Guidance for the Content of Premarket Notifications for Biopsy Devices Used in Gastroenterology and Urology
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.
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