Guidance for Industry and FDA Staff 
Vocal Fold Medialization Devices - 
Premarket Notification [510(k)] 
Submissions 
Document issued on: February 13, 2004 
For questions regarding this document contact Karen H. Baker, MSN, RN, at 240-276-4242 or 
karen.baker@fda.hhs.gov.   
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
Ear, Nose and Throat Devices Branch 
Division of Ophthalmic and Ear, Nose, and Throat Devices 
Office of Device Evaluation  Contains Nonbinding Recommendations 
Preface 
Public Comment 
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.  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/1535.pdf, or CDRH Facts-On-Demand.  To 
receive this 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 document.  Enter the document number
(1535) followed by the pound sign (#).  Follow the remaining voice prompts to complete
your request. Contains Nonbinding Recommendations 
Table of Contents 
1. INTRODUCTION....................................................................................................................1
2.  BACKGROUND......................................................................................................................2 
3.  THE CONTENT AND FORMAT OF AN ABBREVIATED 510(K) SUBMISSION.......2 
4.  SCOPE......................................................................................................................................4 
5.  RISKS TO HEALTH...............................................................................................................5 
6. BIOCOMPATIBILITY...........................................................................................................5
7.  MATERIAL AND PERFORMANCE CHARACTERIZATION.......................................6 
8.  BENCH, ANIMAL, OR PRECLINICAL TESTING...........................................................6 
9.  STERILIZATION...................................................................................................................7 
10.  CLINICAL INFORMATION...............................................................................................7 
11.  LABELING............................................................................................................................8 
12. REFERENCES.......................................................................................................................9 Contains Nonbinding Recommendations 
Guidance for Industry and FDA Staff 
Vocal Fold Medialization 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 vocal fold medialization devices, which are class II devices.  These devices are 
intended to medialize a paralyzed vocal fold to improve voice quality and/or airway protection.  
The scope of this document is limited to vocal fold medialization devices, identified as procode 
MIX (system, vocal cord medialization) or KHJ [polymer, Ear, Nose and Throat (ENT) 
synthetic-polyamide (mesh or foil material)].  21 CFR 874.3620. 
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: https://www.fda.gov/downloads/MedicalDevices/
DeviceRegulationandGuidance/GuidanceDocuments/UCM588914.pdf
FDA.  s guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agencys 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 Contains Nonbinding Recommendations 
 
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 vocal fold 
medialization devices (refer to Section 4).  In addition, other sections of this guidance document 
provide additional information to manufacturers on addressing risks related to these devices in 
premarket notifications (510(k)s).   
 
This document supplements other FDA documents regarding the specific content requirements 
of a 510(k).  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 
describe how this guidance document was used during the device development and testing and 
should briefly describe the methods or tests used.  We recommend that you also include 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 21 CFR 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. 
 
  2 Contains Nonbinding Recommendations 
 
Proposed labeling 
Proposed labeling should be sufficient to describe the device, its intended use, and the 
directions for its use.  (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 report1 contain a: 
 
  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.  You should also 
submit an "indications for use" enclosure.2   
 
  Description of device design requirements.  
 
  Identification of the Risk Analysis method(s) used to assess the risk profile in 
general as well as the specific devices design and the results of this analysis.  
(Refer to Section 5 for the risks to health generally associated with the use of this 
device that FDA has identified.) 
 
  Discussion of the device characteristics that address the risks identified in this 
guidance document, as well as any additional risks identified in your risk analysis.  
 
  Brief description of the test method(s) you have used or intend to use to address 
each performance aspect identified in Sections 6-10 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.) 
                                                 
1 A Summary Technical Documentation for Demonstrating Conformity to the Essential 
Principles of Safety and Performance of Medical Devices (STED document) that contains the 
information we recommend in this guidance may suffice in place of the summary report.  Please 
refer to Announcement of a Pilot Program for Device Submissions (The STED Initiative) 
http://www.fda.gov/cdrh/international/sted.html. 
 
2 Refer to http://www.fda.gov/cdrh/ode/indicate.html for the recommended format. 
 
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 
  3 Contains Nonbinding Recommendations 
 If any part of the device design or testing relies on a recognized standard, (1) a
statement that testing will be conducted and meet specified acceptance criteria before
the product is marketed, or (2) a declaration of conformity to the standard.4  Please
note that testing must be completed before submitting a declaration of conformity to a
recognized standard. (Section 514(c)(1)(B) of the Act).  This means that testing must
be completed before you submit a declaration of conformity.  For more information,
refer to 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.
We may request additional information about aspects of the devices performance characteristics 
or information 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 may submit a Traditional 510(k) that 
provides all of the information and data required under 21 CFR 807.87.  A Traditional 510(k) 
should include all of your methods, data, acceptance criteria, and conclusions.   
4. Scope
The scope of this document is limited to vocal fold medialization devices, identified as procode 
MIX (system, vocal cord medialization) or KHJ (polymer, ENT synthetic-polyamide [mesh or 
foil material]).  21 CFR 874.3620. 
These vocal fold medialization devices include both injectable materials and other materials used 
in a Type I thyroplasty procedure to medialize the vocal fold through an external cervical skin 
incision. 
The devices listed below are regulated under 21 CFR 874.3620 but are not within the scope of 
this guidance: 
 MIB  elastomer, silicone block
 NHB  polymer, Ear, Nose and Throat, synthetic
 JOF  polymer, ENT synthetic, porous polyethylene
 ESH  polymer, ENT synthetic-PIFE, silicon elastomer, polyethylene, polyurethane.
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. 
4 Contains Nonbinding Recommendations 
5. Risks to Health
In the table below, FDA has identified the risks to health generally associated with the use of 
vocal fold medialization devices addressed in this document.  The information we recommend 
you include in your 510(k) to address these identified risks are given in this guidance document, 
as shown in the table below.  We recommend that you conduct a risk analysis, before submitting 
your 510(k), to identify any other risks specific to your device.  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, you 
should provide sufficient detail to support the approach you have used to address that risk. 
Identified risk  Recommended mitigation measures 
Airway compromise  Sections  8, 10, 11 
Extrusion/migration of the device  Sections   8, 10, 11 
Particle migration  Sections 6, 7, 8,  
Improper placement  Section 11 
Infection  Section 9, 11 
Adverse tissue reaction/granuloma formation  Sections 6, 10 
Device breakage  Section 7, 8, 10, 11 
Poor voice quality  Section 10, 11 
Revision surgery  Section 10, 11 
6. Biocompatibility
We recommend that you evaluate the biocompatibility of the patient contacting materials as 
described in the International Standard Organization (ISO) standard ISO-10993, 
"Biological Evaluation of Medical Devices Part 1: Evaluation and Testing, according to 
Parts 5 and 10, for tissue/bone contacting, long-term implanted devices.  We also recommend 
that you document the results in your design history file as a part of the Quality Systems 
Requirements (21 CFR 820.30).  If identical materials are used in a predicate device with the 
same type and duration of patient contact, you may identify the predicate device in lieu of 
performing biocompatibility testing.  Generally, for devices containing new materials FDA 
recommends long-term animal studies (e.g., one year implantation studies at tissue sites 
simulating the clinical situation). 
Use of injectable polytetrafluoroethylene for vocal fold medialization has been associated with 
migration of the material to local lymph nodes and a localized foreign body granulomatous 
5 Contains Nonbinding Recommendations 
reaction (i.e., Teflon granuloma) at the site of injection (Varvares,1995; Benjamin, 1987; Ellis, 
1987).  Teflon granulomas may lead to progressive dysphonia and airway compromise in some 
patients. Surgical removal of the material in affected patients has been extremely difficult and 
typically results in some degree of residual phonatory deficit (Billante, 2000).  Animal models 
are useful in predicting the occurrence of this significant complication (Stein, 2000) and should 
be used to demonstrate lack of granulomatous inflammation in the larynx when the device 
consists of a material that has not been previously cleared for laryngeal use.  Such a study should 
include appropriate control animals (e.g., injection of product vehicle, Teflon as positive control) 
and should be of sufficient duration to assess any possible migration and tissue interactions (at 
least six months to one year following injection). 
7. Material and Performance Characterization
Solid silicone, solid and particulate hydroxylapatite, titanium, and certain absorbable materials 
have been used successfully to construct vocal fold medialization devices of this generic type.  
Any material selected for the design of this device should have chemical stability sufficient to 
withstand the intended physiological environment for the proposed duration of effectiveness (i.e., 
permanent vs. temporary vocal fold medialization). 
You should evaluate a solid materials integrity with the appropriate in vitro mechanical test 
methods (e.g., modulus, fatigues, fracture toughness, fatigue crack propagation, flexural strength, 
compressive strength, sheer strength, and tensile strength for solid materials). 
For injectable materials, physical and chemical analyses are used to characterize particulate 
materials that are suspended in a carrier gel.  You should identify:  
 the ingredients
 any additives in the formulation of the device, along with their respective amounts
 the time to absorption
 residual substances.
If your device includes a carrier gel, we recommend that you evaluate the carrier gel for its 
biocompatibility.  In addition, the carrier gel should have physiological pH. 
8. Bench, Animal, or Preclinical Testing
As stated in Sections 6 and 7, bench and animal studies may be used to demonstrate stability and 
biocompatibility of implanted materials in the acute period as well as long term.  For suspended 
particles, animal studies are invaluable to demonstrate whether there is particle migration into 
surrounding or lymphatic tissues.  Particles less than 65m may migrate to regional lymph nodes 
as well as to distant sites (Sittel, 2000; Henley, 1995; Beisang, 1992; Allen, 1992).  You should 
provide results from bench studies on the distribution of particle size when administered through 
the proposed delivery system.  Animal studies should demonstrate that there is no material 
migration when used in the larynx. 
6 Contains Nonbinding Recommendations 
9. Sterilization
For devices sold as sterile5 we recommend that you provide the following information: 
 the sterilization method used in the sterilization cycle (e.g., dry heat, ethylene oxide
(ETO), steam, radiation)
 a description of the method that will be used to validate the sterilization cycle (but not the
validation data)
 a description of the packaging that maintains the devices sterility (but not the package
integrity testing data)
 the sterility assurance level specification (SAL)
 a description of the method used to make the determination, e.g., the limulus amebocyte
lysate (LAL) method, if the product is labeled pyrogen free
 the maximum levels of ETO and ethylene chlorohydrin residues, if sterilized by ETO
 the radiation dose, if sterilized by radiation.
10. Clinical Information
In accordance with the Least Burdensome provisions of 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.  While, in general, clinical studies will not be needed for most vocal fold 
medialization devices, FDA may recommend that you collect clinical data for devices with any 
one of the following:  
 material formulation or designs dissimilar from material formulation or designs
previously cleared under a premarket notification
 new technology, i.e., technology different from that used in legally marketed vocal fold
medialization device
 indications for use dissimilar from vocal fold medialization devices of the same type.
FDA will always consider alternatives to clinical testing when the proposed alternatives are 
supported by an adequate scientific rationale.  The Ear, Nose, and Throat Devices Branch is 
available to discuss any questions you may have.  
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 in accordance with the 
Investigational Device Exemptions (IDE) regulation, 21 CFR Part 812.   
5 If your device is labeled sterile, we recommend that you follow the guidance for devices 
intended for contact with intact skin in Updated 510(k) Sterility Review Guidance 
K90-1; Final Guidance for Industry and FDA, https://www.fda.gov/downloads/
MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm109897.pdf. 
7 Contains Nonbinding Recommendations 
FDA believes that a vocal fold medialization device addressed by this guidance document is a 
significant risk device as defined in 21 CFR 812.3(m).6  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 indications reviewed in the 510(k), including clinical design validation 
studies conducted in accordance with the quality systems regulation, are exempt from the 
investigational device exemptions (IDE) requirements.  21 CFR 812.2(c).  However, such studies 
must be performed in conformance with 21 CFR Part 56 and 21 CFR Part 50.  
11. Labeling
The premarket notification 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 801.7 
Directions for 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), seethe device should have 
clear and concise instructions that delineate the technological features of the specific device 
and how the device is to be used by trained professionals on patients.  Instructions should 
encourage use of local/institutional training programs designed specifically to familiarize 
users with the features of the device and how to use it in a safe and effective manner. 
Surgeons instructions should be very clear and precise and include the following: 
 surgical technique to implant the device
 revision surgery
 special considerations for administration of injected materials
 airway protection/compromise
 postoperative complications
 special patient instructions
 cautions and precautions
 warnings.
6 Refer to Blue Book Memorandum entitled Significant Risk and Non-Significant Risk Medical 
Device Studies at http://www.fda.gov/cdrh/d861.html.  
7 Although final labeling is not required for 510(k) clearance, final labeling must comply with 
the requirements of 21 CFR Part 801 before a device is introduced into interstate commerce.  In 
addition, final labeling for prescription devices must comply with 21 CFR 801.109.  Labeling 
recommendations in this guidance are consistent with the requirements of part 801. 
8 Contains Nonbinding Recommendations 
12. References
1. Varvares, MA et al. Teflon granuloma of the larynx: Etiology, pathophysiology, and
management.  Ann Otol Rhinol Laryngol.104(7):511-5. 1995
2. Benjamin, B et al. Giant Teflon granuloma of the larynx. Head Neck 13(5):453-6.1991.
3. Ellis J et al. Migration of Teflon after vocal cord injection. Otolaryngol Head Neck Surg
96:63-6. 1987.
4. Billante CR et al.  Voice outcome following lateral laryngotomy to remove Teflon
granuloma. ORL J Otorhinolaryngol Relat Spec. 63(5):302-6.2001.
5. Stein J et al. Histopathological study of alternative substances for vocal fold
medialization. Ann Otol Rhinol Laryngol 109:221-6. 2000.
6. Sittel, C, et al. Textured polydimethylsiloxane elastomers in the human larynx: Safety
and efficiency of use. J. Biomedical Materials Research. 43(6):646-650. 2000.
7. Henley, DR et al. Particulate silicone for use in periurethral injections: Local tissue
effects and search for migration. J. Urol. 153:2039-2043. 1995.
8. Beisang, AA and Ersek, RA. Mammalian response to subdermal implantation of textured
microimplants. Aesth. Plast. Surg. 16:83-90. 1992.
9. Allen, O. Response to subdermal implantation of textured microimplants in humans.
Aesthet. Plast. Surg. 16:227-230. 1992.
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