Synthesis Ph.I.S.I.O. is a sterile, nonpyrogenic device intended for use in cardiopulmonary bypass circuits as substitute for the lungs (transfer of oxygen and removal of carbon dioxide), to control the arterial/venous temperature, and as venous blood reservoir and filter element to eliminate gas emboli and remove blood component aggregates larger than 40 m. SYNTHESIS Ph.I.S.I.O. is an adult oxygenator intended for use in operations on adult patients. SYNTHESIS Ph.I.S.I.O. must not be used for longer than 6 hours. Contact with blood for longer periods is inadvisable.

Synthesis M Ph.I.S.I.O. is intended for use in cardiopulmonary bypass circuits as substitute for the lungs (transfer of oxygen and removal of carbon dioxide), to control the arterial/venous temperature, and as filter element to eliminate gas emboli and remove blood component aggregates larger than 40 µm. Synthesis M Ph.I.S.I.O. is an adult oxygenator intended for use in operations on adult patients. Synthesis M Ph.I.S.I.O. must not be used for longer than 6 hours. Contact with blood for longer periods is inadvisable.

Synthesis R Ph.I.S.I.O. has been specifically designed for cardiovascular procedures requiring cardiopulmonary by-pass. It collects venous blood and it defoams, filters and stores the blood from the operating field through thoracic, intracardiac and general suction. Synthesis R Ph.I.S.I.O. can be used postoperatively for chest drainage. It is suggested not to use Synthesis R Ph.I.S.I.O. for more than 6 hours,

Synthesis C Ph.I.S.I.O. is intended for use in cardiopulmonary bypass circuits as substitute for the lungs (transfer of oxygen and removal of carbon dioxide), to control the arterial/venous temperature, and as venous blood reservoir and filter element to eliminate gas emboli and remove blood component aggregates larger than 40 µm. Synthesis C Ph.I.S.I.O. is an adult oxygenator intended for use in operations on adult patients. Synthesis C Ph.I.S.I.O. must not be used for longer than 6 hours. Contact with blood for longer periods is inadvisable,

Device Description

SYNTHESIS Ph.I.S.I.O. Adult Membrane Oxygenator With Integrated Arterial Filter and Hardshell Venous/Cardiotomy Reservoir with PhosphoryIcholine (Ph.I.S.I.O.) hereinafter called the SYNTHESIS Ph.I.S.I.O., is a high efficiency microporous hollow fiber membrane oxygenator integrated with a heat exchanger and an arterial filter and connected to a hardshell cardiotomy venous reservoir. The SYNTHESIS Ph.I.S.I.O. (and other modified versions) have been modified for the change in coating material applied to the arterial filter and for some ergonomic and cosmetic enhancements. The arterial filter of the device is now coated with a new coating containing the same phosphorylcholine monomer currently used for coating of the device. No modification to the intended use has been made as result of the modifications.

AI/ML Overview

The provided text describes a medical device, the SYNTHESIS Ph.I.S.I.O. Adult Oxygenator, and its clearance through a 510(k) submission. This type of submission relies on demonstrating substantial equivalence to a predicate device, rather than a full clinical trial with acceptance criteria and a human-in-the-loop study as would be seen for AI/ML devices.

Therefore, many of the requested sections pertaining to AI/ML device studies (such as sample size for test sets, ground truth establishment, expert adjudication, MRMC studies, standalone performance, training set size) are not applicable to this document because it describes a physical medical device (an oxygenator) and its regulatory clearance process, not a software-based diagnostic or therapeutic AI/ML device.

However, I can extract information related to the device's performance and the testing conducted to demonstrate its substantial equivalence to a predicate device, which serves a similar function to acceptance criteria and demonstration of meeting them.

Here's a breakdown of the requested information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The "acceptance criteria" for this device are primarily based on demonstrating substantial equivalence to the predicate device (SYNTHESIS MIMESYS) and meeting established specifications outlined in relevant ISO standards and FDA guidances. The performance is reported in terms of meeting these specifications and comparability to the predicate.

Acceptance Criteria / Performance Metric	Reported Device Performance
Biocompatibility:
Hemolysis	Met established specifications
Hemocompatibility (including thrombosis & blood compatibility)	Met established specifications (new coating biocompatible)
Cytotoxicity	Met established specifications
Irritation	Met established specifications
Acute Systemic Toxicity	Met established specifications
Mutagenicity	Met established specifications
Sterility	Met established specifications (production techniques effective)
Pyrogenicity	Met established specifications (device non-pyrogenic)
ETO residuals	Met established specifications
Package integrity	Met established specifications (shipping carton provided adequate protection)
In Vitro Performance (Arterial Filter Characterization):
Priming Efficiency	Met established specifications
Pressure Drop	Met established specifications
Hemolysis/Cell Depletion	Met established specifications
Visual Inspection	Met established specifications
Filtration Efficiency	Met established specifications
Air Handling	Met established specifications
Structural Integrity	Met established specifications
Pressure Integrity	Met established specifications
In Vitro Performance (Stability of Coating):
Leaching Flaking of Coating	Met established specifications
Cracking of Coating	Met established specifications
In Vitro Performance (Hardshell Cardiotomy/Venous Reservoir Characterization):
Breakthrough Time and Volume	Met established specifications
Graduated Scale Accuracy	Met established specifications
Hemolysis/Cell Depletion	Met established specifications
Filtration Efficiency	Met established specifications
Overall Comparison to Predicate Device:
Technological characteristics, operating principles, and materials	Essentially identical, characteristics comparable
Performance (gas transfer, operating blood volumes, heat exchanger, PC coating	Performance is equivalent to predicate device
uniformity, softshell reservoir, residual blood volume, defoaming capacity)

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

Sample Size: The document does not specify exact sample sizes for each in vitro test. It generally refers to "a complete battery of tests" and "the device was aged up to 3 (+1 year considered as a worst case) was tested for...". For comparative purposes, "the same testing, when applicable, has been conducted also on the SYNTHESIS MIMESYS predicate device."
Data Provenance: The testing was conducted in vitro, in accordance with international standards (ISO 10993-1:1995, ISO 15675:2001, ISO 15674:2001) and FDA guidances ("Guidance for Cardiopulmonary Bypass Arterial line Blood Fitter 510(k) Submission," "Guidance for Blood Extracorporeal Blood Circuit Defoamer 510(k) Submission"). The country of origin of the data is not explicitly stated but implied to be from the manufacturer's testing facilities, likely in Italy (Sorin Group Italia S.r.l.). The data is retrospective in the sense that it's laboratory testing results rather than dynamically generated patient data.

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

Not applicable. This pertains to an AI/ML device relying on expert-labeled data for ground truth. This document describes a physical medical device and its laboratory performance testing, which does not typically involve experts establishing a "ground truth" in the same way as, for example, image interpretation. The "truth" is established by the performance against pre-defined engineering and safety specifications within the testing standards.

4. Adjudication Method for the Test Set

Not applicable. No adjudication method, such as 2+1 or 3+1, is mentioned because this is not a study involving human interpretation or subjective assessment that would require 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

Not applicable. This is not an AI/ML device.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Not applicable. This is not an AI/ML device.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The "ground truth" here is the adherence to pre-defined engineering specifications, safety parameters, and performance benchmarks as established by relevant international standards (ISO 10993, ISO 15675, ISO 15674) and FDA guidances. The device's performance is compared against these objective criteria and shown to be substantially equivalent to a predicate device that also meets these criteria. For example, "Hemolysis... met established specifications" means the measured hemolysis fell within the acceptable range defined by the standard.

8. The Sample Size for the Training Set

Not applicable. This is not an AI/ML device that requires a training set in the machine learning sense.

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

Not applicable. This is not an AI/ML device.

Summary

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Ko73380

Synthesis Ph.I.S.I.O. Adult Oxygenator Sorin Group Italia S.r.I.

510(k) SUMMARY
----------------	--

SUBMITTER:	Sorin Group Italia S.r.l.86, Via Statale 12 Nord41037 Mirandola (MO) Italy	FEB 29 2008
CONTACT PERSON:	Luigi VecchiPhone: 011 39 0535 29811Fax: 011 39 0535 25229
DATE PREPARED:	November 30, 2007
DEVICE TRADE NAME:	SYNTHESIS Ph.I.S.I.O.: Adult Membrane OxygenatorWith Integrated Arterial Filter and HardshellVenous/Cardiotomy Reservoir with Phosphorylcholine(Ph.I.S.I.O.) coatingSYNTHESIS C Ph.I.S.I.O.: Adult Membrane OxygenatorWith Integrated Arterial Filter and Softshell VenousReservoir with Phosphorylcholine (Ph.I.S.I.O.) coatingSYNTHESIS M Ph.I.S.I.O.: Adult Membrane OxygenatorWith Integrated Arterial Filter with Phosphoryulcholine(Ph.I.S.I.O.) CoatingSYNTHESIS R Ph.I.S.I.O: Hardshell Venous andCardiotomy Reservoir with Phosphorylcholine(Ph:I.S.I.O.) Coating
COMMON NAME:	Hollow Fiber Membrane Oxygenator/Integrated ArterialFilter/ReservoirHollow Fiber Membrane Oxygenator/Softshell VenousReservoir/Integrated Arterial FilterHollow Fiber Membrane Oxygenator/Integrated ArterialFilterHollow Fiber Membrane Oxygenator/Integrated ArterialFilterSoftshell Venous Reservoir
CLASSIFICATION NAME:	Cardiopulmonary Bypass Oxygenator/ CardiopulmonaryBypass Heat Exchanger/ Cardiopulmonary BypassBlood Reservoir/ Cardiopulmonary Bypass Defoamer/Cardiopulmonary Bypass Arterial Line Blood Filter
PREDICATE DEVICES:	SYNTHESIS MIMESYS Adult Membrane Oxygenatorwith Integrated Arterial Filter and HardshellVenous/Cardiotomy Reservoir Mimesys treated(Phosphorylcholine coating hereinafter called PCcoating) (K031233)SYNTHESIS C MIMESYS: Adult Membrane OxygenatorWith Integrated Arterial Filter and Softshell VenousReservoir Mimesys Treated (Phosphorylcholine coatinghereinafter called PC coating)

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SYNTHESIS M MIMESYS Adult Membrane Oxygenator Integrated with Arterial Filter Mimesys treated (PhosphoryIcholine coating hereinafter called PC coating) SYNTHESIS R MIMESYS: Hardshell Venous and Cardiotomy Reservoir Mimesys treated (PhosphoryIcholine coating hereinafter called PC coating)

DEVICE DESCRIPTION:

INDICATION FOR USE:

SYNTHESIS Ph.I.S.I.O. is a sterile, nonpyrogenic device intended for use in cardiopulmonary bypass circuits as substitute for the lungs (transfer of oxygen and removal of carbon dioxide), to control the arterial/venous temperature, and as venous blood reservoir and filter element to eliminate gas emboli and remove blood component aggregates larger than 40 m. SYNTHESIS Ph.I.S.I.O. is an adult oxygenator intended for use in operations on adult patients. SYNTHESIS Ph.I.S.I.O. must not be used for longer than 6 hours. Contact with blood for longer periods is inadvisable.

TECHNOLOGICAL CHARACTERISTICS:

The SYNTHESIS Ph.I.S.I.O. Adult Membrane Oxygenator with Integrated Arterial Filter and Hardshell Venous/Reservoir with Phopsporilcholine (Ph.l.S.I.O.) coating, is essentially identical to the SYNTHESIS MIMESYS predicate device with respect to operating principles, control mechanisms and biocompatibility of the new phosphorylcholine coating. The major modification made to the SYNTHESIS Ph.I.S.I.O. (and other modified versions) is the application of the new phoshorylcholine coating on the integrated arterial filter. No modification has been made to the current phosphorylcholine coating already present on the entire oxygenating module with heat exchanger and hardshell venous reservoir (except the fillering media of the reservoir) and softshell venous reservoir. The hardshell venous reservoir present in both SYNTHESIS Ph.I.S.I.O. and SYNTHESIS MIMESYS predicate device share the same technological characteristics, operating principles and materials except for some ergonomic modifications to ensure a more effective use.

The oxygenator is ethylene oxide sterilized and has a nonpyrogenic fluid path. It is for single use only.

BIOCOMPATIBILITY TEST RESULTS:

A complete battery of tests were carried out in accordance with the requirements of ISO 10993-1:1995 and the FDA May 1, 1995 Memorandum on the use of the ISO 10993 standard for biocompatibility

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Synthesis Ph.I.S.I.O. Adult Oxygenator	Traditional 510(k)
Sorin Group Italia S.r.I.	November 30, 2007

testing on the raw materials. Testing was performed on the SYNTHESIS Ph.I.S.I.O. (accelerated aging). The device was tested for Hemolysis, Hemocompatibility (including thrombosis and blood compatibility study with human blood), Cytotoxicity, Irritation, Acute Systemic Toxicity and Mutagenicity, Sterility, Pyrogenicity. ETO residuals and package integrity testing were also conducted. The resting met established specifications.

IN VITRO TEST RESULTS:

In vitro testing were carried out in accordance with the requirements of "Guidance for Cardiopulmonary Bypass Arterial line Blood Fitter 510(k) Submission" Final Guidance for industry and FDA issued on November 29, 2000; "Guidance for Blood Extracorporeal Blood Circuit Defoamer 510(k) Submission" Final Guidance for Industry and FDA issued on November 29, 2000 - ISO 15675:2001 "Cardiovascular implants and artificial organs - Cardiopulmonary bypass systems - Arterial line blood filters" and ISO 15674:2001 - "Cardiovascular implants and artificial organs - Hardshell cardiotomy/venous reservoir systems (with/without filter) and soft venous reservoir bags", where applicable for providing the data necessary to demonstrate both the substantial equivalence with the predicate device and also compliant with safety and effectiveness requirements. The device was aged up to 3 (+1 year considered as a worst case) was tested for: Arter Characterization (including Priming Efficiency, Pressure Drop, Hemolysis/Cell Depletion & Visual Inspection. Filtration Efficiency, Air Handling, Structural Integrity, Pressure Integrity); Stability of Coating (including Leaching Flaking of Coating, Cracking of Coating); Hardshell Cardiotomy(Venous Reservoir Characterization (including: Breakthrough Time and Volume, Graduated Scale Accuracy, Hemolysis/Cell Depletion, Filtration Efficiency). The results of these tests met established specifications. For comparative purposes, the same testing, when applicable, has been conducted also on the SYNTHESIS MIMESYS predicate device. This 510(k) crosses reference performance data previously submitted in the SYNTHESIS MIMESYS 510k (K031233) for the gas transfer studies, operating blood volumes, heat exchanger performance evaluation, uniformity of PC coating on coated surfaces, softshell venous reservoir characterization (micorembolic activity and filtration efficiency), residual blood volume, defoaming capacity and breakthroughtime and volume of the cardiotomy section as the above mentioned aspects are not affected by the modification. The shipping carton passed the basic testing and was still capable of providing adequate protection for further handling.

The results of the study showed the device characteristics between SYNTHESIS Ph.I.S.I.O. and SYNTHESIS MIMESYS were comparable.

CONCLUSIONS:

The results of in vitro studies demonstrate that the SYNTHESIS Ph.I.S.I.O. (and other modified versions) devices perform in a manner substantially equivalent to the predicate devices. Biocompatibility studies demonstrate that the new phosphorylcholine-based coating is biocompatible and functional tests demonstrate that its performance is equivalent to the SYNTHESIS MIMESYS predicate device, according to its intended use. Additional testing has demonstrated the effectiveness of production techniques to assure that the oxygenator is sterile and non-pyrogenic.

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Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

FEB 2 9 2008

Sorin Group Italia, S.r.1. c/o Mr. Barry Sall Principal Consultant Parexel Consulting 200 West Street West Street, Waltham, MA 02451-1163

Re: K073380

Synthesis Ph.I.S.I.O. Adult Membrane Oxygenator with Integrated Arterial Filter and Hardshell Venous/Cardiotomy Reservoir with Phosphorylcholine (Ph.J.S.I.O.) Coating Regulation Number: 21 CFR 870.4350 Regulation Name: Cardiopulmonary bypass oxygenators Regulatory Class: Class II Product Code: DTZ Dated: November 30, 2007 Received: December 3, 2007

Dear Mr. Sall:

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 (PMA), 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.

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Page 2 - Mr. Barry Sall

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. 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 Center for Devices and Radiological Health's (CDRH's) Office of Compliance at (240) 276-0120. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

suma R. Wchmer

· Bram D. Zuckerman, M.D. Director Division of Cardiovascular Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known): _长�73380

Device Name: Synthesis Ph.I.S.I.O. Adult Membrane Oxygenator with Integrated Arterial Filter and Hardshell Venous/Cardiotomy Reservoir with PhosphoryIcholine (Ph.1.S.I.O.) Coating

Indications For Use:

Synthesis Ph.J.S.I.O. is intended for use in cardiopulmonary bypass circuits as substitute for the lungs (transfer of oxygen and removal of carbon dioxide), to control the arterial/venous temperature, and as venous blood reservoir and filter element to eliminate gas emboli and remove blood component aggregates larger than 40 um. Synthesis Ph.I.S.I.O. is an adult oxygenator intended for use in operations on adult patients. Synthesis Ph.I.S.I.O. must not be used for longer than 6 hours. Contact with blood for longer periods is inadvisable.

Synthesis M Ph.I.S.I.O. Adult Membrane Oxygenator with Integrated Arterial Filter with PhosphoryIcholine (Ph.I.S.I.O.) Coating

Indications For Use:

Synthesis M Ph.1.S.I.O. is intended for use in cardiopulmonary bypass circuits as substitute for the lungs (transfer of oxygen and removal of carbon dioxide), to control the arterial/venous temperature, and as filter element to eliminate gas emboli and remove blood component aggregates larger than 40 µm. Synthesis M Ph.I.S.I.O. is an adult oxygenator intended for use in operations on adult patients. Synthesis M Ph.I.S.I.O. must not be used for longer than 6 hours. Contact with blood for longer periods is inadvisable.

Synthesis R Ph.I.S.I.O. Hardshell Venous/Cardiotomy Reservoir with Phosphorycholine (Ph.J.S.I.O.) Coating

Indications For Use:

Synthesis C Ph.I.S.I.O. Adult Membrane Oxygenator with Integrated Arterial Filter and Softshell Venous Reservoir with PhosphoryIcholine (Ph.I.S.I.O.) Coating

Indications For Use:

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-the-Counter Use (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)
(Division Sign-Off)

Division of Cardiovascular Devices

5 (UIK) Number Ko + 55 80

Regulation Number and Section

§ 870.4350 Cardiopulmonary bypass oxygenator.

(a)
Identification. A cardiopulmonary bypass oxygenator is a device used to exchange gases between blood and a gaseous environment to satisfy the gas exchange needs of a patient during open-heart surgery.(b)
Classification. Class II (special controls). The special control for this device is the FDA guidance document entitled “Guidance for Cardiopulmonary Bypass Oxygenators 510(k) Submissions.”