SAM is a web 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 (Hgb) levels in hemodialysis patients. The device is intended to help clinicians manage chronic anemia.

The device is not a substitute for, but rather intended to assist, clinical judgment. The ESA dosing regimen options calculated by this device are intended 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 clinicians' judgment. No medical decision should be based solely on the patient Hgb response to dosing regimen options calculated by this device.

Device Description

Healthcare professionals access SAM using a web-enabled application (for example, a web browser or a web-enabled electronic health record system) communicating with the SAM web application server. Patient information is obtained by SAM from healthcare provider Electronic Medical Records. No components of SAM are required to be installed at end user or healthcare provider locations.

SAM estimates individual patient's Hgb response to ESAs. The results of this estimation are used to generate new patient-specific ESA dose recommendation to achieve target Hgb level specified by the physician. The ESA dose recommendation is reviewed by the physician, who after considering any additional relevant information about patient's condition, decides whether to follow or override the presented ESA dose recommendation.

AI/ML Overview

Here's an analysis of the acceptance criteria and study detailed in the provided text for the Smart Anemia Manager (SAM) device:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" for the study in a pass/fail sense with numerical targets. Instead, it describes demonstrating "non-inferiority to AMP 1 and 2 in mean hemoglobin, percent in target range and hemoglobin standard deviation." The clinical trials then provide performance measures.

Here's a table summarizing the performance metrics and implicit targets/comparisons:

Metric	Implicit Acceptance Criterion (vs. AMP1/AMP2 or Predicate)	Reported Dosis SAM Performance (Simulation, Noise = 0.0 g/dL)	Reported Dosis SAM Performance (Clinical Trial 1)	Reported Dosis SAM Performance (Clinical Trial 2, range)
Mean Hgb (g/dL)	Non-inferior to AMP1/AMP2	10.9	Not explicitly stated (implied similar to control)	Not explicitly stated (implied similar to predicate)
Hgb Standard Deviation (g/dL)	Non-inferior (preferably lower) than AMP1/AMP2	0.2	Not explicitly stated	Not explicitly stated
Percent Hgb 10 to 12 g/dL	Non-inferior (preferably greater) than AMP1/AMP2	74.1	72.5% (vs. 61.9% for control, p=0.003)	76.8% to 86.3% (vs. 73.5% to 89.1% for predicate)
ESA Dose (units)	Preferably lower than AMP1/AMP2	7356	Not explicitly stated	Not explicitly stated
Time to Target (weeks)	Non-inferior to AMP1/AMP2	12.6	Not explicitly stated	Not explicitly stated
Composite Safety Event (CSE)	No difference from standard of care (Clinical Trial 1)	N/A	No difference from control	N/A
Hgb concentrations above 12.9 g/dL	Non-inferior to predicate (Clinical Trial 2)	N/A	N/A	1.5% to 8.7% (vs. 5.9% to 9.4% for predicate)

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

Simulation Testing:
- Test Set Sample Size: A pool of 2430 simulated patients were created. Each protocol (SAM, AMP1, AMP2) was run for 26,730 simulations (likely meaning 26,730 unique scenarios or patient instances within the pool).
- Data Provenance: In silico simulation. The concepts for patient response to ESA were based on published pharmacodynamics (Uehlinger et al. Clin Pharmacol Ther 51:76-89, 1992). This is synthetic data, not real patient data.
Clinical Studies:
- Clinical Trial 1 (Randomized, Controlled, Double-Blind):
  - Test Set Sample Size: 62 subjects (52 completed the study).
  - Data Provenance: Prospective clinical trial.
- Clinical Trial 2 (Case-Controlled & Cross-Sectional):
  - Test Set Sample Size: Not explicitly stated but compared to PhySoft AMS™ over a 45-month follow-up period.
  - Data Provenance: Retrospective, comparing long-term follow-up of SAM and PhySoft AMS™ performance.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts

Simulation Testing: No human experts were used to establish ground truth. The ground truth was defined by the in silico model of patient response to ESA, based on published pharmacodynamics.
Clinical Studies: The document does not specify how ground truth was established for the clinical trials beyond stating that Hgb levels were measured and safety events tracked. It implies that standard clinical measurements and outcomes served as the "ground truth." There is no mention of an expert panel to adjudicate individual cases or outcomes.

4. Adjudication Method (for the test set)

Simulation Testing: Not applicable, as it's a simulated environment.
Clinical Studies: Not explicitly stated. For Clinical Trial 1, safety events (CSE) were tracked, but the adjudication method for these events is not described (e.g., whether an independent clinical events committee adjudicated them). For Hgb levels, standard laboratory measurements would be considered the ground truth, not requiring expert adjudication.

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

No, an MRMC study was not done. This device (Smart Anemia Manager, SAM) is an algorithm that provides dosage recommendations, not an imaging device or diagnostic tool that humans interpret. Therefore, the concept of "human readers improving with AI vs. without AI assistance" as typically studied in MRMC designs for diagnostic AI is not directly applicable here.
The clinical trials assess the effectiveness of the recommendations provided by SAM compared to standard of care/predicate, rather than how humans perform with those recommendations versus without them. The device produces the recommendation; it doesn't assist human interpretation in the typical MRMC sense.

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

Yes, the simulation testing represents a standalone evaluation of the algorithm's performance. In the simulation, SAM's dosing recommendations were directly applied to simulated patients, and the outcomes (Hgb levels, variability, ESA dose) were compared to other algorithmic protocols (AMP1, AMP2).
The clinical trials, by definition, involve human clinicians using the SAM recommendations (or standard of care/predicate recommendations), but SAM itself is intended to generate recommendations. The study's focus is on the clinical outcomes resulting from following those recommendations.

7. The type of ground truth used

Simulation Testing: Mathematically defined in silico model of patient pharmacodynamics (response to ESA and red blood cell life spans).
Clinical Studies:
- Clinical Trial 1: Measured hemoglobin concentrations, and a Composite Safety Event (CSE) based on medical outcomes (mortality, MI, CVA, CHF). This is outcomes data combined with standard clinical measurements.
- Clinical Trial 2: Measured hemoglobin concentrations and the incidence of high hemoglobin concentrations (above 12.9 g/dL). This is standard clinical measurements.

8. The sample size for the training set

The document does not provide information regarding the sample size for the training set used to develop or train the SAM algorithm. It describes the technology as using an "individualized dose response model" but doesn't detail how this model was trained.

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

Since the document does not specify a training set or its sample size, it also does not explain how the ground truth for any training set was established.

Summary

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

Image /page/0/Picture/0 description: The image contains the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.

January 16, 2019

Dosis, Inc. % E.J. Smith Consultant Smith Associates 1468 Harwell Ave. Crofton, MD 21114

Re: K180410

Trade/Device Name: Smart Anemia Manager (SAM) Regulation Number: 21 CFR§ 876.5820 Regulation Name: Hemodialysis System and Accessories Regulatory Class: II Product Code: MQS Dated: December 7, 2018 Received: December 11, 2018

Dear E.J. Smith:

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.

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

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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see

https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/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 -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

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

Indications for Use

510(k) Number (if known) K180410

Device Name Smart Anemia Manager (SAM)

Indications for Use (Describe)

X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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

510(k) Summary

Company Name:Company Address:	Dosis, Inc.353 Sacramento StreetSuite 1811San Francisco, CA 94111
Telephone:Contact Person:	650 383 0186Shivrat Chhabra
Summary Preparation Date:	01/14/2019
Device Description:Device Name:Common Name:Classification NameRegulatory Class:Product Code:C.F.R. Section:	Smart Anemia Manager (SAM)Anemia Software ManagementHemodialysis System and AccessoriesClass IIMQS21 CFR 876.5820

PREDICATE DEVICE:

Manufacturer	Product Name	510(k) Number
Physician Software Systems, LLC	PhySoft AMS™	K130579

DEVICE DESCRIPTION:

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

INDICATIONS FOR USE:

	Dosis	Physicians SoftwareSystem, LLC	Similarities andDifference
Product Name	SAM	PhySoft AMS™
Indications for UseStatement	SAM is a web applicationused to obtain, track andtrend patient datapertaining to themanagement of anemia,and to provide a schedule oferythropoiesis-stimulatingagent (ESA) dosagerecommendations to helpachieve and maintain targethemoglobin (Hgb) levels inhemodialysis patients. Thedevice is intended to helpclinicians manage chronicanemia.The device is not asubstitute for, but ratherintended to assist, clinicaljudgment. The ESA dosingregimen options calculatedby this device are intendedto inform the optimizationof the dosage of ESAs inaccordance with theirapproved labeling inconjunction with clinicalhistory, symptoms, andother diagnosticmeasurements, as well asthe clinicians' judgment. Nomedical decision should be	PhySoft AMS™ is a webapplication used to obtain,track and trend patient datapertaining to themanagement of anemia, andto provide a schedule oferythropoiesis-stimulatingagent (ESA) dosagerecommendations to helpachieve and maintain targethemoglobin levels in dialysispatients. PhySoft AMS™ isintended to help physicians,nurses, clinicians and anemiamanagers manage anemia inadult stage 5 chronic kidneydisease (CKD) patients.The PhySoft AMS™ is not asubstitute for, but ratherintended to assist, clinicaljudgment. The ESA dosingregimen options calculated bythis device are intended to beused by qualified and trainedmedical personnel to informthe optimization of thedosage of ESAs in accordancewith their approved labelingin conjunction with clinicalhistory, symptoms, and otherdiagnostic measurements as	Same

SUBSTANTIALLY EQUIVALENCE DISCUSSION:

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

K180410

Page 3 of 9

based solely on the patientHgb response to dosingregimen options calculatedby this device.	well as the medicalprofessional's clinicaljudgment. No medicaldecision should be basedsolely on thepatient Hgb response todosing regimen optionscalculated by this device.
--------------------------------------------------------------------------------------------------------	--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	--

Parameters	Dosis	Physicians Software System, LLC	Similarities and Differences
510(k) Number:		K130579
Product Code	MQS	MQS	Same
Regulation Number	21 CFR 876.5820	21 CFR 876.5820	Same
Principle of Operation	Track and trend Hgb and ESAdosages which can be used todetermine future ESA dosages	Track and trend Hgb and ESAdosages which can be used todetermine future ESA dosages	Same
Technology	Application used to trendpatient data collected duringeach dialysis treatment	Application used to trendpatient data collected duringeach dialysis treatment	Same
Patient Demographics	Adult stage 5 chronic kidneydisease patients	Adult stage 5 chronic kidneydisease patients	Same
Intended User	Physician/Clinicians/Nurses	Physician/Clinicians/Nurses	Same
Data Storage	Data is stored electronically	Data is stored electronically	Same
Data Management	Generates reports and graphsto assist anemia management	Generates reports and graphsto assist anemia management	Same
Safeguards/Alerts	System flags patients whoexceed limits	System flags patients whoexceed limits	Same
Technological Characteristics
Parameters	Dosis	Physicians Software System, LLC	Similarities and Differences
510(k) Number:Product Code	MQS	K130579MQS	Same
Regulation Number	21 CFR 876.5820	21 CFR 876.5820	Same
Principle of Operation	Track and trend Hgb and ESA dosages which can be used to determine future ESA dosages	Track and trend Hgb and ESA dosages which can be used to determine future ESA dosages	Same
Technology	Application used to trend patient data collected during each dialysis treatment	Application used to trend patient data collected during each dialysis treatment	Same
Patient Demographics	Adult stage 5 chronic kidney disease patients	Adult stage 5 chronic kidney disease patients	Same
Intended User	Physician/Clinicians/Nurses	Physician/Clinicians/Nurses	Same
Data Storage	Data is stored electronically	Data is stored electronically	Same
Data Management	Generates reports and graphs to assist anemia management	Generates reports and graphs to assist anemia management	Same
Technology/Algorithm	Uses individualized dose response model to compute patient dose response.	Uses individualized dose response model to compute patient dose response.	Same
	Account for effects of last ESA dose.	Account for effects of multiple prior ESA dosages.	In SAM effect of multiple prior ESA dose is embedded in Hgb trend.
	Estimates ongoing dosing schedules to achieve target Hgb levels using close-loop approach.	Estimates ongoing dosing schedules to achieve target Hgb levels using open-loop approach.	In SAM close-loop allows for potential mismatch
Technological Characteristics
Parameters	Dosis	Physicians SoftwareSystem, LLC	SimilaritiesandDifferencesbetweenmodel andpatient.
Data Entry	Patient data is transferredelectronically from existinghealthcare providerinformation systems.	Patient data is transferredelectronically from existinghealthcare providerinformation systems.	Same
Data Storage	Data is storedelectronically in a remotedatabase server	Data is storedelectronically on local orremote database server	SAM does notstore datalocally
Data Network Access	Data is accessed oversecure internetconnections.	Data is accessed oversecure internetconnections.	Same
Safeguards/Alerts	System flags patients whoexceed limits	System flags patients whodo not respond aspredicted and may haveundetected health issuesthat do not fit the mostprobable model.	SAM does notflagundetectedhealth issues.
Minimum DataRequirement		Evaluates patient readinessfor application of algorithmto model ESA dose-Hgbresponse (sufficient historyof Hgb and ESA dosing).	SAM does nothave aminimumdosing historyrequirementonly requiresa single HgBmeasurement.

{6}------------------------------------------------

{7}------------------------------------------------

Discussion of Similarities and Differences:

Similarities

. SAM has the same indications for use, principle of operation, technology, patient demographics, intended users, data storage, data management, safe guards and alerts, technology/algorithm, data entry, and data network access and raises no new issues of safety and effectiveness, as a result of this submission.
. SAM has a similar algorithm as the predicate device. Both software systems were verified and validated using the recommendations found in FDA's Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices,

{8}------------------------------------------------

Document issued on: May 11, 2005 and the results raises no new issues of safety and effectiveness.

Differences

The combination of past ESA doses will impact future HgB concentrations and SAM uses the most recent ESA dose as a predictor of future HgB. Additional information on past ESA dose is present in HgB trend. Both methods use past ESA dose in different ways for the same end result.
. SAM uses close loop control and therefore can better acknowledge and adjust for errors in drug dosing and the measurement of HgB. This should lead to at least similar accuracy compared to the predicate and is a superior method when compared to open loop control.
. SAM only stores data on a remote HIPPA compliant server and avoids the potential problem with local data storage and potential data incursion. There is no effect on predictive performance due to data storage methods.
SAM and the predicate both identify when the observed HgB is different from the prediction. SAM uses this information in the close loop control methodology to improve the prediction in the future. The predicate only flags the individual as not responding as expected and might be able to suggest the cause but does not adjust the prediction to account for this error like a close loop control method. The impact should not be substantially different between methods except that close loop control can potentially lead to improved future predictions.
. SAM does not have a minimum data requirement to estimate patient response and can make recommendations based on a single HgB measurement. This difference will allow SAM to make recommendations in patients that the predicate cannot.

Non-clinical Performance Tests

Simulation Testing

The performance of the SAM software was tested through simulation and comparison to anemia management using usual practice in the form of an anemia management protocol in use at 2 large dialysis providers.

Purpose

Demonstrate the efficacy and safety of the SAM software in the dosing of erythropoietin (ESA) for the treatment of anemia in a simulated patient population compare to usual care.

Subjects

Anemic subjects were simulated based on their response to an ESA using the concepts published on the pharmacodynamics of erythropoietin (Uehlinger et al. Clin Pharmacol

{9}------------------------------------------------

Ther 51:76-89, 1992). Subject had a broad range of responsiveness that encompassed that observed in the target population.

Study Design

In silico three way cross over simulation.

Outcome Variables

Methods

A pool of 2430 patients were created based on a range of ESA response measures and red blood cell life spans essentially generating a cohort of test subjects that range to hyper to hypo responsive to ESA. ESA dosing was then simulated to achieve steady state hemoglobin concentrations using the SAM software or conventional therapy using an anemia management protocol 1 or 2 (AMP1 or AMP2). Noise was introduced into the system to simulate the uncertainty in the measurement of hemoglobin between 0.0 and 1.0 g/dL. We recorded the mean achieve hemoglobin, time to steady state, hemoglobin variability, percent in target range, and mean ESA/week. A total of 26,730 simulations were run for each protocol. Target range was a hemoglobin between 10.0 and 12.0 g/dL. The goal was to demonstrate non-inferiority to AMP 1 and 2 in mean hemoglobin, percent in target range and hemoglobin standard deviation.

Results

The results of the simulations are shown in the following tables:

	Time to Target (weeks)			Mean Hgb (g/dL)			Hgb Standard Deviation(g/dL)
Noise(g/dL)	AMP1	AMP2	SAM	AMP1	AMP2	Dosis SAM	AMP1	AMP2	Dosis SAM
0.0	5.2	4.5	12.6	11.2	12.3	10.9	0.5	1.4	0.2
0.1	5.4	4.5	12.4	11.2	12.3	10.9	0.6	1.4	0.3
0.2	5.3	4.6	11.9	11.1	12.3	10.9	0.6	1.5	0.4
0.3	5.3	4.8	11.6	11.1	12.4	10.9	0.7	1.6	0.4
0.4	5.5	4.5	11.0	11.1	12.4	10.9	0.8	1.7	0.5
0.5	5.5	4.7	10.2	11.0	12.4	10.9	0.9	1.8	0.6
0.6	5.5	4.5	9.8	11.0	12.4	10.9	1.0	1.8	0.7
0.7	5.2	4.8	9.5	11.0	12.5	10.8	1.1	1.9	0.9
0.8	5.2	4.7	8.9	11.0	12.6	10.8	1.2	2.0	0.9
0.9	5.7	4.7	8.3	11.0	12.7	10.8	1.3	2.1	1.1
1.0	5.7	4.5	7.7	11.0	12.7	10.8	1.4	2.2	1.2

Time to target, Mean achieved Hgb, and Standard Deviation for AMP1, AMP2, and SAM

The approaches resulted in differences in respect to time to target with SAM taking longer to reach the target Hgb. The mean Hgb achieved was similar between SAM and AMP1, but AMP2 routinely exceeded the target Hgb range of 10 to 12 g/dL. SAM had lower Hgb variability. The impact of these observations can be seen in the next table

{10}------------------------------------------------

Noise(g/dL)	Percent Hgb 10 to 12			ESA Dose (units)
	AMP1	AMP2	SAM	AMP1	AMP2	Dosis SAM
0.0	67.7	50.1	74.1	11217	11554	7356
0.1	67.2	50.6	74.0	11186	11575	7352
0.2	65.5	49.3	73.9	11116	11759	7344
0.3	61.4	47.5	72.7	10869	11834	7337
0.4	57.6	46.1	70.6	10709	11910	7338
0.5	53.5	44.1	66.8	10455	12013	7307
0.6	51.0	41.7	62.7	10282	12147	7289
0.7	47.4	38.1	58.2	10252	12560	7277
0.8	45.4	36.7	55.8	10218	12651	7239
0.9	42.9	34.7	51.0	10131	12925	7232
1.0	40.2	33.2	48.0	9852	13074	7167

comparing the percent of Hgb concentrations within the target range of 10 to 12 g/dL and the amount of ESA used to achieve this result.

SAM resulted in a greater percent of Hgb observations within the target range and a lower utilization of ESA.

Other Testing

. ISO 14971 Second edition 2007-03-01, Medical devices - Application of risk management to medical devices.
. Software Verification and Validation were conducted based on the use of Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices, Document issued on: May 11, 2005

Clinical Studies

Executive Summary

SAM software was tested in 2 clinical trials. The first trial was a randomized, controlled, double blind trial against standard of care conducted in 62 subjects over a 12 month period. 52 subject completed the study. The proportion of hemoglobin concentrations within the target range was greater for SAM (72.5%) than control (61.9%) (p=0.003). There was no difference in a Composite Safety Event (CSE) as a combination of All-Cause Mortality (ACM), Myocardial Infarction (MI), Cerebrovascular Accident (CVA), and (exacerbation of) Congestive Heart Failure (CHF). The second trial was a combination of a case controlled and cross sectional study. Efficacy was maintained over the 45 month long term follow up where hemoglobin concentrations within the target range ranged from 76.8% to 86.3% for SAM compared to 73.5% to 89.1% for PhySoft AMS™. Safety was maintained over the 45 month long term follow up where hemoglobin concentrations above 12.9 g/dL ranged from 1.5% to 8.7% for SAM compared to 5.9% to 9.4% for PhySoft AMS™. No statistical difference was observed between SAM and PhySoft AMS™ performance.

{11}------------------------------------------------

Conclusion

Smart Anemia Manager (SAM) is substantially equivalent in Indications for Use, principle of operation and technological characteristics to the predicate device. SAM is substantially equivalent in clinical performance as demonstrated in comparison of published performance measures with the predicate device. Dosis. Inc.'s software validation and verification has demonstrated the safety and effectiveness of the SAM software in anemia management for hemodialysis patients and it is the conclusion of Dosis, Inc., that the SAM raises no new questions of safety and effectiveness and is substantially equivalent to the 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.