The NxStage Water Purification System is a stand-alone water treatment system designed to pretreat and purify water for use in hemodialysis applications. The purified water can be used in preparation of dialysate, equipment rinsing and disinfection, and dialyzer reprocessing. It is intended to be used in a variety of environments, including acute or chronic care facility or home.

Device Description

The NxStage Water Purification System is a stand-alone water System designed to pre-treat and purify water for use with hemodialysis applications. The purified water can be used in preparation of dialysate, equipment rinsing and disinfection, and dialyzer reprocessing. The System is intended to be used in a variety of environments, including an acute or chronic care facility or the home. There are no known contraindications with the use of the NxStage Water Purification System.

The System is single patient use and is comprised of three major components: 1) a pretreatment system which consists of a check valve, sediment filter and air vent to remove trapped air, sediment, and any impurities, 2) a Pump Controller unit which contains the control and safety software that controls the flow rate, monitors pressure, water quality and system operation and 3) a replaceable resin system that removes organic and inorganic chemical contaminants as well as microbiological contaminants such as bacteria and endotoxins. The System flow rate is specified by the end user.

With proper use, the System will produce water that meets or exceeds the requirements of the standard issued by the American National Standard Institute and the Association for the Advancement of Medical Instrumentation: ANSI/AAMI RD62:2001, Water Treatment Equipment for Hemodialysis Applications.

AI/ML Overview

Here's an analysis of the provided text regarding the NxStage Water Purification System, focusing on acceptance criteria and study details.

Important Note: The provided document is a 510(k) Summary of Safety & Effectiveness and an FDA clearance letter. These documents typically summarize testing and do not contain detailed study protocols, raw data, or comprehensive statistical analyses. Therefore, some information, especially regarding specific sample sizes for training sets, adjudication, or detailed effect sizes for MRMC studies, is not present in this type of document and cannot be extracted. The focus of this document is on demonstrating substantial equivalence to predicate devices and meeting established standards.

Acceptance Criteria and Device Performance

The core acceptance criteria for the NxStage Water Purification System are defined by its ability to meet or exceed the requirements of the American National Standard Institute and the Association for the Advancement of Medical Instrumentation (ANSI/AAMI) RD62:2001, Water Treatment Equipment for Hemodialysis Applications.

Table 1: Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Standard)	Reported Device Performance
ANSI/AAMI RD62:2001, Water Treatment Equipment for Hemodialysis Applications: Specifies permissible levels of various impurities (e.g., chemical contaminants, microbiological contaminants like bacteria and endotoxins) in water used for hemodialysis applications.	"With proper use, the System will produce water that meets or exceeds the requirements of the standard issued by the American National Standard Institute and the Association for the Advancement of Medical Instrumentation: ANSI/AAMI RD62:2001, Water Treatment Equipment for Hemodialysis Applications."
System Functionality Indicators:
Removal of trapped air, sediment, and impurities.	Accomplished by a pretreatment system (check valve, sediment filter, air vent).
Control of flow rate.	Managed by a Pump Controller unit.
Monitoring of pressure, water quality, and system operation.	Managed by a Pump Controller unit with control and safety software.
Removal of organic and inorganic chemical contaminants.	Achieved by a replaceable resin system.
Removal of microbiological contaminants (bacteria and endotoxins).	Achieved by a replaceable resin system.

Study Information

Based on the provided text, the study conducted was a non-clinical performance testing to demonstrate that the NxStage Water Purification System is substantially equivalent to predicate devices and meets the specified ANSI/AAMI standard.

1. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
* Test Set Sample Size: The document does not specify a numerical sample size for the test set (e.g., number of water samples tested, number of systems tested). It broadly refers to "Performance testing." For a water purification system, this would typically involve testing multiple units over a period of time with various water sources.
* Data Provenance: The document does not specify the country of origin of the data. It is internal testing conducted by "NxStage Medical." The study is described as "performance testing," which implies it was prospective testing of the device's functionality.

2. 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):
* N/A. This device is a water purification system, not an imaging or diagnostic device that requires expert interpretation for establishing ground truth. Ground truth for water purity is established through chemical and microbiological laboratory analysis processes against industry standards.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
* N/A. Adjudication methods like 2+1 or 3+1 are relevant for subjective interpretations, often in medical imaging. For a water purification system, the performance is assessed against objective, measurable chemical and microbiological standards, which do not typically involve human adjudication in this manner.

4. 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:
* No. This is not applicable to a water purification system. An MRMC study is relevant for diagnostic devices involving human interpretation.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
* Yes, in essence. The performance testing demonstrated the device's ability to purify water to specified standards "with proper use" of the system itself. While human interaction is required to operate and maintain the system, the purification process and its effectiveness are tested in a standalone manner (device's output measured against standards), independent of human "interpretation" of the water quality. The "Pump Controller unit which contains the control and safety software" functions as the "algorithm only" component controlling the purification process.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
* Objective Laboratory Analysis against Industry Standards. The ground truth for water purity is established by quantitative chemical and microbiological analysis of the treated water samples, compared directly to the specified maximum contaminant levels outlined in the ANSI/AAMI RD62:2001 standard.

7. The sample size for the training set:
* N/A. The concept of a "training set" is typically associated with machine learning or AI models. This device is a physical water purification system with a controller and safety software. While the software itself would have undergone development and testing, there's no mention or implication of machine learning that would necessitate a "training set" in the conventional sense.

8. How the ground truth for the training set was established:
* N/A. As mentioned above, the concept of a training set and its associated ground truth derivation (like for AI development) does not apply to this type of device based on the provided information.

Summary

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K042089
Page 1 of 3

Section VII: 510(k) Summary of Safety & Effectiveness

This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of SMDA 1990.

A. Submitter's Information:

Name:	NxStage Medical, Inc.
Address:	439 South Union Street, Suite 50Lawrence, MA 01843
Phone:	(978) 687-4700
Fax:	(978) 687-4800
Contact Person:	Norma LeMayManager, Regulatory Affairs
Date of Preparation:	July 13, 2004

B. Device Name:

Trade Name:	NxStage Water Purification System
Common/Usual Name:	Water Purification System
Classification Name:	Water Purification System for Hemodialysis (ClassII medical device under 21 CFR 875.5665(Product Code 78 FIP))

C. Substantial Equivalence/Predicate Devices:

The proposed NxStage Water Purification System is substantially equivalent to the following legally marketed predicate devices previously cleared by FDA:

AmeriWater Portable RO+ Model MROS09, (K030059, cleared 04/07/03) .
. HydroPure Deionization Systems, (K022747, cleared 02/11/03)
Water & Power Technologies of Texas, Inc. (K994292, cleared 01/02/01) .
. Total Water Treatment System, (K002045, cleared 02/16/01)

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NxStage Medical, Inc. Water Purification System 510(k) Premarket Notification

K042089
Page 2 of 3

Section VII: 510(k) Summary of Safety & Effectiveness

D. Device Description/Indications for Use:

Indications for use:

E. Technological Characteristics:

The proposed device has the same technological characteristics and is similar in design and configuration as compared to the predicate devices. The proposed device is designed and assembled with components commonly found in the predicate devices.

F. Summary of Non-Clinical Test/Performance Testing

NxStage Medical believes that the information and data provided in this submission clearly describes the proposed device and demonstrates that the device is adequately designed for the labeled indications for use. Performance testing was conducted to characterize performance of the proposed NxStage Water Purification System to provide a basis of comparison to the predicate devices. Results of the

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NxStage Medical, Inc. Water Purification System 510(k) Premarket Notification

KC42089
Page 3 of 3

Section VII: 510(k) Summary of Safety & Effectiveness

performance testing have demonstrated that the NxStage Water Purification System is substantially equivalent to the predicate devices and is suitable for the labeled indications 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 circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles three overlapping human figures or abstract shapes, possibly representing people or services provided by the department.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

NOV 2 4 2004

NxStage Medical, Inc. c/o Mr. Casey Conry Staff Engineer - Medical Devices Intertek Testing Services NA, Inc. 70 Codman Hill Road BOXBOROUGH MA 01719

Re: K042089

Trade/Device Name: NxStage Water Purification System Regulation Number: 21 CFR §876.5665 Regulation Name: Water Purification System for Dialysis Regulatory Class: II Product Code: 78 FIP Dated: November 1, 2004 Received: November 2, 2004

Dear Mr. Conry:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such 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 requirements, including, but not limited to registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); 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.

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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance at one of the following numbers, based on the regulation number at the top of this letter:

21 CFR 876.xxxx	(Gastroenterology/Renal/Urology)	240-276-0115
21 CFR 884.xxxx	(Obstetrics/Gynecology)	240-276-0115
21 CFR 892.xxxx	(Radiology)	240-276-0120
Other		240-276-0100

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsmaldsmamain.html

Sincerely yours,

Nancy C. Brogdon

Nancy C. Brogdon Director, Division of Reproductive, Abdominal, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE

510(k) Number (if known):

Device Name:

Indications for Use:

K042089

NxStage Water Purification System

Prescription Use _ X Use (Part 21 CFR 801 Subpart D) AND/OR Over-The-Counter

(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)

Nancy Brogdon
(Division Sign-Off)

Division of Renrodu and Radiological Dev 510(k) Number

Page 1 of 1

Regulation Number and Section

§ 876.5665 Water purification system for hemodialysis.

(a)
Identification. A water purification system for hemodialysis is a device that is intended for use with a hemodialysis system and that is intended to remove organic and inorganic substances and microbial contaminants from water used to dilute dialysate concentrate to form dialysate. This generic type of device may include a water softener, sediment filter, carbon filter, and water distillation system.(b)
Classification. Class II (special controls). The device, when it is a water purification subsystem disinfectant, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 876.9.