The MARS® is indicated for the treatment of drug overdose and poisonings. The only requirement is that the drug or chemical be dialyzable (in unbound form) and bound by charcoal and/or ion exchange resins.

The MARS® is indicated in the treatment of Hepatic Encephalopathy (HE) due to a decompensation of a chronic liver disease. Clinical trials conducted with MARS® treatments in HE patients having a decompensation of chronic liver disease demonstrated a transient effect from MARS® treatments to significantly decrease their hepatic encephalopathy scores by at least 2 grades compared to standard medical therapy (SMT).

Device Description

The MARS® is a blood detoxification device comprised of dialyzers, adsorption columns, tubing connectors and a monitor unit. It is designed for the combined removal of watersoluble low and middle molecular weight substances and albumin bound molecules. The treatment is based on the dialysis of blood against an albumin-containing dialysate solution.

AI/ML Overview

Here's an analysis of the provided text regarding the MARS® system, focusing on acceptance criteria and supporting studies:

It's important to note that the provided document is a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device rather than outright proving performance against predefined acceptance criteria for a novel device. Therefore, the "acceptance criteria" here are implicitly linked to the performance claimed for the new indication, and the "study" is the information provided to support that new indication and equivalence.

Acceptance Criteria and Reported Device Performance

The core "acceptance criterion" in this 510(k) summary is the demonstration that for a new specific indication, the MARS® system performs at least as safely and effectively as the identified predicate devices, and achieves a specific clinical outcome.

Acceptance Criterion (Implicit)	Reported Device Performance (for the new indication)
For Hepatic Encephalopathy (HE) due to decompensation of chronic liver disease: Demonstrate a significant decrease in HE scores.	"Clinical trials conducted with MARS® treatments in HE patients having a decompensation of chronic liver disease demonstrated a transient effect from MARS® treatments to significantly decrease their hepatic encephalopathy scores by at least 2 grades compared to standard medical therapy (SMT)." Additionally, the device performs "at least as safe and effective as the identified predicate devices."

Acceptance Criterion (Implicit)

Reported Device Performance (for the new indication)

For Hepatic Encephalopathy (HE) due to decompensation of chronic liver disease: Demonstrate a significant decrease in HE scores.

"Clinical trials conducted with MARS® treatments in HE patients having a decompensation of chronic liver disease demonstrated a transient effect from MARS® treatments to significantly decrease their hepatic encephalopathy scores by at least 2 grades compared to standard medical therapy (SMT)." Additionally, the device performs "at least as safe and effective as the identified predicate devices."

Study Details

The document mentions "clinical trials" but provides very limited detail about their methodology. The primary purpose of this 510(k) is to extend the indications for use based on existing (or newly provided) clinical data, not to detail the full protocol of those trials.

Sample size used for the test set and the data provenance:
- Sample Size: Not explicitly stated in the provided text for the Hepatic Encephalopathy (HE) indication. The text only mentions "Clinical trials conducted with MARS® treatments in HE patients."
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). The wording "Clinical trials conducted" generally implies prospective studies, but this is not confirmed.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not specified. This document summarizes the device's regulatory submission, not the detailed clinical trial report.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not specified.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not applicable. This device is a medical apparatus (Molecular Adsorbent Recirculating System), not an AI imaging or diagnostic algorithm that involves human "readers." The "comparative effectiveness" mentioned is between MARS® treatment and Standard Medical Therapy (SMT) for HE patients. The effect size stated is a "decrease [in] hepatic encephalopathy scores by at least 2 grades."
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Not applicable. As noted above, this is a medical device for blood detoxification, not an algorithm.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The "ground truth" for the HE indication appears to be the "hepatic encephalopathy scores" themselves. These scores are clinical assessments, typically made by medical experts (e.g., neurologists, hepatologists) based on standardized scales. So, it would likely involve expert clinical assessment and outcomes data (change in HE scores).
The sample size for the training set:
- Not applicable. As this is not an AI/ML device, there isn't a "training set" in the conventional sense. The "clinical trials" mentioned would be considered the main data set used to demonstrate performance.
How the ground truth for the training set was established:
- Not applicable due to the device type. The outcomes (HE scores) were established through clinical assessment during the trials.

Summary

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GAMBRO.Renal Products

Traditional 510(k) for the Molecular Adsorbent Recirculating System (MARS®)

DEC 1 4 2012

5.0 510(k) SUMMARY

This summary of 510(k) safety and effectiveness has been submitted in accordance with the requirements of the Safe Medical Devices Act (SMDA) of 1990 and 21 CFR 807.92. All data included in this document are accurate and complete to the best of Gambro's knowledge.

Submitter's Name	Gambro Renal Products, Inc.
Address	14143 Denver West Parkway, Suite 400Lakewood, Colorado 80401
Establishment Registration No.	2087532
Contact Person	Kae Miller, Regulatory Affairs Manager, Americas
Telephone Number	303.222.6724
Fax Number	303.222.6916
Date of Summary	December 14, 2012
Device under clearance
Name of the Device	Molecular Adsorbent Recirculating System (MARS®)
Common or Usual Name	Apparatus, Hemoerfusion, Sorbent
Classification Name	Sorbent Hemoperfusion System
Device Class	III
Product Code	78 FLD
Regulation Number	21 CFR 876.5870
Predicate Device Information (1)
Name of the Device	BioLogic-DT® System (BioLogic-DT-1000 with DT-1000-TK)
510(k) Number	K984546 (cleared on August 13, 1999)
Classification Name	Sorbent Hemoperfusion System
Device Class	III
Product Code	78 FLD
Regulation Number	21 CFR 876.5870
Predicate Device Information (2)
Name of the Device	BioLogic-DT® System (BioLogic-DT-1000 with DT-1000-TK)
510(k) Number	K99216 (cleared on September 10, 1999)
Classification Name	Sorbent Hemoperfusion System
Device Class	III
Product Code	78 FLD and FKT
Regulation Number	21 CFR 876.5870
Predicate Device Information (3)
Name of the Device	Molecular Adsorbent Recirculating System (MARS®)
510(k) Number	K033262 (cleared on May 27, 2005)
Classification Name	Sorbent Hemoperfusion System
Device Class	III
Product Code	FLD and NKL
Regulation Number	21 CFR 876.5870

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GAMBROsRenal Products

Traditional 510(k) for the Molecular Adsorbent Recirculating System (MARS®)

Additional Precaution:

Patients treated with MARS® may experience a decrease in blood platelet counts during their treatment due to loss of platelets in the extracorporeal circuit, as with other extracorporeal blood treatments involving medical devices (i.e. acute and chronic hemodialysis, membrane plasmapheresis, continuous renal replacement therapy (CRRT), etc.).

INDICATIONS FOR USE

The MARS® is indicated in the treatment of Hepatic Encephalopathy (HE) due to a decompensation of a chronic liver disease. Clinical trials conducted with MARS® treatments in HE patients having a decompensation of chronic liver disease demonstrated a transient effect from MARS® treatments to significantly decrease their hepatic encephalopathv scores bv at least 2 grades compared to standard medical therapy (SMT).

Contraindication:

The MARS® is not indicated as a bridge to liver transplant. Safety and efficacy has not been demonstrated for this indication in controlled, randomized clinical trials.

The effectiveness of the MARS® device in patients that are sedated could not be established in clinical studies and therefore cannot be predicted in sedated patients.

DEVICE DESCRIPTION

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Image /page/2/Picture/1 description: The image shows the logo for Gambro Renal Products. The logo consists of the word "GAMBRO" in a bold, sans-serif font, followed by ".Renal Products" in a smaller font. There is a small, circular graphic to the left of the word "GAMBRO."

Traditional 510(k) for the Molecular Adsorbent Recirculating System (MARS®)

BRIEF DISCUSSION CLINICAL PERFORMANCE DATA:

The presented data from controlled, multi-center clinical trials support the following new indication for use for MARS® and demonstrate that the device is performing at least as safe and effective as the identified predicate devices.

The MARS® performs albumin dialysis to remove low molecular weight water-soluble solutes and albumin-bound solutes such as drugs and toxins, from the patient's blood.

See Attachment 1.

SUBSTANTIAL EQUIVALENCE

The MARS® is substantially equivalent to the predicate devices since the basic features function and technologies are the same. The minor differences raise no new issues of safety and effectiveness.

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Ku3313

Image /page/3/Picture/1 description: The image shows the logo for Gambro Renal Products. The logo consists of a stylized letter "G" followed by the words "GAMBRO. Renal Products" in a sans-serif font. The word "GAMBRO" is larger and bolder than the words "Renal Products".

Molecular Adsorbent Recirculating System (MARS®)

DEVICE COMPARISION TABLE 5.1

CATEGORY	DEVICE:MARS®	PREDICATE:MARS® K033262	PREDICATE:BioLogic-DT SystemK984546 and K992196
Indications for use	The MARS® isindicated for thetreatment of drugoverdose andpoisonings. The onlyrequirement is thatthe drug or chemicalbe dialyzable (inunbound form) andbound by charcoaland/or ion exchangeresins.The MARS® isindicated in thetreatment of HepaticEncephalopathy (HE)due to adecompensation of achronic liver disease.Clinical trialsconducted withMARS® treatments inHE patients having adecompensation ofchronic liver diseasedemonstrated atransient effect fromMARS® treatments tosignificantly decreasetheir hepaticencephalopathy scoresby at least 2 gradescompared to standardmedical therapy(SMT)	The MARS® is indicated forthe treatment of drugoverdose and poisonings.The only requirement is thatthe drug or chemical bedialyzable (in unboundform) and bound by charcoaland/or ion exchange resins.	Acute HepaticEncephalopathy:The BioLogic-DT System isindicated for the treatment ofacute HepaticEncephalopathy due todecompensation of chronicliver disease or fulminanthepatic failure.Drug Overdose andPoisonings:The BioLogic-DT System isindicated for the treatment ofdrug overdose andpoisonings. The onlyrequirement is that the drugor chemical be dialyzable (inunbound form) and boundby charcoal, such asacetaminophen, tricyclics,barbiturates, tranquilizers,anticancer agents,antimicrobials, theophylline,herbicides, and insecticides.
CATEGORY	DEVICE:MARS®	PREDICATE:MARS® K033262	PREDICATE:BioLogic-DT SystemK984546 and K992196
Contraindications	The MARS® is notindicated as abridge to livertransplant. Safetyand efficacy has notbeen demonstratedfor this indication incontrolled,randomized clinicaltrials.The effectiveness ofthe MARS® device inpatients that aresedated could not beestablished inclinical studies andtherefore cannot bepredicted in sedatedpatients.	The MARS® is not indicatedfor the treatment of chronicliver disease conditions or asa bridge to liver transplant.Safety and efficacy has notbeen demonstrated for theseindications in controlled,randomized clinical trials.	The BioLogic DT is notindicated for the treatment ofchronic liver conditions as abridge to liver transplant.
Treatment kitcomponents	2 dialyzers2 sorbent columnsActivated carbonIon exchanger1 tubing setconsisting of tubing/connectors/clamps/hydrophobic andparticle filters/heaterbag/air traps	2 dialyzers2 sorbent columnsActivated carbonIon exchanger1 tubing set consistingof tubing/connectors/clamps/hydrophobic and particlefilters/heaterbag/air traps	1 dialyzerChemical sorbentsActivated charcoal(carbon)Ion exchanger (powdered)Tubing set
Dialyzer type/membranematerial (bloodcontacting)	Hollow fiberdialyzer/polyamix(PAES)	Hollow fiberdialyzer/polyamix(PAES)	Plate membrane dialyzer/Cellulose acetate
Sorbents	Activated Charcoal(contained in acolumn)Ion exchanger(contained in acolumn)	Activated Charcoal(contained in acolumn)Ion exchanger(contained in acolumn)	Finely powdered ActivatedCharcoal (in suspension)Powdered carbon exchanger(in suspension)
Carrier	Albumin in saline	Albumin in saline	Polyvinylpyrrolidone (PVP)and Pluronic polyols insaline
CATEGORY	DEVICE:MARS®	PREDICATE:MARS® K033262	PREDICATE:BioLogic-DT SystemK984546 and K992196
Bloodcirculationmethod	None: hemodialysissystem controlsblood flow	None: hemodialysis systemcontrols blood flow	Alternating pressure andvacuum ("push-pull" effect)to propel blood throughcircuit (positive pressure andvacuum pump)
Sorbent/dialysatecirculationmethod	Roller pump	Roller pump	Alternating pressure andvacuum
Operationmodes	Preparation(priming)Treatment	Preparation (priming)Treatment	Preparation (priming)Treatment
User interfacecontrol(display)	Selectmanual/automaticoperationReview/changetreatment parametersMonitor devicestatus	Selectmanual/automatic operationReview/changetreatment parametersMonitor device status	Automatic Operation onlyMonitor device status
Automatedmonitoring	In-line pressureAlbumin dialysatetemperatureBlood leakAlbumin dialysateflow ratePump door positionLine voltage	In-line pressureAlbumin dialysatetemperatureBlood leakAlbumin dialysateflow ratePump door positionLine voltage	Sorbent temperatureBlood leakAir bubbleBlood flow rate
Alarms	Blood leakPressureTemperature	Blood leakPressureTemperature	Blood leakAir detector
Blood volumein circuit	200-250mL	200-250mL	200-250mL

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GAMBRO.Renal Products

Molecular Adsorbent Recirculating S10(k) for the
Molecular Adsorbent Recirculating System (MARS*)

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Kizu 6Ko

KII3313

GAMBRO.Renal Products

Molecular Adsorbent Recirculating System (MARS®)

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular pattern around the symbol. The logo is black and white and appears to be a scanned image.

Public Health Service

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

December 14, 2012

Gambro Renal Products, Inc. % Ms. Kae Miller RA Manager, Americas 14143 Denver West Parkway, Suite 400 LAKEWOOD CO 80401

Re: K113313

Trade/Device Name: Molecular Adsorbent Recirculating System (MARS®) Regulation Number: 21 CFR§ 876.5870 Regulation Name: Sorbent hemoperfusion system Regulatory Class: III Product Code: FLD Dated: December 5, 2012 Received: December 10, 2012

Dear Ms. Miller:

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 or any Federal statutes and regulations administered by other Federal agencies.

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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 (reporting of medical 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/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Herbert R. Lerner

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

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GAMBRO Renal Products

Traditional 510(k) for the Molecular Adsorbent Recirculating System (MARS®)

Indications for Use

K113313 510(k) Number (if known):

Molecular Adsorbent Recirculating System (MARS®) Device Name:

Indications for Use Statement

Contraindication:

The MARS® is not indicated as a bridge to liver transplant. Safety and efficacy has not been demonstrated for this indication in controlled, randomized clinical trials. The effectiveness of the MARS® device in patients that are sedated could not be established in clinical studies and therefore cannot be predicted in sedated patients.

Over-The-Counter Use Prescription Use X AND/OR (21 CFR 801 Subpart C) (Part 21 CFR 801 Subpart D) (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

RA 11-063 Revised

(Division Sign-Off) Division of Reproductive, Gastro-Renal, and Urological Devices K113313 510(k) Number

Page 18 of 69

Regulation Number and Section

§ 876.5870 Sorbent hemoperfusion system.

(a)
Identification. A sorbent hemoperfusion system is a prescription device that consists of an extracorporeal blood system similar to that identified in the hemodialysis system and accessories (§ 876.5820) and a container filled with adsorbent material that removes a wide range of substances, both toxic and normal, from blood flowing through it. The adsorbent materials are usually activated-carbon or resins which may be coated or immobilized to prevent fine particles entering the patient's blood. The generic type of device may include lines and filters specifically designed to connect the device to the extracorporeal blood system. The device is used in the treatment of poisoning, drug overdose, hepatic coma, or metabolic disturbances.(b)
Classification. (1) Class II (special controls) when the device is intended for the treatment of poisoning and drug overdose. The special controls for this device are:(i) The device must be demonstrated to be biocompatible;
(ii) Performance data must demonstrate the mechanical integrity of the device (e.g., tensile, flexural, and structural strength), including testing for the possibility of leaks, ruptures, release of particles, and/or disconnections under anticipated conditions of use;
(iii) Performance data must demonstrate device sterility and shelf life;
(iv) Bench performance testing must demonstrate device functionality in terms of substances, toxins, and drugs removed by the device, and the extent that these are removed when the device is used according to its labeling, and to validate the device's safeguards;
(v) A summary of clinical experience with the device that discusses and analyzes device safety and performance, including a list of adverse events observed during the testing, must be provided;
(vi) Labeling must include the following:
(A) A detailed summary of the device-related and procedure-related complications pertinent to the use of the device;
(B) A summary of the performance data provided for the device, including a list of the drugs and/or poisons the device has been demonstrated to remove, and the extent for removal/depletion; and
(vii) For those devices that incorporate electrical components, appropriate analysis and testing must be conducted to verify electrical safety and electromagnetic compatibility of the device.
(2) Class III (premarket approval) when the device is intended for the treatment of hepatic coma and metabolic disturbances.
(c)
Date premarket approval application (PMA) or notice of completion of product development protocol (PDP) is required. A PMA or notice of completion of a PDP is required to be filed with FDA by April 17, 2014, for any sorbent hemoperfusion system indicated for treatment of hepatic coma or metabolic disturbances that was in commercial distribution before May 28, 1976, or that has, by April 17, 2014, been found to be substantially equivalent to any sorbent hemoperfusion device indicated for treatment of hepatic coma or metabolic disturbances that was in commercial distribution before May 28, 1976. Any other sorbent hemoperfusion system device indicated for treatment of hepatic coma or metabolic disturbances shall have an approved PMA or declared completed PDP in effect before being placed in commercial distribution.