(302 days)
Hemoflow dialyzers are designed for acute and chronic hemodialysis. Hemoflow dialyzers are also appropriate for single or multiple use when reprocessed with 1.5% Citric Acid/95℃.
The submission describes a procedure and components used in the reprocessing of Fresenius polysulfone hemodialyzers with 95°C/1.5% citric acid. This involves using radiant heat (moist or dry) at 95°C for 24 hours with the addition of 1.5% citric acid solution.
The provided text is related to a 510(k) submission for a hemodialyzer reprocessing procedure using 95°C/1.5% citric acid. It focuses on demonstrating the substantial equivalence of this new reprocessing method to existing ones. The information required for acceptance criteria and study details is largely based on sterilization and disinfection effectiveness, as well as material compatibility and performance for the reprocessed dialyzers.
Here's an analysis based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Microbial Reduction (Disinfection/Sterilization) | Minimum 6 log reduction in bacterial concentration (standard accepted sterilization log reduction). | Achieved at least an 18 log reduction in B. stearothermophilus (indicator organism) with 95°C/1.5% citric acid for 24 hours. A single run at 90°C for 24 hours demonstrated at least a 12 log reduction. No growth observed in SCD media after 95°C for 24 hours and a 96-hour set period. |
| Bacteriostatic Effect | Solution should not promote microbial proliferation; ideally, a bacteriostatic effect. | 1.5% citric acid solution did not meet USP antimicrobial effectiveness test for bactericide, but no organisms proliferated in the solution. Demonstrated to be bacteriostatic. |
| Material Compatibility (Heat Exposure) | Polysulfone hemodialyzers should not be adversely affected by the disinfection process; heat-labile components require lower temperatures than 121°C. | Plastic components were found heat-labile at 121°C, justifying the need for 95°C. Studies showed "no difference in heat penetration studies of F60 or F80 dialyzers" and "no 'cold' position within the dialyzer" during the 95°C process. Citric acid had "no chemical effect on components." |
| Toxicity | No evidence of toxicity according to ISO 10993-1 guidelines (with specified exception). | Results indicate no evidence of toxicity based on one of three carcinogenicity tests on dialyzer samples reprocessed ≥15 times. |
| In Vitro Performance (Membrane Function) | No significant difference in membrane performance (flux rates) compared to non-reprocessed or formaldehyde-reprocessed dialyzers. | No difference in membrane performance due to heat reprocessing with 95°C/1.5% citric acid when compared to non-reprocessed dialyzers or dialyzers reprocessed with 1.5% HCHO and 40°C. Data for low, mid, and high flux polysulfone dialyzers were provided. |
| In Vivo Product Performance | No significant difference in product performance compared to non-reprocessed or formaldehyde-reprocessed dialyzers. | No difference in product performance due to heat reprocessing with 95°C/1.5% citric acid compared to non-reprocessed hemodialyzers or dialyzers reprocessed with 1.5% HCHO with 40°C incubation. |
| In Vivo Clinical Data (Patient Outcomes) | No significant differences in patient parameters or intradialytic episodes when using dialyzers reprocessed with the new method compared to the predicate method. | No differences were noted between the two reprocessing procedures (1.5% formaldehyde/40°C vs. 95°C/1.5% citric acid) in patient parameters and intradialytic episodes (hypotension, reactions, etc.). |
2. Sample Size Used for the Test Set and Data Provenance
-
Microbial Reduction (Disinfection/Sterilization):
- Test dialyzers were selected after exposure to blood in "at least 10 reprocessing procedures."
- For kill effectiveness, "10X blood contacted reprocessed F80 dialyzers biologically seeded with approximately 1,000,000 B. stearothermophilus spores" were used.
- "Three test runs were conducted."
- A single run was done at 90°C.
- "24 dialyzers were seeded with the test organism B. stearothermophilus" for a subsequent growth observation test.
- Data Provenance: The studies were conducted by Fresenius Medical Care, suggesting internal, prospective experimental data. The country of origin is not explicitly stated but implies US-based submission context.
-
Toxicity Testing:
- "Dialyzer samples that were reprocessed a minimum of 15 times" were used. The exact number of samples is not specified beyond "samples."
- Data Provenance: Internal, prospective experimental data.
-
In Vitro Performance:
- "Each membrane family of Fresenius polysulfone dialyzers; low (F4, F6 and F8), mid (F60M and F80M) and high flux (F60 and F80)" were evaluated. The specific number of dialyzers per family/reprocessing condition is not detailed.
- Data Provenance: Internal, prospective experimental data.
-
In Vivo Product Performance:
- "All Fresenius polysulfone membrane configurations" were compared. The specific number of devices tested is not detailed.
- Data Provenance: Internal, prospective experimental data (possibly animal or human surrogate studies, but the text doesn't specify which, just "in vivo product performance").
-
In Vivo Clinical Data:
- "Patients dialyzed with hemodialyzers reprocessed with 1.5% formaldehyde and 40℃ incubation who were then transferred to dialyzers heat reprocessed with 95°C/1.5% citric acid." The number of patients is not specified.
- Data Provenance: Clinical study data, likely prospective given the "transferred" description and follow-up.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The text does not provide information on the number or qualifications of experts used to establish a "ground truth" in the traditional sense related to a diagnostic or AI device. The ground truth for the device's performance here is based on objective measurements (e.g., microbial counts, temperature, flux rates, toxicity assays, patient monitoring). The regulatory body (FDA) and Fresenius's internal scientists (e.g., Director, Product Development) are involved in reviewing and generating the data, respectively, but not in establishing a subjective "ground truth" through consensus for a test set.
4. Adjudication Method for the Test Set
This concept is not relevant to the type of device and study described. Adjudication methods (like 2+1, 3+1) are typically used for establishing ground truth in diagnostic studies involving human interpretation or subjective assessments. Here, the studies involve objective, measurable outcomes (e.g., sterilization effectiveness, physical performance, toxicity) that don't require such adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size
No, an MRMC comparative effectiveness study was not done. MRMC studies are typically used to assess the performance of diagnostic imaging devices or algorithms where human readers interpret medical images or data, and their performance is compared with and without AI assistance. This submission describes an industrial reprocessing procedure for a medical device (hemodialyzer), not an AI-enabled diagnostic tool.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
This question is not applicable as the device is a reprocessing procedure, not an algorithm or AI system. The "standalone performance" of the reprocessing procedure itself (i.e., its ability to disinfect, maintain performance, and be non-toxic) was demonstrated through the various tests described (microbial reduction, in vitro/in vivo performance, toxicity).
7. The Type of Ground Truth Used
The "ground truth" in this context refers to the verifiable outcomes against which the reprocessing procedure's effectiveness is measured. The types of ground truth used include:
- Microbial Counts: Direct measurement of viable organisms (e.g., B. stearothermophilus) to establish log reduction, indicating disinfection/sterilization.
- Physical/Chemical Measurements: Temperature readings (thermocouples), pH measurements, and quantitative assessment of membrane flux rates.
- Laboratory Assays: USP antimicrobial effectiveness test, ISO 10993-1 guidelines for toxicity, indicating specific biological and chemical properties.
- Clinical Observations/Outcomes Data: Monitoring patient parameters and intradialytic episodes (hypotension, reactions) in clinical use.
8. The Sample Size for the Training Set
This question is not applicable. The context is the validation of a reprocessing procedure for a medical device, not a machine learning algorithm. Therefore, there is no "training set" in the sense of data used to train an AI model. All described studies are essentially "test sets" or validation experiments for the reprocessing method itself.
9. How the Ground Truth for the Training Set Was Established
This question is not applicable as there is no training set for an AI/algorithm in this submission.
§ 876.5820 Hemodialysis system and accessories.
(a)
Identification. A hemodialysis system and accessories is a device that is used as an artificial kidney system for the treatment of patients with renal failure or toxemic conditions and that consists of an extracorporeal blood system, a conventional dialyzer, a dialysate delivery system, and accessories. Blood from a patient flows through the tubing of the extracorporeal blood system and accessories to the blood compartment of the dialyzer, then returns through further tubing of the extracorporeal blood system to the patient. The dialyzer has two compartments that are separated by a semipermeable membrane. While the blood is in the blood compartment, undesirable substances in the blood pass through the semipermeable membrane into the dialysate in the dialysate compartment. The dialysate delivery system controls and monitors the dialysate circulating through the dialysate compartment of the dialyzer.(1) The extracorporeal blood system and accessories consists of tubing, pumps, pressure monitors, air foam or bubble detectors, and alarms to keep blood moving safely from the blood access device and accessories for hemodialysis (§ 876.5540) to the blood compartment of the dialyzer and back to the patient.
(2) The conventional dialyzer allows a transfer of water and solutes between the blood and the dialysate through the semipermeable membrane. The semipermeable membrane of the conventional dialyzer has a sufficiently low permeability to water that an ultrafiltration controller is not required to prevent excessive loss of water from the patient's blood. This conventional dialyzer does not include hemodialyzers with the disposable inserts (Kiil type) (§ 876.5830) or dialyzers of high permeability (§ 876.5860).
(3) The dialysate delivery system consists of mechanisms that monitor and control the temperature, conductivity, flow rate, and pressure of the dialysate and circulates dialysate through the dialysate compartment of the dialyzer. The dialysate delivery system includes the dialysate concentrate for hemodialysis (liquid or powder) and alarms to indicate abnormal dialysate conditions. This dialysate delivery system does not include the sorbent regenerated dialysate delivery system for hemodialysis (§ 876.5600), the dialysate delivery system of the peritoneal dialysis system and accessories (§ 876.5630), or the controlled dialysate delivery system of the high permeability hemodialysis system § 876.5860).
(4) Remote accessories to the hemodialysis system include the unpowered dialysis chair without a scale, the powered dialysis chair without a scale, the dialyzer holder set, dialysis tie gun and ties, and hemodialysis start/stop tray.
(b)
Classification. (1) Class II (performance standards) for hemodialysis systems and all accessories directly associated with the extracorporeal blood system and the dialysate delivery system.(2) Class I for other accessories of the hemodialysis system remote from the extracorporeal blood system and the dialysate delivery system, such as the unpowered dialysis chair, hemodialysis start/stop tray, dialyzer holder set, and dialysis tie gun and ties. The devices subject to this paragraph (b)(2) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 876.9.