K010350) and STA® - Hepanorm® H (K854762) in indication/intended use, technology and performance, thus yielding no new questions in safety and effectiveness.

The primary difference between the subject product and predicate devices is that the new calibrator kit is intended for use with both Unfractionated and Low Molecular Weight Heparin testing.

- STA® Quality HNF/UFH is substantially equivalent to the predicate device STA -> Heparin Control (K943520) in indication/intended use, technology and performance, thus yielding no new questions in safety and effectiveness.

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Image /page/3/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in a serif font, with a stylized graphic above it. The graphic appears to be an abstract shape, possibly representing a stylized leaf or a geometric design. The logo is in black and white.

- STA® Quality HBPM/LMWH is substantially equivalent to the predicate device STA® -> HBPM/LMWH (K010324) in indication/intended use, technology and Quality performance, thus yielding no new questions in safety and effectiveness. The new STA® - Quality HBPM/LMWH is a modification to the current kit STA® - Quality HBPM/LMWH, the primary difference is that the new STA® - Quality HBPM/LMWH is intended for use with LMWH testing performed by STA® - Liquid Anti-Xa in addition to the current assay STA® - Rotachrom® Heparin (K010455).
# Summary Performance Characteristics

- Precision >
Precision studies were performed according to the CLSI guideline EP5-A2 using samples containing heparin (22 days, 2 runs per day). The following results have been obtained:

| Hybrid calibration (5-point calibration) | | Sample 1<br>(UFH) | Sample 2<br>(UFH) | Sample 3<br>(UFH) | Sample 4<br>(LMWH) | Sample 5<br>(LMWH) | Sample 6<br>(LMWH) | |
|------------------------------------------|------|-------------------|-------------------|-------------------|--------------------|--------------------|--------------------|-------|
| Mean | $X¯$ | IU/mL | 0.21 | 0.55 | 0.97 | 0.86 | 1.48 | 1.75 |
| Repeatability | SD | IU/mL | 0.013 | 0.017 | 0.033 | 0.027 | 0.045 | 0.050 |
| | CV | % | 6.2 | 3.1 | 3.4 | 3.1 | 3.0 | 2.9 |
| Within-<br>laboratory<br>precision | SD | IU/mL | 0.021 | 0.036 | 0.053 | 0.041 | 0.075 | 0.087 |
| | CV | % | 9.9 | 6.6 | 5.5 | 4.8 | 5.1 | 5.0 |

| Dedicated calibration (3-point calibration) | | | Sample 1<br>(UFH) | Sample 2<br>(UFH) | Sample 3<br>(UFH) | Sample 4<br>(LMWH) | Sample 5<br>(LMWH) | Sample 6<br>(LMWH) |
|---------------------------------------------|----------------|-------|-------------------|-------------------|-------------------|--------------------|--------------------|--------------------|
| Mean | $\overline{X}$ | IU/mL | 0.22 | 0.55 | 0.97 | 0.86 | 1.48 | 1.75 |
| Repeatability | SD | IU/mL | 0.012 | 0.017 | 0.034 | 0.028 | 0.045 | 0.050 |
| | CV | % | 5.6 | 3.0 | 3.5 | 3.2 | 3.1 | 2.8 |
| Within-<br>laboratory<br>precision | SD | IU/mL | 0.020 | 0.033 | 0.050 | 0.045 | 0.078 | 0.089 |
| | CV | % | 9.2 | 6.1 | 5.1 | 5.2 | 5.3 | 5.1 |

- V Detection Limit - Working Range
The limit of detection and linearity were assessed for each method according to the CLSI quidelines EP17-A and EP6-A respectively.

In the UFH/LMWH method with the STA® - Multi Hep Calibrator (5-point calibration) the detection threshold on the STA-R® is 0.10 IU/ml (UFH and LMWH) and the linearity range extends to 1.10 IU/ml for the UFH and to 2.00 anti-Xa IU/ml for the LMWH. In the UFH method with the STA® - Multi Hep Calibrator (UFH 3-point calibration), the detection threshold on the STA-R® is 0.10 IU/ml and the linearity range extends to 1.10 IU/ml.

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In the LMWH method with the STA® - Multi Hep Calibrator (LMWH,3-point calibration) the detection threshold on the STA-R® is 0.10 anti-Xa IU/ml and the linearity range extends to 2.00 anti-Xa IU/ml.

#### > Interfering substances

The STA® - Liquid Anti-Xa method (UFH and LMWH protocols) is insensitive to the following substances: hemoglobin (up to 1.5 g/l), conjugated bilirubin (up to 288 mg/l -342 µmol/), unconjugated bilirubin (up to 138 mg/l - 236 µmol/l) and triglycerides (up to 6.9 g/l - 8 mmol/l). The tests were performed according to the CLSI guideline EP7-A2.

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# DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/2 description: The image shows a seal for the Department of Health & Human Services. The seal is circular, with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES" arranged around the left side of the circle. On the right side of the circle is an abstract symbol that resembles an eagle.

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

Diagnostica Stago, S.A.S. c/o Mr. Carlo d'Alessandro Director, IVD Quality and Regulatory Donawa Lifescience Consulting Srl Piazza Albania, 10 Rome, Italy 00153

OCT 2 6 2011

Re: k111822

Trade/Device Name: STA®- Liquid Anti-Xa STA®-Multi Hep Calibrator STA®-Quality HNF/UFH STA®-HBPM/LMWH Regulation Number: 21 CFR § 864.7525 Regulation Name: Heparin Assay Regulatory Class: Class II Product Code: KFF; JIS; GGN Dated: September 22, 2011

Received: September 26, 2011

Dear Mr. d'Alessandro:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21

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Page 2 – Mr. Carlo d'Alessandro

CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed nredicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportalProblem/default.h1m for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

tor

Leuch. S.

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Image /page/7/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in a serif font, with a stylized graphic above it. The graphic appears to be an abstract shape, possibly representing a stylized leaf or a curved, geometric form. The logo is simple and clean, with a focus on the company name and a distinctive visual element.

#### Indications for Use Statements 1.3

510(k) Number (if known): KII 1822

Device Name: STA® - Liquid Anti-Xa

Indications for Use:

The STA® - Liquid Anti-Xa kits are intended for use with STA-R®, STA Compact® and STA Satellite® analyzers, for the quantitative determination of the plasma levels of unfractionated (UFH) and low molecular weight (LMWH) heparins by measuring their anti-Xa activity on antithrombin in a competitive assay using a synthetic chromogenic substrate.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Leve R. L.

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

510(k) K111822

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Image /page/8/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in a serif font, with a stylized graphic above it. The graphic appears to be three curved shapes arranged in a circular pattern, resembling a stylized flower or abstract design. The logo is black and white.

510(k) Number (if known): k111822

Device Name: STA® - Multi Hep Calibrator

Indications for Use:

The STA® - Multi Hep Calibrator is a set of calibrator plasmas intended for use with STA-R®, STA Compact® and STA Satellite® analyzers, for the calibration of heparin (UFH and LMWH) activity assay by measuring the anti-Xa activity.

Prescription Use × (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K111822

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Image /page/9/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in a serif font, with a stylized graphic above it. The graphic appears to be three curved shapes arranged in a circular pattern, resembling a stylized eye or a partially opened flower. The logo is black and white.

510(k) Number (if known): k111822

Device Name: STA® - Quality HNF/UFH

Indications for Use:

The STA® - Quality HNF/UFH kit is a set of two plasmas intended for the quality control of unfractionated heparin (UFH) activity assay by measuring the anti-Xa activity performed on STA-R®, STA Compact® and STA Satellite® analyzers.

Prescription Use × (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Semt. L. Si.

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

510(k) K111822

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Image /page/10/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in a sans-serif font, with a stylized graphic above it. The graphic appears to be composed of three curved shapes arranged in a circular fashion, creating a sense of movement or rotation.

510(k) Number (if known): k111822

Device Name: STA® - Quality HBPM/LMWH

Indications for Use:

--------

The STA® - Quality HBPM/LMWH kit is a set of two plasmas intended for the quality control of low molecular weight heparin (LMWH) activity assay by measuring the anti-Xa activity performed on STA-R®, STA Compact® and STA Satellite® analyzers.

Prescription Use × (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Leach R.S.

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

510(k) K111822