(266 days)
Not Found
No
The summary describes a physical medical device (a dialyzer) and its performance characteristics, with no mention of software, algorithms, or AI/ML capabilities.
Yes
The device is described as being "intended for patients with acute kidney injury or chronic kidney disease when conservative therapy is judged to be inadequate," and its function involves "diffusion and/or ultrafiltration to transport toxins and excess fluid from the blood compartment (fiber lumen) to the dialysate compartment," which directly treats a medical condition.
No
Explanation: The device is a hemodialyzer used for treating kidney disease by removing toxins and excess fluid, which is a therapeutic function, not a diagnostic one.
No
The device description clearly states it is a physical hemodialyzer containing a membrane and intended for single-use in hemodialysis, which is a hardware component.
Based on the provided information, the Optiflux® Enexa™ dialyzer is not an In Vitro Diagnostic (IVD) device.
Here's why:
- Intended Use: The intended use is for treating patients with kidney conditions by removing toxins and excess fluid from their blood. This is a therapeutic process performed on the patient's body, not a test performed on a sample taken from the body.
- Device Description: The description details a device that interacts directly with the patient's blood extracorporeally (outside the body) to filter it. It describes a physical process of diffusion and ultrafiltration across a membrane.
- Lack of IVD Characteristics: The description does not mention any analysis of biological samples, detection of substances in samples, or providing information for diagnosis or monitoring based on sample analysis.
IVD devices are typically used to examine specimens derived from the human body (like blood, urine, tissue) to provide information for diagnosis, monitoring, or screening. The Optiflux® Enexa™ dialyzer is a therapeutic device used to treat a condition by directly processing the patient's blood.
N/A
Intended Use / Indications for Use
Optiflux® Enexa™ dialyzers are intended for patients with acute kidney injury or chronic kidney disease when conservative therapy is judged to be inadequate.
Product codes (comma separated list FDA assigned to the subject device)
KDI
Device Description
The Optiflux Enexa F500 dialyzer is a high-flux, single-use, e-beam sterilized hemodialyzer that contains the additive Endexo SMM1 blended into the fiber. The dialyzer is provided blood pathway sterile and non-pyrogenic. The membrane surface area is 1.5 m².
The Optiflux Enexa F500 dialyzer is a high-flux, sterile device designed for single-use in acute and chronic hemodialysis. The dialyzer is configured to connect to a bloodline set which connects to a patient's vascular access system when used with a hemodialysis machine equipped with ultrafiltration control. During hemodialysis, blood is pumped from the patient's body through an extracorporeal circuit, one component of which is the dialyzer. The dialyzer contains a semi-permeable membrane that allows for diffusion and/or ultrafiltration to transport toxins and excess fluid from the blood compartment (fiber lumen) to the dialysate compartment. Dialyzers utilize a counter-current flow in which dialysate and blood flow in opposite directions in the dialyzer. The counter-current flow maintains the concentration gradient across the membrane for waste and fluid removal.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
The Optiflux Enexa F500 dialyzers are used in environments where acute and chronic hemodialysis are performed.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Performance testing was conducted in accordance with ISO 8637-1:2017 and Guidance for the Content of Premarket Notifications for Conventional and High Permeability Hemodialyzers, August 1998. Testing conducted to support the determination of substantial equivalence is summarized in Table 2.
In vitro tests conducted:
- Blood Compartment Volume: Calculated, considering the fiber inner diameter, fiber crimp, the minimum and maximum blood volume, O-ring compression volume, dialyzer housing length, and polyurethane height.
- Clearance – Sodium (marker for urea), Creatinine, Phosphate, Vitamin B12, and Lysozyme: Calculated by analyzing test samples over the specified range of blood and dialysate flow rates.
- Protein Sieving Coefficient: The test circuit was stabilized for blood and filtrate flows. All air was removed from the dialyzer. Paired samples for blood and filtrate flows were collected after 15 min. Samples were taken again after another 15 min. Sieving coefficient was calculated in accordance with Section 5.6.2.4 of ISO 8637-1:2017.
- Ultrafiltration: Calculated as the slope from a plot of the measured transmembrane pressure versus the ultrafiltration rate.
- Pressure Drop: The dialysate and blood compartments were filled with dialysate and bovine blood, respectively. Inlet and outlet pressures of the blood and dialysate compartments were measured across the range of flow rates with the dialyzers in a horizontal position.
- Structural Integrity: The positive and negative pressure decay was measured by a pressure monitor connected at one end of the dialyzer while applying 900 mmHg and -700 mmHg from the opposite end.
- Blood Compartment Integrity: Air and water were added to the top blood port and the dialysate side, respectively. A pressure differential was applied across the dialyzer membrane.
- Simulated Shipping and Distribution: Testing was conducted per ASTM D4169-16. Performance testing was conducted before and after simulated shipping to demonstrate that product and package integrity and sterility are maintained throughout the intended product shelf life.
All testing met predetermined acceptance criteria. Results of the proposed device design verification tests met the requirements and demonstrated that, like the predicate device, the Optiflux Enexa F500 dialyzer is safe and effective for its intended use.
Biocompatibility Testing:
The following testing was performed to support the biological safety of the Optiflux Enexa F500 dialyzer:
- Chemical Analysis Extractables and Leachables
- Cytotoxicity, ISO Elution Method with MEM
- Sensitization, Guinea Pig Maximization
- Intracutaneous Irritation
- Acute Systemic Toxicity
- Subchronic Toxicity, Dual Routes of Parental Administration
- Material-Mediated Pyrogenicity
- Genotoxicity, Bacterial Reverse Mutation Assay
- Genotoxicity, in vitro Mouse Lymphoma Gene Mutation Assay
- Genotoxicity, ISO in vitro Mouse Lymphoma Gene Mutation Assay
- Hemocompatibility, ASTM Hemolysis (Direct and Indirect - Extract)
- Hemocompatibility, Complement Activation C3a and SC5b-9 fragment
- Hemocompatibility, ASTM Partial Thromboplastin Time
- Hemocompatibility, Mechanical Hemolysis
- Hemocompatibility, in vitro Thrombogenicity Assay
- PVP Assay
- SMM1 Assay
- In vivo Toxicity Studies.
A toxicological risk assessment was also performed.
Human Factors Validation Testing:
Human Factors (HF) validation testing was leveraged for the Optiflux Enexa F500 dialyzer to demonstrate its safe and effective use in accordance with FDA guidance Applying Human Factors and Usability Engineering to Medical Devices (03 February 2016).
Clinical Studies:
Eighteen (18) hemodialysis (HD) subjects with chronic renal failure were administered 664 HD treatments with the Optiflux® Enexa™ F500 in a prospective, multi-center, open-label clinical study. Mean treatment duration was 207 ± 20 min, blood flow rate 447.7 ± 37.7 mL/min. and dialysate flow rate 698 ± 62.8 mL/min. Mean Kuf was 16.36 ± 9.92 mL/hr/mmHg, and spKt/V 2.06 ± 0.42. Mean urea and ß2-microglobulin removal rates were 81.49 ± 5.95% and 63.04 ± 16.86%. respectively. Mean pre-HD serum albumin levels remained unchanged; an increase from 3.94 ± 0.21 g/dL to 4.23 ± 0.41 g/dL was observed from pre-HD to post-HD. There was no evidence of overt complement activation as C5a and C3a levels remained largely unchanged from pre-HD levels. A decrease in mean C3a levels from 1318.8 ± 886.7 ng/mL to 1301.2 ± 335.7 ng/mL and in mean C5a levels from 8.8 ± 6.1 ng/mL to 7.62 ± 4.7 ng/mL was observed pre-HD and 30 mins post-HD. A slight increase in mean sC5b- 9 level from 224.3 ± 51.3 ng/mL to 304.22 ± 71.6 ng/mL was observed at 30 min post-HD. No clinically meaningful changes were observed in hematologic parameters and mean platelet counts. Adverse events that occurred during the study were not related to the device. Eleven (11) out of the 18 subjects (61.1%, 32 AEs) reported at least 1 AE during the study. No deaths or AEs leading to discontinuation were reported during the study. Three (3) serious adverse events were reported but none were related to the device. The mean thrombus score (1-4, clear to fully clotted) was 1.29 ± 0.52. None of the treatments with the Optiflux® Enexa™ F500 showed a Grade 4 Thrombus.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Key metrics include:
- Urea clearance: 271 (using Sodium as marker)
- Mean Kuf: 16.36 ± 9.92 mL/hr/mmHg
- spKt/V: 2.06 ± 0.42
- Mean urea removal rates: 81.49 ± 5.95%
- Mean ß2-microglobulin removal rates: 63.04 ± 16.86%
- Mean pre-HD serum albumin levels: 3.94 ± 0.21 g/dL
- Mean post-HD serum albumin levels: 4.23 ± 0.41 g/dL
- Mean C3a levels (pre-HD): 1318.8 ± 886.7 ng/mL
- Mean C3a levels (post-HD): 1301.2 ± 335.7 ng/mL
- Mean C5a levels (pre-HD): 8.8 ± 6.1 ng/mL
- Mean C5a levels (post-HD): 7.62 ± 4.7 ng/mL
- Mean sC5b-9 level (30 min post-HD): 304.22 ± 71.6 ng/mL (pre-HD: 224.3 ± 51.3 ng/mL)
- Mean thrombus score: 1.29 ± 0.52
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.”
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food & Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" in a square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in a sans-serif font.
July 9, 2020
Fresenius Medical Care Renal Therapies Group LLC Denise M. Oppermann Senior Director, Regulatory Affairs 920 Winter Street Waltham, MA 02451
Re: K192928
Trade/Device Name: Optiflux Enexa F500 Dialyzer Regulation Number: 21 CFR 876.5860 Regulation Name: High Permeability Hemodialysis System Regulatory Class: II Product Code: KDI Dated: June 2, 2020 Received: June 4, 2020
Dear Denise M. Oppermann:
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.
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
1
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); 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,
for
Carolyn Y. Neuland, Ph.D. Assistant Director DHT3A: Division of Renal, Gastrointestinal, Obesity and Transplant Devices OHT3: Office of GastroRenal, ObGyn, General Hospital and Urology Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K192928
Device Name
Optiflux Enexa F500 Dialyzer
Indications for Use (Describe)
Optiflux® Enexa™ dialyzers are intended for patients with acute kidney injury or chronic kidney disease when conservative therapy is judged to be inadequate.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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Image /page/3/Picture/0 description: The image shows the Fresenius Medical Care logo. The logo consists of a blue geometric shape on the left and the text "FRESENIUS MEDICAL CARE" on the right. The geometric shape is made up of three downward-pointing chevrons stacked on top of each other. The text is in a bold, sans-serif font, with "FRESENIUS" on the top line and "MEDICAL CARE" on the bottom line.
ട. 510(K) SUMMARY
This 510(k) Summary is in accordance with the requirements of the Safe Medical Device Act (SMDA) of 1990. The content of this 510(k) summary is provided in conformance with 21 CFR §807.92.
5.1. Submitter's Information
| Name: | Fresenius Medical Care Renal Therapies Group, LLC |
|---|---|
| Address: | 920 Winter Street |
| Waltham, MA | |
| 02451-1457 | |
| Phone: | (781) 996-9103 |
| Fax: | (781) 699-9635 |
| Contact Person: | Denise Oppermann, Senior Director |
| Regulatory Affairs – Devices | |
| Preparation Date: | 16 October 2019 |
5.2. Device Name
| Trade Name: | Optiflux Enexa F500 Dialyzer |
|---|---|
| Common Name: | Dialyzer |
| Regulation Name: | High permeability hemodialysis system |
| Regulatory Class: | Class II per 21 CFR §876.5860 |
| Product Code: | KDI |
| Product Code Name: | Dialyzer, High Permeability With Or Without Sealed Dialysate |
| System | |
| Classification Panel: | Gastroenterology/Urology |
5.3. Legally Marketed Predicate Device
The legally marketed predicate device is the Optiflux F160NR dialyzer cleared under K152367. This device is not currently subject to a design-related recall.
5.4. Device Description
Device Identification 5.4.1.
The Optiflux Enexa F500 dialyzer is the subject of this 510(k).
5.4.2 Device Characteristics
The Optiflux Enexa F500 dialyzer is a high-flux, single-use, e-beam sterilized hemodialyzer that contains the additive Endexo SMM1 blended into the fiber. The dialyzer is provided blood pathway sterile and non-pyrogenic. The membrane surface area is 1.5 m².
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Image /page/4/Picture/0 description: The image contains the logo for Fresenius Medical Care. The logo consists of a blue symbol on the left and the text "FRESENIUS MEDICAL CARE" on the right. The symbol is made up of three downward-pointing chevrons stacked on top of each other. The text is in a bold, sans-serif font, with "FRESENIUS" on the top line and "MEDICAL CARE" on the bottom line.
5.2.2.1 Environment of Use
The Optiflux Enexa F500 dialyzers are used in environments where acute and chronic hemodialysis are performed.
5.4.2.2. Brief Written Description of the Device
The Optiflux Enexa F500 dialyzer is a high-flux, sterile device designed for single-use in acute and chronic hemodialysis. The dialyzer is configured to connect to a bloodline set which connects to a patient's vascular access system when used with a hemodialysis machine equipped with ultrafiltration control. During hemodialysis, blood is pumped from the patient's body through an extracorporeal circuit, one component of which is the dialyzer. The dialyzer contains a semi-permeable membrane that allows for diffusion and/or ultrafiltration to transport toxins and excess fluid from the blood compartment (fiber lumen) to the dialysate compartment. Dialyzers utilize a counter-current flow in which dialysate and blood flow in opposite directions in the dialyzer. The counter-current flow maintains the concentration gradient across the membrane for waste and fluid removal.
5.4.2.3. Materials of Use
The Optiflux Enexa F500 is classified as an externally communicating, blood path indirect, prolonged contact (> 24 hours to 30 days) duration, Class II device in accordance with FDA guidance Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" (16 June 2016). Testing performed met or exceeded these requirements.
| Component | Material |
|---|---|
| Housing | Polycarbonate |
| Potting Resin | Polyurethane |
| Fiber Bundle | Polysulfone w/Endexo SMM1 |
| Screw Flange | Polycarbonate |
| O-Ring | Silicone |
| Blood Port Cap(s) | High Density Polyethylene |
| Dialysate Port Cap(s) | High Density Polyethylene |
The Optiflux Enexa F500 dialyzer is composed of the following materials:
Kev Performance Characteristics 5.4.2.4.
Urea clearance is a key performance specification of the Optiflux Enexa F500 dialyzer. FMCRTG uses sodium clearance as a marker for urea clearance because sodium and urea exhibit similar movement across a membrane. Sodium clearance data from the Instructions for Use (IFU) for the Optiflux Enexa F500 dialyzer is provided in Table 1.
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Image /page/5/Picture/0 description: The image shows the Fresenius Medical Care logo. On the left side of the logo, there is a blue symbol that consists of three downward-pointing chevrons stacked on top of each other. To the right of the symbol, the words "FRESENIUS MEDICAL CARE" are written in blue, with "FRESENIUS" on the top line and "MEDICAL CARE" on the bottom line.
In vitro Urea Clearance for the F500 Dialyzer* Table 1:
| Trade Name | Typical Urea Clearance
(Sodium Used as Marker) |
|---------------------|---------------------------------------------------|
| Optiflux Enexa F500 | 271 |
*Qb = 300 mL/min, Qd = 500 mL/min, Quf = 0 mL/min
5.5. Intended Use
Optiflux Enexa dialyzers are designed for single use acute and chronic hemodialysis.
Indications for Use 5.6.
Optiflux® Enexa™ dialyzers are intended for patients with acute kidney injury or chronic kidney disease when conservative therapy is judged to be inadequate.
5.7. Comparison of Technological Characteristics with the Predicate Device
The following technological characteristics of the Optiflux Enexa F500 dialyzer are substantially equivalent to those of the predicate Optiflux F160NR dialyzer (K152367).
- Intended use
- Principle of operation ●
- Design characteristics ●
- Patient fluid-contacting materials .
5.8. Performance Data
Performance testing was conducted in accordance with ISO 8637-1:2017 and Guidance for the Content of Premarket Notifications for Conventional and High Permeability Hemodialyzers, August 1998. Testing conducted to support the determination of substantial equivalence is summarized in Table 2.
| Test Conducted | Test Method Description |
|---|---|
| Blood Compartment Volume | Calculated, considering the fiber inner diameter, fiber |
| crimp, the minimum and maximum blood volume, O- | |
| ring compression volume, dialyzer housing length, and | |
| polyurethane height. | |
| Clearance – Sodium (marker | |
| for urea), Creatinine, | |
| Phosphate, Vitamin B12, and | |
| Lysozyme | Calculated by analyzing test samples over the specified |
| range of blood and dialysate flow rates. |
Table 2: Performance Testing Summary
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Image /page/6/Picture/0 description: The image shows the Fresenius Medical Care logo. The logo consists of a blue symbol on the left and the text "FRESENIUS MEDICAL CARE" on the right. The symbol is made up of three downward-pointing chevrons stacked on top of each other. The text is in a bold, sans-serif font, with "FRESENIUS" on the top line and "MEDICAL CARE" on the bottom line.
| Test Conducted | Test Method Description |
|---|---|
| Protein Sieving Coefficient | The test circuit was stabilized for blood and filtrate |
| flows. All air was removed from the dialyzer. Paired | |
| samples for blood and filtrate flows were collected after | |
| 15 min. Samples were taken again after another 15 min. | |
| Sieving coefficient was calculated in accordance with | |
| Section 5.6.2.4 of ISO 8637-1:2017. | |
| Ultrafiltration | Calculated as the slope from a plot of the measured |
| transmembrane pressure versus the ultrafiltration rate. | |
| Pressure Drop | The dialysate and blood compartments were filled with |
| dialysate and bovine blood, respectively. Inlet and outlet | |
| pressures of the blood and dialysate compartments were | |
| measured across the range of flow rates with the | |
| dialyzers in a horizontal position. | |
| Structural Integrity | The positive and negative pressure decay was measured |
| by a pressure monitor connected at one end of the | |
| dialyzer while applying 900 mmHg and -700 mmHg | |
| from the opposite end. | |
| Blood Compartment Integrity | Air and water were added to the top blood port and the |
| dialysate side, respectively. A pressure differential was | |
| applied across the dialyzer membrane. | |
| Simulated Shipping and | |
| Distribution | Testing was conducted per ASTM D4169-16. |
| Performance testing was conducted before and after | |
| simulated shipping to demonstrate that product and | |
| package integrity and sterility are maintained throughout | |
| the intended product shelf life. |
All testing met predetermined acceptance criteria. Results of the proposed device design verification tests met the requirements and demonstrated that, like the predicate device, the Optiflux Enexa F500 dialyzer is safe and effective for its intended use.
Biocompatibility Testing 5.8.1.
The following testing was performed to support the biological safety of the Optiflux Enexa F500 dialyzer:
- Chemical Analysis Extractables and Leachables ●
- Cytotoxicity, ISO Elution Method with MEM ●
- Sensitization, Guinea Pig Maximization ●
- Intracutaneous Irritation ●
- Acute Systemic Toxicity ●
- Subchronic Toxicity, Dual Routes of Parental Administration
7
Image /page/7/Picture/0 description: The image shows the logo for Fresenius Medical Care. The logo consists of a blue symbol on the left and the text "FRESENIUS MEDICAL CARE" on the right. The symbol is made up of three downward-pointing chevrons stacked on top of each other. The text is in a bold, sans-serif font, with "FRESENIUS" on the top line and "MEDICAL CARE" on the bottom line.
- Material-Mediated Pyrogenicity ●
- Genotoxicity, Bacterial Reverse Mutation Assay ●
- Genotoxicity, in vitro Mouse Lymphoma Gene Mutation Assay ●
- Genotoxicity, ISO in vitro Mouse Lymphoma Gene Mutation Assay
- Hemocompatibility, ASTM Hemolysis (Direct and Indirect - Extract)
- Hemocompatibility, Complement Activation C3a and SC5b-9 fragment ●
- Hemocompatibility, ASTM Partial Thromboplastin Time ●
- Hemocompatibility, Mechanical Hemolysis ●
- Hemocompatibility, in vitro Thrombogenicity Assay ●
- PVP Assay
- SMM1 Assay ●
- In vivo Toxicity Studies .
A toxicological risk assessment was also performed.
5.8.2. Human Factors Validation Testing
Human Factors (HF) validation testing was leveraged for the Optiflux Enexa F500 dialyzer to demonstrate its safe and effective use in accordance with FDA guidance Applying Human Factors and Usability Engineering to Medical Devices (03 February 2016).
Electrical Safety and Electromagnetic Compatibility (EMC) 5.8.3.
Not applicable. The Optiflux Enexa F500 dialyzer is not an electrical mechanical device.
5.8.4. Software Verification and Validation Testing
Not applicable. The Optiflux Enexa F500 dialyzer does not contain software.
5.8.5. Animal Studies
No animal studies were performed.
5.8.6. Clinical Studies
Eighteen (18) hemodialysis (HD) subjects with chronic renal failure were administered 664 HD treatments with the Optiflux® Enexa™ F500 in a prospective, multi-center, open-label clinical study. Mean treatment duration was 207 ± 20 min, blood flow rate 447.7 ± 37.7 mL/min. and dialysate flow rate 698 ± 62.8 mL/min. Mean Kuf was 16.36 ± 9.92 mL/hr/mmHg, and spKt/V 2.06 ± 0.42. Mean urea and ß2-microglobulin removal rates were 81.49 ± 5.95% and 63.04 ± 16.86%. respectively. Mean pre-HD serum albumin levels remained unchanged; an increase from 3.94 ± 0.21 g/dL to 4.23 ± 0.41 g/dL was observed from pre-HD to post-HD. There was no evidence of overt complement activation as C5a and C3a levels remained largely unchanged from pre-HD levels. A decrease in mean C3a levels from 1318.8 ± 886.7 ng/mL to 1301.2 ± 335.7 ng/mL and in mean C5a levels from 8.8 ± 6.1
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ng/mL to 7.62 ± 4.7 ng/mL was observed pre-HD and 30 mins post-HD. A slight increase in mean sC5b- 9 level from 224.3 ± 51.3 ng/mL to 304.22 ± 71.6 ng/mL was observed at 30 min post-HD. No clinically meaningful changes were observed in hematologic parameters and mean platelet counts. Adverse events that occurred during the study were not related to the device. Eleven (11) out of the 18 subjects (61.1%, 32 AEs) reported at least 1 AE during the study. No deaths or AEs leading to discontinuation were reported during the study. Three (3) serious adverse events were reported but none were related to the device. The mean thrombus score (1-4, clear to fully clotted) was 1.29 ± 0.52. None of the treatments with the Optiflux® Enexa™ F500 showed a Grade 4 Thrombus.
5.9. Conclusion
The intended use, principle of operation, design characteristics, and patient fluid-contacting materials of the Optiflux Enexa F500 dialyzer are substantially equivalent to that of the predicate device. FMCRTG concludes that within the meaning of the Medical Device Amendments Act of 1976, the Optiflux Enexa F500 device is safe and effective for its intended use.