(445 days)
No
The device description and performance studies focus on a standard immunoturbidimetric assay and its analytical and clinical performance metrics. There is no mention of AI, ML, or any computational algorithms beyond basic data processing for quantitative determination and statistical analysis.
No
Explanation: This device is an in-vitro diagnostic assay used for the quantitative determination of von Willebrand antigen, aiding in the evaluation of patients with suspected or confirmed von Willebrand factor disorders. It is not used to treat or prevent a disease, but rather to diagnose or monitor.
Yes
The "Intended Use / Indications for Use" section explicitly states that this device is "In-vitro diagnostic automated assay for the quantitative determination of the von Willebrand antigen (VWF:Ag)" and "As an aid used in the evaluation of patients... with suspected or confirmed von Willebrand factor disorders." This language directly indicates its use for diagnostic purposes.
No
The device is an in-vitro diagnostic assay kit consisting of physical reagents (Latex Reagent, Reagent Diluent, Buffer) used on a specific hardware analyzer (SYSMEX® CS-2500). It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The description explicitly states "In-vitro diagnostic automated assay for the quantitative determination of the von Willebrand antigen (VWF:Ag) in human plasma collected from venous blood samples...". This clearly indicates the device is intended for use on biological samples in vitro (outside the body) to diagnose or aid in the diagnosis of a condition (von Willebrand factor disorders).
- Device Description: The description details a laboratory assay that uses reagents to react with components in a human plasma sample. This is characteristic of an in vitro diagnostic test.
- Performance Studies: The document describes various studies (Measuring Interval, Specificity, Reference Interval, Precision/Reproducibility, Method comparison) that are standard for evaluating the performance of an IVD device.
- Predicate Device: The mention of a "Predicate Device(s)" with a K number (K962675; STA® - Liatest® VWF:Ag) is a strong indicator that this device is being submitted for regulatory review as an IVD, as predicate devices are used for comparison in the regulatory process for new IVDs.
N/A
Intended Use / Indications for Use
In-vitro diagnostic automated assay for the quantitative determination of the von Willebrand antigen (VWF:Ag) in human plasma collected from venous blood samples in 3.2% sodium citrated tubes on the SYSMEX® CS-2500 analyzer.
As an aid used in the evaluation of patients aged 4 weeks and older with suspected or confirmed von Willebrand factor disorders and intended for prescription use.
Results of this test should always be interpreted in conjunction with the patient's medical history, clinical presentation and other laboratory findings.
Product codes
GGP
Device Description
The vWF Ag is an immunoturbidimetric assay for the quantitative, WHO-standardized determination of von Willebrand factor (VWF) antigen concentration.
The vWF Aq kit consist of a Latex Reagent (4 x 2 mL) which is a suspension of small polystyrene particles (latex) coated with rabbit anti-human VWF antibodies. The Reagent Diluent (4 x 4 mL) is provided within the kit which is a solution containing glycine. The Reagent Diluent is intended for dilution of the Latex Reagent. The vWF Ag kit is completed by the Buffer (4 x 5 mL) which is a glycine buffer. All components contain sodium azide ( 20% of norm was ±10.0% (relative).
- Result: Measuring interval for the VWF Ag assay established as 4 to 300% of norm.
- Specificity:
- Investigation of potentially interfering substances according to CLSI document EP07 'Interfering Testing in Clinical Chemistry. 3rd ed.' and CLSI document EP37.
- Dose-response and paired-difference experiments were carried out.
- Tested VWF antigen levels: Low level, medical decision levels (30% of norm, 50% of norm), and high level.
- Result: No interference observed up to indicated concentrations for endogenous interferents (Hemoglobin, Bilirubin, Lipids, Rheumatoid Factors) and a panel of exogenous substances (e.g., Acetaminophen, Acetyl salicylic acid, Ibuprofen, etc.). No susceptibility to HAMAs or lupus anticoagulant. The presence of rheumatoid factors may lead to an overestimation of VWF:Ag.
Clinical Studies:
- Reference Interval:
- Study conducted at three (3) clinical study sites in the United States with apparently healthy subjects following CLSI document EP28-A3c.
- Sample size: n = 147 (blood group O), n = 159 (blood group non-O), n = 306 (blood group independent).
- Results:
- Blood group O: Median 92.9% of norm, 2.5th – 97.5th percentile 46.6 - 202.1% of norm.
- Blood group non-O: Median 135.5% of norm, 2.5th – 97.5th percentile 54.3 — 293.6% of norm.
- Blood group independent: Median 111.3% of norm, 2.5th – 97.5th percentile 50.6 – 271.2% of norm.
- Measurements of VWF:Ag in healthy pediatric population:
- Study investigated apparently healthy subjects > 4 weeks to 4 weeks to 4 weeks to
§ 864.7290 Factor deficiency test.
(a)
Identification. A factor deficiency test is a device used to diagnose specific coagulation defects, to monitor certain types of therapy, to detect coagulation inhibitors, and to detect a carrier state (a person carrying both a recessive gene for a coagulation factor deficiency such as hemophilia and the corresponding normal gene).(b)
Classification. Class II (performance standards).
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June 2, 2023
Siemens Healthcare Diagnostics Products GmbH % Petra Dissmann Regulatory Affairs Manager Emil-von-Behring Strasse 76 Marburg, Hesse 35041 Germany
Re: K220728
Trade/Device Name: vWF Ag Regulation Number: 21 CFR 864.7290 Regulation Name: Factor Deficiency Test Regulatory Class: Class II Product Code: GGP Dated: February 10, 2023 Received: February 10, 2023
Dear Petra Dissmann:
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. 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 located 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.
1
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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-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).
Sincerely.
Min Wu -S
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
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Indications for Use
510(k) Number (if known) K220728
Device Name vWF Ag
Indications for Use (Describe)
In-vitro diagnostic automated assay for the quantitative determination of the von Willebrand antigen (VWF:Ag) in human plasma collected from venous blood samples in 3.2% sodium citrated tubes on the SYSMEX® CS-2500 analyzer.
As an aid used in the evaluation of patients aged 4 weeks and older with suspected or confirmed von Willebrand factor disorders and intended for prescription use.
Results of this test should always be interpreted in conjunction with the patient's medical history, clinical presentation and other laboratory findings.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ------------------------------------------------- | -- |
X 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 and follows the FDA guidance '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: | Dr. Petra M. Dissmann |
| Email: | petra.dissmann@siemens-healthineers.com |
| Phone: | + 49 172 369 245 9 |
| Date Prepared: | June 02, 2023 |
2. Device
| Name of Device: | vWF Ag |
|---|---|
| Regulation Number: | 21 CFR 864.7290 |
| Regulation Description: | Factor deficiency test |
| Product Code: | GGP |
| Device Classification Name: | Test, Qualitative And Quantitative Factor Deficiency |
| Regulatory Class: | Class II |
| 510(k) Review Panel | Hematology (81) |
3. Predicate Device
| Name of Device: | STA® - Liatest® VWF:Ag (K962675) |
|---|---|
| Regulation Number: | 21 CFR 864.7290 |
| Regulation Description: | Factor deficiency test |
| Product Code: | GJT |
| Device Classification Name: | Plasma, Coagulation Factor Deficient |
| Regulatory Class: | Class II |
| 510(k) Review Panel | Hematology (81) |
One recall associated with the predicate were found on the FDA Medical Device Recalls database. However, this recall from 2013 was specific to the software design of the affected product (analyzer) and customers were informed by the manufacturer Diagnostica Stago Inc. (original applicant was American Bioproducts Company) how to deal with the problem. The recall topic has no bearing on the studies and content of this premarket notification. No reference devices were used in this submission.
4
4. Device Description / Test Principle
The vWF Ag is an immunoturbidimetric assay for the quantitative, WHO-standardized determination of von Willebrand factor (VWF) antigen concentration.
The vWF Aq kit consist of a Latex Reagent (4 x 2 mL) which is a suspension of small polystyrene particles (latex) coated with rabbit anti-human VWF antibodies. The Reagent Diluent (4 x 4 mL) is provided within the kit which is a solution containing glycine. The Reagent Diluent is intended for dilution of the Latex Reagent. The vWF Ag kit is completed by the Buffer (4 x 5 mL) which is a glycine buffer. All components contain sodium azide ( 105% the test setting allows
re-dilution 1:8 (upper linear range
105%, 4 x $105% = 420%$ ). |
| Control Level | 3 Control levels
(sold separately from the assay): | 2 Control levels
(sold separately from the assay): |
| | Control Plasma N
(K042333, normal range) | STA®-Liatest® Control N
(normal range) |
| | Control Plasma P and
Control Plasma P 1:6 diluted
(K042209, pathological range) | STA®-Liatest® Control P
(pathological range) |
| Stability Once
Opened | 4 weeks at 2 – 8°C | Not specified in package insert |
| On Board Stability | In original vials the vWF Ag Reagent
and vWF Ag Buffer may be left on
board the instrument for 100 hours.
The reagent vials can stay
continuously on board or be removed
and stored closed at 2 to 8 °C before
the next placement on board.' | With STA® - mini Reducer and
perforated cap in place the stability of
Reagent 2 after dilution is 15 days on
STA-R® and STA Compact® |
| Differences between vWF Ag and STA®-Liatest® VWF:Ag | | |
| Item | Proposed Device
vWF Ag | Predicate Device (K962675)
STA®-Liatest® VWF:Ag |
| Ambient
Temperature | The 510(k) data confirms that the
correctness of the measured results
for the vWF Ag assay is assured
within the operating range
temperatures of the SYSMEX CS-
2500 analyzer.
(8 - 12 °C). | Not specified in package insert |
| Sample Stability | • Maximal storage at 15 to 25 °C in
primary cups
(plasma stored over cells) =
4 hours
• Maximal storage at 15 to 25 °C in
secondary cup
(plasma siphoned from cells) =
4 hours
• Maximal storage at ≤ -20 °C in
secondary cups
(plasma siphoned from cells) =
3 months
• Maximal storage at ≤ -74 °C in
secondary cups
(plasma siphoned from cells) =
6 months
Furthermore, the 510(k) data confirms
that once frozen samples can be
measured within 4 hours after thawing. | • 8 hours at 20 ± 5 °C
• 24 hours at 2 - 8 °C
• 1 month at -20 °C. |
| High Dose Hook
Effect | The vWF Ag assay on the
SYSMEX® CS-2500 system
shows no high dose hook effect
up to 1213% of norm VWF:Ag. | If there is a dose-hook effect, the test
setup takes it into account. |
| Sample Carryover | The 510(k) data confirms that
there is no cross-contamination
caused by one sample into
another. | Not specified in package insert |
| Reagent Carryover | The 510(k) data confirms that
there is no cross-contamination
caused by one application into
another. | Not specified in package insert |
| Comparison between Calibrators | | |
| Item | Proposed Device
vWF Ag | Predicate Device (K962675)
STA®-Liatest® VWF:Ag |
| Intended Use | Standard Human Plasma is used for
the calibration of the following
coagulation and fibrinolysis tests:
- Prothrombin time (PT)
- Fibrinogen (Clauss method)
- Coagulation factors II, V, VII, VIII,
IX, X, XI, XII and VWF - Inhibitors: Antithrombin III, protein
C, protein S, α2-antiplasmin - Plasminogen
The percentage values given in the
enclosed table of values relate to a
pool of fresh citrated human plasma,
which by definition, exhibits 100 %
of the norm for all the factors.
Coagulation factors and inhibitors
for which a WHO Standard is
available are referenced to this
standard and the values are given in
International Units (IU). | Unknown |
| Matrix | Normal human plasma (lyophilized) | Unknown |
| Directly traceable to
WHO Standard | Yes, traceable to
WHO 6th International Standard
Factor VIII / Von Willebrand Factor
(07/316) | Unknown |
| Calibration Concept | Calibrator including analytical value
(sold separately):
Standard Human Plasma
A standard curve is generated by
automatic determination of different
dilutions of Standard Human
Plasma and Dade® Owren's
Veronal Buffer.
The respective levels are defined by
the actual concentration of the
Standard Human Plasma lot as
provided in the enclosed Table of
Analytical Values, and by the
system-specific dilution settings for
calibration. | Calibrator including analytical value
(sold separately):
STA® - VWF:Ag Calibrator
Assay calibration is performed with
STA® - VWF:Ag Calibrator. Prepare
STA® - VWF:Ag Calibrator and scan
the information contained in the
barcode of the Assay Value insert
to the instrument. The standards
are automatically prepared by the
analyzer by dilution with STA®
Owren-Koller according to the
parameters entered in the
instrument for the assay.
STA® - Owren-Koller alone
represents the 0 %-point. |
| Comparison between Calibrators | | |
| Item | Proposed Device
vWF Ag | Predicate Device (K962675)
STA®-Liatest® VWF:Ag |
| Stability / Shelf Life | 24 months | Unknown |
| On Board Stability | Because calibrators are intended to
be used immediately, Siemens does
not claim the on-board stability of
Standard Human Plasma in the
labeling. | Unknown |
| Stability after
Reconstitution | 4 hours stored at 15 to 25 °C and
4 weeks stored at -20 °C | Unknown |
6. Comparison of Technological Characteristics with the Predicate Device
- A) Assay
5
6
7
8
9
B) Calibrator
10
The above described differences do not raise new questions as to safety and effectiveness of the new device.
7. Performance Data
The following performance data were provided in support of the substantial equivalence determination.
Non-Clinical Studies 7.1.
7.1.1 Measuring Interval (Limit of Quantitation and Linearity)
The measuring interval of the application was established with respect to the limit of quantitation (LoQ) and the linearity study.
The LoQ study was carried out in accordance with the CLSI document EP17-A2 'Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures: Approved Guideline-Second Edition'. The verification of the LoQ was performed with five independent low-analyte plasma pools. Normal plasma pools were diluted with von Willebrand factor (VWF) deficient plasma. The LoQ was defined as 3.12% of norm. The greatest observed total error was 2.09% of norm. The study result confirms that the lower limit of the measuring interval of the vWF Ag assay (4% of norm) can be accurately measured with the proposed device.
The linearity study was performed in accordance with the CLSI document EP06 2nd ed. 'Evaluation of Linearity of Quantitative Measurement Procedures'. The linearity of the application was evaluated for three (3) lots of the vWF Ag assay across the measuring range (4 to 300% of norm). A dilution series was prepared using a high plasma sample pool and a low plasma sample pool to equal 12 different dilutions spanning a VWF:Ag concentration of 3.6 to 399.7% of norm. The deviation from linearity according to EP06 2nd ed. was calculated for each concentration of the dilution series investigated. The predefined maximum deviation in the measured range of ≤ 20% of norm (absolute). The highest predefined maximum deviation in the measured range of > 20% of norm was ±10.0% (relative).
Based on the results of the LoQ and linearity study, the measuring interval for the VWF Ag assay was established as 4 to 300% of norm.
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7.1.2. Specificity
The effects of potentially interfering substances were investigated in interference studies according to CLSI document EP07 'Interfering Testing in Clinical Chemistry. 3rd ed.'. Siemens investigated the test concentrations as recommended in CLSI document EP37 'Supplemental Tables for Interference Testing in Clinical Chemistry, 1st Edition'.
Dose-response experiments were carried out to determine the degree of interference as a function of the interferent concentration for endogenous interferents (hemoglobin, unconjugated bilirubin, conjugated bilirubin, lipids, and rheumatoid factors).
Paired-difference experiments were carried out to evaluate the amount of interferent up to which no interference is to be expected. Individual native samples with and without interferent were compared within the studies. Such interference testing was performed with a panel of exogenous substances including Over the Counter and Prescription Drugs.
The interferent test concentrations were investigated regarding four (4) different von Willebrand factor (VWF) antigen levels: Low level, medical decision levels (30% of norm, 50% of norm), and high level. The evaluation regarding the endogenous interferents rheumatoid factors was carried out with single native plasmas.
Following concentrations of listed endogenous substances were found to cause no interference up to the indicated concentrations:
| Interferent | No interference up to: |
|---|---|
| Hemoglobin | 712 mg/dL |
| Bilirubin ( unconjugated) | 30 mg/dL |
| Bilirubin (conjugated) | 100 mg/dL |
| Lipids* | 549 mg/dL |
| Rheumatoid Factors | 23 IU/mL |
| Interferent | No interference up to: |
| Acetaminophen (Paracetamol) | 156 µg/mL |
| Acetyl salicylic acid | 30 µg/mL |
| Amitriptyline hydrochloride | 543 ng/mL |
| Atorvastatin calcium salt trihydrate | 812 ng/mL |
| Budesonide | 6.3 ng/mL |
| Carbimazol | 3.6 µg/mL |
| Ciprofloxacin | 12 µg/mL |
| Cisplatin | 33 µg/mL |
| Citalopram hydrobromide | 6.79 µg/mL |
| Clopidogrel hydrogensulfate | 24 ng/mL |
| Diclofenac sodium salt | 26 µg/mL |
| Emicizumab | 300 µg/mL |
| Estradiol | 7.5 pg/mL |
| Ibuprofen sodium salt | 240 µg/mL |
| Lenalidomide | 2.13 µg/mL |
| Lisinopril dihydrate | 268 ng/mL |
| L-Thyroxin | 180 ng/mL |
| Metformin Hydrochloride | 15.4 µg/mL |
| Pantoprazole sodium sesquihydrate | 34 µg/mL |
| Progesterone | 540 ng/mL |
| Ramipril | 156 ng/mL |
| RFVIIa: NovoSeven® (Eptacog alfa activated) | 4.5 µg/mL |
| RFVIII: ELOCTA® (Efmoroctocog alfa) | 1.875 IU/mL |
| RFVIII: Esperoct® (Turoctocog alfa pegol) | 1.875 IU/mL |
| Tetracycline | 24 µg/mL |
| Theophylline | 60 µg/mL |
| Thiouracil (2-Thiouracil) | 15.9 µg/mL |
| Ticagrelor | 108 µg/mL |
| Tranexamic Acid | 162.9 µg/mL |
| Valproic Acid | 318 µg/mL |
| Valsartan | 11.7 µg/mL |
- Evaluated with Intralipid® equivalent (Lipovenoes®) spiked samples.
Patient samples may contain heterophilic antibodies that could react in immunoassays to give a falsely elevated or depressed result.
No susceptibility of the vWF Ag assay was observed towards human anti-mouse antibodies (HAMAs) or the potential interference by antibodies (lupus anticoagulant, named Lupus in the following) caused by the autoimmune disease lupus erythematosus.
The presence of rheumatoid factors may lead to an overestimation of VWF:Ag. The diagnosis or exclusion of any type of von Willebrand disease (VWD) should therefore never be based solely on the vWF Ag assay's result.
12
In addition, no interferences up to the indicated concentrations of following exogenous substances were observed:
13
7.2. Clinical Studies
7.2.1. Reference Interval
A reference interval study was conducted at three (3) clinical study sites in the United States with apparently healthy subjects following the guidance of CLSI document EP28-A3c 'Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline – Third Edition'. Fresh plasma specimens obtained from apparently healthy donors were tested with the following results:
| Reference Interval Study | ||||
|---|---|---|---|---|
| ABO | n | Median | ||
| (% of norm) | 2.5th - 97.5th percentile | |||
| (% of norm) | ||||
| Blood group O | 147 | 92.9 | 46.6 - 202.1 | |
| Blood group non-O | 159 | 135.5 | 54.3 — 293.6 | |
| Blood group independent* | 306 | 111.3 | 50.6 – 271.2 |
- The blood group independent reference range is calculated from pooled sample results (n = 147 blood group O and n = 159 blood group non-O).
7.2.2. Measurements of VWF:Ag in healthy pediatric population
For the 'measurements of VWF:Ag in a healthy pediation' apparently healthy subjects > 4 weeks to 4 weeks to 4 weeks to 4 weeks to 2.03 – 5.96 |
| Evaluation of 3x5x2x3 Precision Study at Single Sites (USA) | ||||
|---|---|---|---|---|
| CV (%) | ||||
| Study Site | Repeatability | |||
| (Within-Run) | Between-Run | Between-Day | Total | |
| (Within-Site) | ||||
| Site 1 | 0.73 - 3.08 | 0.00 - 1.21 | 0.00 - 1.89 | 0.83 - 3.48 |
| Site 2 | 1.11 - 4.32 | 0.00 - 1.56 | 0.00 - 2.48 | 1.30 - 4.99 |
| Site 3 | 1.42 - 5.16 | 0.00 - 1.89 | 0.00 - 2.09 | 1.95 - 5.44 |
| Evaluation of 3x20x2x2 Precision Study at Single Site (Germany)
| Investigation of reagent variability (reagent lots combined) | ||||
|---|---|---|---|---|
| CV (%) | ||||
| Repeatability | ||||
| (Within-Run) | Between-Run | Between-Day | Between- | |
| Reagent Lot | Total | |||
| (combined | ||||
| reagent lots) | ||||
| 1.32 – 6.68 | 0.00 - 2.67 | 0.00 – 1.88 | 0.87 - 3.22 | 2.53 - 7.37 |
| Evaluation of 3x20x2x2 Precision Study at Single Site (Germany)
| Investigation of calibrator variability (calibrator lots combined) | ||||
|---|---|---|---|---|
| CV (%) | ||||
| Repeatability | ||||
| (Within-Run) | Between-Run | Between-Day | Between- | |
| Calibrator Lot | Total | |||
| (combined | ||||
| calibrator lots) | ||||
| 1.11 – 6.06 | 0.00 – 2.94 | 0.00 - 1.55 | 1.09 - 4.73 | 2.55 - 6.88 |
| Evaluation of 3x5x2x4 Precision Study at Single Site (Germany)
| Investigation of instrument variability | |||||
|---|---|---|---|---|---|
| CV (%) | |||||
| Repeatability | |||||
| (Within-Run) | Between-Run | Between-Day | Between- | ||
| Instrument | Total | ||||
| (combined | |||||
| instruments) | |||||
| 1.47 – 3.16 | 0.0 - 0.94 | 0.33 - 1.56 | 0.00 - 4.08 | 1.77 - 5.30 |
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7.2.4. Method comparison
Method comparison studies designed according to EP09c CLSI Guideline 'Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline-Third Edition' were conducted at one (1) external site in Germany (Site 1) and two (2) external sites in the United States (Site 2 and Site 3). All sites used the same protocol but only Site 3 performed measurements on the predicate device.
Samples were measured on both the predicate device (STA® Liatest® VWF:Ag on the STA R Max® analyzer) as well as on the proposed device (the vWF Ag assay on the Sysmex® CS-2500 analyzer). The samples tested ensured the intended use population was tested. Results were compared by Passing-Bablok regression analysis. Results from each application met the predetermined acceptance criteria. The following summary of Passing-Bablok regression shows that the proposed and predicate devices provide equivalent results when used in a clinical setting.
| Method Comparison Results (Passing-Bablok Regression):
Proposed Device = vWF Ag on the Sysmex® CS-2500 analyzer and
| Predicate Device = STA® Liatest® VWF:Ag on the STA R Max® analyzer | |||
|---|---|---|---|
| Site 1 | Site 2 | Site 3 | Sites Combined |
| N = 107 | N = 115 | N = 117 | N = 339 |
| y = 1.07x - 4.67% of norm | y = 1.07x - 5.56% of norm | y = 0.99x - 4.36% of norm | y =1.04x - 4.60% of norm |
| r = 0.996 | r = 0.972 | r = 0.978 | r = 0.982 |
| (r2 = 0.992) | (r2 = 0.944) | (r2 = 0.956) | (r2 = 0.965) |
8. Conclusion
The non-clinical and clinical data support the safety of the proposed device, the vWF Ag assay.
The clinical data demonstrates that the vWF Ag assay on the SYSMEX® CS-2500 analyzer performs comparably to the predicate device (STA® Liatest® VWF:Ag on the STA R Max®) that is currently marketed for the same intended use.
The data submitted for this premarket notification demonstrates that the device raises no concerns with regard to safety and effectiveness.