The Synthesis 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. The Synthesis is an adult oxygenator intended for use in operations on adult patients. Synthesis must not be used for longer than 6 hours. Contact with blood for longer periods is inadvisable.

Device Description

The Synthesis Adult Membrane Oxygenator With Integrated Arterial Filter and Hardshell Venous/Cardiotomy Reservoir Mimesys treated is a high efficiency microporous hollow fiber membrane oxygenator integrated with an heat exchanger and with an arterial filter and connected to a an hardshell venous/cardiotomy reservoir.

AI/ML Overview

The provided text discusses the SYNTHESIS Adult Membrane Oxygenator With Integrated Arterial Filter and Hardshell Venous/Cardiotomy Reservoir, hereafter referred to as "the device." The information describes its characteristics, indications for use, and the studies conducted to demonstrate its substantial equivalence to predicate devices.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly list "acceptance criteria" in a typical quantitative pass/fail table format. Instead, it states that various tests "met established specifications" and that the device was found to be "comparable to the predicate devices concerning with all characteristics" and "substantially equivalent" in relevant functional parameters.

Therefore, the "acceptance criteria" are implied to be the established specifications and performance characteristics of the predicate devices. The "reported device performance" is that it met these specifications and demonstrated substantial equivalence.

Performance Characteristic	Predicate Device Acceptance Criteria (Implied)	Reported Device Performance
Biocompatibility	Requirements of ISO 10993-1:1995 and FDA May 1, 1995 Memorandum for raw materials	Met established specifications
Hemolysis	Established specifications	Met established specifications
Cytotoxicity	Established specifications	Met established specifications
Irritation	Established specifications	Met established specifications
Acute Systemic Toxicity	Established specifications	Met established specifications
Mutagenicity	Established specifications	Met established specifications
Sterility	Established specifications	Met established specifications
Pyrogenicity	Established specifications	Met established specifications
ETO residuals	Established specifications	Met established specifications
Package integrity	Established specifications	Met established specifications
In Vitro Functional Performance (Oxygenator)	"Guidance for Cardiopulmonary Bypass Oxygenators 510(k) submissions - Final Guidance for Industry and FDA Staff" (Nov 13, 2000), ISO 7199 (1996)	Met established specifications; Comparable and substantially equivalent to D 903 Avant 2 Ph.I.S.I.O. predicate
Gas transfer characteristics	Established specifications	Met established specifications
Pressure drop	Established specifications	Met established specifications
Plasma leakage data	Established specifications	Met established specifications
Operating blood volumes	Established specifications	Met established specifications; Advantageous (lower operating blood volumes) compared to predicate for integrated arterial filter feature
Heat exchanger performance	Established specifications	Met established specifications
Hemolysis/cell depletion	Established specifications	Met established specifications
Mechanical integrity	Established specifications	Met established specifications
In Vitro Functional Performance (Arterial Filter)	"Guidance for Cardiopulmonary Bypass Arterial Line Blood Filter 510(k) Submission" (Nov 29, 2000)	Met established specifications; Comparable and substantially equivalent to D 734 Micro 40u predicate
Filtration efficiency	Established specifications	Met established specifications
Air removal (handling)	Established specifications	Met established specifications
In Vitro Functional Performance (Venous/Cardiotomy Reservoir)	"Guidance for Blood Extracorporeal Blood Circuit Defoamer 510(k) Submission" (Nov 29, 2000)	Met established specifications
Breakthrough times and volumes	Established specifications	Met established specifications
Reservoir graduated scale accuracy	Established specifications	Met established specifications
Residual blood volume	Established specifications	Met established specifications
Defoaming capacity	Established specifications	Met established specifications
Filtration efficiency	Established specifications	Met established specifications
Leaching studies	Established specifications	Met established specifications
Blood compatibility characterization	Established specifications	Met established specifications

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Sample Size: The document does not specify the exact numerical sample sizes for the "test set" for any of the in vitro or biocompatibility tests. It states that "A complete battery of tests were carried out" and "In vitro testing were carried out."
Data Provenance: The studies were performed by the manufacturer, Dideco S.p.A., located in Mirandola (MO), Italy. The tests were conducted according to US FDA guidance documents and international ISO standards. The data is prospective, as it describes a series of tests performed on the device.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This product is a medical device (oxygenator, filter, reservoir) for cardiopulmonary bypass. The evaluation of its performance relies on objective laboratory testing and adherence to published performance standards and guidance documents, not on human expert interpretation of data like in an imaging study. Therefore, the concept of "experts used to establish ground truth" with specific qualifications in the context of interpretation (e.g., radiologists) is not applicable here.

The "ground truth" for device performance is defined by the established specifications and requirements outlined in the relevant guidance documents and ISO standards (e.g., ISO 10993-1, ISO 7199, FDA guidances for oxygenators, defoamers, and arterial filters). The experts involved would be the engineers, scientists, and technicians who designed the tests, performed them, and analyzed the results according to these standards, but their number and specific qualifications are not detailed.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

The concept of an "adjudication method" (like 2+1 or 3+1) is typically relevant for studies where subjective expert opinion is used to establish ground truth from complex medical data (e.g., images for diagnostic AI). For this device, the tests are primarily objective laboratory measurements against predefined performance metrics and specifications. Therefore, an adjudication method in the sense of resolving conflicting expert opinions is not applicable. The results are either within specifications or they are not.

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

MRMC Study: No, an MRMC comparative effectiveness study was not done. This type of study design is used for evaluating diagnostic or interpretive AI systems that assist human readers (e.g., radiologists interpreting images). The device in question is a mechanical medical device, not an AI system.
Effect Size of Human Readers with/without AI: Not applicable, as there is no AI component or human reader interaction with an AI system described for this device.

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

No, a standalone (algorithm only) performance study was not done. This concept is typically relevant for AI algorithms. The studies performed were in vitro laboratory tests evaluating the device's physical and functional performance (e.g., gas transfer, filtration, biocompatibility) as a standalone medical product. While these tests evaluate the device without a human "in-the-loop" in the sense of interpretation, it's not an "algorithm only" study as understood in the context of AI.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The "ground truth" for the performance of this medical device is established by:

Referenced Standards and Guidances: Adherence to established international standards (ISO 10993-1, ISO 7199) and US FDA guidance documents for cardiopulmonary bypass oxygenators, defoamers, and arterial filters. These documents define the accepted performance metrics and test methodologies.
Predicate Device Performance: The functional and safety characteristics of the legally marketed predicate devices (D 903 Avant 2 Ph.I.S.I.O. and D 734 Micro 40u Arterial Filter) served as the benchmark for substantial equivalence. The "ground truth" is that the new device must perform comparably or equivalently to these established devices across all functional parameters.
Established Specifications: The document repeatedly refers to "established specifications" for various tests, which represent the target performance metrics that the device must meet.

8. The sample size for the training set

This device is a physical medical device, not an AI model. Therefore, the concept of a "training set" (used to train a machine learning algorithm) is not applicable.

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

Not applicable, as there is no training set for this type of medical device.

Summary

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KC22450

OCT 2 2 2002

510(k) SUMMARY

SUBMITTER:	Dideco S.p.A.86, Via Statale 12 Nord41037 Mirandola (MO) Italy
CONTACT PERSON:	Luigi VecchiPhone: 011 39 0535 29811Fax: 011 39 0535 25229
DATE PREPARED:	July 12, 2001
DEVICE TRADE NAME:	SYNTHESIS: Adult Membrane Oxygenator With IntegratedArterial Filter and Hardshell Venous/Cardiotomy ReservoirMimesys treated (Phosphorylcholine coating hereinaftercalled PC coating)
COMMON NAME:	Hollow Fiber Membrane Oxygenator withHardshellVenous/Cardiotomy Reservoir and Integrated Arterial FilterHollow Fiber Membrane Oxygenator with Integrated ArterialFilterHardshell Venous/Cardiotomy Reservoir
CLASSIFICATION NAME:	Cardiopulmonary Bypass OxygenatorCardiopulmonary Bypass Heat ExchangerCardiopulmonary Bypass Blood ReservoirCardiopulmonary Bypass DefoamerCardiopulmonary Bypass Arterial Line Blood Filter.
PREDICATE DEVICES:	D 903 Avant 2 Ph.I.S.I.O. Adult Hollow Fiber OxygenatorOxygenator with Integral Hardshell Cardiotomy / VenousReservoir with Biocompatible Treatment Surface (Ph.I.S.I.O.)(K020351)
	D 734 Micro 40u Adult Arterial Filter with 40u Screen (K952270)

DEVICE DESCRIPTION:

INDICATION FOR USE:

The Synthesis Adult Membrane Oxygenator With Integrated Arterial Filter and Hardshell Venous/Cardiotomy Reservoir Mimesys treated (PC coating) hereinafter called the Synthesis, is a sterile, nonpyrogenic device intended for use in cardiopylmonary bypass circuits as substitute for the lungs (transfer of oxygen and removal of carbon dioxide), to control the arterial/temperature, and as venous blood reservoir and filler element to eliminate gas emboli and remove blood component aggregates larger than 40 um. Synthesis is an adult oxygenator intended for use in operations on adult patients. Synthesis must not be used for longer than 6 hours. Contact with blood for longer periods is inadvisable.

TECHNOLOGICAL CHARACTERISTICS:

The Synthesis adult membrane oxygenator with Integrated hardshell venous/cardiotomy reservoir, heat exchanger and arterial filter, is essentially identical to the D 903 Avant 2 Ph.l.S.l.O. predicate device with

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: espect to operating principles, control mechanisms and biocompatibility of the hardshell cardiotomy/venous reservoir present in both Synthesis and Avant Ph.J.S.I.O. share the same technological characteristics, operating principles and materials. The only modification made on the reservoir consists of a complete revision of the cardiotomy filter geometry and housing design. The Synthesis with reference to the integrated arterial filter is also substantially equivalent to the D 734 Micro 40u predicate device with resoect to the expected main function given to an ordinary arterial filter. The coating is identical to the phosphorylcholine coating used on the D 903 Avant Ph.J.S.I.O. predicate device.

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 testing on the raw materials. Testing were performed on the Synthesis. (accelerated aging). The device aged up to three years was tested for Hemolysis, Cytotoxicity, Irritation, Acute Systemic Toxicity and Mutagenicity, Sterility, Pyrogenicity, ETO residuals and package integrity testing were also conducted. The results of this testing met established specifications.

IN VITRO TEST RESULTS:

In vitro testing were carried out in accordance with the requirements of "Guidance for Cardiopulmonary Bypass Oxygenators 510(k) submissions - Final Guidance for Industry and FDA Staff" issued on November 13, 2000 - "Guidance for Blood Extracorporeal Blood Circuit Defoamer 510(k) Submission" Final Guidance for industry and FDA issued on November 29, 2000 - "Guidance for Cardiopulmonary Bypass Arterial Line Blood Filter 510(k) Submission" Final Guidance for industry and FDA issued on November 29, 2000 and when applicable, following the ISO 7199 (1996) standard for "Cardiovascular Implants and Artificial Organs -Extra Corporeal Blood-Gas Exchangers (Oxygenator)" for providing the data necessary to demonstrate both the substantial equivalence with the predicate devices and also complying with safety and effectiveness requirements. The device aged up to 3 years was tested for gas transfer characteristics, pressure drop, plasma leakage data, operating blood volumes, heat exchanger performance evaluation, hemolysis/cell depletion, mechanical integrity, arterial filter characterization efficiency and air removal). venous cardiotomy reservoir characterization (including breakthrough times and volumes, reservoir graduated scale accuracy and residual blood volume, defoaming capacity and filtration efficiency and leaching studies and blood compatibility characterization. The results of this tests met established specifications. For comparative purposes, the same testing, when applicable, has been conducted also on the D 903 Avant 2 Ph.l.S.l.O. and on the D 734 Micro Arterial Filter predicate device.

The result of the study showed that the device is comparable to the predicate devices concerning with all characteristics.

MARKETING HISTORY:

Up to now the Synthesis is in commercial distribution in Europe since January 2002 and currently about 150 units have been placed on the market. No reports of adverse events involving patient safety due to malfunctioning have been received.

CONCLUSIONS:

The results of in vitro studies demonstrate that the Synthesis performs in a manner substantially equivalent to the D 903 Avant 2 Ph.I.S.I.O. adult hollow fiber oxygenator with respect to the relevant functional parameters. Furthermore the Synthesis performs in a manner substantially equivalent to the D 734 Micro 40 p arterial filter predicate device with respect to the filtration efficiency and air handling. Data collected show that the feature of integration of the arterial filter to the oxygenating module is advantageous in terms of lower operating blood volumes during procedures. Biocompatibility studies demonstrate that the phosphorylcholine coating is biocompatible and functional tests demonstrate that its performance are equivalent to the D 903 Avant Ph.I.S.I.O. predicate device, according to its intended use. Additional testing has also demonstrated the effectiveness of production techniques to assure that the oxygenator is sterile and non-pyrogenic.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of a human figure, with three flowing lines representing the head, body, and legs. The figure is positioned to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA", which is arranged in a circular pattern around the figure.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

OCT 22 2002

Dideco S.p.A. c/o Mr. Barry Sall Parexel International Corporation 195 West Street Waltham, MA 02451-1163

Re: K022450

Synthesis Adult Membrane Oxygenator with Integrated Arterial Filter Regulation Number: 870.4350 Regulation Name: CPB Oxygenator Regulatory Class: II (two) Product Code: DTZ Dated: July 25, 2002 Received: July 26, 2002

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. 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

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Page 2 - Mr. Barry Sall

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 and additionally 21 CFR Part 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4646. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html

Sincerely yours,

Megal Moyna

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):

Device Name: SYNTHESIS Adult Membrane Oxygenator with Integrated Arterial Filter and Hardshell Venous/Cardiotomy Reservoir

Indications For Use:

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NECESSARY)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Mefamagnan for BOZ
Division of Cardiovascular & Respiratory Devices
510(k) Number 46022450

Prescription Use (Per 21 CFR 801.109) OR Over-The-Counter Use .

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.”