(266 days)
Optiflux® Enexa™ dialyzers are intended for patients with acute kidney injury or chronic kidney disease when conservative therapy is judged to be inadequate.
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.
The provided document is for a medical device called the "Optiflux Enexa F500 Dialyzer," which is a high-permeability hemodialysis system. The document outlines the device's characteristics, intended use, and performance data from various tests, including a clinical study, to demonstrate its substantial equivalence to a predicate device.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and the Reported Device Performance:
The document doesn't explicitly list specific quantitative acceptance criteria in a table format for all tests. However, it states that "All testing met predetermined acceptance criteria" and "Results of the proposed device design verification tests met the requirements and demonstrated that... the Optiflux Enexa F500 dialyzer is safe and effective for its intended use."
Here's a table combining the key performance characteristics mentioned, with the understanding that "acceptable" means meeting the undefined predetermined acceptance criteria. The In vitro Urea Clearance is the only performance number explicitly given with a standard testing configuration.
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance (as presented) |
|---|---|---|
| In vitro Urea Clearance (Sodium as marker) | Not explicitly stated, but implies equivalence to predicate/standards | 271 (at Qb = 300 mL/min, Qd = 500 mL/min, Quf = 0 mL/min) |
| Blood Compartment Volume | Met predetermined acceptance criteria | Calculated as meeting requirements |
| Clearance (Urea, Creatinine, Phosphate, Vitamin B12, Lysozyme) | Met predetermined acceptance criteria | Calculated by analyzing test samples over specified ranges |
| Protein Sieving Coefficient | Met predetermined acceptance criteria | Calculated per ISO 8637-1:2017 Section 5.6.2.4 |
| Ultrafiltration | Met predetermined acceptance criteria | Calculated as the slope from a plot of transmembrane pressure vs. ultrafiltration rate |
| Pressure Drop | Met predetermined acceptance criteria | Measured across range of flow rates |
| Structural Integrity (Positive & Negative Pressure Decay) | Met predetermined acceptance criteria | Measured with 900 mmHg and -700 mmHg applied |
| Blood Compartment Integrity | Met predetermined acceptance criteria | Pressure differential applied, no specific values given |
| Simulated Shipping and Distribution | Met predetermined acceptance criteria | Testing per ASTM D4169-16, demonstrated maintenance of integrity and sterility |
| Biocompatibility (Chemical Analysis, Cytotoxicity, Sensitization, Intracutaneous Irritation, Acute Systemic Toxicity, Subchronic Toxicity, Material-Mediated Pyrogenicity, Genotoxicity, Hemocompatibility, PVP/SMM1 Assay) | Met predetermined acceptance criteria | All testing performed and results met or exceeded requirements. Toxicological risk assessment also performed. |
| Human Factors Validation | Demonstrated safe and effective use | Leveraged for the device, in accordance with FDA guidance |
| Clinical Safety & Performance (Acute Kidney Injury/Chronic Kidney Disease patients) | Demonstrated safety and effectiveness; no device-related adverse events, clinically meaningful changes, or Grade 4 Thrombus | Mean spKt/V 2.06 ± 0.42. Mean urea removal 81.49 ± 5.95%. Mean ß2-microglobulin removal 63.04 ± 16.86%. Serum albumin unchanged pre/post-HD. No overt complement activation. No clinically meaningful changes in hematologic parameters/platelet counts. No device-related AEs. Mean thrombus score 1.29 ± 0.52 (no Grade 4). |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
-
Clinical Study (as a test set for human subjects):
- Sample Size: Eighteen (18) hemodialysis (HD) subjects with chronic renal failure. They received 664 HD treatments.
- Data Provenance: The document does not explicitly state the country of origin. It indicates it was a "prospective, multi-center, open-label clinical study."
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In Vitro Performance Tests: The sample size for in vitro tests (clearance, ultrafiltration, structural integrity, etc.) is not specified in the summary, but it states "All testing met predetermined acceptance criteria." The tests were conducted according to ISO 8637-1:2017 and FDA Guidance.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This question is not directly applicable to a medical device like a hemodialyzer in the way it would be for an AI diagnostic algorithm. Ground truth for a hemodialyzer's performance is typically established through:
- In vitro measurements: Using standardized laboratory methods for analyzing fluid samples and physical properties. This doesn't involve "experts" establishing ground truth in the sense of image interpretation.
- Clinical outcomes/physiological measurements: In the clinical study, ground truth for patient health and device performance (e.g., urea removal, complement activation, adverse events) is established by direct measurement of patient parameters and clinical observation by medical staff (physicians, nurses). The document does not specify the number or qualifications of these clinical experts, but it is implied they are qualified medical professionals responsible for patient care and data collection in a clinical trial setting.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
The concept of an adjudication method (like 2+1, 3+1 for consensus in image interpretation) is not applicable to this type of device and study. The "ground truth" or performance assessment is based on direct measurements and clinical observation in the clinical study, not on expert consensus reading of independent data.
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 a medical device (hemodialyzer), not an AI diagnostic algorithm or imaging device requiring human reader interpretation. No MRMC study was conducted or is relevant to this device.
6. If a standalone (i.e. algorithm only, without human-in-the-loop performance) was done
Not Applicable. This is a medical device, not an algorithm. Therefore, "standalone performance" in the context of an algorithm is not relevant.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
For the Optiflux Enexa F500 Dialyzer, the "ground truth" for its performance and safety validation was established through:
- In vitro quantitative measurements: For characteristics like urea clearance, ultrafiltration, pressure drop, structural integrity, and various other physical and chemical properties.
- Biocompatibility testing: Standardized in vitro and in vivo (e.g., guinea pig, mouse lymphoma) biological tests for material safety, often following ISO 10993.
- Clinical Outcomes Data: For the clinical study, the ground truth was derived from direct physiological measurements (e.g., spKt/V, urea removal rates, ß2-microglobulin removal rates, serum albumin, C5a, C3a, sC5b-9, hematologic parameters, platelet counts) and observed adverse events, including thrombus scores. These are objective measures collected during clinical practice.
8. The sample size for the training set
Not Applicable. This device is a hemodialyzer, not an AI algorithm that requires a "training set."
9. How the ground truth for the training set was established
Not Applicable. As no AI algorithm is involved, there is no "training set" or "ground truth for the training set" in the context of this device.
§ 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.”