**Guidance for Industry and FDA Staff**

**Class II Special Controls Guidance Document: Vascular and
Neurovascular Embolization Devices**

**Document issued on:**

For questions regarding this document, contact:

-   Peter L. Hudson, Ph.D., Plastic and Reconstructive Surgery Branch,
    at 301-594-3090, ext.194 or by email at <plh@cdrh.fda.gov>

-   Elisa D. Harvey, D.V.M., Ph.D., Peripheral Vascular Devices Branch,
    at 301-443-8262, ext.167 or by email at <edh@cdrh.fda.gov>

-   Colin M. Pollard, Obstetrics and Gynecology Devices Branch, at
    301-594-1180 or by email at <cmp@cdrh.fda>.

**This document will supersede "Guidance for Neurological Embolization
Devices" dated November 1, 2000" and the draft guidance "Class II
Special Controls Guidance Document: Vascular and Neurovascular
Embolization Devices" dated February 25, 2004.**

![](media/image1.png)

**U.S. Department of Health and Human Services**

**Food and Drug Administration**

**Center for Devices and Radiological Health**

**Office of Device Evaluation**

**Division of General, Restorative, and Neurological Devices**

**Plastic and Reconstructive Surgery Devices Branch**

**Division of Cardiovascular Devices**

**Peripheral Vascular Devices Branch**

**Division of Reproductive, Abdominal, and Radiological Devices**

**Obstetrics and Gynecology Devices Branch**

**Preface**

**Public Comment**

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.fda.gov/dockets/ecomments>. When submitting comments, please
refer to **Docket No. 2003D-0568**. 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/1234.pdf>, or to receive this
guidance document via your fax machine, call the CDRH Facts-On-Demand
system at 800-899-0381 or 301-827-0111 from a touch-tone telephone.
Press 1 to enter the system. At the second voice prompt, press 1 to
order a guidance document. Enter the guidance document number (**1234**)
followed by the pound sign (#). Follow the remaining voice prompts to
complete your request.

**Table of Contents**

[1. Introduction 1](#introduction)

[2. Background 2](#background)

[3. The Content and Format of an Abbreviated 510(k) Submission
3](#the-content-and-format-of-an-abbreviated-510k-submission)

[4. Scope 5](#scope)

[5. Device Description 6](#device-description)

[6. Risks to Health 7](#risks-to-health)

[7. Preclinical Testing 7](#preclinical-testing)

[8. Sterility 10](#sterility)

[9. Animal Testing 10](#animal-testing)

[10. Clinical Testing 10](#clinical-testing)

[11. Labeling 13](#labeling)

**Guidance for Industry and FDA Staff**

#### 

**Class II Special Controls Guidance Document: Vascular and
Neurovascular Embolization Devices**

***This guidance document 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 document. If you cannot identify the
appropriate FDA staff, call the appropriate number listed on the title
page of this guidance document.***

# 1. Introduction

This guidance document was developed as a special controls guidance
document to support the reclassification of the vascular embolization
device and the neurovascular embolization device into class II. The
vascular embolization device is intended to control hemorrhaging due to
aneurysms, certain types of tumors (e.g., nephroma, hepatoma, and
uterine fibroids), and arteriovenous malformations. The neurovascular
embolization device is intended to permanently occlude blood flow to
cerebral aneurysms and cerebral arteriovenous malformations. FDA
believes that the risks to health associated with the intended uses of
the vascular embolization and the neurovascular embolization devices are
the same. Therefore, FDA believes that a single guidance document can
serve as the special control for both device types.

This guidance document is issued in conjunction with a Federal Register
notice announcing the reclassification of the vascular embolization
device and the neurovascular embolization device types. Following the
effective date of the final rule reclassifying these devices, any firm
submitting a 510(k) for a vascular embolization device or a
neurovascular embolization device will need to address the issues
covered in the special control guidance document. However, the firm need
only show that its device meets the recommendations of the guidance
document or in some other way provides equivalent assurances of safety
and effectiveness.

FDA\'s guidance documents, including this guidance, do not establish
legally enforceable responsibilities. Instead, guidance documents
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 guidance
documents means that something is suggested or recommended, but not
required.

**The Least Burdensome Approach**

The issues identified in this guidance document represent those that we
believe need to 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

> FDA believes that special controls, when combined with the general
> controls, will be sufficient to provide reasonable assurance of the
> safety and effectiveness of the vascular embolization device and the
> neurovascular embolization device. Thus, a manufacturer who intends to
> market a device of one of these generic types should (1) 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, (2) address the specific risks to health
> associated with these devices identified in this guidance document,
> and (3) obtain a substantial equivalence determination from FDA prior
> to marketing the device.

This special control guidance document identifies the classification
regulations and product codes for these devices (Refer to Section 4 --
**Scope)**. In addition, other sections of this special control guidance
document list the risks to health identified by FDA and describe
measures that, if followed by manufacturers and combined with the
general controls, will generally address the risks associated with these
devices and lead to a timely 510(k) review and clearance. This document
supplements other FDA documents regarding the content requirements of a
510(k) submission. You should also refer to CDRH's **Device Advice**
<http://www.fda.gov/cdrh/devadvice/> and 21 CFR § 807.87.

As described in the guidance document entitled, **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 a class II special controls guidance
document has been issued. 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 describe how this special
control guidance document was used 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 special controls
> 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** for specific information that should be included in the
> labeling for devices of the types covered by this guidance document.)
>
> **Summary report**

We recommend that the summary report contain:

> **Description of the device and its intended use**
>
> We recommend that the description include a complete discussion of the
> performance specifications and, when appropriate, 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 devices of the types covered by this
> guidance document.) You should also submit an "indications for use"
> enclosure.[^1]
>
> **Description of device design requirements**
>
> 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 device's
> design and the results of this analysis. (Please refer to **Section
> 6**. **Risks to Health** for the risks to health generally associated
> with the use of this device that FDA has identified.)
>
> **Discussion of the device characteristics**
>
> We recommend that you discuss the device characteristics that address
> the risks identified in this class II special controls 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 class II special
> controls 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]{.underline}** (2) describe the acceptance criteria that
> you will apply to your test results.[^2] (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 a:

-   statement that testing will be conducted and meet specified
    acceptance criteria before the product is marketed; or

-   declaration of conformity to the standard.[^3]

> 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 device's 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.)

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 document.
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 general discussion above applies to any device subject to a special
controls guidance document. The following is a specific discussion of
how you should apply this special controls guidance document to a 510(k)
submission for a vascular embolization device or a neurovascular
embolization device. The recommendations made in this guidance document
apply to both, unless vascular or neurovascular is specified.

# 4. Scope 

The scope of this document is limited to the following two device types:

+-------------+-----------+--------------------+-----------------------+
| **Device    | **Class   | **Product Code**   | **Examples**          |
| Type**      | ification |                    |                       |
|             | Reg       |                    |                       |
|             | ulation** |                    |                       |
|             | (21 CFR)  |                    |                       |
+-------------+-----------+--------------------+-----------------------+
| Vascular    | §         | KRD (device,       | -   embolization      |
| e           | 870.3300  | embolization,      |     coils             |
| mbolization |           | arterial)          |                       |
| device      |           |                    | -   detachable        |
|             |           |                    |     balloons          |
|             |           |                    |                       |
|             |           |                    | -   polyvinyl alcohol |
|             |           |                    |     particles         |
|             |           |                    |                       |
|             |           |                    | -   nonresorbable     |
|             |           |                    |     particles         |
+-------------+-----------+--------------------+-----------------------+
|             |           | NAJ (agents,       | -   nonresorbable     |
|             |           | embolic, for       |     particles         |
|             |           | treatment of       |                       |
|             |           | uterine fibroids)  |                       |
+-------------+-----------+--------------------+-----------------------+
| Ne          | §         | HCG (device,       | -   embolization      |
| urovascular | 882.5950  | artificial         |     coils             |
| e           |           | embolization)      |                       |
| mbolization |           |                    | -   polyvinyl alcohol |
| device      |           |                    |     particles         |
|             |           |                    |                       |
|             |           |                    | -   nonresorbable     |
|             |           |                    |     particles         |
+-------------+-----------+--------------------+-----------------------+
|             |           | MZQ (balloon,      | -   detachable        |
|             |           | detachable, for    |     balloons          |
|             |           | neurovascular      |                       |
|             |           | occlusion)         |                       |
+-------------+-----------+--------------------+-----------------------+

In the companion final rule, FDA is revising the names and
identifications of these embolization device types, §§ 870.3300 and
882.5950, as described below.

> **§ 870.3300 -- Vascular embolization device.**

(a) *Identification*. A vascular embolization device is an intravascular
    implant intended to control hemorrhaging due to aneurysms, certain
    types of tumors (e.g., nephroma, hepatoma, uterine fibroids), and
    arteriovenous malformations. This does not include cyanoacrylates
    and other embolic agents, which act by polymerization or
    precipitation. Embolization devices used in neurovascular
    applications are also not included in this classification, see 21
    CFR 882.5950.

> *(b) Classification*. Class II (special controls). The special control
> for the device is the FDA guidance document entitled "Class II Special
> Controls Guidance Document: Vascular and Neurovascular Embolization
> Devices."

**§ 882.5950 -- Neurovascular embolization device.**

(a) *Identification*. A neurovascular embolization device is an
    intravascular implant intended to permanently occlude blood flow to
    cerebral aneurysms and cerebral arteriovenous malformations. This
    does not include cyanoacrylates and other embolic agents, which act
    by polymerization or precipitation. Embolization devices used in
    other vascular applications are also not included in this
    classification, see 21 CFR 870.3300.

(b) *Classification*. Class II (special controls). The special control
    for the device is the FDA guidance document entitled "Class II
    Special Controls Guidance Document: Vascular and Neurovascular
    Embolization Devices."

Cyanoacrylates and other embolic devices (product code NPE), which act
by polymerization or precipitation, continue to be regulated as
postamendments class III devices and require premarket approval (PMA)
applications.

# 5. Device Description

We recommend that you identify your device by regulation number and
product code and include the following information:

-   identity of the reagents and raw materials (i.e., reagent source,
    purity, Certificates of Analyses (CoA), or Material Safety Data
    Sheets (MSDS)) used in the construction of the device and any
    voluntary material conformity standards

-   identity and quantity of any manufacturing reagent (e.g., organic
    solvents, heavy metals, cross-linking reagents remaining in the
    device) that is potentially toxic

-   a description of the components of the device and its assembly

-   a description of any accessories and ancillary devices used with the
    device (e.g., delivery catheters)

-   the range of dimensions, shapes, and device designs

-   engineering drawings

-   a description of the principle of operation (i.e., method of
    deployment and embolization)

-   a description of how the device is provided (e.g., sterile,
    assembled, single use).

# 6. Risks to Health

In the table below, FDA has identified the risks to health generally
associated with the use of the 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, prior to submitting your 510(k), to
identify any other risks specific to your device. For example, a device
with gynecological indications may present additional risks, such as
damage to the uterine wall, diffuse uterine necrosis, primary ovarian
failure, reproductive toxicity, or carcinogenicity, as well as other
risks related to the chemistry, toxicology, and healing response in the
uterine environment. The 510(k) should describe the risk analysis
method. 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.

+--------------------------------+-------------------------------------+
| **Identified Risk**            | **Recommended Mitigation Measures** |
+--------------------------------+-------------------------------------+
| Blood vessel perforation or    | Section 7: Preclinical Testing      |
| rupture                        |                                     |
|                                | Section 9: Animal Testing           |
|                                |                                     |
|                                | Section 10: Clinical Testing        |
|                                |                                     |
|                                | Section 11: Labeling                |
+--------------------------------+-------------------------------------+
| Unintended thrombosis          | Section 7: Preclinical Testing      |
|                                |                                     |
|                                | Section 9: Animal Testing           |
|                                |                                     |
|                                | Section 10: Clinical Testing        |
|                                |                                     |
|                                | Section 11: Labeling                |
+--------------------------------+-------------------------------------+
| Adverse tissue reaction        | Section 7: Preclinical Testing      |
|                                |                                     |
|                                | Section 9: Animal Testing           |
|                                |                                     |
|                                | Section 10: Clinical Testing        |
+--------------------------------+-------------------------------------+
| Infection                      | Section 8: Sterility                |
+--------------------------------+-------------------------------------+
| Hematoma formation             | Section 7: Preclinical Testing      |
|                                |                                     |
|                                | Section 9: Animal Testing           |
|                                |                                     |
|                                | Section 10: Clinical Testing        |
|                                |                                     |
|                                | Section 11: Labeling                |
+--------------------------------+-------------------------------------+

# 7. Preclinical Testing

We recommend that you conduct the preclinical testing below to establish
the performance characteristics of the device.

> **Polyvinyl Alcohol (PVA) Particle Testing**
>
> We recommend that you provide the following for PVA particles:

-   chemical analysis of the final sterilized device, including
    identification and quantification of any processing additives,
    contaminants, etc.

-   if applicable, an explanation of how formaldehyde and/or other
    processing materials are removed from the particles and data
    evaluating the removal process

-   particle size ranges

-   assessment of particle size compatibility with the recommended
    delivery catheter(s)

-   evaluation of the uniform dispersion and suspension of particles
    within the catheter when mixed with the recommended contrast
    agent(s) or other interactive material(s) according to the labeled
    instructions.

> **Detachable Balloon Testing**
>
> We recommend that you provide the following for detachable balloons:

-   the inflation/deflation rates for each balloon size

-   the pressure(s) and volume(s) required to rupture the balloon(s) and
    the release specification for the maximum inflation pressure and
    volume

-   a plot of volume versus inflation pressure

-   the force needed to detach the balloon

-   the balloon permeability with recommended contrast

-   the reliability of the detachment mechanism.

> **Embolization Coil Testing**
>
> We recommend that you provide the following for embolization coils:

-   the coil strength (i.e., the force required to deform the coil shape
    -- primary and secondary diameters, as well as coil tensile
    strength, torsional resistance and fatigue)

-   the ease of delivery, as measured by friction when advancing and/or
    retracting the coil through a recommended catheter positioned in a
    simulated tortuosity

-   for coils with fibers, a description of the fiber attachment
    mechanism and pull-out force

-   a description of the detachment mechanism and data on the detachment
    time

-   the reliability of the detachment mechanism.

> **Delivery Catheter Testing**
>
> If your 510(k) includes a new delivery catheter, we recommend that you
> provide the following information for that catheter:

-   length and outside diameter of the catheter

-   tensile strength

-   catheter burst/leakage pressure

-   flexibility

-   a plot comparing the flow rate of fluid through the catheter versus
    the applied internal pressure

-   hub attachment strength

-   kink resistance

-   radiopacity

-   coefficient of friction of the external surface of the catheter

-   if the catheter is coated, a description of the coating material,
    coating process and data supporting the purpose of the coating

-   corrosion resistance.

> For additional details regarding catheter information and testing, FDA
> suggests that you refer to **International Standard ISO-10555,
> Sterile, Single-Use Intravascular Catheters**.
>
> **Shelf Life**
>
> We recommend that you conduct both preclinical and packaging testing
> to establish the shelf life (i.e., expiration date) of the device as a
> part of the validation activities required by the Quality Systems
> Requirements (21 CFR Part 820). Accelerated test results should be
> supported by validated test information, and, depending on the device
> component, should also be supported by real time test data. For
> mechanical testing, you should conduct both preclinical and packaging
> testing on representative aged samples. For packaging testing, we
> recommend that you conduct testing on the final finished package
> measuring initial integrity and the maintenance of integrity. We
> recommend that you use test methods that are either validated or
> standardized. The documentation from these validation activities must
> be maintained in the Design History File for the device (21 CFR §
> 820.30).
>
> **Biocompatibility**
>
> FDA recommends that you select tests appropriate for implant devices
> with tissue/bone and blood contact 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>.
>
> We recommend that you perform carcinogenicity studies with devices in
> which a positive genotoxicity test result was obtained. We recommend
> that you take into consideration identities of the chemical components
> and available information regarding their toxicity in your evaluations
> of potential carcinogenicity.
>
> For neurovascular embolization devices, because ethylene oxide (EO)
> may cause neurotoxicity, in addition to measuring the EO residue
> levels, we recommend that you provide biocompatibility information on
> the finished EO-sterilized device using intracranial implantation to
> assess any adverse tissue response, or cite other equivalent legally
> marketed predicate products that undergo EtO sterilization. You should
> demonstrate that the level of sterilant residues remaining in the
> device do not raise concerns over the safe use of the product.
>
> **Pyrogenicity**
>
> Because of the potential for contact with the intrathecal space, the
> amount of endotoxin in the final, sterilized, neurovascular
> embolization device should be less than 0.06 Endotoxin Unit (EU)/mL
> and in the vascular embolization devices, less than 0.5 EU. These
> recommendations are described in the "Guideline on validation of the
> Limulus Amebocyte Lysate test as an end-product endotoxin test for
> human and animal parenteral drugs, biological products, and medical
> devices," December 1987,
> <http://www.fda.gov/cder/guidance/old005fn.pdf>.

# 8. Sterility

FDA recommends that you provide sterilization information as described
in the **Updated 510(k) Sterility Review Guidance K90-1; Final Guidance
for Industry and FDA**, <http://www.fda.gov/cdrh/ode/guidance/361.html>.
The device should be sterile with a sterility assurance level (SAL) of 1
x 10^-6^. Refer to the Biocompatibility section above for testing
related to EO-sterilized devices.

# 9. Animal Testing 

We generally recommend that you conduct a pre-clinical animal model
evaluation to evaluate these devices to show that you have adequately
addressed the risks identified in this guidance document. Animal testing
should be considered in the absence of an appropriate bench model. For
new device design features affecting the embolic agent itself (e.g.,
coatings to coils, coil structural design, coil materials, particle
materials, particle shape, sizes), the mechanism of detachment, or the
catheter itself, we recommend that the animal study evaluate:

-   ease of delivery (friction and tortuosity)

-   acute complications (e.g., rupture or puncture of the blood vessels)

-   recanalization of the vessels/durability of occlusion

-   local and systemic foreign body reactions

-   device migration

-   embolization effectiveness.

Because changes in embolization agent design and materials of
construction may influence the healing process of the embolization site,
we recommend that you perform follow-up evaluations with appropriate
frequency and after sufficient time has passed to evaluate acute as well
as chronic toxicity. Evaluating chronic toxicity helps ensure that the
response to the embolic agent has stabilized or is in the process of
resolution. We also recommend that you provide an explanation of how the
animal model relates to the human condition through any pertinent
literature references and/or supporting testing.

# 10. Clinical Testing 

In accordance with the least burdensome provisions of the Act, FDA 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. While, in general, clinical
studies will not be needed for most vascular or neurovascular
embolization devices, FDA may recommend that you collect clinical data
for a vascular or neurovascular embolization device with:

-   designs or material formulations (e.g., coatings to coils, coil
    structural design, coil materials, particle materials, particle
    shape, sizes, mechanism of detachment, novel catheter design)
    dissimilar from designs or material formulations used in legally
    marketed devices of the same type

-   new technology (i.e., technology different from that used in legally
    marketed devices of the same type)

-   indications for use dissimilar from devices of the same type.

Vascular and neurovascular embolization devices are classified as
different generic types of devices, thus FDA does not consider them to
be "of the same type" in the criteria described above.

FDA will always consider alternatives to clinical testing when the
proposed alternatives are supported by an adequate scientific rationale.
The review branches identified on the cover of this guidance document
are available to discuss any clinical testing with you before you
initiate your studies.

If a clinical study is needed to demonstrate substantial equivalence
(i.e., conducted prior to obtaining 510(k) clearance of the device), the
study must be conducted under the Investigational Device Exemptions
(IDE) regulation, 21 CFR Part 812. FDA believes that the vascular and
neurovascular embolization devices addressed by this guidance document
are significant risk devices as defined in 21 CFR § 812.3(m).[^4] In
addition to the requirement of having an FDA-approved IDE, sponsors of
such trials must comply with the regulations governing institutional
review boards (21 CFR Part 56) and informed consent (21 CFR Part 50).

After FDA determines that the device is substantially equivalent,
clinical studies conducted in accordance with the cleared indications,
including clinical design validation studies conducted in accordance
with the quality systems regulation, are exempt from the investigational
device exemptions (IDE) requirements. However, such studies must be
performed in conformance with 21 CFR Part 56 and 21 CFR Part 50.

We recommend that you consider the information below specific to
embolization clinical studies.

> **Endpoints**
>
> We recommend that the study protocol include clearly defined primary
> and secondary endpoints and specific success/fail criteria for the
> study. We recommend that you define and report all adverse events.
>
> We recommend that effectiveness endpoints include the reduction in
> size of the vascular lesion, percentage occlusion of an aneurysm, or
> the occlusion of a parent vessel as measured by angiography. We also
> recommend that you consider other endpoints, such as the
> recanalization rate of the embolized vascular lesion and/or the
> determination of the clinical benefit. For example, for devices used
> for presurgical embolization, a reduction in surgical time and blood
> loss may be appropriate endpoints.
>
> For **neurovascular** embolization devices, we recommend that the
> safety evaluation include:

-   the incidence of new neurological deficits (transient and permanent)

-   neurological outcome assessment

-   the rate of neurological and non-neurological complications

-   distal migration of particular material.

> We recommend that you identify the measurement tools used to assess
> patient neurological endpoints. We recommend that you evaluate all
> patients, at a minimum, pre-embolization, immediately
> post-embolization, and at a follow-up examination using a standard
> neurological examination that tests:

-   cranial nerves

-   sensory function

-   motor function and reflexes

-   gait and coordination

-   mentation.

> We recommend that you provide a copy of the neurological examination
> as a case report form on which the clinician will record results.
> Other means of measuring endpoints may include:

-   functional outcome scales

-   patient self-reports

-   clinician or surgeon self-reports (World Federation of Neurosurgeons
    grade (WFNS), Glasgow Outcome Scale (GOS), Glasgow Coma Scale (GCS),
    NIH Stroke Scale, and/or Barthel Index).

> We recommend that the evaluation of endpoints be independent and
> masked. For any scale used, we recommend that the directions for
> determining values in the test be part of the case report form and
> that the scale range be indicated on the case report form where the
> score will be entered.
>
> **Description of Embolization Procedure**
>
> We recommend that you provide a full description of the embolization
> procedure in the protocol, including:

-   device/component assembly and preparation

-   use of anticoagulation medication (e.g., drug, dose)

-   use of antibiotics

-   circumstances under which adjunctive embolization devices may be
    used during the procedure

-   whether there is a plan for staged embolization and the features of
    that plan

-   the therapy available in the event of stroke or other complication
    during the embolization procedure

-   the time interval between embolization and definitive resection if
    embolization is a pre-surgical procedure.

> In addition, we recommend that you monitor the neurological function
> during implantation of neurovascular embolization devices in patients
> under local anesthesia.
>
> **Imaging**
>
> Pre-operative imaging procedures are standard of care for patients
> requiring embolization. In addition to pre-operative evaluation,
> post-embolization angiography and short-term and long-term follow-up
> imaging scans may be appropriate when evaluating embolization agents
> with novel design features. We recommend that you describe the methods
> used to measure the lesion (e.g., angiography, MRI, MRA, CT), as well
> as the follow-up intervals. Because the vascular disorder and device
> use may determine which imaging tools are used and the length and
> interval of follow-up, we recommend that you provide the rationale for
> these protocol elements along with any supporting literature/studies.
>
> **Patient Follow-up**
>
> We recommend that you specify how often patients should be evaluated
> during follow-up.

# 11. Labeling

The 510(k) should 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.[^5]

> **Prescription Use**
>
> As a prescription device, under 21 CFR § 801.109, the device is exempt
> from having adequate directions for lay use. Nevertheless, under 21
> CFR § 807.87(e), we expect to see clear and concise instructions that
> delineate the technological features of the specific device and how
> the device is to be used on patients. Instructions should encourage
> appropriate training programs designed to familiarize users with the
> features of the device and how to use it in a safe and effective
> manner.
>
> **Instructions for Use**
>
> We recommend that the instructions for use include:

-   the minimum and maximum internal diameter of the embolization
    delivery catheter

-   information on any contrast media and flushing agent used with your
    device

-   for a detachable balloon, the pressure required to rupture the
    balloon and the specification for the maximum inflation pressure and
    volume.

[^1]: Refer to
    [http://www.fda.gov/cdrh/ode/indicate.html](http://www.fda.gov/cdrh/ode/indicate.pdf)
    for the recommended format.

[^2]: 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).

[^3]: 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]{.underline}.

[^4]: Refer to Blue Book Memorandum entitled "SIGNIFICANT RISK AND
    NONSIGNIFICANT RISK MEDICAL DEVICE STUDIES" at
    <http://www.fda.gov/cdrh/d861.html>.

[^5]: 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 document are consistent with the requirements of Part 801.