(379 days)
For non-invasive monitoring, in real time, of the estimated relative blood volume percent for patients undergoing hemodialysis so that technicians may make system adjustments in order to remove the maximum amount of fluid from the dialysis patient without the patient experiencing the common symptoms of dialysis which include nausea, cramping and vomiting.
The device can also provide estimated values of: (1) relative blood volume trend; (2) hematocrit; (3) hemoglobin and (4) blood water content or mass fraction of blood water in the total blood mass.
The device is ONLY to be used in conjunction with the Fresenius Dialysis System 2008H.
There are a variety of method for measuring relative blood volume (RBV), and all make use of the fact that certain constituents of blood (cells, haemoglobin, plasma protein, total protein) remain confined to the vascular compartment, whereas the plasma water can pass both the capillary membrane (into the interstitial compartment) and the dialyser membrane (into the dialysis fluid compartment). Therefore the blood volume change can be determined from the concentration change of these blood constituents.
The Fresenius Blood Volume Monitor is only to be installed in an available bay of the Fresenius Dialysis System 2008H machine. It uses ultrasound pulses from a transmitter through a polycarbonate cuvette installed into the arterial blood line and received on the opposite side. The primary signal measure is the transient time of the sound pulse through the blood sample, from which the sound velocity is calculated. Silicone rubber is used as sound coupling for the cuvette, with the blood passing through from bottom to top to avoid accumulation of air bubbles. Blood temperature is also measure, and a temperature controlled block prevents interference from ambient temperature changes.
The sound speed depends on the blood density, which in turn depends on the mass fraction of protein and the mass fraction of water or blood water content (BWC). Since the mass of blood protein is virtually unchanged during ultra filtration, the mass of blood water changes, and thereby the density changes. Changes in BWC can be detected by changes of sound velocity, and can be converted to relative blood volume changes. Since sound velocity not only depends on density, but also on temperature, a high precision temperature measurement is also required.
Here's an analysis of the acceptance criteria and supporting studies for the Fresenius Blood Monitor, based on the provided text:
Acceptance Criteria and Reported Device Performance
Although explicit "acceptance criteria" in a quantitative table format are not directly stated, the document emphasizes the device's accuracy in comparison to existing methods. The primary performance metric mentioned is agreement with the centrifuge method and correlation with hemoglobin concentration.
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Accuracy of blood volume information | Approximately ±2% (compared to predicate device) |
| Correlation with hemoglobin concentration | r = 0.98 (for relative blood volume) |
| Agreement with centrifuge method (mean difference) | 0.1% ± 1.8% |
1. Sample Size Used for the Test Set and Data Provenance
- Study 1:
- Sample Size: 45 patients
- Number of Examinations: Each patient examined three times, with six values each time.
- Data Provenance: Not explicitly stated, but the device was "developed in Europe and currently marketed outside the United States," suggesting the studies may have originated from Europe. The document refers to "6 centers," which could imply a multicenter study. It's unclear if this was retrospective or prospective, but the phrasing "examined three times" suggests a prospective collection for this specific study.
- Study 2:
- Sample Size: 9 patients
- Number of Comparisons: 104 comparisons with the centrifuge method.
- Data Provenance: Not explicitly stated, but likely from similar European sources as Study 1. The phrasing "underwent 104 comparison" suggests a prospective design for this specific comparative study.
2. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not mention the use of experts to establish a "ground truth" for the test set in the traditional sense of clinical diagnosis or interpretation. Instead, the ground truth was established by established measurement methods:
- Standard Method (for correlation with hemoglobin concentration): This refers to a method used to determine hemoglobin concentration, which then allows for the calculation of relative blood volume. The qualifications of who performed this "standard method" are not specified.
- Centrifuge Method: This is a laboratory technique for separating blood components to determine hematocrit, which can be an input for blood volume calculations. The qualifications of the individuals performing the centrifuging are not specified, but it's a standard lab procedure.
3. Adjudication Method for the Test Set
Not applicable. The ground truth was established by direct measurement methods (e.g., centrifuge, standard hemoglobin measurement), not by expert consensus requiring adjudication.
4. 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
No, an MRMC comparative effectiveness study involving human readers and AI assistance was not conducted or reported. The device is a monitor providing real-time data, not an AI diagnostic tool requiring human interpretation improvement. The document describes studies comparing the device's measurements to other physical measurement methods.
5. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described are essentially "standalone" performance evaluations of the device. The device itself (the Fresenius Blood Monitor) directly measures and outputs values for relative blood volume. The reported studies evaluate the accuracy of these device-generated measurements against established "ground truth" methods (like centrifuge or hemoglobin concentration measurement) without human intervention in the interpretation of the device's primary output. The human aspect comes in subsequent clinical decision-making based on the device's output.
6. The Type of Ground Truth Used
The ground truth used was based on:
- "Standard method" for obtaining blood volume/hematocrit values (presumably laboratory-based methods) in the study correlating with hemoglobin.
- The "centrifuge method" for blood volume comparison.
These are objective, quantitative measurement methods, not expert consensus, pathology, or outcomes data in the context of diagnostic interpretation.
7. The Sample Size for the Training Set
The document does not mention a "training set" or any machine learning/AI training process. The Fresenius Blood Monitor operates based on physical principles (ultrasound sound velocity related to blood density) and algorithms derived from those principles, rather than being a machine learning model that requires a training dataset in the typical sense.
8. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no mention of a training set for a machine learning model.
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SEP -3 1999
Fresenius Medical Care
North America
Renal Product Technologies
510(k) Summary Fresenius Blood Monitor August 19, 1998
| Contact: | Arthur E. EilinsfeldManager, Regulatory AffairsFresenius Medical Care North Americatwo Ledgemont Center95 Hayden DriveLexington, MA 02173 |
|---|---|
| ---------- | --------------------------------------------------------------------------------------------------------------------------------------------------------------- |
Telephone: 781-402-9000
- Prepared by: K. M. Associates 10 Oak Point Wrentham, MA 02093
Contact: Donald A. Lincoln
Telephone: 508-384-2546
Trade Name: FRESENIUS Blood Monitor
Common Name: Blood Monitor
Classification Name: System, Hemodialysis, Access Recirculation Monitoring
Substantial Equivalence is claimed to: CRIT-Line Monitor III (K972470)
Device Description: There are a variety of method for measuring relative blood volume (RBV), and all make use of the fact that certain constituents of blood (cells, haemoglobin, plasma protein, total protein) remain confined to the vascular compartment, whereas the plasma water can pass both the capillary membrane (into the interstitial compartment) and the dialyser membrane (into the dialysis fluid compartment). Therefore the blood volume change can be determined from the concentration change of these blood constituents.
The Fresenius Blood Volume Monitor is only to be installed in an available bay of the Fresenius
Page 1 of 2
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Dialysis System 2008H machine. It uses ultrasound pulses from a transmitter through a polycarbonate cuvette installed into the arterial blood line and received on the opposite side. The primary signal measure is the transient time of the sound pulse through the blood sample, from which the sound velocity is calculated. Silicone rubber is used as sound coupling for the cuvette, with the blood passing through from bottom to top to avoid accumulation of air bubbles. Blood temperature is also measure, and a temperature controlled block prevents interference from ambient temperature changes.
The sound speed depends on the blood density, which in turn depends on the mass fraction of protein and the mass fraction of water or blood water content (BWC). Since the mass of blood protein is virtually unchanged during ultra filtration, the mass of blood water changes, and thereby the density changes. Changes in BWC can be detected by changes of sound velocity, and can be converted to relative blood volume changes. Since sound velocity not only depends on density, but also on temperature, a high precision temperature measurement is also required.
Intended use: To non-invasively provide real time information about relative blood volume, only in conjunction with the Fresenius Dialysis System 2008H, so that adjustments in the rate at which fluid is removed from the patient can be made to limit or eliminate the common symptoms of dialysis such as nausea, cramping and vomiting.
Comparison with predicate device: Both devices provide non-invasive information related to blood volume changes so that corrections in dialysis rates can be made to avoid unwanted side affects. The predicate device can be used with any dialysis system, this current device is for use only with the Fresenius Dialysis System 2008H. Both provide information with an accuracy of approximately ±2% and compare well with other methods such as centrifuging, which is a periodic measurement. The principal difference between the two BVM's is that the predicate device makes its measurements using infa-red technologies while the current device uses ultrasound.
Clinical testing: Several studies have been reported upon. One comprising 6 centers and 45 patients examined three times, each time six values of blood volume and/or hematrocite were compared to a standard method. The relative blood volume of the current device and the relative blood volume calculated from the hemoglobin concentration had a high correlation of r = . 98.
In another study, 9 patients underwent 104 comparison with the centrifuge method. The agreement to the centrifuge was excellent. The mean difference between ultrasonic and centrifuge measurement was 0.1%±1.8%.
Compliance to standards and regulations: The current device, developed in Europe and currently marketed outside the United States, has been tested and found to be in compliance with relevant standards within the EC for devices of this type.
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Image /page/2/Picture/13 description: The image shows the logo for the Department of Health & Human Services - USA. 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 or bird-like figure with three curved lines representing its wings or body.
Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850
SEP -3 1999
Fresenius Medical Care North America c/o Mr. Donald A. Lincoln K. M. Associates 10 Oak Point Wrentham, Massachusetts 02093
Re: K982926 Fresenius Blood Volume Monitor Dated: February 4, 1999 Received: February 5, 1999 Regulatory Class: III 21 CFR 876.5860/Procode: 78 KDI
Dear Mr. Lincoln:
We have reviewed your section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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. You may, therefore, market the device, subject to the general controls provisions Act (Act). The general controls provisions of the Act include requirements for registration, listing of devices, good manufacturing practices, labeling, and prohibitions against misbranding and adulteration.
This determination of substantial equivalence applies to the following transducer intended for use with the Fresenius Blood Volume Monitor, as described in your premarket notification:
| Device Model | Transducer Model Number |
|---|---|
| BVM with Control Module | Ultrasonic Sensor Head (20mW/cm2) |
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval) it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP inspections, the FDA will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, the Food and Drug Administration (FDA) may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification does not affect any obligation you may have under sections 531 and 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
This determination of substantial equivalence is granted on the condition that prior to shipping the first device, you submit a postclearance special report. This report should contain complete information, including acoustic output measurements based on production line devices, requested in Appendix G,
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Page 2 - Mr. Donald Lincoln
(enclosed) of the Center's February 17, 1993 "Revised 510(k) Diagnostic Ultrasound Guidance for 1993." If the special report is incomplete or contains unacceptable values (e.g., acoustic output greater than approved levels), then the 510(k) clearance may not apply to the production units which as a result may be considered adulterated or misbranded.
The special report should reference the manufacturer's 510(k) number. It should be clearly and prominently marked "ADD-TO-FILE" and should be submitted in duplicate to:
Food and Drug Administration Center for Devices and Radiological Health Document Mail Center (HFZ-401) 9200 Corporate Boulevard Rockville, Maryland 20850
This letter will allow you to begin marketing your device as described in your 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 market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4591. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or at (301) 443-6597 or at its Internet address "dsmo@fdadr.cdrh.fda.gov".
If you have any questions regarding the content of this letter, please contact Richard J. Williams at (301) 594-1220.
Sincerely yours,
David A. Lezman
CAPT Daniel G. Schultz, M.D. Acting Director, Division of Reproductive, Abdominal, Ear, Nose and Throat, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Page 1 of 1
510(k) Number: K982926
Device Name(s): Fresenius Blood Volume Monitor
Indications For Use:
For non-invasive monitoring, in real time, of the estimated relative blood volume percent for patients undergoing hemodialysis so that technicians may make system adjustments in order to remove the maximum amount of fluid from the dialysis patient without the patient experiencing the common symptoms of dialysis which include nausea, cramping and vomiting.
The device can also provide estimated values of: (1) relative blood volume trend; (2) hematocrit; (3) hemoglobin and (4) blood water content or mass fraction of blood water in the total blood mass.
The device is ONL Y to be used in conjunction with the Fresenius Dialysis System 2008H.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONȚINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
David R. Legnon
Division Sign Off
Division Sign-Of ivision of Reproductive, Abdomina and Radiological Devic 510(k) Number
§ 876.5860 High permeability hemodialysis system.
(a)
Identification. A high permeability hemodialysis system is a device intended for use as an artificial kidney system for the treatment of patients with renal failure, fluid overload, or toxemic conditions by performing such therapies as hemodialysis, hemofiltration, hemoconcentration, and hemodiafiltration. Using a hemodialyzer with a semipermeable membrane that is more permeable to water than the semipermeable membrane of the conventional hemodialysis system (§ 876.5820), the high permeability hemodialysis system removes toxins or excess fluid from the patient's blood using the principles of convection (via a high ultrafiltration rate) and/or diffusion (via a concentration gradient in dialysate). During treatment, blood is circulated from the patient through the hemodialyzer's blood compartment, while the dialysate solution flows countercurrent through the dialysate compartment. In this process, toxins and/or fluid are transferred across the membrane from the blood to the dialysate compartment. The hemodialysis delivery machine controls and monitors the parameters related to this processing, including the rate at which blood and dialysate are pumped through the system, and the rate at which fluid is removed from the patient. The high permeability hemodialysis system consists of the following devices:(1) The hemodialyzer consists of a semipermeable membrane with an in vitro ultrafiltration coefficient (K
uf ) greater than 8 milliliters per hour per conventional millimeter of mercury, as measured with bovine or expired human blood, and is used with either an automated ultrafiltration controller or anther method of ultrafiltration control to prevent fluid imbalance.(2) The hemodialysis delivery machine is similar to the extracorporeal blood system and dialysate delivery system of the hemodialysis system and accessories (§ 876.5820), with the addition of an ultrafiltration controller and mechanisms that monitor and/or control such parameters as fluid balance, dialysate composition, and patient treatment parameters (e.g., blood pressure, hematocrit, urea, etc.).
(3) The high permeability hemodialysis system accessories include, but are not limited to, tubing lines and various treatment related monitors (e.g., dialysate pH, blood pressure, hematocrit, and blood recirculation monitors).
(b)
Classification. Class II. The special controls for this device are FDA's:(1) “Use of International Standard ISO 10993 ‘Biological Evaluation of Medical Device—Part I: Evaluation and Testing,’ ”
(2) “Guidance for the Content of 510(k)s for Conventional and High Permeability Hemodialyzers,”
(3) “Guidance for Industry and CDRH Reviewers on the Content of Premarket Notifications for Hemodialysis Delivery Systems,”
(4) “Guidance for the Content of Premarket Notifications for Water Purification Components and Systems for Hemodialysis,” and
(5) “Guidance for Hemodialyzer Reuse Labeling.”