The PhySoft Anemia Management System® (PhySoftAMS®) is a software application used to obtain, track and trend patient data pertaining to the management of anemia, and to provide a schedule of erythropoiesis-stimulating agent (ESA) dosage recommendations to help achieve and maintain target hemoglobin levels in dialysis patients. PhySoftAMS® is intended to help physicians. nurses, clinicians, and anemia managers manage anemia in adult stage 5 chronic kidney disease (CKD) patients.

PhySoftAMS® is not a substitute for, but is rather intended to assist, clinical judgment. The erythropoiesis-stimulating agent (ESA) dosing regimen options calculated by this device are intended to be used by qualified and trained medical personnel to inform the optimization of the dosage of ESAs in accordance with their approved labeling in conjunction with clinical history, symptoms, and other diagnostic measurements, as well as the medical professional's clinical judgment. No medical decision should be based solely on the patient Hgb response to dosing regimen options calculated by this device.

Device Description

PhySoftAMS® is a software application used to obtain, track and trend patient data pertaining to the management of anemia and to provide a schedule of erythropoiesis-stimulating agent (ESA) dosage recommendations to help achieve and maintain target hemoglobin levels in dialysis patients. PhySoftAMS® is intended to help physicians, nurses, clinicians and anemia managers manage anemia in adult stage 5 chronic kidney disease (CKD) patients.

PhySoftAMS® is intended for use by medical personnel such as clinicians, nurses, and physicians in dialysis clinics or other settings where anemia management for hemodialysis patients is conducted.

Healthcare professionals access PhySoftAMS® directly using a web application graphical user interface (GUI) or indirectly using the drug dosing-related screens of a third party's electronic health record (EHR) system via an application programming interface (API) provided by the PhySoftAMS® application server.

PhySoftAMS® evaluates whether adequate historical data is available to model patient ESA dose-Hgb response dynamics and project future ESA dose-Hgb response. If adequate data is available, PhySoftAMS® enables a physician to model a patient and select from one or more dosing schedule options most likely to result in achieving target Hgb levels or, at the physician's discretion. override the presented dosing schedule options.

AI/ML Overview

The provided text describes a 510(k) premarket notification for a medical device called PhySoftAMS®, a software application for managing anemia in dialysis patients. However, the document does not contain the detailed information necessary to answer all the questions regarding acceptance criteria and the study proving the device meets those criteria.

Specifically, the document states:

"Bench testing results demonstrate the modified device performance is computationally equivalent to the performance of the predicate device."
"Software verification and validation of the device modifications that are the subject of this submission demonstrated that the enhancements for the subject (modified) device perform as intended and have no effect on the modeling process or other device functions of PhySoftAMS®."

This indicates that internal testing (bench testing, software V&V) was performed to show computational equivalence and proper function of the modifications, but it does not detail a clinical study or performance study with acceptance criteria, sample sizes, ground truth establishment, or multi-reader multi-case studies as requested.

Therefore, many of the requested details cannot be extracted from this document. I can only provide information directly inferable from the given text.

Here's an attempt to answer based only on the provided text, highlighting what is not available:

Acceptance Criteria and Study for PhySoftAMS®

The provided 510(k) summary (K232283) focuses on demonstrating substantial equivalence of a modified PhySoftAMS® to its predicate device (PhySoft AMS™, K130579), primarily regarding the new integration with EHR systems via an API. The performance data presented relates to computational equivalence and software functionality, rather than a clinical performance study with defined acceptance criteria for diagnostic or clinical accuracy.

1. Table of Acceptance Criteria and Reported Device Performance

Based on the provided text, formal acceptance criteria for a clinical performance study (e.g., sensitivity, specificity, accuracy targets) and corresponding reported performance metrics are not explicitly stated. The "Performance" section focuses on computational and functional equivalence to the predicate.

Acceptance Criteria	Reported Device Performance
Not explicitly stated as numerical performance targets for clinical outcomes. The document states the goal was to demonstrate "computational equivalence to the performance of the predicate device" and that modifications "perform as intended and have no effect on the modeling process or other device functions."	Computationally equivalent to the predicate device. Enhancements perform as intended and have no effect on the modeling process or other device functions of PhySoftAMS®.

2. Sample Size Used for the Test Set and Data Provenance

The document does not specify a sample size for a "test set" in the context of a clinical or retrospective/prospective performance study. The evaluations described (bench testing, software V&V) typically do not involve patient-level test sets in the same manner as a diagnostic study. The data provenance (country, retrospective/prospective) is also not mentioned.

3. Number of Experts Used to Establish Ground Truth and Qualifications

The document does not mention using experts to establish ground truth for a test set, as no such clinical or performance test set is described. The device provides "dosing recommendations," which would typically be compared against clinical outcomes or expert judgment in a performance study, but this is not detailed here.

4. Adjudication Method for the Test Set

Since no test set adjudicated by experts is described, the adjudication method is not applicable/not mentioned.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No MRMC study is described in the provided text. The device offers dosing recommendations and assists human users, but there is no information on a study comparing human readers with and without AI assistance, or an effect size.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

The text indicates the device "provides a schedule of erythropoiesis-stimulating agent (ESA) dosage recommendations to help achieve and maintain target hemoglobin levels" and is "intended to help physicians, nurses, clinicians, and anemia managers manage anemia." It explicitly states, "PhySoftAMS® is not a substitute for, but is rather intended to assist, clinical judgment." This implies a human-in-the-loop design. No standalone algorithmic performance study results are detailed in the document. The "computational equivalence" refers to the underlying modeling process itself.

7. The Type of Ground Truth Used

For the software verification and validation, the "ground truth" would be the expected behavior and output of the algorithms and software functions, based on predefined specifications and the known performance of the predicate device. For potential clinical application, the ultimate ground truth would relate to actual patient hemoglobin levels and clinical outcomes, but the studies described do not detail the collection or establishment of such ground truth.

8. The Sample Size for the Training Set

The document does not mention a training set size. This device appears to use PK/PD modeling of patient response rather than a deep learning model that typically requires a large training set of annotated data. The system tracks and trends past Hgb and ESA dosages for individual patient modeling, not a general training dataset for an AI model.

9. How the Ground Truth for the Training Set Was Established

As no training set (in the context of machine learning) is explicitly mentioned, the method for establishing its ground truth is not detailed. The modeling is described as "PK/PD modeling of patient response to ESAs," which is typically based on physiological and pharmacological principles, not a data-driven training set with established ground truth labels in the same way an image classification AI might be trained.

Summary

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December 14, 2023

Physician Software Systems, LLC Lewis Mitchell CEO 3333 Warrenville Road, Suite 200 Lisle, Illinois 60532

Re: K232283

Trade/Device Name: PhySoftAMS® Regulation Number: 21 CFR 876.5820 Regulation Name: Hemodialysis System and Accessories Regulatory Class: II Product Code: MQS Dated: November 23, 2023 Received: November 24, 2023

Dear Lewis Mitchell:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

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(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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

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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,

Maura Rooney Assistant Director DHT3A: Division of Renal, Gastrointestinal, Obesity and Transplant Devices OHT3: Office of Gastrorenal, 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

Submission Number (if known)

K232283

Device Name

PhySoftAMS®

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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510(k) Summary

510(k) Number: K232283

1. Submitter Information

Submitter Name:	Physician Software Systems, LLC3333 Warrenville Road, Suite 200Lisle, Illinois 60532Phone: 331-213-9000Fax: 331-213-9009
Contact Person:	Lewis A. MitchellChief Executive Officer
Date Prepared:	November 16, 2023
Type of Submission:	Traditional 510(k) Submission

2. Name of Device

Common Name:	Anemia Management System
Trade Name:	PhySoftAMS®
Classification Name:	Hemodialysis System and Accessories
Classification Panel:	76 Gastroenterology/Urology
Classification Regulations:	21 CFR 876.5820
Product Code:	MQS
Device Classification	Class II

3. Predicate Device Information

Common Name:	Anemia Management System
Trade Name:	PhySoft AMS™
510(k):	K130579
Classification Name:	Hemodialysis System and Accessories
Classification Panel:	76 Gastroenterology/Urology

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Classification Regulations:	21 CFR 876.5820
Product Code:	MQS
Device Classification	Class II

4. Reference Device Information

Common Name:	Anemia Management System
Trade Name:	Dosis Smart Anemia Manager
510(k):	K180410
Classification Name:	Hemodialysis System and Accessories
Classification Panel:	76 Gastroenterology/Urology
Classification Regulations:	21 CFR 876.5820
Product Code:	MQS
Device Classification	Class II

The Dosis Smart Anemia Manager cleared under K180410 is included as a reference device in support of the subject device's capability to use the client EHR as a user-interaction alternative to the predicate device's GUI. Both the subject device and the reference device can be accessed via a web browser or web-enabled electronic health record [EHR] system. The reference device was found substantially equivalent to the PhySoftAMS® predicate device under K180410.

5. Device Description

PhySoftAMS® is intended for use by medical personnel such as clinicians, nurses, and physicians in dialysis clinics or other settings where anemia management for hemodialysis patients is conducted.

PhySoftAMS® evaluates whether adequate historical data is available to model patient ESA dose-Hgb response dynamics and project future ESA dose-Hgb response. If adequate data is

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available, PhySoftAMS® enables a physician to model a patient and select from one or more dosing schedule options most likely to result in achieving target Hgb levels or, at the physician's discretion. override the presented dosing schedule options.

6. Intended Use

Indications for use of the subject device

Comparison of indications for use statements

PhySoftAMS® has the same intended use and indications for use as the predicate device, cleared under K130579.

The indications for use statement for both the predicate device and the subject (modified) device are identical, except that "web application" in the first sentence of the first paragraph has been changed to "software application." The subject device includes an option to integrate the software directly into the user's internal EHR systems using an API, whereas the predicate device is accessible only as a web application through a secure virtual private network (VPN).

Like the subject device, the reference device cleared under K180410 is also accessible via a web browser or web-enabled EHR system.

7. Technological Characteristics

PhySoftAMS® is a modified version of the predicate device. The software codebase remains unchanged with the exception of updates and maintenance performed since its initial release in 2013 to improve the overall user experience and the modifications that are the subject of this 510(k) submission. The table below contains the key technological characteristics that remain identical between the predicate and the modified device.

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Characteristic	PhySoftAMS®	Predicate(PhySoft AMSTM)
Indications for Use	Management of anemia in dialysis patients under ESAtreatment (full indications for use statement providedabove)	Identical
Principle ofOperation	Track and trend past Hgb and ESA dosages to determinefuture ESA dosages based on PK/PD modeling ofpatient response to ESAs	Identical
Technology	Application used to trend patient data collected duringeach dialysis treatment	Identical
PatientDemographics	Adult stage 5 chronic kidney disease patients	Identical
Intended Users	Physicians, clinicians, nurses, anemia managers	Identical
Data Storage	Data is stored electronically	Identical
Data Management	Generates reports and graphs to assist with anemiamanagement	Identical
Safeguards/Alerts	System flags patients who exceed limits	Identical

Differences between the modified version of PhySoftAMS® and the predicate are summarized in the table below. The modifications allow integration of PhySoftAMS® with users' EHR systems.

Characteristic	Modified PhySoftAMS®(Subject Device)	Predicate (PhySoft AMSTM)(K130579)
User Interface	The web-based version offers thesame GUI accessed online viaVPN-secured HTTPS connection.	GUI accessed online via VPN-secured HTTPS connection.
	Integration with users' EHRsystems via API is also availableas an option.	While the predicate device wasnot accessible through users'EHR systems, the Dosis SmartAnemia Manager cleared underK180410 is included as areference device in support of thesubject device's capability to usethe client EHR as a user-interaction alternative to thepredicate device's GUI. Both thesubject device and the referencedevice can be accessed via a webbrowser or web-enabled EHRsystem. FDA determined thereference device was substantiallyequivalent to the predicate device.
	Modified PhySoftAMS®(Subject Device)	Predicate (PhySoft AMSTM)(K130579)
Characteristic
Data Entry	The web-based versionelectronically obtains patient datarequired for anemia managementfrom the healthcare provider'sEHR at regular intervals.For those using the API, theapplication directly interacts withthe user's EHR for access topatient data.	Electronically obtains patient datarequired for anemia managementfrom the healthcare provider'sEHR at regular intervals
Recommendation Delivery	The web-based version deliversrecommendations via web-basedGUI.For those using the API, a DosingRecommendation Manager(DRM) routes recommendationsfrom the recommendationdatabase to external systems.	Delivers recommendations viaweb-based GUI.
Patient Modeling Trigger	Users of the web-based versionmanually trigger the modelingfunction with a GUI button wheninformed that the datarequirements for patient modelinghave been satisfied.For those using the API, wherethe GUI button is not available, aModeled Patient DosingRecommendation Engine(MPDRE) automatically activatesthe modeling process when thedata requirements for patientmodeling have been satisfied.Healthcare professionals are stillrequired to review the results ofthe model in conjunction withclinical history, symptoms, andother diagnostic measurements, aswell as the medical professional'sclinical judgment, and no medicaldecision related to the model'srecommendations should bebased solely on the patient Hgbresponse to dosing regimen	User manually triggers themodeling function with a GUIbutton when informed that thedata requirements for patientmodeling have been satisfied

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8. Performance

Bench testing results demonstrate the modified device performance is computationally equivalent to the performance of the predicate device.

Software verification and validation of the device modifications that are the subject of this submission demonstrated that the enhancements for the subject (modified) device perform as intended and have no effect on the modeling process or other device functions of PhySoftAMS®.

9. Conclusion

The modified PhySoftAMS® that is the subject of this submission and PhySoft AMS™ as cleared under K130579 are substantially equivalent with respect to intended use, technological characteristics, and performance. The bench testing and software verification and validation results demonstrate that the modified device is as safe, as effective, and performs as well as the legally marketed predicate device.

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.