Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes a mechanical aspiration system for clot removal and does not mention any AI or ML components.

Therapeutic

Yes
The device is indicated for revascularization and thrombus removal in patients with acute ischemic stroke, which are therapeutic interventions.

Diagnostic

No

The device is indicated for revascularization and thrombus removal, not for diagnosing a condition.

SaMD (Software as a Medical Device)

No

The device description explicitly states it is a "Penumbra 3D Revascularization Device" and describes its physical mechanism of action (drawing clot into a catheter). The performance studies include bench-top testing and animal studies, which are typical for physical medical devices, not software-only devices. The device is also described as being provided sterile and intended for single use, further indicating it is a physical component.

IVD (In Vitro Diagnostic)

Based on the provided information, this device is not an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use clearly describes a device used in vivo (within the body) for the revascularization of patients with acute ischemic stroke. This involves physically removing blood clots from arteries.
Device Description: The description details a system that uses aspiration to draw clot into a catheter, which is a mechanical process performed inside the patient's body.
Lack of IVD Characteristics: There is no mention of the device being used to examine specimens (like blood, urine, or tissue) in vitro (outside the body) to provide information for diagnosis, monitoring, or screening.

The device is a medical device used for a therapeutic procedure, not an in vitro diagnostic test.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Penumbra Reperfusion Catheters and Separators: As part of the Penumbra System, the Reperfusion Catheters and Separators are in the revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (within the internal carotid, middle cerebral - M1 and M2 segments, basilar, and vertebral arteries) within 8 hours of symptom onset. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy are candidates for treatment.

Penumbra 3D Revascularization Device: As part of the Penumbra System, the Penumbra 3D Revascularization Device is indicated for use in the revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (within the internal carotid, middle cerebral-Ml and M2 segments) within 8 hours of symptom onset. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy are candidates for treatment.

Penumbra Aspiration Tubing: As part of the Penumbra System, the Penumbra Sterile Aspiration Tubing is indicated to connect the Penumbra Reperfusion Catheters to the Penumbra Aspiration Pump.

Penumbra Aspiration Pump: The Penumbra Aspiration Pump is indicated as a vacuum source for Penumbra Aspiration Systems.

Product codes (comma separated list FDA assigned to the subject device)

NRY

Device Description

The Penumbra 3D Revascularization Device is an additional component to the currently available Penumbra System. The Penumbra System's fundamental mechanism of action is aspiration. Aspiration draws clot into the Penumbra Reperfusion Catheter to remove the clot. The 3D Revascularization Device is designed to assist the Reperfusion Catheter with thrombus removal if needed. The device is provided sterile, non-pyrogenic, and intended for single use only.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Intracranial large vessel occlusive disease (within the internal carotid, middle cerebral - M1 and M2 segments, basilar, and vertebral arteries)

Indicated Patient Age Range

From 18 to 85 years of age

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Primary Effectiveness Cohort: 150 patients (74 in the 3D / Penumbra System group and 76 in the Penumbra System group).
Data Source: Prospective, randomized, concurrent controlled, non-inferiority design, multi-center clinical study (Penumbra 3D Trial).
Annotation protocol: Angiographic results were adjudicated by an independent Core Laboratory.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Summary of Non-Clinical Data

Biocompatibility Testing: Tests conducted in accordance with EN ISO 10993 -1 guidelines for limited duration (

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).

Summary

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

April 20, 2017

Penumbra, Inc. Ms. Michaela Mahl Senior Manager of Regulatory Affairs One Penumbra Place Alameda, California 94502

Re: K162901

Trade/Device Name: Penumbra 3D Revascularization Device Regulation Number: 21 CFR 870.1250 Regulation Name: Percutaneous Catheter Regulatory Class: Class II Product Code: NRY Dated: March 20, 2017 Received: March 21, 2017

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.

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 devicerelated 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.

1

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education 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. 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 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 Industry and Consumer Education 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.

Carlos L. Pena-S

Carlos L. Peña, PhD, MS Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

2

Indications for Use

510(k) Number (if known) K162901

Device Name Penumbra 3D Revascularization Device

Indications for Use (Describe)

Penumbra Reperfusion Catheters and Separators

As part of the Penumbra System, the Reperfusion Catheters and Separators are in the revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (within the internal carotid, middle cerebral - M1 and M2 segments, basilar, and vertebral arteries) within 8 hours of symptom onset. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy are candidates for treatment.

Penumbra 3D Revascularization Device

As part of the Penumbra System, the Penumbra 3D Revascularization Device is indicated for use in the revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (within the internal carotid, middle cerebral-Ml and M2 segments) within 8 hours of symptom onset. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy are candidates for treatment.

Penumbra Aspiration Tubing

As part of the Penumbra System, the Penumbra Sterile Aspiration Tubing is indicated to connect the Penumbra Reperfusion Catheters to the Penumbra Aspiration Pump.

Penumbra Aspiration Pump The Penumbra Aspiration Pump is indicated as a vacuum source for Penumbra Aspiration Systems.

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)	☑
Over-The-Counter Use (21 CFR 801 Subpart C)	☐

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510(k) Summary

(as required by 21 CFR 807.92)

Pursuant to Section 12, Part (a)(i)(3A) of the Safe Medical Devices Act of 1990, Penumbra Inc. is providing the summary of Substantial Equivalence for the Penumbra System 3D Revascularization Device.

Sponsor/Applicant Name and Address 1

Penumbra, Inc. One Penumbra Place Alameda, CA 94502 USA

ನ Sponsor Contact Information

Michaela Mahl Senior Manager, Regulatory Affairs Phone: (510) 748-3288 FAX: (510) 217-6414 Email: mmahl@penumbrainc.com

3 Date of Preparation of 510(k) Summary

April 19, 2017

4 Device Trade or Proprietary Name

Penumbra 3D Revascularization Device

Device Classification 5

Regulatory Class:	II Classification Panel:
	Neurology
Classification Name:	Percutaneous Catheter
Regulation Number:	21 CFR §870.1250
Product Code:	NRY (Catheter, Thrombus Removal)

Predicate and Reference Devices 6

| 510(k) Number/

Clearance Date	Name of Predicate Device	Name of Manufacturer
Predicate Device
K160449 [25May2016]	Penumbra System and Penumbra Pump MAX	Penumbra, Inc.
Reference Devices
K153071 [23Dec2015]	Solitaire™ Platinum Revascularization
Device	Micro Therapeutics, Inc. d/b/a
ev3 Neurovascular
K161640 [12Jul2016]	Penumbra System ACE 68 Reperfusion
Catheter	Penumbra, Inc.

4

7 Predicate Comparison

	Predicate Device	Primary Reference Device	Subject Device
Predicate 510(k)	Penumbra System : K160449	Solitaire™ Platinum
Revascularization Device:
K153071	Penumbra 3D Revascularization Device:
K162901
Classification	Class II, NRY	Same	Same
Indication for Use	Penumbra Reperfusion Catheters and
Separators
As part of the Penumbra System, the
Reperfusion Catheters and Separators are
indicated for use in the revascularization of
patients with acute ischemic stroke
secondary to intracranial large vessel
occlusive disease (within the internal carotid,
middle cerebral – M1 and M2 segments,
basilar, and vertebral arteries) within 8 hours
of symptom onset.

Penumbra Aspiration Tubing
As part of the Penumbra System, the
Penumbra Sterile Aspiration Tubing is
indicated to connect the Penumbra
Reperfusion Catheters to the Penumbra
Pump MAX.

Penumbra Pump MAX
The Penumbra Pump MAX is indicated as a
vacuum source for Penumbra Aspiration
Systems. | The Solitaire™ Platinum
Revascularization Device is
intended to restore blood flow by
removing thrombus from a large
intracranial vessel in patients
experiencing ischemic
stroke within 8 hours of symptom
onset. Patients who are ineligible
for intravenous tissue
plasminogen activator (IV t-PA)
or who fail IV t-PA therapy are
candidates for treatment. | Penumbra Reperfusion Catheters and
Separators
As part of the Penumbra System, the
Reperfusion Catheters and Separators are
indicated for use in the revascularization of
patients with acute ischemic stroke
secondary to intracranial large vessel
occlusive disease (within the internal
carotid, middle cerebral - M1 and M2
segments, basilar, and vertebral arteries)
within 8 hours of symptom onset. Patients
who are ineligible for intravenous tissue
plasminogen activator (IV t-PA) or who fail
IV t-PA therapy are candidates for
treatment.

5

6

7

8 Device Description

The Penumbra 3D Revascularization Device is an additional component to the currently available Penumbra System. The Penumbra System's fundamental mechanism of action is aspiration. Aspiration draws clot into the Penumbra Reperfusion Catheter to remove the clot. The 3D Revascularization Device is designed to assist the Reperfusion Catheter with thrombus removal if needed. The device is provided sterile, non-pyrogenic, and intended for single use only.

9 Indications for Use

Penumbra Reperfusion Catheters and Separators

As part of the Penumbra System. the Reperfusion Catheters and Separators are indicated for use in the revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (within the internal carotid, middle cerebral - M1 and M2 segments, basilar, and vertebral arteries) within 8 hours of symptom onset. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy are candidates for treatment.

Penumbra 3D Revascularization Device

As part of the Penumbra System, the Penumbra 3D Revascularization Device is indicated for use in the revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (within the internal carotid, middle cerebral - M1 and M2 segments) within 8 hours of symptom onset. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy are candidates for treatment.

Penumbra Aspiration Tubing

As part of the Penumbra System, the Penumbra Sterile Aspiration Tubing is indicated to connect the Penumbra Reperfusion Catheters to the Penumbra Aspiration Pump.

Penumbra Aspiration Pump

The Penumbra Aspiration Pump is indicated as a vacuum source for Penumbra Aspiration Systems.

8

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 substantial equivalence of the device follows.

Included in this section are descriptions of the testing, which substantiates the safe and effective performance of the Penumbra 3D Revascularization Device as well as its substantial equivalence to the predicate devices:

Biocompatibility .
. Design Verification (Bench-Top Testing)
. Design Validation (GLP Animal Testing)

The subject Penumbra 3D Revascularization Device met all established requirements.

10.1 Biocompatibility Testing

Evidence of the biocompatibility of the Penumbra 3D Revascularization Device is derived from the testing used to support the current FDA cleared Penumbra System Separators and a series of studies listed and summarized in the table below.

Biocompatibility tests conducted on the materials of the Penumbra 3D Revascularization Device were selected in accordance with EN ISO 10993 -1 guidelines (Biological Evaluation of Medical Devices) for limited duration (2.5mm in diameter) in the cerebral circulation were assigned to either the 3D Revascularization Device with Penumbra

11

System arm (3D/Penumbra System) or the Penumbra System alone arm. Each treated patient was assessed for 3 months after randomization.

Statistical Analysis

The objective of the statistical analysis was to assess if the effectiveness of 3D/ Penumbra System was non-inferior to Penumbra System alone as defined by a modified Thrombolysis In Cerebral Infarction scale (mTICI) score of 2-3. The pre-specified primary efficacy analysis was conducted in the per protocol population. The primary effectiveness analysis was the difference between the 3D/ Penumbra System group and the Penumbra System alone group (control). A binomial comparison was used to test the null hypothesis that the difference in proportions was less than or equal to -0.15 (Ho: P3D - Pcontrol ≤ -0.15; i.e., that revascularization in the 3D/ Penumbra System group is worse than for the Penumbra System alone group) vs. the one-sided alternative (Hr: P3D - PControl > -0.15). This was equivalent to evaluating that the lower bound of the 90% confidence interval for the difference was above -15%. The sample size calculations assume that 80% of the standard Penumbra System patients experience success (mTICI of 2 to 3) and 80% of the 3D/Penumbra System patients experience success.

Study Procedures

Acute ischemic stroke patients presenting within 8 hours of onset with NIHSS score ≥8 underwent 1:1 randomization to 3D/ Penumbra System or Penumbra System alone. The primary effectiveness endpoint was mTICI score of 2-3 with a 15% margin for non-inferiority. Device and procedure-related serious adverse events (SAEs) at 24 hours were the primary safety endpoint. Key secondary endpoints were functional independence at 90 days defined by a modified Rankin Scale (mRS) score of 0-2, symptomatic intracranial hemorrhage (sICH) and all cause mortality. All patients were followed for 90 days.

Key Inclusion Criteria

From 18 to 85 years of age .
Present with symptoms consistent with an acute ischemic stroke for . revascularization within 8 hours from symptom onset
. Refractory to or not eligible for IV rtPA therapy, e.g., presenting between 0 and 3 hours from symptom onset AND contraindicated for IV rtPA, or presenting between 3 and 8 hours of symptom onset, or evidence from vascular imaging of persistent occlusion after IV rtPA
Evidence of a large vessel (>2.5mm in diameter) occlusion in the cerebral . circulation
NIH Stroke Scale (NIHSS) score >8 .
Signed informed consent ●

Key Exclusion Criteria

History of stroke in the past 3 months ●
Females who are pregnant

12

Pre-existing neurological or psychiatric disease that could confound the study results such as a pre-stroke mRS score >1
Known severe allergy to contrast media
Uncontrolled hypertension (defined as systolic blood pressure >185 mmHg ● or diastolic blood pressure >110 mmHg)
CT evidence of the following conditions at randomization:
Significant mass effect with midline shift
Large infarct region >1/3 of the middle cerebral artery territory
-Evidence of intracranial hemorrhage
Angiographic evidence of an arterial stenosis proximal to the occlusion that ● could prevent thrombus removal
Angiographic evidence of preexisting arterial injury
Rapidly improving neurological status prior to enrollment
Bilateral stroke
Intracranial tumors
Known history of cerebral aneurysm or arteriovenous malformation
Known hemorrhagic diathesis, coagulation deficiency, or on anticoagulant therapy with an International Normalized Ratio (INR) of >1.7
Baseline platelets 1.5 times the normalized ● ratio
Baseline glucose 300mg/dL
Life expectancy less than 90 days prior to stroke onset ●
Participation in another clinical investigation that could confound the ● evaluation of the study device

Summary of reasons for exclusion of enrolled subjects, especially those based on angiographic criteria

Of the 198 patients enrolled, a total of 15 patients were excluded for angiographic reasons. These patients along with 5 patients who did not meet key inclusion/exclusion criteria and 5 patients who did not receive the assigned treatment were excluded from the Per Protocol analysis.

	Randomized (ITT)*
	All
Patients
(N=198**)	3D /
Penumbra
System
(N=98)	Penumbra
System
(N=100)	All
Patients
(N=150)	3D /
Penumbra
System
(N=74)	Penumbra
System
(N=76)
Completed
Study	70.2%
(139/198)	68.4%
(67/98)	72.0%
(72/100)	68.7%
(103/150)	63.5%
(47/74)	73.7%
(56/76)
Died prior to
90 day follow-
up	22.7%
(45/198)	19.4%
(19/98)	26.0%
(26/100)	24.0%
(36/150)	23.0%
(17/74)	25.0%
(19/76)
Early
termination
Subject Lost
to Follow-Up	5.1%
(10/198)	8.2% (8/98)	2.0% (2/100)	6.0%
(9/150)	10.8%
(8/74)	1.3% (1/76)

Patient Disposition Summary of Patient Disposition

13

	Randomized (ITT)*
Subject
Withdrawal	2.0%
(4/198)	4.1% (4/98)	0%
(0/100)	1.3%
(2/150)	2.7%
(2/74)	0%
(0/76)

All patients who were consented and randomized were included in the intent to treat (IT) population. The ITT population included all subjects with data for a given endpoint; results were assessed according to randomized assignment regardless of the treatment actually received.

** There were 8 patients not treated with any component of the Penumbra System due to the resolution of thrombus, inability to access target vessel due to tortuous anatomy and angiographic exclusion.

-The primary effectiveness cohort excluded patients that did not meet angiographic criteria (n=15), inclusion or exclusion criteria was not met (n=5), treatment was not as assigned (n=5), patients received tPA > 3 hours (n=14) or patients that had a baseline TICI ≥ 2a (n=9), which resulted in a primary effectiveness cohort of 150 patients.

The large vessel occlusions randomized include the following target vessels.

	Randomized (ITT)			Primary Effectiveness Cohort
Target
Vessel	All Patients
(N=198)	3D / Penumbra
System
(N = 98)	Penumbra
System
(N = 100)	All
Patients
(N=150)	3D / Penumbra
System
(N =74)	Penumbra
System
(N =76)
ICA	19.7% ( 39 /

| 15.3% ( 15 / 98) | 24.0% ( 24 /
```
       | 19.3%
```

(29/150) | 14.9% (11/74) | 23.7%
(18/76) |
| MCA M1 | 63.6% (126/
198) | 66.3% ( 65 / 98) | 61.0% ( 61 /
100) | 68.7%
(103/150) | 71.6%
(53/74) | 65.8%
(50/76) |
| MCA M2 | 13.6% ( 27 /
198) | 15.3% ( 15 / 98) | 12.0% ( 12 /
100) | 10.7%
(16/150) | 13.5% (10/74) | 7.9% (6/76) |
| PCA | 1.0% ( 2 /
198) | 1.0% ( 1 / 98) | 1.0% ( 1 / 100) | 0.7%
(1/150) | 0%
(0/74) | 1.3% (1/76) |
| Basilar | 1.0% ( 2 /
198) | 1.0% ( 1 / 98) | 1.0% ( 1 /
100) | 0.7%
(1/150) | 0%
(0/74) | 1.3% (1/76) |

Patient Target Vessels in Penumbra 3D Trial

Primary Effectiveness Endpoint

The Primary Effectiveness Endpoint was revascularization of the occluded target vessel. Revascularization was defined by a mTICI score of 2 to 3 following use of the 3D/Penumbra System and prior to the use of any additional therapies or adjunctive devices. Use of IA lytic was considered a treatment failure. Patients administered IV rtPA > 3 hours from stroke symptom onset or having an mTICI score of 2a or greater prior to intervention are excluded. Angiographic results were adjudicated by an independent Core Laboratory.

Primary Effectiveness Endpoint	All Patients	3D / Penumbra System	Penumbra System	Difference (90 % CI)†
mTICI score of 2 to 3, Per Protocol,
% (n/N)	86.0%
(129/150)	86.5 %
(64/74)	85.5%
(65/76)	1.0 %
(-8.4%, 10.3%)

*Wald confidence intervals

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Primary Safety Endpoint

The Primary Safety Endpoint was incidence of device and procedure-related serious adverse events that occurred within 24 hours post-procedure. The primary safety endpoint was adjudicated by a Clinical Events Committee. Each site was permitted two roll-in patients and these patients were the first patients the physicians used the 3D Revascularization Device. The primary safety endpoint data for the roll-in patients is included.

	Roll-In	Randomized (As Treated)
Primary Safety Endpoint (As Treated)	Roll-In	All Patients	3D /
Penumbra
System	Penumbra
System
Procedure Related Serious Adverse Event,
% (n/N)	7.9% (6/76)	12.7% (23/181)	10.2% (9/88)	15.1% (14/93)
Device Related Serious Adverse Event, %
(n/N)
SAE during the procedure	6.6% (5/76)	5.0% (9/181)	4.5% (4/88)	5.4% (5/93)

Secondary Endpoint

The Secondary Endpoint was functional outcome at 90 days post-procedure. Patients administered IV rtPA > 3 hours from stroke symptom onset (n=14) or having an mTICI score of 2a or greater prior to intervention (n=9) are excluded. Eight (8) patients who were not treated with any component of the Penumbra System are also excluded. Patients who received any additional therapies or adjunctive devices following the use of the Penumbra System (+3D) are imputed as an outcome failure.

Functional Outcome at 90 Days Post-Procedure (modified ITT)

Outcome (ITT)	All Patients (N=167)	3D / Penumbra System (n=82)	Penumbra System (n=85)	p-value
mRS 0-2	37.5% (57/152)	38.0% (27/71)	37.0% (30/81)	1.0

Note: P-value from two-sided Fisher's Exact test for categorical assessment between groups.

Each specific SAE through 90 days occurring in more than 2% of patients (As Treated)

| Serious Adverse Event MedDRA
Preferred Term | All Patients
(N=181) | 3D / Penumbra
System
(N=88) | Penumbra
System
(N=93) |
|------------------------------------------------|-------------------------|-----------------------------------|------------------------------|
| Stroke in evolution | 15.5% (28/181) | 12.5% (11/88) | 18.3% (17/93) |
| Haemorrhagic transformation stroke | 2.8% (5/181) | 2.3% (2/88) | 3.2% (3/93) |
| Haemorrhage intracranial | 2.2% (4/181) | 2.3% (2/88) | 2.2% (2/93) |
| Respiratory failure | 5.0% (9/181) | 2.3% (2/88) | 7.5% (7/93) |

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| Serious Adverse Event MedDRA
Preferred Term | All Patients
(N=181) | 3D / Penumbra
System
(N=88) | Penumbra
System
(N=93) |
|------------------------------------------------|-------------------------|-----------------------------------|------------------------------|
| Acute respiratory failure | 2.8% ( 5/181) | 4.5% ( 4/88) | 1.1% ( 1/93) |
| Pulmonary embolism | 2.2% ( 4/181) | 2.3% ( 2/88) | 2.2% ( 2/93) |
| Dysphagia | 8.3% (15/181) | 9.1% (8/88) | 7.5% ( 7/93) |
| Atrial fibrillation | 3.3% ( 6/181) | 3.4% ( 3/88) | 3.2% ( 3/93) |
| Deep vein thrombosis | 2.2% ( 4/181) | 1.1% ( 1/88) | 3.2% ( 3/93) |
| Renal failure acute | 2.2% ( 4/181) | 4.5% ( 4/88) | 0.0% ( 0/93) |
| Anaemia | 2.2% ( 4/181) | 2.3% ( 2/88) | 2.2% ( 2/93) |

Categorization of SAEs through 90 days by Body System (As Treated)

| Serious Adverse Event by Body System | All Patients
(N=181) | 3D / Penumbra
System (N=88) | Penumbra System
(N=93) |
|------------------------------------------------------------|-------------------------|--------------------------------|---------------------------|
| Number of Patients with at Least one Serious Adverse Event | 48.1% (87/181) | 43.2% (38/88) | 52.7% (49/93) |
| Nervous system disorders | 26.0% (47/181) | 21.6% (19/88) | 30.1% (28/93) |
| Respiratory, thoracic and mediastinal disorders | 11.0% (20/181) | 10.2% (9/88) | 11.8% (11/93) |
| Gastrointestinal disorders | 9.9% (18/181) | 9.1% (8/88) | 10.8% (10/93) |
| Cardiac disorders | 9.4% (17/181) | 11.4% (10/88) | 7.5% (7/93) |
| Vascular disorders | 5.5% (10/181) | 1.1% (1/88) | 9.7% (9 /93) |
| Infections and infestations | 4.4% (8/181) | 2.3% (2/88) | 6.5% (6/93) |
| Renal and urinary disorders | 2.8% (5/181) | 4.5% (4/88) | 1.1% (1/93) |
| Blood and lymphatic system disorders | 2.2% (4/181) | 2.3% (2/88) | 2.2% (2/93) |
| Injury, poisoning and procedural complications | 2.2% (4/181) | 2.3% (2/88) | 2.2% (2/93) |
| Metabolism and nutrition disorders | 1.7% (3/181) | 2.3% (2/88) | 1.1% (1/93) |
| Endocrine disorders | 0.6% (1/181) | 0.0% (0/88) | 1.1% (1/93) |
| General disorders and administration site conditions | 0.6% (1/181) | 1.1% (1/88) | 0.0% (0/93) |
| Immune system disorders | 0.6% (1/181) | 0.0% (0/88) | 1.1% (1/93) |
| Investigations | 0.6% (1/181) | 0.0% (0/88) | 1.1% (1/93) |

12 Summary of Substantial Equivalence

The subject Penumbra 3D Revascularization Device is substantially equivalent to the predicate device with regard to intended use, operating principle, design concept, materials, shelf-life, packaging and sterilization processes.