Guidance for Industry and/or for FDA
Reviewers/Staff and/or Compliance
Guidance for the Preparation of a
Premarket Notification Application
for a Surgical Mesh
Document issued on:  March 2, 1999
U.S. Department Of Health And Human Services
Food and Drug Administration
Center for Devices and Radiological Health
Plastic and Reconstructive Surgery Devices Branch
Division of General and Restorative Devices
Office of Device Evaluation Preface
Public Comment
Comments and suggestions may be submitted at any time for Agency consideration to
Plastic and Reconstructive Surgery Branch, HFZ-410, 9200 Corporate Boulevard,
Rockville, MD  20850.  Comments may not be acted upon by the Agency until the
document is next revised or updated.  For questions regarding the use or interpretation of
this guidance contact Charles N. Durfor, Ph.D. at (301) 594-3090, ext.134 or by
electronic mail at cmd@cdrh.fda.gov.
Additional Copies
World Wide Web home page:  http://www.fda.gov/cdrh/index.html, or CDRH Facts on
Demand at 1-800-899-0381 or 301-827-0111, specify number 2247 when prompted for
the document shelf number. 1 
Guidance for the Preparation of a
Premarket Notification Application
for a Surgical Mesh
This guidance document serves as a supplement to Premarket Notification 510(K): Regulatory
Requirements For Medical Devices, (HHS Publication FDA 95-4158) and provides specific
guidance regarding the information to be contained in a premarket notification submission for general
surgical meshes described in 21 CFR 878.3300.  This guidance is not intended to address meshes for
orthopedic or dental uses.  Specifically, this guidance covers Surgical Mesh (79 FTM) and Polymeric
Surgical Mesh (79 FTL) for general surgical uses such as implantation to reinforce soft tissue where
weakness exists (e.g., hernia repair, suture line/staple line reinforcement, muscle flap reinforcement,
gastric banding, etc.).
Manufacturers who seek permission to market these devices must demonstrate substantial equivalence of
their product to a device that is legally marketed in the United States.  To obtain marketing clearance for a
surgical mesh, manufacturers should supply the following information:
I. Introductory information
A. The trade or proprietary name of the device.
B. The common or usual name or classification name of the device.
C. The establishment registration number, if applicable, of the owner or operator submitting
the premarket notification submission.
D. The class in which the device has been placed under section 513 of the Act and the panel.
E. The name, address, and telephone number of the contact person responsible for the
submission.
II. Table of Contents
III. Summary of information regarding safety and effectiveness upon which an equivalence
determination can be made, or a statement that such information will be made available to
interested persons upon request.
1This document is intended to provide guidance.  It represents the Agencys current thinking on this topic.  It
does not create nor confer any rights for or on any person and does not operate to bind FDA or the public.  An
alternative approach may be used if such approach satisfies the requirements of the applicable statute,
regulations or both.
page 1 IV. Statement of intended use for the device (see Attachment #1).  The indications for use for the
device should comply with the labeling recommendations in Section XI of this document.
V. A Truthful and Accuracy Statement (see Attachment #2).
VI. Description of the device.
Provide a complete description of the mesh, including the physical dimensions, materials, and
physical properties of the device.  A table comparing the similarities and differences in these
parameters between the proposed product and a legally marketed device should also be
presented.
VII. Specification of all material components of the device.
All material components of the device should be described. Such information should identify the
source and purity of each component.  Such information may also be supplied by reference to a
Master File(s), (if the appropriate letter of cross reference is included).  Submission of a
Certificate(s) of Analysis (CoA) and/or a Materials Safety Data Sheet(s) (MSDS) can also
greatly simplify review of components.
If collagen or other animal-derived material is a device component, the application should also
identify:
1. The species and tissue from which the animal material was derived (including the specific
type of collagen or other material used).
2. How the health of herd is maintained and monitored, e.g.,
a. Is the herd closed?
b. What vaccinations are standard for the herd (e.g., focus on live modified
viruses)?
c. Are veterinarian inspections performed and if so how frequently?
d. What is the composition of the animal feed?
e. Is the abattoir USDA approved (or inspected)?
f. If the animal material is of bovine origin, certification that the herd is from a Bovine
Spongiform Encephalopathy-free country.
3. How the health of each animal is maintained and monitored, e.g.,
a. What is the age of the animal at sacrifice?
b. Are pre and/or post morteum inspections performed?
c.  What tests are performed to determine that the material is accessible for further
processing or pooled with material from other animals?
If  the product contains synthetic (e.g., polymeric or metallic) components, the application
should identify the concentration in the final device of any component (e.g., organic solvents,
heavy metals, cross-linking reagents) that is potentially toxic, carcinogenic or immunogenic.
page 2 VIII. Device manufacture.
The application should contain information about all reagents and processing steps used in
device manufacture.  Information similar to that discussed above for device comments (i.e.,
reagent source, purity, CoA and/or MSDS) can be very helpful in evaluating the substantial
equivalence of the proposed and legally marketed devices.
With regard to device sterilization the application should state:
1. The method of sterilization;
2. The validation method for the sterilization cycle;
3. The sterility assurance level (SAL) to be achieved; and
4. The method for monitoring the sterility of each production lot.
If radiation sterilization is performed, the dose should be specified.   If the method of sterilization
is ethylene oxide (EtO) exposure, the maximum levels of ethylene oxide, ethylene chlorohydrin,
and ethylene glycol residues which remain on the device should be identified.  Residual levels of
ethylene oxide, ethylene chlorhydrin, and ethylene glycol which remain on the device following
EtO sterilization should comply with the maximum limits proposed in the Federal Register of
June 23, 1978 for small (<10 grams), medium (10-100 grams) or large (>100 grams) implantable
medical devices (see below).
[Parts per million]
Implant Size Ethylene Ethylene Ethylene
                                        Oxide           Chlorohydrin          Glycol
Small 250 250 5,000
Medium 100 100 2,000
Large   25   25    500
In general, a SAL of 10-6 is necessary for all devices unless there is substantial justification why
this level cannot be achieved.   The sterility assurance level should be determined by an
appropriate and recognized Standard or a complete description of the validation process should
be provided.
In addition to demonstrating the ability of sterilization methods to inactivate bacteria, yeast and
fungi, the processing methods and sterilization techniques for devices derived from animal
material should be validated with regard to the inactivation and removal of viruses.  In specific,
sterilization methods should reduce the amount of virus in the final product below 1 infectious
particle per 106 devices.  Such data can be obtained by determining the amount of virus in the
unprocessed source material and the viral inactivation properties of scaled down versions of
specific production and sterilization methods (e.g., acid extraction of collagen or dry heat
sterilization) using appropriate model viruses.  Review of  Viral Safety Evaluation of
Biotechnology Products Derived from Cell Lines of Human or Animal Origin, (ICH
Harmonized Tripartite Draft Guideline) is recommended with regard to the design of such
studies and the selection of model viruses.   The final results of these studies should
demonstrate that the sum of the log clearance of virus from the selected processing steps
and sterilization processes are at least six logs greater than the concentration of virus
anticipated in the unprocessed source material.
page 3 IX. A description of the packaging to be used to maintain the sterility of the device.
X. Product Characterization
1. Biocompatibility - In accordance with the Blue Book Guidance G95-1, (Use of
International Standard ISO-10993,   "Biological Evaluation of Medical Devices Part 1:
Evaluation and Testing"), acceptable test results should be supplied for the biological
tests listed below.  Standard protocols such as those identified by the USP or ASTM
should be used in conducting the biocompatibility testing, if possible.  Such tests should be
performed on devices ready for surgical use (i.e., after manufacture, sterilization and
packaging for commercial distribution).
Cytotoxicity 
Sensitization
Irritation or Intracutaneous reactivity
Systemic toxicity (acute)
Genotoxicity
Implantation (with histology of the surrounding tissue)
Hemolysis
Pyrogenicity
For products that remain in the body for greater than 30 days, the following additional
tests are recommended:
Subchronic toxicity
Chronic toxicity
Long term carcinogenicity studies should be performed with any device in which a
positive genotoxitiy test result was obtained.
The above tests may not be relevant or necessary in all cases, such as when a manufacturer
submits a marketing application for a device which has the exact same material
specifications as a previously marketed product, and/or for which the tradename and
device claims are the only changes being made.
2.  Product Characterization - Information about the product structure is critical in
determining the equivalence of a proposed device.  For a surgical mesh, such data would
include information about:
Mesh thickness
Mesh weave characteristics
Pore size
Mesh density
Tensile strength
Device stiffness
Suture pullout strength
Burst strength
Tear resistance
page 4 3. Final Product Specification - The sponsor should provide information about the relevant
in-process and final product tests.  Such data should identify the test method and time of
testing during manufacture.  Examples of final product release specifications can include:
Device Thickness
Pore Size
Bursting Strength
Residual levels of manufacturing reagents
Residual levels of heavy metals
Pyrogen levels
Sterility
For biodegradable devices information should be provided that documents the rate of
product resorption and how specific device properties (e.g., suture pullout strength,
burst strength and/or tear resistance) change as a function of time.  Such studies
should be performed in vivo or in a manner expected to accurately predict product
decomposition (e.g., in comparable cellular and proteolytic environments at 37(cid:176) C).
4. Product Expiration Dating - Data supporting the expiration date for a product should
be submitted.  Such data should be collected from at least three production lots.
Stability studies should monitor the critical parameters of a device that are required to
insure it will perform consistently during its entire shelf-life.
The appropriateness of accelerated stability data is determined by device composition.
The value of accelerated stability test data relies on identical decomposition
mechanisms at both standard and elevated temperatures.   When device
failure/decomposition occurs by different mechanisms at the standard and elevated
temperatures of accelerated stability testing, (e.g., loss of sterility at 25(cid:176) C versus
protein denaturation at 50(cid:176) C), accelerated stability test data should not be used to
support claims for product stability.
Finally, changes in device expiration date do not require a new 510(k) (see Deciding
When to Submit a 510(k) for a Change to an Existing Device).  Such changes are
properly within the scope of GMPs.  However, where methods or protocols, not
described in the original 510(k), are used to support new package integrity or shelf-
life claims, a new 510(k) may be necessary.
XI. Labeling.
All labeling information for the surgical mesh should be supplied, including individual package
labeling, package inserts, and available promotional literature.  The labeling should specify the
intended use of the device, contraindications, warnings, precautions, directions for use if
applicable, and product claims.  The following issues should be considered for product labeling:
1. If the mesh is to be labeled "pyrogen free" or "nonpyrogenic," satisfactory results from the
USP Pyrogen Test (Rabbit) or an equivalent test, performed on the final end product,
should be provided and lot release criterion for pyrogenicity need  to be identified (see
section X.3.) above.
page 5 2. The device may not be labeled as a treatment for reducing the incidence and/or the
severity of post-surgical adhesions.  A PMA application is required for this intended use.
XII. Final consideration.
Recent technological advances have resulted in surgical mesh and film devices that involve
device formation, assembly or polymerization after introduction into the patient.  Review of
such products may require additional information than that described in this Guidance
document, because the products can raise new types of questions about device safety and
effectiveness, e.g.,
1. Will the device assemble in a safe and effective manner?
2. Will excess, unreacted material migrate to new locations in the body and form
unwanted polymer at new anatomic sites?
3. Will chemical reactions with adjacent human tissues occur?
page 6 Attachment #1
Indications for Use Form
Page       of
510(k) Number (if known):       _______________
Device Name:
Indications For Use:
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF
NEEDED)
                                                                 
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use        OR Over-The-Counter Use
(Per 21 CFR 801.109) (Optional Format 1-2-96) Attachment #2
PREMARKET NOTIFICATION
TRUTHFUL AND ACCURATE STATEMENT*
(As Required By 21 CFR 807.87(j))
I certify that, in my capacity as [The Position Held In Company] of
[Company Name], I believe to the best of my knowledge, that all data
and information submitted in the premarket notification are truthful and
accurate and that no material fact has been omitted.
          [Signature]
__________________________________________________________________
[Typed Name and Title]
__________________________________________________________________
[Company] [Date]
________________________________________
[Premarket Notification (510(k)) Number]
* Must be signed by a responsible person of the firm required to submit the premarket notification
(e.g., not a consultant for the 510(k) submitter.)