BIOPHEN LMWH CONTROL, LMWH CONTROL LOW, UFH CONTROL, HEPARIN CALIBRATOR & UFH CALIBRATOR

K051472 · Hyphen Biomed · GGN · Dec 23, 2005 · Hematology

Device Facts

• Record ID: K051472
• Device Name: BIOPHEN LMWH CONTROL, LMWH CONTROL LOW, UFH CONTROL, HEPARIN CALIBRATOR & UFH CALIBRATOR
• Applicant: Hyphen Biomed
• Product Code: GGN · Hematology
• Decision Date: Dec 23, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.5425
• Device Class: Class 2

Intended Use

The Biophen LMWH Control Kit is a set of control plasmas for the quality control of Low Molecular Weight Heparin (LMWH) measurements, using anti-Xa colorimetric assays. The Biophen LMWH Control Low Kit is a set of control plasmas for the quality control of Low Molecular Weight Heparin (LMWH) measurements, using anti-Xa colorimetric assays. The Biophen UFH Control Kit is a set of control plasmas for the quality control of Low Molecular Weight Heparin (LMWH) measurements, using anti-Xa colorimetric assays. The Biophen UFH Calibrator is a set of calibration plasmas for Unfractionated Heparin (UFH) measurements, using anti-Xa colorimetric assays. The Biophen Heparin Calibrator is a set of calibration plasmas for Heparin (UFH and LMWH) measurements, using anti-Xa colorimetric assays.

Device Story

Biophen Heparin/UFH Control Plasmas and Calibrators are in vitro diagnostic reagents used in clinical laboratories. Controls assess precision and accuracy of anti-Xa colorimetric assays (e.g., Biophen Heparin 3 & 6); calibrators establish the calibration curve for these assays. The device consists of plasma samples with known heparin concentrations. Laboratory technicians use these to validate assay performance before patient sample testing. By ensuring accurate measurement of heparin levels, the device assists clinicians in monitoring anticoagulant therapy, thereby optimizing therapeutic dosing and minimizing bleeding or clotting risks.

Clinical Evidence

No clinical data. Bench testing only. Precision/reproducibility studies demonstrated intra-assay %CV ranging from 0.5% to 2.3% across all control and calibrator levels. Traceability established via NIBSC International Standards for LMWH (85/600) and UFH (97/578).

Technological Characteristics

In vitro diagnostic plasma-based controls and calibrators. Principle of operation: chromogenic anti-Xa assay calibration and quality control. Form factor: liquid/lyophilized plasma. Connectivity: none (standalone reagents).

Indications for Use

Indicated for quality control and calibration of anti-Xa colorimetric assays used to measure Low Molecular Weight Heparin (LMWH) and Unfractionated Heparin (UFH) in human plasma samples.

Regulatory Classification

Identification

A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.

Special Controls

*Classification.* Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.

Predicate Devices

• Instrumentation Laboratories Control Plasma LMW Heparin (K030965)
• American Bioproducts Heparin Control (K943520)
• Instrumentation Laboratories Calibration Plasma LMW Heparin (K030964)
• Dade Behring Heparin Calibrators and Controls (K042941)

Submission Summary (Full Text)

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K 051472

# Section O. Biophen LMWH and UFH Control Plasma

(Summary of Safety and Effectiveness)

#### Submitted by:

Hyphen BioMed 95000 Neuville sur Oise, France Phone # [phone] Fax# [phone]

#### Contact Person:

Dr. Jean Amiral, President &Scientific Director [e-mail]

#### Summary prepared by:

15th April 2005

#### Name of the device:

Biophen LMWH Control Biophen LMWH Control Low ಹಿ Biophen UFH Control

#### Classification Name:

Plasma Coagulation Control

#### Classification: Class II

## Regulation#: 864.5425, for Biophen LMWH & LMWH Low Control Plasma 864.5425 for Biophen UFH control plasma

- Product Code: GGN for Biophen LMWH & LMWH Low Control Plasma GGN for Biophen UFH Control Plasma
#### Predicate Device Information:

Biophen LMWH & LMWH Low Control Plasma: Control Plasma LMW Heparin (K030965) Siophen Linker Pasma: Heparin Control Plasma: Sontrol Plasma: Biomor Plasma: Biogrich Control (Kosopori
Biophen UFH Control Plasma: Heparin Control (K943520) — Theri

#### Description of the Device/intended use:

Biophen LMWH, LMWH Low and UFH Control Plasma is an in vitro diagnostic quality control intended for use with chromogenic assays to assess precision and accuracy at Heparin low and high levels (in the usual recommended therapeutic range).

## Statement of how the technological Characteristics of the device compare to the Predicate device:

Biophen LMWH control uses the same principle as the predicate device Control Plasma LMW Heparin and is substantially equivalent in performance, intended use and safety and effectiveness.

Hyphen Biomed 510(k) for Biophen LMWH, LMWH Low control and UFH Control Plasma

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Biophen UFH control uses the same principle as the predicate device Heparin Control and is substantially equivalent in performance, intended use and safety and effectiveness.

#### Summary of Performance data:

A reproducibility results for the Biophen LMWH, LMWH low and UFH Control plasma is given below:

| Biophen<br>LMWH<br>Control | LMWH<br>Concentration<br>(IU/ml) | Acceptable<br>Range (IU/ml) | N | SD |
|----------------------------|----------------------------------|-----------------------------|----|------|
| Level 3 | 0.79 | 0.69 -0.89 | 69 | 0.03 |
| Level 4 | 1.25 | 1.10-1.40 | 69 | 0.05 |

| Biophen<br>LMWH<br>Control<br>Low | LMWH Low<br>Concentration<br>(IU/ml) | Acceptable<br>Range (IU/ml) | N | SD |
|-----------------------------------|--------------------------------------|-----------------------------|----|------|
| Level I | 0.25 | 0.17-0.33 | 43 | 0.02 |
| Level II | 0.50 | 0.40-0.60 | 43 | 0.03 |
| Biophen<br>UFH<br>Control | UFH<br>Concentration<br>(IU/ml) | Acceptable<br>Range (IU/ml) | N | SD |
| Level 1 | 0.21 | 0.11-0.31 | 30 | 0.01 |
| Level 2 | 0.51 | 0.36-0.66 | 30 | 0.02 |

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(Summary of Safety and Effectiveness)

#### Submitted by:

Hyphen BioMed 95000 Neuville sur Oise, France Phone # [phone] Fax# [phone]

## Contact Person:

Dr. Jean Amiral, President &Scientific Director Phone number : ([phone] [e-mail]

## US Agent :

Mr. Ola Andersson Phone number : [phone] [e-mail]

## Summary prepared by:

3rd November 2005

## Name of the device:

Biophen Heparin Calibrator Biophen UFH Calibrator

# Classification Name:

Calibrator, Secondary

#### Classification:

Class II

Regulation#: 862.1150

# Product Code: JIT

Predicate Device Information: K030964 Calibration Plasma LMW Heparin K042941 Heparin Calibrators & Controls

# Device intended use:

Biophen Heparin Calibrator is a set of calibration plasmas for Heparin (UFH and LMWH) measurements, using anti-Xa colorimetric assays (BIOPHEN HEPARIN 3 and 6). Biophen Heparin Calibrator allows calibrating the assays of Low Molecular Weight Heparin (LMWH) using chromogenic anti-Xa methods. It can be also used for calibrating the measurements of Unfractionated Heparin (UFH) when the BIOPHEN Heparin kit is used. Biophen heparin is a chromogenic anti-Xa method developed for measuring homogeneously heparin (UFH) and Low Molecular Weight Heparin (LMWH), using the same calibration curve.

K051472 Response to 7/6/05 Deficiency Letter October 31, 2005

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BIOPHEN UFH Calibrator is a set of calibration plasmas for Unfractionated Heparin (UFH) measurements, using anti-Xa colorimetric assays (BIOPHEN HEPARIN 3 and 6). BIOPHEN UFH Calibrator allows calibrating the measurements of Unfractionated Heparin (UFH) when the BIOPHEN Heparin kit is used.

# Performance of the Device:

The concentration of the calibrators is determined from the multiple determinations. The following tables show good reproducibility for the LMWH calibrator and UFH calibrator.

| Calibrator | Concentration in<br>LMWH (IU/ml) | Intra<br>Assay<br>N | Intra<br>Assay<br>CV | Inter<br>Assay<br>N | Inter<br>Assay<br>SD |
|--------------|----------------------------------|---------------------|----------------------|---------------------|----------------------|
| Calibrator 1 | 0 | 10 | NA | 50 | 0.01 |
| Calibrator 2 | 0.38 | 10 | 2.3 | 50 | 0.02 |
| Calibrator 3 | 0.77 | 10 | 0.5 | 50 | 0.03 |
| Calibrator 4 | 1.14 | 10 | 1.0 | 50 | 0.05 |
| Calibrator 5 | 1.5 | 10 | 0.5 | 50 | 0.06 |

| Calibrator | Concentration in<br>Unfractionated<br>Heparin (IU/ml) | Intra<br>Assay<br>N | Intra<br>Assay<br>CV | Inter<br>Assay<br>N | Inter<br>Assay<br>SD |
|--------------|-------------------------------------------------------|---------------------|----------------------|---------------------|----------------------|
| Calibrator 1 | 0 | 10 | NA | 28 | 0 |
| Calibrator 2 | 0.36 | 10 | 1.4 | 28 | 0.02 |
| Calibrator 3 | 0.74 | 10 | 1.0 | 28 | 0.04 |
| Calibrator 4 | 1.08 | 10 | 0.5 | 28 | 0.06 |
| Calibrator 5 | 1.42 | 10 | 0.5 | 28 | 0.08 |

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with three wavy lines representing its body and wings.

Food and Drug Administration HYPHEN Biomed 2098 Gaither Road Rockville MD 20850 c/o Mr. Ola Anderson DEC 2 3 2005 President Aniara Corporation 6560 Gove Court Mason, Ohio 45040 k051472 Re: Trade/Device Name: Biophen Low Molecular Weight Heparin (LMWH) Control Plasma Biophen Low Molecular Weight Heparin (LMWH) Control Low Biophen Unfractionated Heparin (UFH) Control Plasma Biophen Heparin Calibrator and Biophen UFH Calibrator Regulation Number: 21 CFR § 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: II Product Code: GGN, GGC, KFF Dated: November 3, 2005

Received: November 8, 2005

Dear Ms. Anderson:

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 for workers 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 either class II (Special Controls) or class III (PMA), it If your de roo is exactional controls. Existing major regulations affecting your device can he 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 r 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 or any I outhal of the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practicc 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 predicate device results in a classification for your device and thus, permits your device to proceed to the market.

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Page 2 -

If you desire specific information about the application of labeling requirements to your device, or you destro specific infortion and advertising of your device, 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" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the I va thay ovain other gefail. 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,

Robert Beckerf

Robert L. Becker, Jr., MD, P Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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# Section D. Statement of Indication for Use Indications for Use

510(k) Number (if known): K051472

Device Name: Biophen Low Molecular Weight Heparin (LMWH) Control Plasma,

Biophen Low Molecular Weight Heparin (LMWH) Control Low,

& Biophen Unfractionated Heparin (UFH) Control Plasma

Indications for Use:

، ﻣﺪﺭ ﻣ

Biophen Low Molecular Weight Heparin (LMWH), Low Molecular Weight Heparin Low (LMWH Low) and Unfractionated Heparin (UFH) control are set of control plasmas for the quality control of Low Molecular weight Heparin(LMWH) and Unfractionated Heparin(UFH) measurements using anti Xa colorimetric assays (Biophen Heparin 3 & 6) .

These control plasmas are within the usual therapeutic range recommended for the low molecular weight heparin (LMWH) and Unfractionated Heparin (UFH).

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 Device Evaluation (ODE)

Josephine Rutati

Division Sign/O

Office of In Vitro Diagnostic Device Evaluation and Sufery

.?)(k)` K051472

November 10, 2005 Amendment 510(k)# K021472

2

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# Section E. Statement of Indication for Use

# Indications for Use

510(k) Number (if known): ___K051472

Device Name: Biophen Heparin Calibrator &

Biophen UFH calibrator

Indications for Use:

Biophen Heparin & Unfractionated heparin (UFH) Calibrators are set of calibration Drophen Freparin of Cow molecular weight heparin (LMWH) and Unfractionated heparin, using anti-Xa colorimetric assays.

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 Device Eyaluation (ODE)

Ausliss Bautista
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) Kc51472

. ...

1

November 10, 2005 Amendment 510(k)# K051472