Guidance for 
Industry and FDA Staff 
 
Coronary and Carotid Embolic 
Protection Devices - Premarket 
Notification [510(k)] Submissions 
 
 
Document issued on: February 15, 2008 
 
 
For questions regarding this document, please contact Ms. Suzanne Kaiser at (240) 276-4222 or 
by email at suzanne.kaiser@fda.hhs.gov for questions about coronary embolic protection devices, 
or Dr. Kenneth Cavanaugh at (240) 276-4141 or by email at kenneth.cavanaugh@fda.hhs.gov for 
questions about carotid embolic protection devices. 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
 
Interventional Cardiology Devices Branch 
Peripheral Vascular Devices Branch 
Division of Cardiovascular Devices 
Office of Device Evaluation 
 
  Contains Nonbinding Recommendations 
 
Preface 
 
 
Public Comments 
 
Written comments and suggestions may be submitted at any time for Agency consideration 
to the Division of Dockets Management, Food and Drug Administration, 5630 Fishers Lane, 
Room 1061, (HFA-305), Rockville, MD, 20852.  Alternatively, electronic comments may be 
submitted to http://www.regulations.gov.  When submitting comments, please refer to the exact 
title of this guidance document.  Comments may not be acted upon by the Agency until the 
document is next revised or updated. 
 
Additional Copies 
 
Additional copies are available from the Internet at:  
http://www.fda.gov/cdrh/ode/guidance/1658.html.  You may also send an e-mail request to 
dsmica@fda.hhs.gov to receive an electronic copy of the guidance or send a fax request to 240-
276-3151 to receive a hard copy.  Please use the document number (1658) to identify the 
guidance you are requesting. 
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Table of Contents 
 
1.  INTRODUCTION.................................................................................................................1 
2.  BACKGROUND...................................................................................................................2 
3.  THE CONTENT AND FORMAT OF AN ABBREVIATED 510(K) SUBMISSION....2 
4.  SCOPE...................................................................................................................................5 
5.  DEVICE DESCRIPTION....................................................................................................6 
6.  RISKS TO HEALTH AND MITIGATION MEASURES................................................6 
7.  BIOCOMPATIBILITY........................................................................................................7 
8.  PERFORMANCE CHARACTERISTICS/BENCH TESTING.......................................9
9.  NON-CLINICAL ASSESSMENT.....................................................................................15 
10.  CLINICAL INFORMATION............................................................................................18 
11.  STERILIZATION AND SHELF LIFE.............................................................................22 
12.  LABELING.........................................................................................................................23 
APPENDIX A: REFERENCED STANDARDS.........................................................................26 
 
 
 
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Guidance for Industry and FDA Staff 
 
Coronary and Carotid Embolic Protection 
Devices - Premarket Notification [510(k)] 
Submissions 
 
This guidance represents the Food and Drug Administration's (FDA's) current thinking on 
this topic.  It does not create or confer any rights for or on any person and does not operate to 
bind FDA or the public.  You can use an alternative approach if the approach satisfies the 
requirements of the applicable statutes and regulations.  If you want to discuss an alternative 
approach, contact the FDA staff responsible for implementing this guidance.  If you cannot 
identify the appropriate FDA staff, call the appropriate number listed on the title page of this 
guidance.  
 
1.  Introduction 
FDA has developed this guidance document to assist industry in preparing premarket notification 
submissions for Coronary and Carotid Embolic Protection Devices.  These devices are designed 
to capture and remove embolic material that may be dislodged during the interventional treatment 
of carotid arteries or saphenous vein bypass grafts with the intention of reducing the incidence of 
adverse cardiac or cerebrovascular events. We recommend that members of industry and FDA 
staff who perform or review clinical and non-clinical evaluations and prepare labeling of coronary 
and carotid embolic protection devices should use this guidance.1   
 
We recommend that you use this guidance to develop and apply clinical and non-clinical 
evaluation protocols, methods, and reports that support the safety and effectiveness of coronary 
and carotid embolic protection devices.  You should also use this guidance to develop labeling for 
these devices. We intend to use this guidance to review clinical and non-clinical evaluation 
protocols, methods, data, and reports provided in 510(k) submissions to demonstrate the 
substantial equivalence of coronary and carotid embolic protection devices.   
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agency's current thinking on a topic and should 
be viewed only as recommendations, unless specific regulatory or statutory requirements are 
cited. The use of the word should in Agency guidances means that something is suggested or 
recommended, but not required.  
 
                                                 
1 The terms you and your in this document refer to members of industry, also known as 
sponsors or applicants.  The terms we, us, and our refer to FDA. 
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The Least Burdensome Approach 
 
The issues identified in this guidance document represent those that we believe should be 
addressed before your device can be marketed.  In developing the guidance, we carefully 
considered the relevant statutory criteria for Agency decision-making.  We also considered the 
burden that may be incurred in your attempt to follow the guidance and address the issues we 
have identified.  We believe that we have considered the least burdensome approach to resolving 
the issues presented in the guidance document.  If, however, you believe that there is a less 
burdensome way to address the issues, you should follow the procedures outlined in the A 
Suggested Approach to Resolving Least Burdensome Issues document.  It is available on our 
Center web page at: http://www.fda.gov/cdrh/modact/leastburdensome.html. 
 
2.  Background 
 
A manufacturer who intends to market a device of this generic type should conform to the general 
controls of the Federal Food, Drug, and Cosmetic Act (the Act), including the premarket 
notification requirements described in 21 CFR 807 Subpart E, and obtain a substantial 
equivalence determination from FDA prior to marketing the device. (See also 21 CFR 807.81 and 
807.87.)  
This guidance document identifies the classification regulation and product codes for coronary 
and carotid embolic protection devices (refer to Section 4: Scope).  In addition, other sections of 
this guidance document provide additional information to manufacturers on addressing risks 
related to these devices in premarket notification submissions (510(k)s).  
This document supplements other FDA documents regarding the specific content requirements of 
a premarket notification submission. You should also refer to 21 CFR 807.87 and "How to 
Prepare a 510(k) Submission" on FDA Device Advice at 
http://www.fda.gov/cdrh/devadvice/314.html.  
Under The New 510(k) Paradigm - Alternate Approaches to Demonstrating Substantial 
Equivalence in Premarket Notifications; Final Guidance, 
http://www.fda.gov/cdrh/ode/parad510.html, a manufacturer may submit a Traditional 510(k) or 
has the option of submitting either an Abbreviated 510(k) or a Special 510(k). FDA believes an 
Abbreviated 510(k) provides the least burdensome means of demonstrating substantial 
equivalence for a new device, particularly once FDA has issued a guidance document addressing 
that device. Manufacturers considering modifications to their own cleared devices may lessen the 
regulatory burden by submitting a Special 510(k). 
3.  The Content and Format of an Abbreviated 510(k) 
Submission  
An Abbreviated 510(k) submission must include the required elements identified in 21 CFR 
807.87, including the proposed labeling for the device sufficient to describe the device, its 
intended use, and the directions for its use.  In an Abbreviated 510(k), FDA may consider the 
contents of a summary report to be appropriate supporting data within the meaning of 21 CFR 
807.87(f) or (g); therefore, we recommend that you include a summary report.  The report should 
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describe how you may have used this guidance document during the device development and 
testing and should briefly describe the methods or tests used and a summary of the test data or 
description of the acceptance criteria applied to address the risks identified in this document, as 
well as any additional risks specific to your device.  This section suggests information to fulfill 
some of the requirements of section 807.87 as well as some other items that we recommend you 
include in an Abbreviated 510(k). 
 
Coversheet 
The coversheet should prominently identify the submission as an Abbreviated 510(k) and cite 
the title of this guidance document. 
 
Proposed Labeling 
Proposed labeling should be sufficient to describe the device, its intended use, and the 
directions for its use.  Please refer to Section 11: Labeling for specific information that 
should be included in the labeling for coronary and carotid embolic protection devices 
covered by this guidance document. 
 
Summary Report 
We recommend that the summary report contain the following: 
 
Description of the device and its intended use   
We recommend that you describe the performance specifications and, when appropriate, 
include detailed, labeled drawings of the device.  Please refer to Section 5. Device 
Description for specific information that we recommend you include in the device 
description for coronary and carotid embolic protection devices of the types covered by 
this guidance document.  You should also submit an indications for use enclosure.2   
 
Description of device design  
We recommend that you include a brief description of the device design requirements. 
 
Identification of the risk analysis method 
We recommend that you identify the risk analysis method(s) you used to assess the risk 
profile, in general, as well as the specific devices design and the results of this analysis.  
Please refer to Section 6: Risks to Health and Mitigation Measures for the risks to 
health generally associated with the use of coronary and carotid embolic protection 
devices that FDA has identified. 
 
 
 
 
Discussion of the device characteristics  
                                                 
2 Refer to http://www.fda.gov/cdrh/ode/indicate.html for the recommended format. 
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We recommend that you discuss the device characteristics that address the risks identified 
in this guidance document, as well as any additional risks identified in your risk analysis.  
 
Description of the performance aspects 
We recommend that you include a brief description of the test method(s) you have used or 
intend to use to address each performance aspect identified in Sections 7- 10 of this 
guidance document.  If you follow a suggested test method, you may cite the method 
rather than describing it.  If you modify a suggested test method, you may cite the method 
but should provide sufficient information to explain the nature of and reason for the 
modification.  For each test, you may either (1) briefly present the data resulting from the 
test in clear and concise form, such as a table, or (2) describe the acceptance criteria that 
you will apply to your test results.3  (See also 21 CFR 820.30, Subpart C - Design 
Controls for the Quality System Regulation.) 
 
Reliance on standards 
If you choose to rely on a recognized standard for any part of the device design or testing, 
you may include either of the following:  
  a statement that testing will be conducted and meet specified acceptance criteria 
before the product is marketed; or  
  a declaration of conformity to the standard.4   
 
Because a declaration of conformity is based on results from testing, we believe you cannot 
properly submit a declaration of conformity until you have completed the testing the 
standard describes.  For more information, please refer to section 514(c)(1)(B) of the Act 
and the FDA guidance, Use of Standards in Substantial Equivalence Determinations; 
Final Guidance for Industry and FDA.http://www.fda.gov/cdrh/ode/guidance/1131.html.  
 
If it is not clear how you have addressed the risks identified by FDA or additional risks identified 
through your risk analysis, we may request additional information about aspects of the devices 
performance characteristics.  We may also request additional information if we need it to assess 
the adequacy of your acceptance criteria.  (Under 21 CFR 807.87(l), we may request any 
additional information that is necessary to reach a determination regarding substantial 
equivalence.)  
                                                 
3 If FDA makes a substantial equivalence determination based on acceptance criteria, the subject 
device should be tested and shown to meet these acceptance criteria before being introduced into 
interstate commerce.  If the finished device does not meet the acceptance criteria and, thus, differs 
from the device described in the cleared 510(k), FDA recommends that submitters apply the same 
criteria used to assess modifications to legally marketed devices (21 CFR 807.81(a)(3)) to 
determine whether marketing of the finished device requires clearance of a new 510(k). 
 
4 See Required Elements for a Declaration of Conformity to a Recognized Standard 
(Screening Checklist for All Premarket Notification [510(k)] Submissions), 
http://www.fda.gov/cdrh/ode/reqrecstand.html. 
 
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As an alternative to submitting an Abbreviated 510(k), you can submit a Traditional 510(k) that 
provides all of the information and data required under 21 CFR 807.87 and described in this 
guidance.  A Traditional 510(k) should include all of your methods, data, acceptance criteria, and 
conclusions.  Manufacturers considering modifications to their own cleared devices should 
consider submitting Special 510(k)s.  
 
The following is a specific discussion of how you should apply this guidance document to 
510(k)s for coronary and carotid embolic protection devices. 
 
4.  Scope 
This guidance document addresses coronary and carotid embolic protection devices.  Typically, 
the embolic protection device is deployed proximal or distal to a lesion (narrowed portion of the 
vessel) prior to other intervention taking place, such as balloon angioplasty or stenting.  The 
embolic protection device is intended to prevent debris generated by the intervention from 
traveling downstream in the coronary or carotid circulation where it could impede flow partially 
or fully in smaller vessels, leading to damage to the myocardium or to neurological impairment.  
These devices are classified as percutaneous catheters (21 CFR 870.1250). 
The scope of this guidance includes embolic protection devices used along with other 
interventional devices (e.g., stents or angioplasty balloons) for the treatment of: 
diseased saphenous vein grafts (SVGs) in patients with stable ischemic coronary artery 
 
disease; and 
diseased carotid arteries that could potentially contribute to strokes or other neurological 
 
adverse events. 
 
The scope of this document is limited to the devices shown in Table 1 below. 
 
Table 1: Classification and Product Codes of Coronary and Carotid Embolic Protection 
Devices Addressed in this Guidance 
Classification 
Regulation  
Class Product Code  Description 
(21 CFR) 
870.1250  II  NFA, device, coronary  Temporary device intended for 
saphenous vein bypass graft,  placement in a coronary 
temporary, for embolization  saphenous bypass graft for the 
protection  purpose of providing 
embolization protection. 
870.1250  II  NTE, catheter, carotid,  Temporary device intended for 
temporary, for embolization  placement in a native carotid 
artery for the purpose of 
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capture  providing embolization 
protection. 
 
This guidance also cites a number of voluntary standards, many of which are recognized by FDA. 
You may access a list of the FDA-recognized standards from the CDRH web site, 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. See also the guidance, 
Recognition and Use of Consensus Standards, http://www.fda.gov/cdrh/ost/guidance/321.html. 
This document does not address thrombectomy devices or embolic protection devices used for 
peripheral indications other than in the carotid vasculature.  You should contact the Peripheral 
Vascular Devices Branch in the Division of Cardiovascular Devices for information about 
embolic protection devices used in peripheral indications outside the carotid arteries.  
5.  Device Description  
We recommend that you identify your device by the regulation and product code described in 
Section 4.  Scope, that you describe the device characteristics and performance specifications, 
and that you include detailed, labeled drawings of the device. We recommend that you describe 
the method of operation for the device.  You should also provide a comparison between your 
device and the predicate device(s) to which you claim substantial equivalence that covers the 
relevant device attributes such as device design, size, materials, indications for use, and principle 
of operation. 
 
6.  Risks to Health 
In the table below, FDA has identified the risks to health generally associated with the use of the 
coronary and carotid embolic protection devices addressed in this document.  The measures 
recommended to mitigate these identified risks are given in this guidance document, as shown in 
the table below.  We recommend that you also conduct a risk analysis, before submitting your 
510(k), to identify any other risks specific to your device and include the results of this analysis.  
If you elect to use an alternative approach to address a particular risk identified in this document, 
or have identified risks additional to those in this document, then you should provide sufficient 
detail to support the approach you have used to address that risk. 
 
FDA encourages manufacturers of embolic protection devices to work with FDA early in your 
product development, especially if your device incorporates novel technology or you plan to 
conduct a non-traditional clinical study.  The Interventional Cardiology Devices Branch and 
Peripheral Vascular Devices Branch are available to discuss non-clinical test protocols and 
clinical trial designs for embolic protection devices through the Pre-IDE process.5   
 
 
Table 2: Risks to Health for Coronary and Carotid Embolic Protection Devices 
                                                 
5 For additional information regarding the Pre-IDE process, please refer CDRH Device Advice, 
http://www.fda.gov/cdrh/devadvice/ide/approval.shtml#pre_ide and ODE Blue Book 
Memorandum D99-1, http://www.fda.gov/cdrh/ode/d99-1.pdf. 
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Identified Risk  Recommended Mitigation Measures 
Tissue and Blood Damage  Section 7. Biocompatibility  
Device Failure   Section 8. Bench Testing 
Embolization  Section 9. Animal Assessment 
Section 10. Clinical Information 
Vessel Damage  Section 9. Animal Assessment 
Section 10. Clinical Information 
Infection  Section 11. Sterilization and Shelf-Life 
 
7.  Biocompatibility 
FDA recommends that you conduct biocompatibility testing as described in the FDA-modified 
Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part-1: 
Evaluation and Testing (http://www.fda.gov/cdrh/g951.html) for external devices in contact 
with the circulating blood for a limited duration (less than 24 hours).  We recommend that you 
select biocompatibility tests appropriate for the duration and level of contact with your device.  If 
identical materials and identical material processing are used in a predicate device with the same 
type and duration of patient contact, you may identify the predicate device in lieu of providing 
biocompatibility testing.    
 
For biocompatibility testing conducted using extraction samples, we recommend that you: 
 
  determine the appropriate amount of test material as outlined in ISO 10993-12 (Biological 
Evaluation of Medical Devices: Sample Preparation and Reference Materials) or an 
equivalent method, using surface area to extractant volume ratios (mass to extractant 
volume ratios should only be used if surface area cannot be calculated); 
 
  use both polar and nonpolar extractants; 
 
  describe the condition of the extraction vehicle (e.g., color, presence of any particles); 
 
  explain any changes in the post-extraction vehicle (compared to pre-extraction); and 
 
  describe the details of storage conditions, if applicable.   
 
If extraction samples are not used immediately, we recommend that you follow the storage 
conditions described in ISO 10993-12 or an equivalent method.  We also recommend that you 
explain how storage does not affect your test results. 
 
FDA recommends that your biocompatibility test regimen incorporate the elements discussed 
below. 
 
Cytotoxicity 
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We recommend that vehicles include both mammalian cell culture media (MEM) and 5% 
serum, as these materials will allow for extraction of both polar and nonpolar constituents 
from the test sample. 
 
Sensitization (Guinea Pig Maximization Method) 
We recommend either that you run concurrent controls, or that the test laboratory run controls 
within 3 months of the test samples.  We also recommend you provide protocols and results 
from positive control testing to confirm that you used the same methods for both the positive 
control testing and the test samples and to demonstrate that the methods continue to be 
capable of detecting a positive sensitization response. 
 
You can conduct local lymph node assay (LLNA) testing as an alternative to guinea pig 
maximization testing to assess sensitization. 
 
Hemocompatibility 
For blood-contacting devices (regardless of contact duration), we recommend that you 
consider hemolysis, immunology (complement activation), and in vivo thromboresistance.   
 
Immunology testing should appropriately address the various complement activation 
pathways.  We recommend that you assess in vitro C3a and SC5b-9 fragment activation using 
standard testing methods, such as those outlined in ASTM F2065-00e1 (Standard Practice 
for Testing for Alternative Pathway Complement Activation in Serum by Solid 
Materials) and ASTM F1984-99 (2003; Standard Practice for Testing for Whole 
Complement Activation in Serum by Solid Materials), or an equivalent method.  
Alternatively, you may provide a rationale for omitting this testing, if all the materials used in 
the formulation and processing of the device have a history of previous use in blood-
contacting devices with similar contact duration. 
 
In addition, you may assess in vivo thrombogenicity during preclinical animal testing in lieu 
of a separate canine in vivo thrombogenicity test. 
 
Material-mediated Pyrogenicity 
We recommend that you assess pyrogenic responses to chemical leachants over the duration 
of device contact with the patient using a standard method, such as those described in USP 30 
<151> Rabbit Pyrogen Test.  We also recommend that you assess material-mediated 
pyrogenicity using traditional biocompatibility extraction methods, such as 50C for 72 hours, 
70C for 24 hours, or 120C for 2 hours). 
 
 
 
Endotoxin-Mediated Pyrogenicity 
We recommend that you consider pyrogenic responses to gram-negative bacterial endotoxin 
using a standard method, such as those outlined in the USP 30 <85> Bacterial Endotoxin 
Limulus Amoebocyte Lysate (LAL) Test, or an equivalent method.  We recommend that 
your specifications include the test procedure and acceptance criteria for endotoxins.  All 
blood-contacting cardiovascular devices and combination products should be pyrogen-free.  
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Pyrogenicity testing is used to help define limits to protect patients from the risk of febrile 
reaction.   
 
8.  Performance Characteristics/Bench Testing 
We recommend that bench testing demonstrate device durability and adequate 
performance/handling characteristics based on the device description and the indications for use 
as described in the instructions for use.  We recommend that you provide complete test reports 
that include presentation of the test results, the test methods, predetermined acceptance criteria, 
study analysis, and a discussion of the results and conclusions drawn from the studies.  You 
should describe the clinical relevance of the acceptance criteria for each bench test and explain 
why the test results demonstrate acceptable clinical performance of your device.  Test conditions 
should simulate the worst-case conditions that your device is likely to encounter during clinical 
use. 
 
We recognize that there is variation in the design of embolic protection systems.  In designing a 
bench testing plan for an embolic protection system, you should address the specific risks and 
performance characteristics for your device.  We recommend that you evaluate the device 
attributes/performance characteristics described below in your bench testing regimen.  If you 
believe that a recommended test is not necessary for your device, you should provide a scientific 
rationale for each recommended test that you do not conduct.  You should also conduct any 
additional testing that your risk analysis identifies as necessary to fully mitigate the device-related 
risks, even if this document does not identify these tests. If you modify the design of your device, 
we recommend that you conduct a new risk analysis based on the modified device design.   
 
1.  Embolic Capture Efficiency and Retrieval Ability 
Significance  
The amount of embolic debris captured and the efficiency of debris removal from the patient 
determines how much embolic material migrates downstream to the end organ.  
 
Recommendation 
We recommend that you quantitatively assess the ability of your device to contain embolic 
debris during simulated clinical use.  Your assessment should compare the amount of debris 
captured by your device to the amount of debris available for capture (typically the total 
amount of embolic material introduced into your test system).  You should specify the 
composition and size distribution of the simulated embolic material and explain its clinical 
relevance.  If your simulated embolic material includes particles of different sizes, you should 
stratify your capture efficiency results according to particle sizes or size ranges. 
 
We also recommend that you quantify how much of the captured embolic debris is liberated 
during retrieval and withdrawal of the filter element.  To simulate worst-case clinical 
conditions, the filter element should be completely full of embolic material when conducting 
this assessment. 
 
2.  Stent Compatibility 
Significance 
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If the target lesion is stented, the embolic protection device should be able to be tracked 
proximally through the stented region and retrieved successfully without entanglement with or 
damage to the deployed stent.  
 
Recommendation 
For embolic protection devices designed for deployment distal to the target lesion, we 
recommend that you demonstrate that the embolic protection device can be tracked 
proximally through a deployed stent or series of stents and retrieved without entanglement or 
other complication.  Overlapping stents should be used if you expect your device to be used in 
this configuration, based on your risk analysis.  If your device is filter-based, you should 
conduct this test using a full filter element to simulate worst-case clinical conditions.  You 
should examine the embolic protection device as well as the stent(s) after testing for any 
evidence of damage, such as coating delamination and strut fractures. 
 
If your device is indicated for use during intervention in previously stented vessels, you 
should also demonstrate that your device can be tracked distally through a previously 
deployed stent or series of stents without complication.  You should use drug-eluting stents in 
this assessment if your embolic protection device is indicated for use during saphenous vein 
graft intervention.  
 
3.  Simulated use 
Significance
The operator should be able to prepare and use the embolic protection device without 
difficulty.  A benchtop model for simulated use assessment allows for data reproducibility and 
comparability of results obtained using different devices. 
 
Recommendations 
FDA recommends that you evaluate the ability to prepare, deliver, and withdraw the embolic 
protection device under conditions that simulate as closely as possible the clinical setting 
without difficulty or damage to the device.  Your evaluation should include performance 
assessment of key attributes that represent the ease or difficulty involved in using your 
embolic protection device.  Examples of key attributes include the following:   
ease of preparing the embolic protection device for use; 
 
compatibility of the embolic protection device with appropriate accessory devices, 
 
such as guidewires, stent delivery systems, and balloon catheters; 
ability to advance/retract the embolic protection device; 
 
ability to deploy and collapse any protective elements, such as filters or balloons; 
 
ability to completely withdraw the embolic protection device after the procedure; and 
 
ability to visualize the embolic protection device under fluoroscopy. 
 
 
Evaluation of these key attributes should include a scoring system or another quantitative 
method, and should involve multiple users.  Any test fixture that you use should mimic the 
target anatomy.  You should provide a schematic of the test fixture(s) and explain how the 
fixture(s) simulate worst-case patient anatomy. 
 
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If you identify the need for any special steps involving device preparation or usage as a result 
of simulated use testing, you should incorporate these steps in the device labeling or training 
program (if any).  
 
4.  Deployment/retrieval forces 
Significance 
The operator typically applies force to the catheter in order to deploy or retrieve the embolic 
protection device.  Excessive deployment or retrieval forces may make the device difficult to 
operate and can lead to vascular adverse events. 
 
Recommendation 
We recommend that you quantify the maximum force required to completely deploy or 
retrieve your embolic protection device during simulated clinical use.  Any test fixture that 
you use should mimic the target anatomy.  You should provide a schematic of the test 
fixture(s) and explain how the fixture(s) simulate worst-case patient anatomy. 
 
5.  Filter capacity 
Significance 
The amount of embolic debris that a filter-based embolic protection system can capture is 
limited by the size of the filter element.  A full filter basket can no longer capture embolic 
debris and may prevent anterograde blood flow within the vessel, potentially leading to 
ischemia of downstream organs or less efficient embolic capture. 
 
Recommendation 
We recommend that you quantify the maximum amount of embolic material that your device 
is expected to capture.  We also recommend you measure this parameter experimentally using 
bench testing data. 
 
6.  Resistance to filter rupture during removal of a fully loaded filter 
Significance 
Retrieval of a filter-based embolic protection device has a risk of filter rupture and subsequent 
release of captured embolic material.  Embolic protection systems should be able to be 
retrieved without damage to the filter element and excessive release of embolic debris. 
 
 
Recommendation 
We recommend that you demonstrate that a completely full filter basket can be retrieved 
under simulated clinical conditions without filter rupture, catheter damage, or other adverse 
device effect.  This assessment may be combined with the assessment described in 2.  Stent 
Compatibility above. 
 
7.  Flow characteristics 
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Significance 
A deployed embolic protection device may have an adverse effect on blood flow.  For filter-
based devices, blood flow perturbation as a result of filter placement could adversely affect 
embolic capture or damage the surrounding endothelium.  For balloon-based devices intended 
to occlude the treatment vessel, lack of complete vessel occlusion can result in incomplete 
embolic capture. 
 
Recommendation 
We recommend that you characterize fluid flow in a simulated vessel after 
activation/deployment of your embolic protection system.  You should explain why the 
observed flow characteristics are clinically acceptable.  If you expect flow characteristics to 
vary depending on vessel geometry, such as in a straight versus a curved vessel segment, you 
should conduct additional assessments that span the range of anticipated vessel geometries. 
 
8.  Radial outward force 
Significance 
It is important to characterize the radial outward force of self-expanding embolic protection 
devices.   Excessive radial force could injure the surrounding tissue, while a radial force that 
is too low can result in incomplete apposition of the device to the vessel wall. 
 
Recommendation 
We recommend that you measure the radial force exerted by the embolic protection device 
against the vessel wall as a result of device expansion.  If a particular device size or model is 
indicated for use in a range of vessel sizes, your assessment should cover the range of possible 
vessel sizes, or should include a rationale for not assessing the entire indicated size range. 
 
9.  Tip flexibility 
Significance 
The distal tip of catheter-based devices can cause vessel dissection or perforation if the tip 
does not buckle sufficiently when force is applied. 
 
Recommendation 
We recommend that you quantify the minimum amount of force needed to deflect the tip of 
your embolic protection device as well as any bundled accessory devices (such as guidewires) 
that may be traumatic to the vasculature.  You should provide a rationale for the critical test 
parameters you select, such as the location(s) at which the force is applied and the extent to 
which the tip is deflected at the time of force measurement.  We recommend that the device 
configuration used for this assessment incorporate any accessory devices that may affect the 
tip stiffness. 
 
10. Tensile Strength 
Significance 
Embolic protection devices should be able to be manipulated axially without failure of any 
joints or bonds, which could lead to device failure and device embolization. 
 
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Recommendation 
We recommend that you assess the tensile strength of all key bonds and joints in your embolic 
protection device.  Each bond and joint should be tested individually, unless you provide a 
scientific rationale for why multiple bonds or joints can be tested without affecting the 
validity of the results. 
 
11. Torque Strength 
Significance 
Embolic protection devices should be able to be manipulated circumferentially without failure 
of catheter shaft integrity or any bonds, which could lead to device failure and device 
embolization. 
 
Recommendation 
We recommend that you assess the torque strength of the catheter shaft and all key bonds in 
your embolic protection device.  The catheter shaft and all bonds should be tested 
individually, unless you provide a scientific rationale for why multiple device elements can be 
tested without affecting the validity of the results. 
   
12. Torque Response 
Significance 
Application of torque to the proximal end of a catheter-based device can potentially result in 
uneven or incomplete force transmission to the distal end.  Potential adverse effects of 
inadequate torque response include lack of torque transmission to the distal end of the device, 
or severe whipping or abrupt and uncontrolled distal rotation due to the buildup of torque 
that can potentially result in vascular trauma. 
 
Recommendation 
We recommend that you demonstrate that application of proximal torque results in adequate 
torque transmission to the distal end of your device.  Your results should demonstrate that the 
distal end of the device experiences a satisfactory torque response after application of torque 
to the proximal end, and that guidewire and/or catheter whip will not be clinically significant. 
 
13. Kink resistance 
Significance 
Tracking the embolic protection device through tortuous vascular anatomy can result in 
permanent deformations within the device.  These deformations may result in device failure or 
other adverse clinical effects. 
 
Recommendation 
We recommend that you demonstrate that your embolic protection device and any bundled 
accessory devices (such as guidewires) can be tracked to the target location under simulated 
clinical conditions without undergoing permanent deformation.  Your test apparatus should 
mimic the size and tortuosity of the vasculature through which the device will be tracked 
  13
  Contains Nonbinding Recommendations 
 
clinically.  Alternatively, you may conduct this assessment by subjecting your device to 
bending deformations using cylindrical mandrels that simulate the most extreme radius of 
curvature that you expect your device will encounter clinically without permanent 
deformation. 
 
14. Occlusion balloon characteristics  
Significance 
Balloon failure can result in unintended balloon deflation or injury to the treated vessel or 
downstream organ, therefore, the performance of the occlusion balloon components of 
embolic protection devices should be sufficiently characterized. 
 
Recommendation 
We recommend that you characterize the performance of any balloon components of your 
embolic protection device.  You should characterize the following performance attributes: 
balloon compliance (balloon diameter vs. inflation pressure), 
 
balloon burst pressure, 
 
inflation/deflation time, and 
 
balloon fatigue. 
 
 
See also Non-Clinical Tests and Recommended Labeling for Intravascular Stents and 
Associated Delivery Systems6 for additional guidance on evaluation of the performance of 
catheter-based balloons. 
 
15. Dimensional verification 
Significance 
The size of embolic protection devices affects the size and location of the vessels in which 
they can effectively be used, therefore, it is important that all dimensions are accurately 
characterized.   
 
 
Recommendation 
We recommend that you measure and report all clinically relevant dimensions for your device 
to verify that these dimensions conform to your design specifications. 
 
16. Catheter coating integrity 
Significance 
Embolic protection devices incorporating surface coatings, such as those intended to increase 
lubricity or decrease thrombogenicity, are at risk for loss of coating integrity due to frictional 
forces generated by blood flow and device manipulation.  Coating delamination can lead to 
loss of coating functionality and embolization of coating particulates. 
 
                                                 
6 http://www.fda.gov/cdrh/ode/guidance/1545.pdf 
  14
  Contains Nonbinding Recommendations 
 
Recommendation 
We recommend that you characterize the resistance of your device coating to delamination.  
As part of this characterization, you should measure the number and size distribution of 
particulate matter generated during simulated clinical use.  You should provide a scientific 
rationale for the test setup and the acceptance criteria for this test.  You should also inspect 
the embolic protection device after testing for signs of focal areas of delamination.  
Additionally, you should characterize the performance or activity of the coating before and 
after particulate generation testing to ensure that coating functionality is not lost during 
simulated clinical use. 
 
17. Electromagnetic compatibility 
Significance 
Electrically powered devices may interfere with other powered devices when active, 
therefore, it is important to characterize the electromagnetic compatibility of any electrically 
powered devices. 
 
Recommendation 
If your device is electrically powered, we recommend that you demonstrate that your device 
can be operated without any interference to or from other powered devices.  We recommend 
that you conduct this assessment as described in EN 60601-1 (General Requirements for 
Safety), EN 60601-1-1 (Safety Requirements for Medical Electrical Systems), EN 60601-
1-2 (Electromagnetic Compatibility  Requirements and Tests), or equivalent methods. 
 
18. Software Validation 
Significance 
Devices that rely on software for operation may not function properly if the software has not 
been appropriately designed and tested. 
 
Recommendation 
If your device incorporates any software, you should demonstrate that the software 
component has been appropriately validated.  We recommend that you conduct this 
assessment following the recommendations in FDAs Guidance for the Content of 
Premarket Submissions for Software Contained in Medical Devices.7  
 
9. Animal Assessment 
We recommend you conduct testing in animals to demonstrate preliminary device safety prior to 
initiating clinical studies in humans.  We recommend that you evaluate coronary and carotid 
embolic protection devices in an animal model with acute and chronic observation timepoints, 
and that you provide this information in the 510(k) submission.  We recommend that you consider 
the following points when conducting non-clinical animal testing of coronary and carotid embolic 
protection devices. 
1.  Animal Model 
                                                 
7 http://www.fda.gov/cdrh/ode/guidance/337.pdf 
  15
  Contains Nonbinding Recommendations 
 
The animal model for your study should mimic as closely as possible the anatomy in which your 
embolic protection device will be used clinically. 
 
For embolic protection devices indicated for use in saphenous vein grafts 
 
We recommend that your animal studies use challenging arterial vessels that reasonably 
simulate the size and shape of saphenous vein grafts, such as swine carotid arteries and larger 
coronary arteries.  
 
For embolic protection devices indicated for use in carotid arteries 
 
FDA does not consider the porcine carotid anatomy to be as tortuous as human carotid artery 
anatomy.  Therefore, we recommend that you use another, more tortuous segment of the 
porcine anatomy for evaluation of device handling characteristics and vascular trauma, such 
as the subclavian vasculature.  It may be appropriate, however, to evaluate other 
characteristics of your device, such as placement accuracy, in the porcine carotid anatomy. 
2.  Study Protocol 
We recommend that your animal studies follow Good Laboratory Practices (GLP) or are GLP-
like in quality.  You should refer to 21 CFR Parts 58 and 812 for additional information on 
reporting requirements for animal studies. 
Your study protocol should mimic, as closely as possible, a coronary or carotid interventional 
procedure in a human, including introduction, deployment, and retrieval of the embolic protection 
device, as well as the use of a stent system or balloon catheter if you expect that these devices 
will also be used.  All study variables, including selection of device models, and implantation 
location, should represent worst-case clinical conditions, and you should support your selections 
with an appropriate rationale.  In addition, you should provide a rationale for the number of 
animals and devices used in the study. 
Your protocol should specify whether the animal will be placed on a mechanical ventilator or 
allowed to breathe spontaneously.  FDA recommends that you allow the animals to breathe 
spontaneously because mechanical ventilation may limit the operators ability to ascertain 
neurological dysfunction during the procedure. 
The studies should use the actual device models proposed for use in the clinical setting, including 
any delivery and retrieval catheters.  The studies should include a reasonable representation of all 
device sizes, and the device-to-artery size ratios should span the range proposed for clinical use. 
We recommend that you evaluate the use of your device when overlapping stents are implanted, if 
your device is indicated for use in this situation.  
We recommend that you simulate embolic debris using a thrombosis model rather than using 
resin or other solid material. Solid particles, such as polyvinyl alcohol, may not be an appropriate 
model for thrombus because thrombus is more friable and more likely to release when the device 
is collapsed for retraction.  We recommend you address whether the embolic material model used 
reflects device performance in the clinical setting by providing a scientific rationale for the 
number, size distribution, and composition of the particles chosen.   
  16
  Contains Nonbinding Recommendations 
 
Because procedure time can affect patient outcomes, we recommend that the minimum device 
deployment time used in your animal study reflects the worst-case device deployment time 
expected in actual clinical use. 
You should explain the method by which you determine whether the embolic protection device 
was deployed at the intended vascular location. 
3.  Study Endpoints 
You should assess the potential for your device to provoke an inflammatory response or injure the 
surrounding vasculature, and ensure that downstream organs are not adversely affected by the use 
of your device.  To this end, pathology evaluations performed on necropsied animals should 
include a gross pathological assessment of the relevant end organ (heart or brain) and a careful 
histological examination of the segment where the embolic protection device was deployed.  Your 
assessment should include evaluation of vessel injury and inflammation in the animals followed 
for both acute and long term assessments (described below).  You should also evaluate the 
neointimal response in animals evaluated for chronic performance.  The descriptive pathology of 
the vascular inflammation and injury should incorporate the use of a validated grading scale, and 
you should explain the criteria for each grade.  The study report should include the full pathology 
report, providing line listings and clear copies of photographs and photomicrographs. 
We recommend that the pathology studies include observations from 2 interventions in each of 4 - 
6 animals at 24 to 72 hours post-treatment for acute assessments and at 1 month post-treatment 
for longer-term assessments.  If healing is not complete at 1 month post-treatment or if your 
device design differs significantly from legally marketed device designs, FDA may recommend 
you collect 6 months animal data to demonstrate that the use of the device does not cause any 
long term effects. 
Your studies should include assessments of the potential to cause hemolysis over the course of the 
procedure.  Examples of appropriate endpoints for this assessment include changes in red blood 
cell count, plasma-free hemoglobin, and/or haptoglobin levels. 
Your study should demonstrate that a device containing embolic material can be removed without 
damage to the device, vessel, and/or a series of stents consistent with its intended use as described 
in the labeling.  This assessment should be conducted using a full filter basket to mimic worst-
case clinical conditions.  You should observe the position of the implanted stent(s) following 
deployment of the embolic protection device.  In addition, you should assess damage to both the 
implanted stent and the embolic protection device.  FDA recommends the use of radiological 
methods to assess damage to the implanted stent because this method will still allow a 
histological analysis at the same site. 
Some filter-based devices may be designed to be only partially retracted into a sheath after 
deployment and embolic capture and prior to removal.  We recommend that your submission 
indicate the extent of retraction of the device necessary for removal.  If the devices instructions 
for use specify that the device should be fully retracted before removal, we recommend you 
conduct this assessment using both partially and fully retracted filters to simulate worst-case 
clinical conditions in which the filter cannot be fully retracted due to filter overload.   
Angiographic assessment during procedures should include evaluation of blood flow rate, 
thrombus formation, and vessel injury. 
  17
  Contains Nonbinding Recommendations 
 
During the procedure, you should assess the handling characteristics and visibility of the embolic 
protection device in as quantitative a manner as possible.  You may wish to compare these device 
characteristics to those of a legally marketed predicate device.  For carotid embolic protection 
devices, you should record any behavioral changes or other neurological abnormalities observed 
in the treated animals.   
Your studies should include targeted observation of potential damage to the embolic protection 
device and deployed stent(s), including high-quality gross images of these devices.  You should 
also assess the extent of thrombus formation on the embolic protection device after use.  In 
addition, you should identify any locations that appear to be damaged or thrombogenic, and 
provide magnified images of these regions. 
4.  Data Presentation 
To facilitate FDA review of your animal studies, we recommend a tabular format that provides an 
overview of all the studies you conducted and a separate table for each study that summarizes the 
study objectives, methods, and results.  We recommend that you include high-quality photographs 
of the images used for your analyses and high-resolution electronic copies of these images.  In 
addition, you should include electronic files that contain the line listing (individual) data used for 
your analyses. 
You should provide the full animal study report as well as signed copies of any pathology reports 
from your studies.  In addition, you should account for all animals proposed for use in the study, 
including those that died prior to the study procedure. 
 
10.  Clinical Information 
 
In accordance with the Act, the agency will rely upon well-designed bench and/or animal testing 
rather than requiring clinical studies for new devices unless there is a specific justification for 
asking for clinical information to support a determination of substantial equivalence.  However, 
FDA has found that animal and bench testing of embolic protection devices is generally not 
adequate to demonstrate the substantial equivalence of these devices due to a number of factors. 
First, in vitro model flow characteristics may not provide an adequate representation of in vivo 
conditions.  Second, ideal animal models do not exist for diseased SVGs and carotid arteries.  
Third, there is no proven model for generating embolic material for use in bench and animal 
testing.  Finally, animal and bench testing may not fully characterize embolic protection devices 
that differ in their fundamental technology from predicate devices.  These differences may have 
unpredictable effects on procedural success and complication rates.  Thus, while satisfactory 
animal and bench testing results are needed to establish preliminary safety before initiating 
clinical trials, data from appropriately designed clinical trials are generally necessary to establish 
substantial equivalence to a legally marketed device.   
 
Clinical data may not be necessary to support minor changes to the device, such as design 
changes to the EPD catheter shaft proximal to the distal tip.  In such cases, bench and/or animal 
data may be sufficient to demonstrate substantial equivalence.  If you believe that clinical data are 
not needed to demonstrate substantial equivalence for your device, you should provide a 
scientifically based rationale for why clinical data are not necessary in your 510(k) submission.  
  18
  Contains Nonbinding Recommendations 
 
We recommend that you contact either the Interventional Cardiology Devices Branch or the 
Peripheral Vascular Devices Branch to discuss your proposed testing plan for coronary and 
carotid embolic protection devices, respectively. 
 
For both coronary and carotid indications, the target patient population may be heterogeneous and 
difficult to characterize using a standard set of measurable risk factors.  Variability in procedure-
related and adverse event outcome rates has been reported in the literature8 across a range of 
embolic protection devices, including devices studied using similar patient populations.  Some 
risk factors for adverse events have been characterized, such as SVG age, carotid artery 
tortuosity, and lesion length, but the association between many other variables and clinical 
outcomes is less well understood.  Because it may be difficult to predict the risk of complications 
for a particular patient population or lesion subset, the baseline clinical and lesion characteristics 
become important considerations and underscore the importance of selecting an appropriate 
control group or performance goal. 
 
There are several approaches to designing a clinical investigation for a new coronary SVG 
embolic protection system.  One approach is a single-arm study using historical controls.  This 
approach may be ideal for a first-generation device trial when there is an appropriate historical 
control group available for comparison and the IDE sponsor has full access to patient-level data 
for the control group.  With access to such a comparative data set, you should employ appropriate 
clinical and statistical methodologies in order to minimize in any comparison the effects of 
possible confounding or bias. 
 
When designing a clinical investigation for a coronary embolic protection device, you should 
consider the need to identify which patients benefit most from embolic protection, particularly 
given potential interactions between a newly developed embolic protection device and baseline 
disease and/or lesion characteristics. If you cannot identify an appropriate control group with 
access to patient-level data (as may be the case if you are seeking a new indication), FDA 
recommends the use of randomized, controlled trials in order to be able to clearly compare 
treatment and control group results.   
 
Single-arm studies employing historical controls may be appropriate for assessing clinical 
performance of a second-generation coronary embolic protection device and/or modifications to a 
currently marketed device, provided the modified device is sufficiently similar to the first-
generation device.  Examples of minor design changes for which a single-arm study may be 
appropriate are modifications to the distal end of a device, or introduction of smaller/larger sizes 
of the same device design. 
 
Carotid embolic protection devices are frequently studied clinically in conjunction with carotid 
stent systems that are also investigational.9  Single-arm studies involving comparisons to either a 
retrospective control group or a performance goal derived from previously reported clinical data 
are able to generate sufficient safety and effectiveness data to support certain carotid stenting 
indications, and it may be impractical to include an active control for the embolic protection 
device alone in these studies.  However, clinical data from a randomized, controlled trial may be 
                                                 
8 Mauri et al., Circulation 113:2651  2656 (2006) 
9 Carotid stents are Class III devices, requiring Premarket Approval. 
  19
  Contains Nonbinding Recommendations 
 
appropriate if your device incorporates indications, technology, or a design that differs 
significantly from those of currently marketed devices. 
 
Clinical Protocol Recommendations for All Indications 
 
Clinical studies conducted in the United States in support of 510(k) clearance must be conducted 
under the Investigational Device Exemptions (IDE) regulation, 21 CFR Part 812.  FDA believes 
that coronary and carotid embolic protection devices addressed by this guidance document are 
significant risk devices as defined in 21 CFR 812.3(m).   Such studies require an FDA-approved 
IDE (21 CFR Part 812) and sponsors must comply with the regulations governing institutional 
review boards (21 CFR Part 56) and informed consent (21 CFR Part 50). 
 
You should conduct your study using a number of patients that provides sufficient statistical 
power for the primary study endpoint.  FDA recommends that your patient population be larger 
than the minimum statistically based sample size to account for patients that withdraw from the 
study or are lost to follow-up over time. FDA recommends that all follow-up visits consist of 
office visits.  Telephone follow-up may not allow you to fully assess the incidence of all primary 
and secondary endpoint events. 
 
You should capture all adverse events and provide a narrative history for each patient in which a 
major adverse event occurs. You should capture all instances of device failure, including 
malfunctions and inaccurate device placement. 
 
Because a high number of protocol deviations can significantly affect the validity of the clinical 
study data, you should capture all protocol deviations that occur during the study.  In addition, 
your 510(k) should include a discussion of the impact of the protocol deviations on the validity of 
the clinical study results. 
 
We recommend that you employ a core laboratory to minimize the introduction of bias or 
subjectivity into the data analysis process. We recommend that you incorporate a sensitivity 
analysis into your statistical plan to quantitatively assess the impact of any missing clinical data 
on the statistical analysis. 
 
FDA recommends that your study employ a Clinical Events Committee (CEC) to provide 
independent adjudication of clinical events.  Similarly, we recommend that you use an 
independent Data Monitoring Committee (DMC) to provide ongoing assessment of safety during 
the course of the clinical trial. 
 
FDA encourages the use of flexible or adaptive study designs to assess the safety and 
performance of embolic protection devices.  We recommend that you contact the Interventional 
Cardiology Devices Branch (for coronary embolic protection devices) or the Peripheral Vascular 
Devices Branch (for carotid embolic protection devices) to discuss the design of such a study 
prior to submission of your IDE. 
 
Saphenous Vein Coronary Artery Bypass Graft Indications 
 
Study Endpoints 
  20
  Contains Nonbinding Recommendations 
 
 
FDA recommends a primary endpoint of the combined rate of major adverse cardiac events 
(MACE) at 30 days post-procedure, including all cardiac deaths, all myocardial infarctions (Q 
wave and non-Q-wave), target vessel revascularization, and emergency coronary artery bypass 
grafting. 
 
Recommended secondary endpoints include the following: 
  component endpoints of MACE 
  device success (delivery, deployment, and retrieval of the device per protocol without 
complication) 
  angiographic endpoints 
  freedom from procedure-related serious adverse events (i.e., clinical success) 
  access site complications 
  post-procedure levels of creatine kinase (CK) or its isoenzyme, CK-MB  
  MACE during the hospital stay for the index procedure  
  post-procedure Thrombosis In Myocardial Infarction (TIMI) flow. 
 
Because of the causal relationship in SVGs between distal embolization of debris and non-Q 
wave myocardial infarction, adequate collection of post-procedure CK or CK-MB is essential to 
rule out these events.  Given that non-Q-wave myocardial infarctions are a component of the 
composite endpoint of MACE, missing enzyme data can confound interpretation of the trial 
results.  FDA recommends that you assess the impact of missing cardiac enzyme data on the trial 
results using sensitivity analysis, or an equivalent method.   
 
We recommend that you evaluate the impact of any unbalanced (random or systematic) baseline 
variables with respect to treatment assignment using a propensity score analysis or an equivalent 
method.  A propensity score analysis should include hypothesis testing using propensity-adjusted 
outcomes.  
 
Carotid Indications 
 
Study Considerations 
 
You should provide a clinically and statistically based rationale for the control group or 
performance goal you select for your study.  Your rationale should include a discussion of the 
comparability of the clinical data from which you derived the performance goal and the clinical 
data that you expect your study to generate.  For example, you should compare the patient 
populations, study endpoints, treatment type, and other factors that may affect the study results.  
This rationale affects the acceptability of the proposed performance goal for your study. 
 
FDA recommends that the statistical hypothesis for any comparison of single-arm study results to 
a performance goal derived from previously reported clinical data incorporate comparisons of the 
study results to the performance goal itself without any claims of non-inferiority or superiority.  
Hypotheses and claims involving non-inferiority or superiority of your device to the performance 
  21
  Contains Nonbinding Recommendations 
 
goal or to any device for which clinical data were used to derive the performance goal may not be 
appropriate statistically.   
 
You may evaluate the performance of your embolic protection device in a study that includes 
either an approved carotid stent system or in a clinical study that is designed to also investigate 
the safety and effectiveness of a carotid stent system.  In the second instance, FDAs assessment 
of the carotid embolic protection device would be linked to our assessment of the investigational 
carotid stent.  Accordingly, FDA could not complete the review of the embolic protection device 
labeling until approval of the stent PMA.  Therefore, if you choose to pursue the latter option 
above, FDA recommends that you submit the 510(k) for your carotid embolic protection device 
either with the PMA for your carotid stent or after the PMA is approved.   
 
Study Endpoints 
 
FDA recommends a primary endpoint of the combined rate of major adverse cardiac and 
cerebrovascular events at 30 days post-procedure, including all deaths, strokes, and myocardial 
infarctions. 
 
Recommended secondary endpoints include:  
  device success (delivery, deployment, and retrieval of the device per protocol without 
complication), 
  freedom from procedure-related serious adverse events (clinical success), 
  access site complications, 
  neurological events at 30 days post-procedure, including strokes and transient ischemic 
attacks, and  
  neurological intolerance to vessel occlusion (for devices designed to occlude the target 
vessel). 
 
11.   Sterilization and Shelf Life 
FDA recommends that you provide sterilization information in accordance with the Updated 
510(k) Sterility Review Guidance K90-1; Final Guidance for Industry and FDA, 
http://www.fda.gov/cdrh/ode/guidance/361.html.  You should sterilize the device to a sterility 
assurance level (SAL) of 1 x 10-6 using a sterilization cycle that has been validated in accordance 
with the Quality System Regulation (21 CFR Part 820). 
 
Because embolic protection devices are in direct contact with circulating blood, we recommend 
you test the devices for pyrogenicity.  We also recommend you provide the following: 
 
  description of the method used to make the determination, such as the limulus amoebocyte 
lysate (LAL) method; 
  identification of the testing endpoint reached and rationale for selecting that endpoint;  
  description of the extraction technique used to obtain the test fluid from the test device, 
showing that all clinically relevant contact surface of the test device were assessed; and 
  22
  Contains Nonbinding Recommendations 
 
  identification of any reference method used, such as AAMI ST72 (Bacterial Endotoxins 
- Test Methodologies, Routine Monitoring, and Alternatives to Batch testing), an 
FDA guidance document, or an equivalent method.   
 
FDA recommends that shelf life testing address package integrity to ensure sterility and stable 
device functionality over the labeled shelf life.  To evaluate device functionality, we recommend 
that you identify the device performance characteristics that may be affected by aging and repeat 
the bench tests that evaluate those characteristics using aged samples.  For example, aging can 
affect the performance of most polymer materials used for embolic protection device catheters; 
therefore, tests that evaluate the integrity and performance of the catheter should be repeated after 
aging.  For those bench tests that you do not repeat, you should provide a rationale explaining 
why the performance characteristics assessed by the tests are not expected to be affected by 
aging.  We also recommend that you provide the protocol used for your shelf life testing, the 
results of the testing, and the conclusions drawn from your results.   
 
12.  Labeling  
The premarket notification must include labeling in sufficient detail to satisfy the requirements of 
21 CFR 807.87(e).  The following suggestions are aimed at assisting you in preparing labeling 
that satisfies the requirements of  21 CFR Part 801.10
 
Directions for use 
As a prescription device, the device is exempt from having adequate directions for lay use 
when the conditions identified in 21 CFR 801.109 are met.  You must provide information for 
use by health care practitioners in the device labeling (21 CFR 801.109(c), (d)).  We 
recommend submitting clear and concise instructions that delineate the technological features 
of the specific device and how the device is to be used on patients.  We recommend the 
directions for use include a comprehensive summary of the results from any clinical study, 
including any applicable warnings or precautions based on those study findings.  In addition, 
we recommend the instructions encourage local/institutional training programs designed to 
familiarize users with the features of the device and how to use it in a safe and effective 
manner. 
 
As part of your 510(k) submission, we recommend that you provide a description of the 
device failure modes and malfunctions observed during non-clinical and clinical evaluation, 
as well as any steps that users should take to minimize the incidence of these events.  You 
should also explain how you will communicate these failure modes and mitigation steps to 
device users, for example, as part of the device training program. 
 
Contraindications 
                                                 
10 Although final labeling is not required for 510(k) clearance, final labeling must comply with 
the requirements of 21 CFR Part 801 before a medical device is introduced into interstate 
commerce.  In addition, final labeling for prescription medical devices must comply with 21 CFR 
801.109.  Labeling recommendations in this guidance are consistent with the requirements of Part 
801. 
  23
  Contains Nonbinding Recommendations 
 
The information for use by health care practitioners that you provide in the labeling must 
address contraindications, where the risk of harm from use in a patient population or situation 
clearly outweighs any possible benefit.  The contraindications for an embolic protection 
device should generally include the following: 
patients for whom anti-coagulant or anti-platelet therapy is contraindicated, 
 
patients with uncorrected bleeding disorders, 
 
patients with vascular anatomy tortuous enough to prevent safe introduction and 
 
passage of interventional devices, and 
patients with a known or suspected allergy to a primary material of construction for 
 
the embolic protection device that will be in prolonged contact with the vasculature. 
 
You should add contraindications if clinical or non-clinical data suggest they might be 
appropriate. 
 
 
 
Warnings 
FDA recommends that you add device warnings for any situation for which there is 
reasonable evidence of a serious hazard with the use of the device, or to identify situations in 
which embolic protection devices are commonly used but for which there is a lack of 
scientific evidence supporting such use.  FDA recommends that you include warnings to 
address the following: 
patient sub-populations with specific anatomic features, co-morbid conditions, or other 
 
characteristics who you suspect would suffer unreasonable risk of harm as a result of 
treatment with your device; and 
clinically important patient sub-populations for whom safety and effectiveness data are 
 
not available (For SVG indications, if you do not have clinical data regarding the use of 
your device in patients that have been treated with drug-eluting stents in the target vessel, 
FDA recommends that you add a warning that the safety and effectiveness of your device 
has not been established in these patients.). 
 
For carotid embolic protection devices, labeling should identify the specific stent-embolic 
protection device combinations for which clinical safety and effectiveness data are available 
and state that the safety and effectiveness of the use of other such combinations has not been 
determined.  Labeling should also identify the specific stent-embolic protection device 
combinations for which bench or animal data are available that show device compatibility and 
state that the compatibility of other such combinations has not been determined. 
 
You should add warnings if clinical or non-clinical data suggest they might be appropriate. 
 
Precautions 
You should include as precautions any special measures, such as handling methods, that the 
operator should take during device preparation and use.  
  24
  Contains Nonbinding Recommendations 
 
  25
  Contains Nonbinding Recommendations 
 
Appendix A: Referenced Standards 
 
The following tables include all standards referenced in this document. 
 
AAMI Standards
ST72 Bacterial Endotoxins - Test Methodologies, Routine Monitoring, and Alternatives to Batch 
Testing 
 
 
ASTM Standards
F1984 Standard Practice for Testing for Whole Complement Activation in Serum by Solid 
Materials 
F2065 Standard Practice for Testing for Alternative Pathway Complement Activation in Serum 
by Solid Materials 
 
 
IEC/EN Standards
60601-1 General Requirements for Safety 
60601-1-1 Safety Requirements for Medical Electrical Systems 
60601-1-2 Electromagnetic Compatibility  Requirements and Tests 
 
 
ISO Standards
10993-1 Biological Evaluation of Medical Devices: Evaluation and Testing 
10993-12 Biological Evaluation of Medical Devices: Sample Preparation and Reference 
Materials 
 
 
USP Standards
USP 30 <85> Biological Tests and Assays, Bacterial Endotoxin Test (LAL) 
USP 30 <151> Pyrogen Test (USP Rabbit Test) 
 
A list of FDA-recognized standards is available at: 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm
 
  26