The Hemoflow F3 and F4 dialyzers are intended for hemodialysis of patients, including pediatric patients, with acute or chronic renal failure when conservative therapy is judged to be inadequate. Consider body and dialyzer surface area, blood flow, body weight, and extracorporeal blood volume when selecting dialyzers for use with pediatric patients.

Device Description

The Hemoflow F3 and F4 dialyzers are low-flux, single-use, ethylene oxide (EO) sterilized hemodialyzers. The dialyzers are provided blood pathway sterile and non-pyrogenic. The membrane surface areas of the F3 and the F4 dialyzers are 0.3 m2 and 0.7 m2, respectively.

The Hemoflow F3 and F4 dialyzers are low-flux, sterile devices designed for single-use acute and chronic hemodialysis. The dialyzers are 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 dialyzers contain 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.

AI/ML Overview

The provided text is related to a 510(k) premarket notification for Hemoflow F3 and F4 Dialyzers, not a study describing acceptance criteria and device performance in the context of AI or software. Therefore, much of the requested information (like sample size for test/training sets, data provenance, number/qualifications of experts, adjudication methods, MRMC studies, standalone performance, and ground truth types) is not applicable or present in this document.

However, I can extract the relevant performance data and highlight the acceptance criteria as stated for the dialyzers themselves and the summary of compliance.

Here's an attempt to structure the available information, noting where information is not present as per your request related to an "AI device":

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

For medical devices like dialyzers, performance is typically demonstrated through various tests meeting established standards. While specific numerical acceptance criteria (e.e.g. "urea clearance must be >X") are not explicitly listed in easily interpretable tables for each test, the text states the ultimate acceptance: "All testing met predetermined acceptance criteria." and "Results of the proposed devices' design verification tests met the requirements and demonstrated that, like the predicate device, the Hemoflow F3 and F4 dialyzers are safe and effective for their intended use."

The key performance characteristic highlighted and its reported value are:

Test Conducted	Acceptance Criteria (Implied)	Reported Device Performance
Urea Clearance (Sodium as Marker)	Adequate clearance for hemodialysis of renal failure patients.	Hemoflow F3 Dialyzer: 117 (Typical Urea Clearance)
		Hemoflow F4 Dialyzer: 155 (Typical Urea Clearance)
Blood Compartment Volume	Met predetermined acceptance criteria.	Calculated values based on design parameters.
Clearance (Creatinine, Phosphate, B12)	Met predetermined acceptance criteria.	Calculated by analyzing test samples.
Ultrafiltration	Met predetermined acceptance criteria.	Calculated as slope from UFR vs. TMP plot.
Pressure Drop	Met predetermined acceptance criteria.	Measured inlet/outlet pressures across flow rates.
Structural Integrity	Met predetermined acceptance criteria.	Measured positive and negative pressure decay.
Blood Compartment Integrity	Met predetermined acceptance criteria.	Applied pressure differential.
Simulated Shipping & Distribution	Product and package integrity/sterility maintained.	Testing per ASTM D4169-16, performance met criteria.
Biocompatibility Testing	Met predetermined acceptance criteria (biological safety).	Multiple tests (e.g., cytotoxicity, sensitization, genotoxicity, hemocompatibility).
Human Factors Validation Testing	Safe and effective use validated per FDA guidance.	Validation testing performed.

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

The document mentions "A retrospective data analysis performed on the Hemoflow F3 and F4 dialyzers included 10 pediatric ESRD patients on HD treated for 12 consecutive weeks." This appears to be a clinical "test set" for the clinical effectiveness aspect (adequate clearance), not for the engineering performance tests.

Sample Size (Clinical): 10 pediatric ESRD patients
Data Provenance (Clinical): Retrospective. Country of origin not specified.

For the engineering performance tests listed in Table 2, the sample size of dialyzers tested is not explicitly stated.

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)

Not applicable. This document describes a medical device (dialyzers), not an AI device that relies on expert human interpretation for ground truth.

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

Not applicable. This document describes a medical device, not a diagnostic or AI system requiring adjudication of expert interpretations.

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 document is for a medical device (dialyzers), not an AI-assisted diagnostic tool.

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

Not applicable. This document is for a medical device (dialyzers), not an AI algorithm.

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

For the clinical study mentioned: "adequate clearance" with a mean spKt/V of 1.78 (F3) and 2.18 (F4) served as the "ground truth" or outcome measure for the clinical effectiveness aspect. This is outcomes data (clinical efficacy in terms of clearance).
For the engineering performance tests, the "ground truth" is typically established by physical measurements and adherence to established engineering standards (e.g., ISO 8637:2010) and regulatory guidance.

8. The sample size for the training set

Not applicable. There is no mention of a training set as this is not an AI device.

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

Not applicable. There is no mention of a training set as this is not an AI device.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

August 23, 2019

Fresenius Medical Care Renal Therapies Group, LLC Denise Oppermann Senior Director, Regulatory Affairs 920 Winter Street Waltham, MA 02451

Re: K190459

Trade/Device Name: Hemoflow™ F3 and F4 Dialyzers Regulation Number: 21 CFR 876.5820 Regulation Name: Hemodialysis system and accessories Regulatory Class: Class II Product Code: FJI Dated: July 25, 2019 Received: July 26, 2019

Dear Denise 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 statutes and regulations administered by other Federal agencies. You must comply with all the Act's

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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 (OS) 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 mediation-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,

Carolyn Y. Neuland, Ph.D. Assistant Division Director DHT3A: Division of Renal, Gastrointestinal, Obesity and Transplant Devices OHT3: Office of Gastro-Renal, ObGyn, General Hospital and Urology Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

K190459

Device Name Hemoflow™ F3 and F4 Dialyzers

Indications for Use (Describe)

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/1 description: The image shows the Fresenius Medical Care logo. On the left side of the logo, there are three blue downward-pointing arrows stacked on top of each other. To the right of the arrows, the words "FRESENIUS MEDICAL CARE" are written in blue, with "FRESENIUS" on the top line and "MEDICAL CARE" on the bottom line.

5. 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 StreetWaltham, MA02451-1457
Phone:	(781) 699-4479
Fax:	(781) 699-9635
Contact Person:	Denise Oppermann, Senior DirectorRegulatory Affairs – Devices
Preparation Date:	22 February 2019

5.2. Device Name

Trade Name:	Hemoflow F3 and F4 Dialyzers
Common Name:	Dialyzer
Regulation Name:	Hemodialysis system and accessories
Regulatory Class:	Class II per 21 CFR § 876.5820
Product Code:	FJI
Product Code Name:	Dialyzer, Capillary, Hollow Fiber
Classification Panel:	Gastroenterology/Urology

5.3. Legally Marketed Predicate Device

The legally marketed predicate devices are the Fresenius Hemoflow F3, F4 dialyzers cleared under K874872. These devices have not been subject to a design-related recall.

The Gambro Polyflux 6H Hemodialyzer (K051520) and Fresenius Optiflux Dialyzers (K152367 and K162488) are used as reference devices.

5.4. Device Description

Device Identification 5.4.1.

The Hemoflow F3 and F4 dialyzers are the subject of this 510(k).

5.4.2. Device Characteristics

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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.

5.4.2.1. Environment of Use

The Hemoflow F3 and F4 dialyzers are used in environments where acute and chronic hemodialysis are performed.

5.4.2.2. Brief Written Description of the Device

5.4.2.3. Materials of Use

The Hemoflow F3 and F4 dialyzers are classified as externally communicating, circulating blood, prolonged contact (> 24 hours to 30 days) duration, Class II (Category B) devices 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).

Component	Material
Housing	Polycarbonate
Potting Resin	Polyurethane
Fiber Bundle	Polysulfone
Screw Flange	Polycarbonate
O-Ring	Silicone
Blood Port Cap(s)	High Density Polyethylene

The Hemoflow F3 and F4 dialyzers' components are composed of the following materials:

Key Performance Characteristics 5.4.2.4.

Urea clearance is a key performance specification of the Hemoflow F3 and F4 dialyzers. 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 Hemflow F3 and F4 dialyzers are provided in Table 1.

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Image /page/5/Picture/0 description: The image contains the logo for Fresenius Medical Care. The logo consists of a blue emblem on the left and the company name on the right. The emblem is made up of three downward-pointing chevron shapes stacked on top of each other. The text "FRESENIUS MEDICAL CARE" is in a bold, sans-serif font, with "FRESENIUS" on the top line and "MEDICAL CARE" on the bottom line.

In vitro Urea Clearance for the F3 and F4 Dialyzer Models* Table 1:

Trade Name	Typical Urea Clearance(Sodium Used as Marker)
Hemoflow F3 Dialyzer	117
Hemoflow F4 Dialyzer	155

*Qb = 200 mL/min, Qd = 500 mL/min, Quf = 0 mL/min

5.5. Intended Use

Hemoflow F3 and F4 dialyzers are designed for single use acute and chronic hemodialysis.

5.6. Indications for Use

5.7. Comparison of Technological Characteristics with the Predicate Device

The following technological characteristics of the Hemoflow F3 and F4 dialyzers are equivalent to those of the predicate Fresenius Hemoflow F3 and F4 dialyzers (K874872).

Intended use ●
Principle of operation
Design characteristics ●
Sterilization method
o Patient fluid-contacting materials: polysulfone, polycarbonate, polyurethane, and silicone

5.8. Performance Data

Performance testing was conducted in accordance with ISO 8637:2010 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-ringcompression volume, dialyzer housing length, andpolyurethane height.

Table 2: Performance Testing Summary
--------------------------------------	--

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Image /page/6/Picture/1 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.

Test Conducted	Test Method Description
Clearance – Sodium (marker forurea), Creatinine, Phosphate, andVitamin B12	Calculated by analyzing the test samples over the specifiedrange of blood and dialysate flow rates.
Ultrafiltration	Calculated as the slope from a plot of the measuredultrafiltration rate UFR (over the applied transmembranepressure (TMP) range) versus the applied TMP.
Pressure Drop	The dialysate and blood compartments were filled withdialysate and bovine blood, respectively. Inlet and outletpressures of the blood and dialysate compartments weremeasured across the range of flow rates with the dialyzers in ahorizontal configuration.
Structural Integrity	The positive and negative pressure decay was measured by apressure monitor connected at one end of the dialyzer whileapplying 900 mmHg and -700 mmHg from opposite ends.
Blood Compartment Integrity	Air and water were added to the top blood port and thedialysate side, respectively. A pressure differential wasapplied across the dialyzer membrane.
Simulated Shipping andDistribution	Testing was conducted per ASTM D4169-16. Performancetesting was conducted before and after simulated shipping todemonstrate that the product and package integrity andsterility are maintained throughout the intended product shelflife.

Performance Testing Summary Table 2:

All testing met predetermined acceptance criteria. Results of the proposed devices' design verification tests met the requirements and demonstrated that, like the predicate device, the Hemoflow F3 and F4 dialyzers are safe and effective for their intended use.

5.8.1. Biocompatibility Testing

Testing was performed to support the biological safety of the Hemoflow F3 and F4 dialyzers.

Chemical analysis extractables and leachables ●
Cytotoxicity, ISO Elution Method with MEM
Sensitization, Guinea Pig Maximization ●
Intracutaneous Irritation ●
Acute Systemic Toxicity ●
Systemic Toxicity, Short-Term Repeated Exposure ●
Material-Mediated Pyrogenicity ●

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Image /page/7/Picture/1 description: The image shows the logo for Fresenius Medical Care. On the left is a blue symbol that looks like three chevrons stacked on top of each other. To the right of the symbol is the text "FRESENIUS MEDICAL CARE" in blue, with "FRESENIUS" on top and "MEDICAL CARE" on the bottom.

Genotoxicity, Bacterial Reverse Mutation Assay ●
Genotoxicity, in vitro Mouse Lymphoma Gene Mutation Assay o
Genotoxicity, Mouse Micronucleus in vivo Assay
Hemocompatibility, ASTM Hemolysis (Direct and Indirect Extract) ●
Hemocompatibility, Complement Activation - SC5b-9 fragment
Hemocompatibility, ASTM Partial Thromboplastin Time ●
Hemocompatibility, Mechanical Hemolysis
Hemocompatibility, in vitro Thrombogenicity Assay ●
0 PVP Testing

A toxicological risk assessment was also performed.

Human Factors Validation Testing 5.8.2.

The Hemoflow F3 and F4 dialyzers were validated for safe and effective use in accordance with FDA guidance Applying Human Factors and Usability Engineering to Medical Devices (03 February 2016).

5.8.3. Electrical Safety and Electromagnetic Compatibility (EMC)

Not applicable. The Hemoflow F3 and F4 dialyzers are not electrical mechanical devices.

Software Verification and Validation Testing 5.8.4.

Not applicable. The Hemoflow F3 and F4 dialyzers do not contain software.

5.8.5. Mechanical and Acoustic Testing

No mechanical or acoustic tests were performed.

5.8.6. Animal Studies

No animal studies were performed.

5.8.7. Clinical Studies

A retrospective data analysis performed on the Hemoflow F3 and F4 dialyzers included 10 pediatric ESRD patients on HD treated for 12 consecutive weeks. Hemoflow F3 and F4 dialyzers provided adequate clearance with a mean spKt/V of 1.78 and 2.18, respectively, and were well tolerated.

5.9. Conclusion

The intended use, principle of operation, design characteristics, sterilization method and patient fluidcontacting materials of the Hemoflow F3 and F4 dialyzers are substantially equivalent to that of the predicate devices. FMCRTG concludes that within the meaning of the Medical Device Amendments Act of 1976, the Hemoflow F3 and F4 devices are safe and effective for their intended use.

Regulation Number and Section

§ 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.