(203 days)
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).
Biophen Heparin & Unfractionated heparin (UFH) Calibrators are set of calibration plasmas for the calibration of Low molecular weight heparin (LMWH) and Unfractionated heparin, using anti-Xa colorimetric assays.
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).
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.
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.
The provided text describes two separate devices: "Biophen LMWH and UFH Control Plasma" and "Biophen Heparin Calibrator/Biophen UFH Calibrator." I will address the acceptance criteria and study information for each.
Device 1: Biophen LMWH and UFH Control Plasma
This device 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.
1. Table of Acceptance Criteria and Reported Device Performance:
The document states that the device is "substantially equivalent in performance" to its predicate devices. The performance data provided focuses on reproducibility. The acceptance criteria are defined by the "Acceptable Range" within which the measured concentration of LMWH or UFH should fall. The device performance is indicated by the reported LMWH/UFH Concentration and the Standard Deviation (SD).
| Biophen LMWH Control | LMWH Concentration (IU/ml) | Acceptable 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 LMWH Control Low | LMWH Low Concentration (IU/ml) | Acceptable 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 UFH Control | UFH Concentration (IU/ml) | Acceptable 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 |
2. Sample size used for the test set and the data provenance:
- Sample sizes (N):
- Biophen LMWH Control (Level 3 & 4): 69 samples each
- Biophen LMWH Control Low (Level I & II): 43 samples each
- Biophen UFH Control (Level 1 & 2): 30 samples each
- Data Provenance: The document does not explicitly state the country of origin or whether the data is retrospective or prospective. Hyphen BioMed is based in France.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
Not applicable. This is a quality control plasma, and the "ground truth" (target concentration and acceptable range) is established by the manufacturer through multiple determinations and validated through reproducibility studies, not by clinical experts in the same way imaging or diagnostic studies requiring expert review would.
4. Adjudication method for the test set:
Not applicable. The performance is based on quantitative measurements and statistical analysis (mean, standard deviation), not subjective expert judgment requiring adjudication.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
Not applicable. This is an in vitro diagnostic quality control plasma, not an AI-assisted diagnostic tool.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Not Applicable. This is an in vitro diagnostic quality control plasma.
7. The type of ground truth used:
The ground truth used is the target concentration of LMWH or UFH, established by the manufacturer through multiple determinations (implied by the reporting of mean concentrations and standard deviations). The "Acceptable Range" serves as the clinical or analytical tolerance around this ground truth.
8. The sample size for the training set:
Not applicable. This is not an AI/ML device; therefore, there is no "training set" in the context of machine learning. The "N" values in the table refer to the number of measurements taken for the reproducibility study.
9. How the ground truth for the training set was established:
Not applicable.
Device 2: Biophen Heparin Calibrator & Biophen UFH Calibrator
This device is a set of calibration plasmas for Heparin (UFH and LMWH) measurements, using anti-Xa colorimetric assays. Its intended use is to calibrate assays for LMWH and UFH.
1. Table of Acceptance Criteria and Reported Device Performance:
Similar to the control plasma, the "ground truth" for the calibrators is their established concentration. The performance is assessed by reproducibility, specifically Intra-Assay and Inter-Assay %CV (Coefficient of Variation) or SD. The acceptance criteria are implicitly that the CV/SD values demonstrate "good reproducibility" as stated in the summary.
Biophen Heparin Calibrator (LMWH)
| Calibrator | Concentration in LMWH (IU/ml) | Intra Assay N | Intra Assay CV | Inter Assay N | Inter Assay 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 |
Biophen UFH Calibrator (Unfractionated Heparin)
| Calibrator | Concentration in Unfractionated Heparin (IU/ml) | Intra Assay N | Intra Assay CV | Inter Assay N | Inter Assay 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 |
2. Sample size used for the test set and the data provenance:
- Sample sizes (N): The tables provide the number of measurements for "Intra Assay" (N=10 for all levels) and "Inter Assay" (N=50 for LMWH calibrators, N=28 for UFH calibrators).
- Data Provenance: The document does not explicitly state the country of origin or whether the data is retrospective or prospective. Hyphen BioMed is based in France.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
Not applicable. Similar to the control plasma, the "ground truth" (concentration) is established by the manufacturer through multiple determinations and validated through reproducibility studies.
4. Adjudication method for the test set:
Not applicable. Performance is based on quantitative measurements and statistical analysis (CV, SD).
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
Not applicable. This is an in vitro diagnostic calibrator, not an AI-assisted diagnostic tool.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Not applicable.
7. The type of ground truth used:
The ground truth used is the target concentration of LMWH or UFH in the calibrator plasma, determined by the manufacturer from "multiple determinations."
8. The sample size for the training set:
Not applicable. This is not an AI/ML device; therefore, there is no "training set." The "N" values in the table refer to the number of measurements taken for the reproducibility study.
9. How the ground truth for the training set was established:
Not applicable. The document states that "The concentration of the calibrators is determined from the multiple determinations." This is how the ground truth for these calibrators was established.
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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 # 01 34 40 6510 Fax# 01 34 487236
Contact Person:
Dr. Jean Amiral, President &Scientific Director jamiral@hyphen-Biomed.com
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:
| BiophenLMWHControl | LMWHConcentration(IU/ml) | AcceptableRange (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 |
| BiophenLMWHControlLow | LMWH LowConcentration(IU/ml) | AcceptableRange (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 |
| BiophenUFHControl | UFHConcentration(IU/ml) | AcceptableRange (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 # (33) 01 34 40 6510 Fax# (33) 01 34 487236
Contact Person:
Dr. Jean Amiral, President &Scientific Director Phone number : (+33)(1)34406510 jamiral@hyphen-Biomed.com
US Agent :
Mr. Ola Andersson Phone number : (513) 770-1993 Ola@aniara.com
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 inLMWH (IU/ml) | IntraAssayN | IntraAssayCV | InterAssayN | InterAssaySD |
|---|---|---|---|---|---|
| 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 inUnfractionatedHeparin (IU/ml) | IntraAssayN | IntraAssayCV | InterAssayN | InterAssaySD |
|---|---|---|---|---|---|
| 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 (240) 276-0484. 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 (800) 638-2041 or (301) 443-6597 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
§ 864.5425 Multipurpose system for in vitro coagulation studies.
(a)
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.(b)
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.