The Penumbra System is intended for use in the revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (in the internal carotid, middle cerebral - M1 and M2 segments, basilar, and vertebral arteries) within 8 hours of symptom onset.

Device Description

The Penumbra System Separator Flex (026, 032, 041, and 054) is an alternative to the current Penumbra System Separators. The Separator Flex utilizes a Nitinol core wire in place of the current stainless steel corewire. The Flex utilizes a Nitinol core wire in all four current sizes (026, 032, 041, and 054). Both the existing Separators and the subject Separator Flex models will be available to address Physician preference of stainless steel and nitinol. The device is provided sterile, nonpyrogenic, and intended for single use only.

AI/ML Overview

The Penumbra System® Separator™ Flex (K100769) is a medical device intended for the revascularization of patients with acute ischemic stroke. The acceptance criteria and the study proving the device meets these criteria are detailed below.

1. Table of Acceptance Criteria and Reported Device Performance

Test	Acceptance Criteria	Reported Device Performance
Biocompatibility
In Vitro Cytotoxicity	No evidence of cell lysis or toxicity	No evidence of cell lysis or toxicity
Acute Intracutaneous Reactivity (Irritation)	No evidence of irritation	No evidence of irritation
Acute Systemic Toxicity	No evidence of systemic toxicity	No evidence of systemic toxicity
Rabbit Pyrogen Study	No evidence of material-mediated pyrogenicity	No evidence of material-mediated pyrogenicity
Sensitization	Non-sensitizing	Non-sensitizing
In Vitro Hemolysis	Non-hemolytic	Non-hemolytic
In Vitro Coagulation (PT, PTT)	Coagulation times within normal range, non-thrombogenic	Coagulation times within normal range, non-thrombogenic
Complement Activation	No greater biological response than corresponding control	No greater biological response than corresponding control
Design Verification (Bench-Top Testing)
Dimensional / Visual Inspection	Met established requirements	All sizes passed successfully
Simulated Use (Reperfusion Catheter / Separator Flex / Aspiration Tubing Assembly Performance)	Met established requirements	All sizes passed successfully
Separator Flexibility Test	Met established requirements	All sizes passed successfully
Separator Flex Bond Joint Test	Met established requirements	Passed successfully

2. Sample Size and Data Provenance

The provided document does not specify the exact sample sizes for each non-clinical test (biocompatibility and bench-top testing). However, it states that "All studies were conducted pursuant to 21 CFR, Part 58, Good Laboratory Practices" for biocompatibility, and for design verification, "All testing was performed using units which met applicable Design Control processed goods release requirements." This indicates that standard laboratory testing practices were followed to ensure sufficient sample sizes for statistically valid results, even if the explicit numbers are not given.

The data provenance is from non-clinical studies conducted by Penumbra, Inc. in the USA (Alameda, CA), as indicated by the sponsor's address and the regulatory context of a 510(k) submission to the FDA. The testing can be considered prospective in the sense that it was specifically designed and executed to support the regulatory submission for this new device.

3. Number of Experts and Qualifications for Ground Truth

This submission pertains to a medical device (catheter/separator) and relies on non-clinical data (biocompatibility and bench-top testing) rather than clinical data requiring expert review of medical images or patient outcomes. Therefore, the concept of "ground truth" derived from experts, as typically understood in studies involving diagnostic devices or AI algorithms, does not apply in this context. The "ground truth" for these tests is based on established scientific methods and pass/fail criteria.

4. Adjudication Method for the Test Set

As the studies are non-clinical (biocompatibility and bench-top testing), an adjudication method in the context of expert review (e.g., 2+1, 3+1) is not applicable. The results are determined by objective measurements and analyses performed according to established scientific protocols.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted. This is a medical device (catheter) and not a diagnostic imaging AI algorithm, so such a study design is generally not relevant. The effectiveness is demonstrated through pre-clinical performance testing.

6. Standalone Performance Study

Yes, a standalone performance study was done in the form of the "Design Verification (Bench-Top Testing)". This section evaluates the physical, mechanical, and performance characteristics of the Penumbra System Separator Flex on its own, without human intervention during the actual tests (after the device is assembled and prepared for testing). The tests included:

Dimensional / Visual Inspection
Simulated Use (Reperfusion Catheter / Separator Flex / Aspiration Tubing Assembly Performance)
Separator Flexibility Test
Separator Flex Bond Joint Test

These tests demonstrate the intrinsic performance of the device against predefined specifications.

7. Type of Ground Truth Used

The "ground truth" for the non-clinical studies is based on established scientific and engineering standards and methods.

For biocompatibility, the ground truth is defined by the accepted criteria outlined in ISO-10993 - I (Biological Evaluation of Medical Devices) for various biological responses (cytotoxicity, irritation, systemic toxicity, pyrogenicity, sensitization, hemolysis, coagulation, complement activation).
For design verification (bench-top testing), the ground truth is based on engineering specifications, physical measurements, and functional performance criteria defined by the manufacturer to ensure the device operates as intended and meets safety and performance requirements.

8. Sample Size for the Training Set

Not applicable. This submission describes a physical medical device (catheter/separator), not an AI algorithm that requires a training set. The performance is assessed through bench-top testing and biocompatibility studies.

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

Not applicable. As a physical medical device, there is no "training set" in the context of machine learning. The ground truth for its performance is established through adherence to engineering design specifications, international standards (like ISO-10993), and good laboratory practices.

Summary

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K100769

Penumbra

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Penumbra System® Separator™ Flex

510(k) SUMMARY OF SAFETY & EFFECTIVENESS 10. (as required by 21 CFR § 807.92)

MAY 2 1 2010

Pursuant to Section 12, Part (a)(i)(3A) of the Safe Medical Devices Act of 1990, Penumbra, Inc.
System Santarant Casino and Final planes for the Repumbra System Separator Fle Pursuant to Section 12, Part (a)(1)(3A) of the Sale Medical Develover 100 Separator Flex.
is providing the summary of Substantial Equivalence for the Penumbra System Separato

10.1 Sponsor/Applicant Name and Address

Penumbra, Inc. 1351 Harbor Bay Parkway Alameda, CA 94502, USA

Sponsor Contact Information 10.2

Michaela Mahl Principal Regulatory Specialist Phone: (510) 748-3288 FAX: (510) 217-6414 Email: michaela.mahl@penumbrainc.com

10.3 Date of Preparation of 510(k) Summary

April 20, 2010

10.4 Device Trade or Proprietary Name

Penumbra System® Separator™ Flex

10.5 Device Classification

Regulatory Class: II Cardiovascular Classification Panel: Percutaneous Catheter Classification Name: 21 CFR § 870.1250 Regulation Number: Product Code: NRY

10.6 Predicate Devices

510(k) Number /Clearance Date	Name of Predicate Device	Name of Manufacturer
K090752 / 21 Sep 2009	Penumbra Reperfusion Catheter054, Penumbra Separator 054	Penumbra, Inc.
K072718 / 28 Dec 2007	Penumbra System [026, 032, 041]	Penumbra, Inc.

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ે.

	Penumbra System Separator[026, 032, 041, 054]	Penumbra System Separator Flex[026, 032, 041, 054]
510(k) No.	K072718 & K090752	To be determined
Classification	Class II, NRY	SAME
Indication	The Penumbra System™ is intendedfor use in the revascularization ofpatients with acute ischemic strokesecondary to intracranial large vesselocclusive disease (within the internalcarotid, middle cerebral - M1 andM2 segments, basilar, and vertebralarteries) within 8 hours of symptomonset.	SAME
Materials
Core wire	Stainless Steel	Nitinol Wire
Coating	PTFE GREEN PC	PTFE GREEN PCLow Cure PTFE
Proximal wire		SAME
Outer coil	Stainless Steel	SAME
Core wire	Stainless Steel Core Wire	Nitinol Core Wire
Solder joint	Silver Solder (95% Sn / 5%Ag)	SAME
Distal tip
Outer coil	Stainless Steel	SAME
Inner coil	Platinum Alloy	SAME
Solder joint	Gold Solder (80% Au / 20% Sn)Silver Solder (95% Sn / 5%Ag)	SAME
Separator conetip	Pebax 40D green (026) ,yellow(032), blue (041), purple (054)	SAME
ID band	Polyolefin (PET)	SAME
Sterilization	EtO	SAME
Shelf Life	36 Months	SAME

10.7 Comparison to Predicate Devices

10.8 Device Description

The Penumbra System Separator Flex (026, 032, 041, and 054) is an alternative The Fenamora System Separator Pish (020) 6027 852 8826 Separators. The Separators. The Separator Flex utilizes a Nitinol core wire in place of the current stainless steel corewire. The I lex attiffees a ritmor off in all four current sizes (026, 032, 041, and 054). Both the existing Separators and the subject Separator Flex models will be available to address Physician preference of stainless steel and nitinol. The device is provided sterile, nonpyrogenic, and intended for single use only.

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Penumbra

10.9 Intended Use

10.10 Summary of Non-clinical Data

As required under Section 12, Part (a)(i)(3A) of the Safe Medical Devices Act of 1990, a summary of any information regarding safety and effectiveness of the device follows.

Included in this section are descriptions of the testing's, which substantiates the safe and effective performance of the Penumbra System Separator Flex as well as its substantial equivalence to the predicate devices:

Biocompatibility ●
Design Verification (Bench-Top Testing) .

The subject Penumbra System Separator Flex met all established requirements.

10.10.1 Biocompatibility

Biocompatibility tests conducted for the Penumbra System Separator Flex were selected in accordance with ISO-10993 - I (Biological Evaluation of Medical Devices) guidelines for a limited exposure (≤ 24 hours), externally communicating device with circulating blood contact. All studies were conducted pursuant to 21 CFR, Part 58, Good Laboratory Practices.

Test	Method	Results
In VitroCytotoxicity	ISO Elution Test (MEMExtract)	No evidence of cell lysisor toxicity
AcuteIntracutaneousReactivity(Irritation)	ISO Intracutaneous(Intradermal) InjectionTest	No evidence of irritation
AcuteSystemicToxicity	ISO Acute SystemicInjection Test	No evidence of systemictoxicity
RabbitPyrogen Study	USP Material-MediatedRabbit Pyrogen Test	No evidence of material-mediated pyrogenicity

ISO, 10003 CI P Testing Summary for Separator Flex

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Penumbra

Penumbra System® Separator™ Flex

Test	Method	Results
Sensitization	ISO Maximization Testfor DelayedHypersensitivity	Non-Sensitizing
Hemo-compatibility
-In VitroHemolysis	ASTM Methode(Extraction & DirectContact)	Non-hemolytic
-In VitroCoagulation(PT, PTT)	Prothrombin Time (PT)AssayPartial ThromboplastinTime (PTT) Assay	Coagulation times arewithin the normal rangeNon-Thrombogenic
-ComplementActivation	C3a and SC5b-9 throughEnzyme Assay	No greater biologicalresponse thancorresponding control

In summary, non-clinical testing found the Penumbra System Separator Flex to be non-cytotoxic, non-mutagenic, non-reactive (short and long-term implantation), nonsensitizing, a negligible irritant, non-pyrogenic, and non-toxic (acute systemic).

Design Verification (Bench-Top Testing) 10.10.2

Design Verification testing was conducted to evaluate the physical and mechanical properties of the Penumbra System Separator Flex. All studies were conducted using properties of the renament of yourselves sampling methods as required by the good scientifie procedures. All testing was performed using units which r chantolu Design Control processed goods release requirements. The packaging used were 2x stermbed and enarator Flex is identical to the predicate Penumbra for the Fenanora oferaging. Therefore, no packaging testing was conducted. The tests performed on the Penumbra System Separator Flex included:

Dimensional / Visual Inspection (all sizes) .
Simulated Use (all sizes): Reperfusion Catheter / Separator Flex / Aspiration . Tubing Assembly Performance
Separator Flexibility Test (all sizes) .
Separator Flex Bond Joint Test .

All performed tests passed successfully.

The physical, mechanical and performance testing of the subject Penumbra The problem, moonstrate that the product is safe and effective for its labeled indications and is Substantially Equivalent to the currently marketed predicate devices.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three lines extending from its head, representing the department's mission to protect the health of all Americans and provide essential human services. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular fashion around the eagle.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

MAY 2 ] 2010

Penumbra, Inc. c/o Ms. Michaela Mahl, MSBE Principal Regulatory Specialist 1351 Harbor Bay Pkwy. Alameda, CA 94502

Re: K100769

13100707
Trade/Device Name: Penumbra System® Separator™ Flex (026, 032, 041, 054) Regulation Number: 21 CFR 870.1250 Regulation Name: Percutaneous Catheter Regulatory Class: Class II Product Code: NRY Dated: April 20, 2010 Received: April 21, 2010

Dear Ms. Mahl:

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.

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Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (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/MedicalDeyices/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/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Eile. Hemm of

Malvina B. Eydelman, M. Director Division of Ophthalmic, Neurological, and Ear, Nose and Throat Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known): K | 00 769

Device Name: Penumbra System® Separator™ Flex

Indications for Use:

Prescription Use _____________________________________________________________________________________________________________________________________________________________ (Part)21 CFR 801 Subpart D)

AND/OR

Over The Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Kristen Bowsher

(Division Sign-Off) Division of Ophthalmic, Neurological and Ear, .Nose and Throat Devices'

510(k) Number_K100 369

Regulation Number and Section

§ 870.1250 Percutaneous catheter.

(a)
Identification. A percutaneous catheter is a device that is introduced into a vein or artery through the skin using a dilator and a sheath (introducer) or guide wire.(b)
Classification. Class II (performance standards).