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U.S. Department of Health and Human Services

Medical Devices

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Guidance for the Content of Premarket Notifications for Biopsy Devices Used in Gastroenterology and Urology (Text Only)

This guidance was written prior to the February 27, 1997 implementation of FDA’s Good Guidance Practices, GGP’s. It does not create or confer 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. This guidance will be updated in the next revision to include the standard elements of GGP’s.

Biopsy devices for gastroenterology and urology are described in the FDA 
regulations under three classifications.  These classifications are 21 CFR 
876.1075 (a) Gastroenterology-Urology Biopsy Instruments, 21 CFR 876.1500 
(a) Endoscopes and Accessories, and 21 CFR 876.4300 (a) Endoscopic 
Electrosurgical Unit and Accessories.

The classification 876.1075 (a), Gastroenterology-Urology Biopsy 
Instruments, includes devices that are "used to remove, by cutting or 
aspiration, a specimen of tissue for microscopic examination.  This generic 
type of device includes the biopsy punch, gastrointestinal mechanical 
biopsy instrument, suction biopsy instrument, gastro-urology biopsy needle 
and needle set, and nonelectric biopsy forceps.  This section does not 
apply to biopsy instruments covered by classification regulations in other 
parts of the device classification regulations."  These are Class II 
devices as stated in 21 CFR 876.1075 (b) and their procodes are:  78 FFF - 
cover, biopsy forceps; 78 FCL - forceps, biopsy, non-electric; 78 KNW - 
instrument, biopsy; 78 FCF - instrument, biopsy, mechanical, 
gastrointestinal; 78 FCK - instrument, biopsy, suction; 78 FCI - punch, 
biopsy; and 78 FCG - set, biopsy needle and needle, gastro-urology.

The classification 876.1500 (a), Endoscopes and Accessories, includes a 
"device ... to allow observation and manipulation of body cavities, hollow 
organs, and canals."  Cytology brushes, as endoscopic accessories, are 
covered under this classification, are Class II devices as stated in 21 CFR 
876.1500 (b), and have the procode 78 FDX - brush, cytology, for 
endoscopes.

The classification 876.4300, Endoscopic Electrosurgical Unit and 
Accessories, includes a "device used to perform electrosurgical procedures 
through an endoscope.  This generic type of device includes ... electric 
biopsy forceps, ... flexible snare, ... self-opening rigid snare, ... "  
These are Class II devices as stated in 21 CFR 876.4300 (b) and their 
procodes are 78 KGE - forceps, biopsy, electric; 78 FDI - snare, flexible; 
and 78 FDJ - snare, rigid self-opening.

The primary reference for the information required to be in a premarket 
notification (510(k)) for a medical device is set forth in 21 CFR 807.87.  
The purpose of this regulation is to provide adequate documented 
information to determine substantial equivalence to a device in commercial 
distribution.  Substantial equivalence is to be established with respect 
to, but not limited to, intended use, design, energy used/delivered, 
materials, performance, safety, effectiveness, labeling, and other 
applicable characteristics.

FDA recommends that each premarket notification for a biopsy device include 
the following information in order to ensure that the submission is 
complete and will permit a determination of substantial equivalence:

I.  The device name, including both the trade or proprietary name and the 
    classification name (Gastroenterology-Urology Biopsy Instrument, 
    Endoscopes and Accessories for cytology brushes, or Endoscopic 
    Electrosurgical Unit and Accessories for electric biopsy forceps) of 
    the device as described in 21 CFR 807.87 (a).

II. The establishment registration number, if applicable, of the owner or 
    operator submitting the premarket notification as described in 21 CFR 
    807.87 (b).

III.The class (Class II) in which the device has been placed under section 
    513 of the act and the appropriate panel (78 Gastroenterology/Urology) 
    as described in 21 CFR 807.87 (c).

IV. Action taken by the person required to register to comply with the 
    requirements of the act under section 513 for Special Controls.  Note 
    that Special Controls are not currently required for biopsy devices 
    under section 513 of the act.

V.  The Safe Medical Devices Act of 1990 (SMDA) requires all persons 
    submitting a premarket notification submission to include either (1) a 
    summary of the safety and effectiveness information in the premarket 
    notification submission upon which an equivalence determination could 
    be based (510(k) summary), OR (2) a statement that safety and 
    effectiveness information will be made available to interested persons 
    upon request (510(k) statement).  Safety and effectiveness information 
    refers to information in the premarket notification submission, 
    including adverse safety and effectiveness information, that is 
    relevant to an assessment of substantial equivalence.  The information 
    could be descriptive information about the new and predicate device(s), 
    or performance or clinical testing information.

VI. Proposed labels, labeling, and advertisements sufficient to describe 
    the biopsy device, its intended use, and the directions for use should 
    be provided with a specific intended use statement and any warnings, 
    contraindications, or limitations clearly displayed as described in 21 
    CFR 807.87 (e).  The label of the device must bear the caution 
    statement as outlined in 21 CFR 801.109 (b) (1):  "CAUTION:  Federal 
    law restricts this device to sale by or on the order of a physician."

     A.  A label includes any identification on the biopsy device and on 
         the package in which it is stored and shipped.  The  package 
         device label should include the device name, U.S. point of 
         contact, corporation name, address, and phone number.  The package 
         label should also include all of the above, as well as sterility 
         status, expiration date, disposable/single use, quantity enclosed, 
         size (diameter and length), energy used/delivered, etc.

     B.  Device labeling for the biopsy device includes the intended use, a 
         description of the device, and directions for use.

     	 1.  The intended use statement should include specific 
         indications.  The anatomical sites, i.e. target organs, and the 
         target population should be defined.

     	 2.  The directions for use should contain comprehensive 
         instructions to include, but not necessarily be limited to, how to 
         prepare the biopsy device for use, how to operate the biopsy 
         device, how to stop operation and retrieve the sample, any special 
         instructions for specimen processing, a description of which parts 
         are single use/disposable or reusable, and a description of the 
         functional test procedures which should be performed for the 
         biopsy device prior to use.  Maintenance and troubleshooting 
         procedures should be outlined with instructions on how to perform 
         the maintenance, the frequency of the maintenance, and a 
         corporation contact point if troubleshooting procedures fail.

     	 3.  Contraindications (e.g. excluded population), precautions 
         (e.g. needle advancement/penetration depth), and warnings should 
         be included in the labeling of the device.

     C.  Advertisements or promotional literature for the biopsy device 
         that will accompany the device should be provided.  Literature or 
         labeling may not imply approval by FDA in any manner.  Guidance on 
         labeling issues is described in Bluebook Memo G91-1 "Device 
         Labeling Guidance (3/8/91)" and a copy may be obtained from the 
         Center for Devices and Radiological Health's Division of Small 
         Manufacturers Assistance at (800) 638-3041 or (301) 443-6597.

VII. A Summary of Equivalence comparing similar devices legally in 
commercial distribution in the United States must be provided.  This 
includes devices in commercial distribution prior to May 28, 1976, the 
enactment date of the Medical Devices Amendments, and any new devices 
introduced subsequently.  A Summary of Equivalence includes similarities 
and differences between the device and the device to which it is compared.  
The biopsy device should be compared with a legally marketed biopsy device, 
including, but not limited to, the following:

       intended use including specific target organs;

       design

     	   needle, cannula(s), and stylet size:  diameter and
     	   gauge;
     	   needle advancement/penetration depth;
     	   sample notch size;
     	   number of samples;
     	   jaw size;
     	   brush size: diameter and length;
     	   mechanics of action (automatic, manual, spring
     	   operated, electrically operated, etc.);
     	   mode of action (single puncture and sample, single
     	   puncture and multiple samples, brush rotation,
     	   suction, scraping: side-to-side or up-and-down,
     	   etc.);
     	   electrical compatibility;
     	   safety features; and
     	   other applicable specifications

       energy used/delivered for electric biopsy forceps and
       biopsy guns;

       materials of all components identifying those that come
       into patient contact;

       performance;

       anatomical sites (i.e. target organs);

       target population justifying any new population cited;

       visualization techniques;

       method of placement; and

       other related information.

State whether the substantially equivalent device is a pre-amendment device 
or a device which has been through the 510(k) process, providing the 510(k) 
document control number if known.  The summary of equivalence information 
should be provided in a manner that is clear and comprehensible, e.g. 
tabular form.

VIII. For a device that has undergone a change or modification that could 
significantly affect the safety or effectiveness of the device, or the 
device is to be marketed for a new or different indication for use, the 
510(k) must include appropriate supporting data to show that the 
manufacturer has considered what consequences and effects the change or 
modification or new use might have on the safety and effectiveness of the 
device, as described in 21 CFR 807.87 (g).

Significant modifications should be supported by a rationale for the 
modification with supporting documentation, including clinical or other 
valid scientific studies which demonstrate that these differences do not 
affect safety and effectiveness, as described in 21 CFR 807.87 (f).

The description of all biopsy devices should include any significant 
changes or modifications from the predicate device that could affect 
safety, effectiveness, or intended use.  Provide any bench, animal, 
clinical, functional, in vitro, and/or any other testing data to support 
your claims.  Provide certification regarding any compliance with voluntary 
standards, if applicable.

IX.  The physical description of each biopsy device to be marketed should 
be provided in the form of a labeled diagram, photograph/picture, 
schematic, etc., which includes all internal/external, 
assembled/unassembled, etc. parts of the biopsy device.  The physical 
description should include the specifications (length, width, height, 
diameter, power requirements, other applicable information) of the biopsy 
device.  The description should also identify any parts which are 
disposable (i.e., needles, sheath, cannula, etc.).  The labeled diagram, 
photograph/picture, schematic, etc., should address the name and function 
of all parts of the biopsy device.  This is especially important for 
automated biopsy guns and electric biopsy forceps where part of the 
mechanics of action is performed without operator intervention.

If the biopsy device is sold in a set that includes accessories, these 
accessories need to be identified and reviewed along with the biopsy device 
and require the same types of information as stated above.  These 
accessories might include cannulas, handles/holders, introducer, spacers, 
stylets, syringes, trocar, etc.  Labeling must state whether the accessory 
is intended for single use and whether it is reusable or disposable. 

X.   An exact identification of all materials used to fabricate the biopsy 
device should be provided and a statement regarding any material 
differences from the pre-amendment or substantially equivalent biopsy 
device should be explicitly stated.  If the materials are identical to the 
pre-amendment or substantially equivalent device and are identically 
processed and sterilized, then this should be explicitly stated.  The 
sponsor will need to provide biocompatibility testing data on any material 
changes that have been implemented or justify why this data is not needed, 
i.e. the material does not come into patient contact.  Biopsy devices are 
considered to be a short-term implants, with the type of tissue it comes in 
contact dependent on the indications for use.  At a minimum, 
biocompatibility data should be provided for the following tests:  
irritation, sensitization, cytotoxicity, acute systemic toxicity, and 
implantation.  Guidance for the testing is provided in the document 
entitled "Tripartite Biocompatibility Guidance for Medical Devices" and a 
copy may be obtained from the Center for Devices and Radiological Health's 
Division of Small Manufacturers Assistance at (800) 638-2041 or (301) 
443-6597.

An exact identification of all colors (ink, dyes, markings, radiopaque 
material, etc.) used to fabricate the biopsy device should be provided and 
a statement regarding any colorant changes from the pre-amendment or 
substantially equivalent biopsy device should be included.  If the colors 
are identical to the pre-amendment or substantially equivalent device then 
this should be explicitly stated.  The sponsor will need to provide 
biocompatibility testing data on any colorant changes that have been 
implemented; state how the markings are processed (etched, bands, in 
material, etc.) and whether the color contacts skin, mucosa, etc.

XI.  The following data should be provided to demonstrate substantial 
equivalence of your biopsy device with respect to functional performance.  
These tests should be conducted in a manner as similar as possible to how 
the biopsy device will be used in a medical procedure.  A statistically 
valid number of biopsy devices should be tested to establish the 
performance of each size.  A sampling of biopsy devices representative of 
the product line, e.g. largest, smallest, longest, and shortest, should be 
tested.  Testing should be conducted in accordance with accepted industry 
standards and explicitly stated as such, or a description and analysis of 
the test procedures used should be provided justifying their validity.  If 
the applicant believes that functional testing is not appropriate for the 
type of biopsy device to be marketed, justification should be provided.

Functional data for a cytology brush (manual or electric) must include, if 
applicable, testing demonstrating electrical compatibility with other 
gastroenterology-urology electrical devices; animal, bench, or other 
testing that defines the appropriate specifications for motor speeds, brush 
rotation, suction pressures, timing, possible electrical hazards to 
patient, etc.; how the tip, if applicable, is attached to the rod and the 
force needed to detach the tip, and brush/bristle attachment and strength.

Functional data for automatic biopsy devices, needles and needle sets must 
include testing demonstrating needle advancement and penetration.  Accurate 
needle advancement is important to ensure the sample is obtained from the 
intended tissue site with minimal trauma to that site and the surrounding 
tissue sites.  If claiming that the device will take multiple samples at 
one site, bench testing data must be presented demonstrating that the gun 
and needle assembly of the biopsy device are capable of being fired and are 
able to obtain the claimed amount of samples without damage to the interior 
mechanisms, and that the quality and size of the biopsy sample taken with 
the later shots are equivalent for the types of tissues and/or tumors for 
which the device is indicated.  If the biopsy device uses electricity, 
electrical safety (isolation) must be demonstrated.

Functional data for electric biopsy forceps must include testing 
demonstrating electrical compatibility with the gastroenterology-urology 
electrosurgical devices recommended in the labeling, electrical safety 
(isolation), and that the device can withstand the maximum currents 
generated without device damage or patient and user (operator) injury.

XII. Complete information regarding biopsy devices that are sold sterile 
must be provided and must include sterilization method; validation method; 
packaging materials and a description of the packaging to ensure sterility 
is maintained; sterility assurance level (SAL), and radiation dose or the 
maximum levels of residuals of ethylene oxide, ethylene chlorohydrin, and 
ethylene glycol which remain on the device, whichever applicable.  If the 
device will be labeled as pyrogen free, or non-pyrogenic, provide a 
description of the method used to make that determination (LAL or Rabbit 
test).  If the entire biopsy device is not sold sterile, labeling must 
clearly identify which parts are sterile and non-pyrogenic.  Guidance on 
sterility issues is described in ODE Bluebook Memo K90-1 510(k) "Sterility 
Review Guidance (2/12/90)" and a copy may be obtained from the Center for 
Devices and Radiological Health's Division of Small Manufacturers 
Assistance at (800) 638-2041 or (301) 443-6597. 

If the biopsy device is sold and labeled nonsterile or can be reprocessed, 
instructions on disassembly, cleaning, disinfection, and/or sterilization 
should be provided, if applicable.  If appropriate, a statement that the 
biopsy device requires high level disinfection should be provided and 
compatible solutions and/or procedures for high level disinfection and/or 
sterilization need to be identified.  Accessories that are disposable 
should be labeled as single use.

The Association for Practitioners in Infection Control (APIC) and the 
Center for Disease Control (CDC) have established definitions and 
guidelines for the selection and use of disinfectants, which depend on the 
site(s) of device contact.  The applicant's recommendations must be based 
on the target organs stated in their labeling.

XIII. If this device is to be marketed as a kit, identify all components 
and provide the certification stated below:

     	 I certify that the following components of my kit are either (1) 
         legally marketed pre-amendments devices, (2) exempt from premarket 
         notification (consistent with the exemption criteria described in 
         the classification regulation(s) and the limitations of exemptions 
         from Section 510(k) of the act (e.g., 862.9), or (3) have been 
         found to be substantially equivalent through the premarket 
         notification process for the use(s) for which the kit is to be 
         intended (i.e., I am not claiming or causing a new use for the 
         component(s)).  

     	 I further certify that these components are not purchased in 
         "bulk", but are purchased in finished form, i.e., they are 
         packaged, labeled, etc., consistent with their pre-amendments, 
         exemption, or premarket notification criteria and status.

     	 If you cannot make the above referenced certification statement 
         (first paragraph) for each component of your kit, you must itemize 
         the components without a pre-amendments, exemption, or premarket 
         notification status.  In this case we will continue our premarket 
         notification review of these components of your kit.

     	 If you cannot make the above referenced certification statement 
         (second paragraph) for each component of your kit, you must 
         itemize these components, state whether they are pre-amendments, 
         exempt, or have been found substantially equivalent through the 
         premarket notification process, and describe how you further 
         process them (e.g., sterile, package/repackage, label/relabel, 
         etc.).

     	 If the device kit contains components which are subject to 
         regulation as drugs, a substantially equivalent determination will 
         not apply to the drug component(s) of the device.  For information 
         on applicable Agency requirements for marketing the drug 
         component(s) in the kit, it is suggested that you contact the 
         Center for Drug evaluation and Research's Division of Drug 
         Labeling Compliance at (301) 295-8063.