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Guidance for Industry and CDRH Reviewers
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Document issued on: August 7, 1998
U.S. Department Of Health And Human Services Food and Drug Administration Center for Devices and Radiological Health Gastroenterology and Renal Devices Branch |
Comments and suggestions on this draft document may be submitted at any time for Agency consideration to Carolyn Y. Neuland, Ph.D., Chief, Gastroenterology and Renal Devices Branch, Office of Device Evaluation, 9200 Corporate Boulevard, HFZ-470, 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 Carolyn Y. Neuland Ph.D., at (240) 276-4151 or by electronic mail to carolyn.neuland@fda.hhs.gov.
World Wide Web/CDRH home page: http://www.fda.gov/cdrh/ode/hemod.pdf, or CDRH Facts on Demand at 1-800-899-0381 or 301-827-0111, specify shelf number 2202 when prompted.
VI. Intended Use/Indications for Use
This guidance document represents the FDA's current thinking on the content of premarket notifications for hemodialysis delivery machines. It does not create or 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.
This guidance is based on (1) current scientific knowledge, (2) clinical experience, (3) previous submissions by manufacturers to the Food and Drug Administration (FDA), and (4) the Safe Medical Devices Act of 1990, the FDA Modernization Act of 1997, and FDA regulations in the Code of Federal Regulations (CFR). As advances are made in science and medicine, and changes occur in implementation of Congressional legislation, these review criteria will be re-evaluated and revised as necessary. Comments and suggestions on this draft document are welcomed and should be submitted to Carolyn Y. Neuland, Ph.D., Chief, Gastroenterology and Renal Devices Branch, Office of Device Evaluation, 9200 Corporate Boulevard, HFZ-470, Rockville, MD, 20850. Comments should be submitted within 90 days of the date of issue of this document to receive consideration for the next revision.
This document is an adjunct to the CFR and other FDA guidance documents for the preparation and review of 510(k) submissions. It does not supersede those publications, but provides additional clarification on what is necessary before the FDA can clear a device for marketing. The submission must provide evidence that the device is safe, effective, and substantially equivalent to a predicate device that is currently legally marketed in the United States.
Hemodialysis delivery systems are described and classified in two sections of the FDA regulation. Under 21 CFR §876.5820, a conventional hemodialysis delivery system is defined as a system that "consists of mechanisms that monitor and control the temperature, conductivity, flow rate, and pressure of the dialysate and circulates dialysate through the dialysate compartment of the dialyzer." This system "includes the dialysate concentrate for hemodialysis (liquid or powder) and alarms to indicate abnormal dialysate conditions."
Under 21 CFR §876.5860, a high permeability hemodialysis delivery system is defined as a machine that contains an ultrafiltration controller and mechanisms that monitor and/or control the system temperature, dialysate conductivity, fluid (e.g., blood, dialysate, effluent) flow rate, pressure, fluid balance, proportioning of the dialysate, pumps, air foam (bubble detectors), alarms, computer interfaces, and patient treatment parameters (e.g., blood pressure, hematocrit, urea, oxygen saturation, etc.). This includes those components that are incorporated into the machine, such as heparin pumps, monitors, etc. (Note that this definition is based on the proposed reclassification of this section and is subject to change.).
The systems described in the above classifications are generally part of the hemodialysis system that also contains the hemodialyzer, extracorporeal and associated tubing lines, water treatment systems, and patient access devices.
For the purpose of this document, a hemodialysis delivery system will refer to both classifications listed above. In addition, you may refer to this guidance when preparing a submission for devices that perform hemoconcentration, hemofiltration, and other related extracorporeal therapies. In addition, a separate section is included in this guidance document that specifically addresses the use of devices that perform on-line hemodiafiltration.
In addition, for the purpose of this document, a "hemodialysis delivery system," "dialysis system," and "hemodialysis system" may be interchanged and generally refer to either the proposed (new) or predicate (currently legally marketed) device.
Recommendations for hemodialyzers may be found in these separate guidance documents: "Guidance for Hemodialyzer Reuse Labeling," and "Guidance for the Content of Premarket Notifications for Conventional and High Permeability Hemodialyzers." Each of these guidances is available from the Center for Devices and Radiological Health's (CDRH) Division of Small Manufacturers Assistance (DSMA) at 1(800) 638-2041 or at the internet address: http://www.fda.gov/cdrh/dsma/dsmamain.html.
The primary reference for the information required to be included in a 510(k) for a medical device is set forth in 21 CFR §807.87. The purpose of this section is to inform the submitter of the information necessary for FDA to determine substantial equivalence of a proposed device to a device in commercial distribution. Substantial equivalence to a currently legally marketed device 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 510(k) for a hemodialysis delivery system include the information in this guidance document in order to ensure that the submission is adequate to permit a determination of substantial equivalence to a predicate hemodialysis delivery system.
Additional guidance on the required elements for a 510(k) submission can be obtained by referring to the "DRAERD Premarket Notification [510(k)] Screening Checklist." A copy may be obtained from DSMA.
This guidance document is intended to aid in the preparation of 510(k) applications for devices with either of the following classifications:
Device Group |
Class |
CFR Section |
Panel/Product Code |
conventional | II |
§876.5820 |
78 FKP |
high permeability | III* |
§876.5860 |
78 KDI |
*subject to change pending reclassification of §876.5860
The 510(k) should include the appropriate CFR classification regulation number, class, panel, and product code for the proposed device. This is a comprehensive guidance that describes the type of information generally needed for the submission of a new hemodialysis delivery system. However, you should also follow this guidance for the submission of modifications to currently legally marketed hemodialysis systems.
The 510(k) should include both the trade/proprietary name of the device, including specific model, and the common/usual, name for the particular type.
The 510(k) should include an identification of the currently legally marketed device(s) to which the proposed device will be compared. Be as specific as possible, e.g., include the proprietary and common name, manufacturer, model number, 510(k) reference number, pre-Amendments status (i.e., marketed in the United States prior to May 28, 1976), etc. The 510(k) should include a tabbed section with product literature (description, specifications, labels and labeling, etc.) for the predicate device.
The 510(k) should include the following information about the applicant:
The 510(k) should include a clear description of the proposed device's intended use/indications for use. This description should identify, at a minimum, the following:
The 510(k) should include a detailed device description that describes the safe and effective features of the dialysis system, which includes a description of the following: (a) physical and/or electronic components, (b) system features/functions, (c) materials and biocompatibility, and (d) software. Each of these areas is described in more detail below.
(1) the ratio of the mixture of concentrates and water used;
(2) the minimum quality of water that is to be mixed with the dialysate (e.g., AAMI quality); and
(3) an identification of the type of concentrates that may be used (i.e., acid and bicarbonate, acetate).
Each of these values should be compared to those for the predicate device. If the proposed device has a range outside of the range for the predicate device, explain why this difference does not affect the safety or effectiveness of the proposed device.
Note that this information should be included, at a minimum, in the troubleshooting section of the operator's manual for the dialysis system.
Provide an identification of the machine components (and the corresponding materials) that are either patient- or patient-fluid contacting. For the purpose of this guidance, a machine component in the dialysate fluid path is considered patient-fluid contacting.
For each of these materials, either identify a currently legally marketed device that uses the identical material for a similar intended use, or provide appropriate biocompatibility testing as recommended in the current FDA guidance on biocompatibility.
Alternatively, you may conduct leach testing that identifies and characterizes the potential leachables using appropriate chemical analyses for patient-fluid contacting materials. In addition, you should conduct a risk assessment of the toxic potential of these leachables obtained from referenced literature.
The requirements for software-controlled medical devices and for the use of off-the-shelf software are described in guidance documents issued by the Office of Device Evaluation. Contact DSMA for the latest version of these guidance documents.
In general, your documentation on the software of the device should be partitioned into the following sections:
The 510(k) should include adequate information describing the performance characteristics of the dialysis system. At a minimum, this should include the following:
Due to changes in technology that may have a significant impact on safety and effectiveness of dialysis, clinical data may be needed to support a marketing application. Please contact FDA for guidance on whether clinical data is needed for your application.
For the purpose of this guidance document, an on-line hemodiafiltration system is a system that receives non-sterile solution, processes it, and delivers it as a sterile replacement priming or rinseback solution to the patient. Further, the phrases "replacement fluid" and "fluid for priming or rinseback on-line" may be used interchangeably in terms of the requirements listed below.
For those devices that either perform on-line hemodiafiltration or produce fluid for priming and rinseback on-line, you should provide the information listed in this section in addition to the other information described elsewhere in this guidance document.
Clinical data is needed to demonstrate the safety of the on-line production of fluid under actual use conditions. We believe that such data should be collected in a multi-center clinical study that reflects current hemodialysis practice in the United States. FDA considers this to be a significant risk study; therefore, clinical studies in the United States must be conducted under an investigation device exemption (IDE). FDA recommends that you contact us before submitting a 510(k) or IDE to discuss clinical data requirements unique to each system.
In general, the study should track adverse events (AEs) (e.g., fluid imbalance, infection, pyrogen reaction, etc.) and compare the AE rates with the new system to those of patients receiving standard dialysis in the United States. Microbiological surveillance of the system will also be needed to demonstrate that the system continues to produce USP Sterile Water for Injection under actual use conditions.
The 510(k) should include a comparison of the proposed device to a predicate device. This comparison may be done in a table that lists the similarities and differences between the proposed device and predicate device(s) in terms of intended use, design features, performance specifications, and other important safety and/or effectiveness information.
The 510(k) should include the device labeling for dialysis machines, which generally consists of the operator's manual, promotional advertising, and labels affixed directly to the machine.
This labeling should include a specific intended use statement and any warnings, contraindications, or limitations clearly displayed as described in 21 CFR §807.87(e). This may be provided in draft form. The device labeling 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." Guidance on labeling issues is described in Bluebook Memo G91-1 "Device Labeling Guidance (3/8/91)." A copy of this guidance may be obtained from DSMA at the telephone number listed above.
The operator's manual should provide detailed information regarding the safe use of the dialysis machine. In general, the manual should include these sections:
While certain aspects of the operator's manual may be specific to the design of a particular hemodialysis delivery machine, we believe that several critical user-related aspects should be included in all manuals. This includes the following:
For modifications to a currently legally marketed dialysis machine, refer to the CDRH guidance titled "Deciding When to Submit a 510(k) for a Change to an Existing Device" on whether a 510(k) is required for this proposed change. In general, a modification that affects the safe and effective use of the dialysis machines (e.g., change in alarm features, performance specifications) requires a 510(k) submission. In addition, a 510(k) should be submitted if the modification is correcting problems or failures associated with one or more components of the machine.
If you submit a 510(k) for a modification to a legally marketed dialysis delivery system, clarify the regulatory status of this device (identify the 510(k) number if known), and clearly describe the differences between the new device and legally marketed dialysis delivery system.
As required by FDA regulation, several documents are needed to complete the administrative record for a 510(k).
The 510(k) should contain the following statement:
I certify in my capacity as (provide title) for (provide manufacturer's name), I believe, to the best of my knowledge, that all data and information submitted in this premarket notification are truthful and accurate and that no material fact has been omitted.
The above statement must be signed and dated by a representative of the company (not by a regulatory consultant).
The 510(k) should include the indications for use for the hemodialysis delivery machine should be provided on a separate page. Note that (1) you should identify the specific device name (including model number, if applicable) on this statement and (2) the indications should agree exactly with the indications for use statement in the device labeling.
The 510(k) should contain either a 510(k) Summary or 510(k) Statement. Refer to 21 CFR §807.92 and §807.93 for the content and format of these documents. The 510(k) Summary should not include any trade secret information or patient identifiers.
If your device is a Class III device, you should provide the Premarket Notification Class III Certification and Summary as required by 21 CFR §807.94(p)(q).
* Note that this may no longer be needed, pending reclassification of §876.5860 from Class III to Class II.
Uploaded on January 7, 1999
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