This device is intended for the treatment of chronic and acute renal failure by hemodialysis.
The intended population of this device is identical to those of the Polyflux HD-C4 (BIG), cleared for marketing in the United States under 510(k) notification K060195 and Polyflux HD-C4 (Small), cleared for marketing in the United States under 510(k) notification K072232.
The membrane used in this device is a blend of polyarylethersulfone (PAES) and polyvinylpyrrolidone (PVP), which is equivalent to the membrane utilized in the Gambro Polyflux HD-C4 (BIG) and Polyflux HD-C4 (Small) single use hemodialyzers cleared for marketing in the United States under 510(k) Notifications (K060195 and K072232).
Blood enters a blood inlet port where it is distributed to the hollow fibers. The patient's blood traverses the inside of the hollow fibers and exits the device via a blood exit port. By means of a hydrostatic pressure or transmembrane pressure which is created by a combination of positive and negative pressures across the membrane, plasma water along with certain lower and middle molecular weight solutes pass through the membrane and into the dialysate or filtrate compartment of the device. Uremic toxins and waste products are removed from the patient's blood in this device by means of both diffusion and convection through the membrane and into the countercurrent flowing dialysis solution during hemodialysis. The dialysate exits the devices via a dialysate outlet port.

AI/ML Overview

Here's an analysis of the acceptance criteria and study detailed in the provided K130039 document for the Gambro Revaclear™ 300 and 400 Dialyzer:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state numerical "acceptance criteria" against which a single "reported device performance" is measured in a clear, tabular format. Instead, it states that performance was determined according to ISO 8637 and compared to predicate devices, and that the device did not induce any adverse biological effects.

However, based on the information provided, we can infer the acceptance criteria and summarize the reported findings for comparability.

Inferred Acceptance Criteria and Reported Device Performance for Gambro Revaclear™ 300 and 400 Dialyzer

Feature/Test	Acceptance Criteria (Inferred from Predicate Equivalence)	Reported Device Performance	Notes
In Vitro Performance (ISO 8637 Compliance)	Performance characteristics must meet the requirements of ISO 8637 for hemodialyzers. Performance should be comparable to predicate devices (Polyflux HD-C4 BIG and Small).	Performance characteristics (Clearances, Flow Resistance, Ultrafiltration coefficient) were "determined according to requirements of ISO 8637" and detailed results are provided in Section 17. The overall conclusion is that they "perform as well as the predicate devices."	Specific numerical values for the criteria are not provided in this summary.
- Clearances (Urea, Creatinine, Vitamin B12)	Comparable clearances to predicate devices, meeting ISO 8637 standards.	Determined and comparable to predicate devices.
- Flow resistance (blood & dialysate compartments)	Comparable flow resistance to predicate devices, meeting ISO 8637 standards.	Determined and comparable to predicate devices.
- Ultrafiltration coefficient	Comparable ultrafiltration coefficient to predicate devices, meeting ISO 8637 standards.	Determined and comparable to predicate devices.
Biocompatibility (ISO 10993-1, G-95-1)	No adverse biological effects (cytotoxicity, sensitization/ intracutaneous reactivity, acute systemic toxicity, subacute systemic toxicity, genotoxicity, hemocompatibility, leachables). Must meet requirements for external communicating devices with circulating blood, prolonged contact.	"did not induce any adverse biological effects." "Available data covers the requirements according to ISO 10993 and FDA Memorandum G-95-1." "approved for its intended use in haemodialysis for chronic and acute treatment of renal disease."	Revaclear 400 (largest product) was chosen as the master product for testing.
Mechanical Hemolysis	No systemic increase in free hemoglobin for Revaclear 300 compared to the predicate device. Indication that filters are comparable regarding hemolysis.	"no systemic increase in free hemoglobin as marker for hemolysis could be detected for the Revaclear 300 filters compared to the predicate device." "These results indicate that the filters are comparable regarding hemolysis."	Three experiments, three filters per experiment (Revaclear 300 vs. predicate).

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

In Vitro Performance Testing:
- Sample Size: Not explicitly stated in the summary, but it notes that "Detailed measurement results are provided in Section 17."
- Data Provenance: Not specified, but generally, in vitro testing is conducted in a laboratory setting, not usually tied to a specific country of origin in the same way clinical data is. It's prospective in nature for device evaluation.
Biocompatibility Evaluation:
- Sample Size: Revaclear 400 was chosen as a "master product" for testing, implying it represents the product family. The specific number of samples tested is not provided in this summary.
- Data Provenance: Not specified, but similar to in vitro testing, it's typically prospective lab testing.
Mechanical Hemolysis:
- Sample Size: "three experiments. In each experiment three filters were tested in parallel" (i.e., at least 9 filters tested in total for Revaclear 300 and predicate devices).
- Data Provenance: Not specified, likely prospective lab testing.

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 section is Not Applicable (N/A).
The studies described are non-clinical (in vitro, biocompatibility, mechanical hemolysis) and do not involve human subject data requiring expert interpretation or ground truth establishment in the way clinical diagnostic studies do. The "ground truth" for these tests is the objective measurement against established standards (ISO 8637, ISO 10993) and comparison to predicate device performance.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This section is Not Applicable (N/A).
Adjudication methods like 2+1 or 3+1 are used in clinical studies, particularly in image interpretation, to resolve discrepancies between readers. The studies described are non-clinical performance and safety tests, not clinical evaluations involving human readers.

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

This section is Not Applicable (N/A).
No MRMC study was conducted. The device is a physical medical device (dialyzer), not an AI-powered diagnostic tool. The document explicitly states "Summary of Clinical Tests: N/A".

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done

This section is Not Applicable (N/A).
The device is a physical medical device, not an algorithm.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

As described in point 3, the concept of "ground truth" as it applies to clinical diagnostic studies is not directly relevant here. However, the closest equivalent is:

In Vitro Performance: Compliance with ISO 8637 physical and chemical specifications and performance metrics (clearances, flow resistance, ultrafiltration coefficient) of the legally marketed predicate devices.
Biocompatibility: Adherence to ISO 10993-1 and FDA Memorandum G-95-1 standards for biological endpoints (cytotoxicity, sensitization, systemic toxicity, genotoxicity, hemocompatibility) and characterization of materials and leachables based on chemical analysis.
Mechanical Hemolysis: Measurement of free hemoglobin levels against established scientific principles indicating hemolysis, and comparison to the predicate device's performance.

8. The sample size for the training set

This section is Not Applicable (N/A).
There is no "training set" in the context of this device's evaluation. Training sets are relevant for AI/machine learning models where data is used to teach the algorithm. This document describes the testing of a physical medical device.

9. How the ground truth for the training set was established

This section is Not Applicable (N/A).
As there is no training set, there is no ground truth for a training set.

Summary

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K130039 page 1 of 3

GAMBRO.Renal Products

5.0 510(k) SUMMARY

MAY 0 2 2013

510(k) Summary

Submitter:	Gambro Renal Products, Inc.14143 Denver West Parkway, Suite 400.Lakewood, Colorado 80401
Contact:	Kae Miller, Regulatory Affairs, AmericasPhone: 303.222.6724Fax: 303.222.6916
Date Prepared:	February 4, 2013
Device Name:	Gambro Revaclear™ 300 and 400 Dialyzer
Common/ClassificationName:	Dialyzer, high permeability with or without sealed dialysatesystem
Regulation Number:	21 CFR 876.5860
Product Code:	KDI
Review Panel:	Gastroenterology / Urology

Predicate Devices:

Polyflux HD-C4 (BIG) (Revaclear Max)	Cleared - April 24, 2006	K060195
Polyflux HD-C4 (Small) (Revaclear)	Cleared - September 7, 2007	K072232

Device Description:

This device is intended for the treatment of chronic and acute renal failure by hemodialysis.

The intended population of this device is identical to those of the Polyflux HD-C4 (BIG), cleared for marketing in the United States under 510(k) notification K060195 and Polyflux HD-C4 (Small), cleared for marketing in the United States under 510(k) notification K072232.

The membrane used in this device is a blend of polyarylethersulfone (PAES) and polyvinylpyrrolidone (PVP), which is equivalent to the membrane utilized in the Gambro Polyflux HD-C4 (BIG) and Polyflux HD-C4 (Small) single use hemodialyzers cleared for marketing in the United States under 510(k) Notifications (K060195 and K072232).

Blood enters a blood inlet port where it is distributed to the hollow fibers. The patient's blood traverses the inside of the hollow fibers and exits the device via a blood exit port. By means of a hydrostatic pressure or transmembrane pressure which is created by a combination of positive and negative pressures across the membrane, plasma water along

Page 16 of 53

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GAMBRO.Renal Products

with certain lower and middle molecular weight solutes pass through the membrane and into the dialysate or filtrate compartment of the device. Uremic toxins and waste products are removed from the patient's blood in this device by means of both diffusion and convection through the membrane and into the countercurrent flowing dialysis solution during hemodialysis. The dialysate exits the devices via a dialysate outlet port.

Indications for Use:

The dialyzer is intended for the treatment of chronic and acute renal failure by hemodialysis.

Technological Characteristics:

The proposed device configurations have the same technological characteristics and are similar in design, function, composition, and operation, to the currently marketed configurations.

Summary of Non-Clinical Tests:

In vitro testing was conducted to compare the performance of the proposed device configurations to the predicate configurations.

In Vitro Performance Testing:

The performance characteristics of the submitted Revaclear 300 and 400 were determined according to requirements of ISO 8637" Cardiovascular implants and extracorporeal systems - Haemodialysers, haemodiafilters, haemofilters and haemoconcentrators".

The following characteristics were determined:

. Clearances of urea, creatinine and vitamin B12
Flow resistance of blood and dialysate compartments .
. Ultrafiltration coefficient

Detailed measurement results are provided in Section 17 of this submission.

Biocompatibility Evaluation:

Biocompatibility of the submitted devices Revaclear 300 and 400 was evaluated according to current ISO 10993-1 and FDA Memorandum G-95-1 the device is classified as external communicating device, body contact with circulating blood and prolonged (>24h to ≤ 30 days) contact duration.

Revaclear 400 was chosen as a master product for testing as it is the biggest product in the product family.

The biological end-points studied for the device were cytotoxicity, sensitization/ intracutaneous reactivity, systemic toxicity (acute), systemic toxicity (subacute), genotoxicity and hemocompatibility. These endpoints are recommended to be evaluated by the ISO 10993-1 and FDA Memorandum G-95-1.

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GAMBRO.Renal Products

In addition, chemical analyses were performed to characterize the materials and to identify and quantify potential leachables as recommended by ISO 10993-1 and ISO 10993-18. According to the results of the biological in vivo testing and of the chemical analyses performed in these studies, Revaclear 300 and 400 dialyzers did not induce any adverse biological effects.

A vailable data covers the requirements according to ISO 10993 and FDA Memorandum G-95-1. Based on chemical and biological test results, Revaclear 300 and 400 is approved for its intended use in haemodialysis for chronic and acute treatment of renal disease.

The complete biological and chemical report is provided in Attachment 4 of the submission.

Mechanical Hemolysis:

Mechanically induced hemolysis was tested in three experiments. In each experiment three filters were tested in parallel, whereas Revaclear 300 and Revaclear 300 filters with alternative materials were compared to Revaclear predicate devices.

Samples were taken every 15 minutes starting at the beginning of recirculation and free hemoglobin (fHb) levels were detected in duplicate according to 405 nm method.

Using the above described conditions for the test set-up no systemic increase in free hemoglobin as marker for hemolysis could be detected for the Revaclear 300 filters compared to the predicate device. These results indicate that the filters are comparable regarding hemolysis.

The complete report is enclosed in Attachment 5 of the submission.

Summary of Clinical Tests: N/A

Conclusion:

Testing performed on the Gambro Revaclear Dialyzers indicates that they are safe, effective and perform as well as the predicate devices, when used in accordance with the instructions for use.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized graphic of an eagle or bird-like figure with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the graphic.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

May 2, 2013

Gambro Renal Products, Inc. % Ms. Kae Miller Regulatory Affairs Manager, Americas 14143 Denver West Parkway, Suite 400 LAKEWOOD CO 80401

Re: K130039

Trade/Device Name: Revaclear™ 300 and 400 Dialyzer Regulation Number: 21 CFR§ 876.5860 Regulation Name: High permeability hemodialysis system Regulatory Class: II Product Code: KDI Dated: February 4, 2013 Received: February 5, 2013

Dear Ms. Miller:

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. 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 statutes and regulations administered by other Federal agencies.

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Page 2 – Ms. Kae Miller

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 (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Herbert P. Lerner -S

for

Benjamin R. Fisher, Ph.D. Director Division of Reproductive, Gastro-Renal, and Urological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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GAMBRO.Renal Products

Indications for Use

510(k) Number (if known): ___K130039

Device Name: Revaclear™ 300 and 400 Dialyzer

Indications for Use:

Revaclear™ 300 and 400 dialyzers are indicated for treatment of chronic and acute renal failure by hemodialysis.

Prescription Use _ Over-The-Counter Use X AND/OR (Part 21 CFR 801 Subpart D) (21 CFR 801 Subpart C) (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Herbert - Berner - S

RA 12-035 Revised 02/04/13

(Division Sign-Off) Division of Reproductive, Gastro-Renal, and Urological Devices K130039 510(k) Number

Page 15 of 53

Regulation Number and Section

§ 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.”