The OLPur H2H Hemodiafiltration (HDF) Module is indicated for use, with a UF controlled hemodialysis machine that provides ultrapure dialysate in accordance with current ANSI/AAMI/ISO standards, for treatment of patients with chronic renal failure as prescribed by a physician. The OLPur MD 220 Hemodiafilter is indicated for use for hemodiafiltration of patients with chronic renal failure. The OLPur MD 220 Hemodiafilter is only to be used with the OLpur H2H Hemodiafiltration Module. Selection of patients, as well as treatment operating parameters, are a medical decision and the responsibility of the prescribing physician.

Device Description

The H₂H™ Hemodiafiltration Module is a programmable electro-mechanical medical device designed to work in conjunction with and in close proximity to a hemodialysis machine during patient treatments. Upon installation, the H₂H Module is placed next to the hemodialysis machine (which can be on either side depending upon type and model of the hemodialysis machine) and is connected to the clinic's water supply, drain, and electricity.

The H₂H Hemodiafiltration Module serves two basic functions. The Module's primary function is to generate on-line substitution fluid for hemodiafiltration. The H₂H Module does this by ultrafiltering dialysate, provided by the hemodialysis machine, through a reusable substitution filter. The secondary function of the H₂H Hemodiafiltration Module is to serve as a substitution filter reprocessing machine. These steps are performed when the H₂H Hemodiafiltration Module is not connected to the hemodialysis machine. More detailed descriptions of the device, its accessories and how the system functions can be found in Section 11 (Device Description) of this submission.

AI/ML Overview

The provided text is a 510(k) summary for the Nephros OLpūr® H₂H H₂H Hemodiafiltration (HDF) Module and OLpūr MD 220 Hemodiafilter. It focuses on device description, intended use, and technological characteristics compared to predicate devices for substantial equivalence.

However, this document does not contain explicit acceptance criteria and a study proving the device meets those criteria in the typical format of a clinical trial report or performance study with detailed results against defined benchmarks. Instead, it refers to "Bench Analyses performed on the subject devices" in Section 18 and "clinical data supporting substantial equivalence" in Section 20 of the full application, which are not provided.

Therefore, many of the requested details about acceptance criteria, study design, sample sizes, expert involvement, and ground truth cannot be extracted directly from the given 510(k) summary.

Here's what can be gathered and what is missing based on the provided text:

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

Acceptance Criteria: Not explicitly stated in terms of specific performance metrics with numerical targets within this summary. Substantial equivalence is the overall goal, meaning the device performs as safely and effectively as predicate devices.
Reported Device Performance: The summary states, "The proposed device has the same technological characteristics and is similar in design as compared to the predicate devices and already approved kidney dialysis therapy." This is a general statement of equivalency rather than specific performance numbers against acceptance criteria. The full submission's Section 18 and 20 would contain these details.

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

Sample Size for Test Set: Not specified in this 510(k) summary.
Data Provenance: Not specified in this 510(k) summary.

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 specified in this 510(k) summary.

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

Not specified in this 510(k) summary.

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 device is a medical module and hemodiafilter, not an AI-assisted diagnostic tool. Therefore, an MRMC study related to human readers improving with AI is irrelevant and not mentioned.

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

This device is a physical medical device (hemodiafiltration module and filter), not a software algorithm. Therefore, "standalone algorithm" performance is not applicable in this context. Its performance would be evaluated during its operation in conjunction with a hemodialysis machine.

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

Not specified in this 510(k) summary. Given the nature of the device, ground truth would likely refer to performance metrics like filtration efficiency, ultrafiltration control accuracy, biocompatibility, and microbiological purity, established through bench testing and potentially in vivo studies (though clinical data reference focuses on substantial equivalence).

8. The sample size for the training set

Not applicable/specified. This is a physical medical device, not an AI/machine learning model that typically has a "training set."

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

Not applicable/specified for the same reasons as point 8.

Summary

{0}------------------------------------------------

510(k) Summary: Nephros OLpūr® H₂H H₂H Hemodiafiltration (HDF) Module and OLpūr MD 220 Hemodiafilter

Submitter:	Nephros Inc.41 Grand Ave, Suite 201River Edge, NJ 07661Establishment Registration # 3003337893
Contact Person	Gregory Collins Ph.D., V.P. of R&D41 Grand Ave, Suite 201River Edge, NJ 07661201-343-5202 (p)201-343-5207 (f)collins@nephros.com
Date Prepared	August 10, 2011
Trade Name	Nephros OLpūr H2H Hemodiafiltration (HDF) Module and OLpūrMD 220 Hemodiafilter
Proposed Class	Class II
Classification Nameand Number	21 CFR Part 876.5665 Water Purification System forHemodialysis; 21 CFR Part 876.5860 Dialyzer, HighPermeability With or Without Sealed Dialysate System
Product Code	FIP, KDI
Predicate Devices	➤ Predicate for the Nephros MD 220 Hemodiafilter -Nephros OLpūr HD190 (K050603)➤ Predicate for the H2H Module with qualified UF-Controlled Hemodialysis Machine - Aksys PHD PersonalHemodialysis System (K010131)➤ Predicate for the H2H Module in the stand-aloneconfiguration - Aksys PHD Personal HemodialysisSystem (K010131)➤ Predicates for the H2H Substitution Fluid Filter --Nephros DSU Dual Stage Ultrafilter (K090885), Minntech

Nephros_510k_K112314_RFI Response-2

Page 573 of 579

{1}------------------------------------------------

2/3

Device Description	Renaguard Dialysate Filter (K945136), Gambro DiaclearUltrafilter (K003957), Fresenius Citric Acid DialyzerReprocessing (K974090)➤ Predicates for the H₂H Water Filter - Nephros DSU DualStage Ultrafilter (K090885), Minntech FiberFlo HollowFiber Capsule Water Filter (K983126)➤ Predicates for the Disposable H₂H Infusion Line andBlood Tubing Extension Set - Codan IV AdministrationSets (K033301), Nipro Blood Tubing Set w/TransducerProtector and Priming Set (K072024)
The H₂H™ Hemodiafiltration Module is a programmable electro-mechanical medical device designed to work in conjunction withand in close proximity to a hemodialysis machine during patienttreatments. Upon installation, the H₂H Module is placed next tothe hemodialysis machine (which can be on either sidedepending upon type and model of the hemodialysis machine)and is connected to the clinic's water supply, drain, andelectricity.The H₂H Hemodiafiltration Module serves two basic functions.The Module's primary function is to generate on-line substitutionfluid for hemodiafiltration. The H₂H Module does this byultrafiltering dialysate, provided by the hemodialysis machine,through a reusable substitution filter. The secondary function ofthe H₂H Hemodiafiltration Module is to serve as a substitutionfilter reprocessing machine. These steps are performed whenthe H₂H Hemodiafiltration Module is not connected to thehemodialysis machine. More detailed descriptions of the device,its accessories and how the system functions can be found inSection 11 (Device Description) of this submission.
Intended Use	The OLpür H₂H Hemodiafiltration (HDF) Module is indicated foruse, with a UF controlled hemodialysis machine that providesultrapure dialysate in accordance with current ANSI/AAMI/ISOstandards, for treatment of patients with chronic renal failure asprescribed by a physician. The OLpūr MD 220 Hemodiafilter isindicated for use for hemodiafiltration of patients with chronicrenal failure. The OLPûr MD 220 Hemodiafilter is only to beused with the OLpūr H₂H Hemodiafiltration Module. Selection ofpatients, as well as treatment operating parameters, are amedical decision and the responsibility of the prescribingphysician.The OLpür H₂H Hemodiafiltration (HDF) Module works inconjunction with a qualified host (UF controlled) hemodialysismachine and it's accessories (i.e., bloodlines, dialysate,concentrates, etc.), the H₂H Module accessories (water andsubstitution fluid filters, infusion / rinse line, and optional bloodextension line), appropriately prepared water and ultrapuredialysate for hemodialysis, and a high permeability hemodiafil-(i.e., the OLPūr MD 220 Hemodiafilter).
Summary of theTechnologicalCharacteristics	The proposed device has the same technological characteristicsand is similar in design as compared to the predicate devicesand already approved kidney dialysis therapy.
Assessment of Non-clinical PerformanceData / Substantial	Refer to Section 18 of this application for Bench Analysesperformed on the subject devices. Refer to Section 20 of thisapplication for clinical data supporting substantial equivalence of

ﺮ ﻣ

Nephros_510k_K112314_RFI Response-2

・ :

{2}------------------------------------------------

イ・

・

. ·

{3}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three stripes forming its wing, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular fashion around the eagle. The eagle is facing to the right. The logo is black and white.

Public Health Service

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

APR 27 2012

Greg Collins, Ph.D. V.P. of R&D Nephros, Inc. 41 Grand Ave. RIVER EDGE NJ 07661

. Re: K112314

Trade/Device Name: Nephros OLPur® H2H Hemodiafiltration (HDF) Module and OLPūr MD 220 Hemodiafilter

Regulation Number: 21 CFR& 876.5860

Regulation Name: High permeability hemodialysis system Regulatory Class: II Product Code: KDI Dated: April 26, 2012 Received: April 27, 2012

Dear Dr. Collins:

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 that I Drines intess and regulations administered by other Federal agencies. You must of any I ederal statuated and regurements, including, but not limited to: registration and listing Compry will an the 100 b ag (21 CFR Part 801); medical device reporting (reporting of medical

{4}------------------------------------------------

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,

Benjamin K. Erhke

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

{5}------------------------------------------------

Indications for Use

510(k) Number (if known): K 112314

Device Name: Nephros OLPuro HzH Hemodiafiltration (HDF) Module and OLPūr MD 220 Hemodiafilter

Indications For Use:

The OLPur H2H Hemodiafiltration (HDF) Module works in conjunction with a qualified host (UF controlled) hemodialysis machine and it's accessories (i.e., bloodlines, dialysate, concentrates, etc.), the HzH Module accessories (water and substitution fluid filters, infusion / rinse line, and optional blood extension line), appropriately prepared water and ultrapure dialysate for hemodialysis, and a high permeability hemodialyzer / hemodiafilter (i.e., the OLPur MD 220 Hemodiafilter).

Prescription Use x AND/OR Over-The-Counter Use (Part 21 CFR 801 Subpart D) (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Beijana R. Ruter

for Sign-Off n of Reproductive, Gastro-Renal, and

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.”