Intravascular Administration Sets Premarket Notification Submissions [510(k)]: Guidance for Industry and FDA Staff
Published: 2008-07-11
Status: Final Type: Guidance Document Category: Premarket (510(k) / PMA / De Novo / IDE) Topics: Premarket, 510(k) Docket: FDA-2020-D-0957
Official Source
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/intravascular-administration-sets-premarket-notification-submissions-510k PDF: https://www.fda.gov/media/71046/download
Official Full Text
FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's 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.
- Background A manufacturer who intends to market a device of this generic type must 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 hemodialysis blood tubing sets (refer to Section 4. Scope). 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 premarket notification submission. You should also refer to 21 CFR 807.87, the guidance, Format for Traditional and Abbreviated 510(k)s,1 and “Premarket Notification 510(k)” on CDRH Device Advice.2
Under “The New 510(k) Paradigm - Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications,”3 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 certain modifications to their own cleared devices may lessen the regulatory burden by submitting a Special 510(k).
- 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), we recommend that you include a descriptive summary report of appropriate supporting data within the meaning of 21 CFR 807.87(f) or (g). The descriptive summary report should explain how this guidance document was used during the device development and testing, briefly describe the methods or tests used, and include a summary of the test data or description of the acceptance criteria applied to address the risks identified in this document and any other additional risks specific to your device. This section suggests information to fulfill some of the requirements of section 21 CFR 807.87 and identifies 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.
Proposed Labeling Proposed labeling must be sufficient to describe the device, its intended use, and the directions for its use. (21 CFR 807.87(e)) (Please refer to Section 11. Labeling for specific information that should be included in the labeling for devices of the type covered by this guidance document.)
Abbreviated 510(k) Summary Report4 In accordance with 21 CFR 807.87, your summary report should contain the following:
Description of the device and its intended use Please describe the device and include an explanation of how the device functions and the specific physical and performance characteristics of the device. Refer to Section 5. Device Description for specific information to include in the device description for devices of the type covered by this guidance document. You should also submit an “indications for use” enclosure.5
Description of device design You must include a brief description of the device design requirements. (21 CFR 807.87(f))
Identification of the risk analysis method We recommend that you identify the risk analysis method(s) you used to assess the risk profile, in general, as well as the risk profile of the specific device’s design and the results of this analysis. Please refer to Section 6. Risks to Health for the risks to health generally associated with the use of this device that FDA has identified.
Discussion of the device characteristics We recommend that you discuss the device characteristics that address the risks identified in this guidance document and any additional risks identified in your risk analysis.
Description of the performance aspects You should describe the nonclinical tests submitted, referenced, or relied on in your submission. See Sections 7-10 of this guidance for specific performance aspects. 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.6 (See also 21 CFR 820.30, Subpart C
- Design Controls for the Quality System Regulation.)
4 This is not the report described in 21 CFR 807.92, which may be submitted to satisfy 21 CFR 807.87(h). 5 Refer to http://www.fda.gov/cdrh/ode/indicate.html for the recommended format. 6 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 Reliance on standards If you choose to rely on a recognized standard for any part of the device design or testing, you may include either a:
• statement that testing will be conducted and meet specified acceptance criteria before the device is marketed; or
• declaration of conformity to the standard.7
Because a declaration of conformity is based on results from testing, you cannot properly submit a declaration of conformity until you have completed the testing the standard describes. For more information, please refer to section 514(c)(1)(B) of the act and the FDA guidance, Use of Standards in Substantial Equivalence Determinations.8
If it is not clear how you have addressed the risks identified by FDA or additional risks identified through your risk analysis, we may request additional information about aspects of the device’s performance characteristics. We may also request additional information if we need it to assess the adequacy of your acceptance criteria. Under 21 CFR 807.87(l), you must submit any additional information that is necessary to reach a determination regarding substantial equivalence.
As an alternative to submitting an Abbreviated 510(k), you can submit a Traditional 510(k) that provides all of the information and data required under 21 CFR 807.87 and described in this guidance. A Traditional 510(k) should include all of your methods, data, acceptance criteria, and conclusions. Manufacturers considering certain modifications to their own cleared devices should consider submitting Special 510(k)s.
The following is a specific discussion of how you should apply this guidance document to a premarket notification submission for IV administration sets and accessories.
- Scope The scope of this document is limited to the device defined in 21 CFR 880.5440, class II, and assigned the product codes described in the table below.
criteria and, thus, differs from the device described in the cleared 510(k), FDA recommends that submitters apply 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). Procod e Common Name FMG IV Set Stopcock (includes manifolds) FPA Intravascular Administration Set (includes needleless access devices/systems and blood flow regulator) BRZ Blood Transfusion Set FPB Infusion Line (In-Line) Filter CAK Blood Transfusion Microfilter FPK Fluid Delivery Tubing LHI IV Fluid Transfer Set (includes vial adapter) Pharmacy compounding systems (procode NEP) classified in the intravascular administration set identification are exempt from the premarket notification procedures, subject to the limitations in 21 CFR 880.9.
Section 880.5440 Intravascular Administration Set An intravascular administration set is a device used to administer fluids from a container to a patient’s vascular system through a needle or catheter inserted into a vein. The device may include the needle or catheter, tubing, a flow regulator, a drip chamber, an infusion line filter, an I.V. set stopcock, fluid delivery tubing, connectors between parts of the set, a side tube with a cap to serve as an injection site, and a hollow spike to penetrate and connect the tubing to an I.V. bag or other infusion fluid container.
IV administration sets administer fluids to a patient’s vascular system by various means, gravity flow, via a pump, subcutaneously, or through implanted vascular ports. These IV sets may include Diethylhexylphthalate (DEHP) and non-DEHP PVC tubing, co-extruded tubing, calibrated burettes, filters, standard and needle free Y-injection sites (swabbable and nonswabbable), anti-siphon valves, and check valves to prevent retrograde fluid flow. 5. Device Description We recommend that you identify your device by regulation and product code described in Section 4. Scope, and include the following information: • indications for use • design features; i.e., materials, configurations, size, safety features • specifications and dimensions • materials, including chemical formulation • conformance with standards.
Side by side comparisons of the information described below, whenever possible, in tabular format are desirable. We recommend that you describe how any differences may affect the comparative safety and effectiveness of the new device.
Material Composition We recommend that you provide a complete listing of all device materials (trade name and chemical formula) and identify any metallic components. Metallic components may affect the safety of the device in an MRI environment. We also recommend that you identify any polyvinylchloride (PVC) plasticizers, lubricants, bonding agents, or other additives (e.g., color additives, ink, dyes, markings, radiopaque materials) and provide their amounts.
It is helpful to present the information in the form of a listing, noting the component name followed by specific material identifier. We believe stating only a generic class (e.g., “PVC”) is not adequate because there are many formulations of material compositions.
Physical Specifications When describing physical specifications, we recommend that you include: • dimensions: inner diameter (ID), outer diameter (OD), length, width • types of configurations • priming volume • residual volume in needleless access ports • dimensions of other features • proximal and distal end configuration: shape, location, and diameter of outlets and side ports • connector types: e.g., Luer lock, slip fit • the color of all components • any other unique physical features and specifications of the device. Mechanical Specifications When providing mechanical specifications, we recommend that you provide: • strength of materials (tensile, flexural) • strength of joints, bonds, connections, hinges, valves, locking mechanisms, etc. • tubing elongation • connector performance criteria; e.g., to prevent leakage • burst pressure • puncture/reseal limits of septa • flow characteristics • material hardness • crimping/flexion when intended for use with infusion pumps.
Design Features We recommend that you describe the design features of your device and any similarities or differences between those features and features of similar legally marketed devices of the same type, which may affect safety and effectiveness.
- Risks to Health In the table below, FDA has identified the risks to health generally associated with the use of intravascular administration sets and accessories 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 to identify any other risks specific to your device and submit the results of this analysis. 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 Device malfunction Section 7. Bench Testing Adverse tissue reaction Section 11. Biocompatibility Infection Section 8. Microbial Ingress Testing Section 9. Simulated Clinical Use Testing Section 10. Sterilization Improper use Section 12. Labeling 7. Bench Testing We recommend that you conduct all testing under both a dry test condition and a wet environment simulating body fluids or fluids being administered. We recommend that you evaluate your device compared with a similar legally marketed device, using worst case simulated static and dynamic forces to the failure point of the components. We also recommend that you describe how you determined the worst case conditions used. Testing should assess: • the force to attach and detach connections • the force to activate and deactivate any safety features present • the number of injection port accesses to failure for needleless port with valves, diaphragms, or membranes • the pressure and leak tolerance for pre-slit septa under extreme conditions of use.
In addition, when your device is intended for use with other manufacturer’s blunt cannulae, we recommend that you conduct the pressure and leak tolerance testing for pre-slit septa under extreme conditions of use with those blunt cannulae.
Where appropriate to your device’s intended use or design, we recommend that you follow the standards listed below or equivalent measures, in addition to the testing described above. • ISO 8536-4: 2004, Infusion Equipment for Medical Use, Part 4 • ANSI/AAMI BF7: R2002, American National Standard for Blood Transfusion Micro Filters • ISO 1135-4: 2004, Transfusion Equipment for Medical Use • ISO 594, Conical Fittings with a 6 % (Luer) Taper for Syringes, Needles, and Certain Other Equipment.
- Microbial Ingress Testing A needleless device that facilitates bi-directional fluid flow may increase the patient’s risk of infection because these features allow the entry of microorganisms into the sterile fluid path. We recommend that you conduct microbial ingress testing of these devices. This testing is intended to simulate repeated access.
We recommend that you provide results from a simulated use test for microbial ingress in your device. Testing should simulate the use of the device in a clinical setting, i.e., the number of microbial challenges in the study should approximate the number of user interactions with the access site that would be expected clinically. The testing should demonstrate that the disinfection procedures you use are effective. We recommend that you provide an analysis of the study results and a summary of the results and conclusions. We recommend that you provide a detailed protocol for your study, which describes the: • study procedure for the subject device • amount and identity of challenge organisms • methods used to prepare the challenge organisms commonly associated with contaminated needleless access devices, i.e. 2 gram negative and 2 gram positive organisms. • method of device contamination/inoculation for all sites of device inoculated • access procedure • time and culture procedures • rationale for the challenge microorganisms used as inoculum (minimum of 103 per device) • type of environment in which the study was conducted • positive (non-disinfected device) and negative controls used in the study • rationale for the sample size used in the study • validation (using microbiological techniques) of the disinfecting procedures for insertion and reinsertion into the needleless access site.
- Simulated Clinical Use Testing For devices that include sharps injury prevention features, we recommend that you conduct simulated clinical use testing; provide an analysis of the results; and a summary of the results and conclusions. For information about this kind of testing, see Training for Development of Innovative Technologies Project,9 and the guidance entitled, Supplementary Guidance on Premarket Notifications for Medical Devices with Sharps Injury Prevention Features.10
We recommend that you provide a detailed protocol for your study that addresses variables in the patient and health care professional user populations. If the device will be exposed to many conditions of use, we recommend that you assess the variables to accurately judge the performance of the device under these conditions. These variables include, but are not limited to training, learning curve, and the experience of users. For information about device design and human factors, see ANSI/AAMI HE48-1993: Human factors engineering guidelines and preferred practices for the design of medical devices and the FDA guidance entitled, Do It By Design - An Introduction to Human Factors in Medical Devices.11
We recommend that you devise protocols, whenever possible, based on statistical considerations, such as sample size, response variables, pass-or-fail criteria, comprehensive report forms, proper controls, and appropriate statistical test methods. (This guidance does not provide a detailed discussion of statistical considerations).
Sterilization FDA recommends that you provide sterilization information as described in the guidance, Updated 510(k) Sterility Review Guidance K90-1.12 The device should be sterile, with a sterility assurance level (SAL) of 1 x 10-6 using a sterilization cycle that has been validated in accordance with the Quality Systems (QS). 21 CFR 820.30.
Biocompatibility We recommend that you conduct biocompatibility testing for your device as a prolonged duration, indirect blood path contacting device as described in the guidance entitled, Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part 1: Evaluation and Testing.13 You should select the tests appropriate for the duration and level of contact and submit your pass/fail criteria. We also recommend that you document the results in your design history file as a part of the QS (21 CFR 820.30). If identical materials are used in a predicate device with the same type and duration of contact, you may identify the predicate device in lieu of performing biocompatibility testing.
Labeling Labeling must provide sufficient detail to satisfy the requirements of 21 CFR 807.87(e). The following information will assist you in meeting the requirements of 21 CFR Part 801.14
Intended Use We recommend that you clearly state the intended use of your device and include the indications for use and include the intended (target) population, e.g., pediatric patients. If your device is intended for use with a specific blunt cannula, infusion pump, or other device, we recommend that you identify that device.
Description of the Device
14 Although final labeling is not required for 510(k) clearance, final labeling must comply with the requirements of 21 CFR 801 before a medical device is introduced into interstate commerce. In addition, final labeling for prescription medical devices must comply with 21 CFR 801.109. Labeling recommendations in this guidance are consistent with the requirements of part 801. We recommend that the description of the device include: • type • set length, in inches and millimeters • inner diameter (ID) • outer diameter (OD) • drops/ml • priming volume • filter • needle gauge and length • single use only, nontoxic, non-pyrogenic fluid path, where applicable • sterile, if package is intact, undamaged, and protective caps are secure.
Directions for Use We recommend that your directions for use include: • a step-by-step procedure for use of the device • a step-by-step procedure for the use of needleless access components, where applicable • special patient instructions (including instructions for contacting the healthcare provider if indicated for home use) • the recommended frequency of replacing the IV set or needless access device, as appropriate, for example “per CDC guidelines or facility protocol” • the duration of use and frequency of replacing IV sets when used for the administration of lipids, blood, or blood products according to their labeling • directions for replacing the sterile cap (needleless access devices without pre-slit septa only) with each use unless a mechanism is in place to keep the cap sterile • instructions for cleaning and disinfecting y-sites • instructions for cleaning and disinfecting pre-slit septa, where applicable • instructions for discarding a used device.
We also recommend that you include illustrations, pictures, posters, cards, and other visual aids that clarify and reinforce the directions for use.
Precautions We recommend that labeling include any special limitations related to opacity or the type of solutions used with the device (e.g., light sensitive solutions, fat emulsions, lipids, blood, and blood products). We also recommend that labeling identify the presence of the plasticizer DEHP in the fluid pathway of PVC tubing, because leaching of the plasticizer is possible on contact with lipids.
Warnings We recommend that labeling warn against use with high-pressure infusion systems, where applicable.
For administration sets that may be used with infusion pumps with no restricted flow feature, labeling should include warnings related to unrestricted flow and instructions for use with gravity flow.
Labeling of Shelf Containers For labeling a multi-unit or shelf container, we recommend that you include: • a description of the contents, in words and/or pictures • the number of infusion sets or accessories • instructions for use in each shelf container • terms describing whether the units are sterile and single use • the year and month of sterilization • the recommended storage conditions, if any.
Appendix I. Glossary of Terms
The terms here are defined for the purpose of this guidance document only, unless otherwise noted.
Anti-Siphon Valve. An accessory to an IV administration set that protects against unregulated gravity fluid infusion or blood. Backcheck Valve. An accessory to an IV administration set that allows for uni-directional fluid flow and serves as a multiple access site for the injection of fluids. Blood Administration Set. A device used as part of a system to administer and filter blood and/or blood components to a patient. Capped Luer Connector. A needleless system that is the same as those commonly used at the catheter end of IV sets. The mating Luer fitting of a syringe or secondary set can be aseptically connected directly to the Luer port. A manual clamp is included on the tubing above the Y-site to prevent fluid flow while attaching or detaching a connection; when the port is not in use, it is capped to maintain a closed system. Alternately, a pre-pierced septum injection adapter, recessed needle injection adapter, or valved connector can be aseptically placed on the Luer connector of the capped Luer Y-site to provide a self-sealing site. See also p.328, Needlestick-prevention Devices, ECRI Health Devices. 23: (8–9) Aug./Sept. 1994. Filter. An accessory to or component of an IV administration set; a device that is designed to eliminate entrapped air or inadvertent particulates and microbial contaminants from solutions prior to patient administration. Intravascular Administration Set. A device used to administer fluids from a container to a patient’s vascular system through a needle or catheter inserted into a vein. The device may include a needle or catheter, tubing, a flow regulator, a drip chamber, an infusion line filter, an IV set stopcock, fluid delivery tubing, connectors between parts of the set, a side tube with a cap to serve as an injection site, and a hollow spike to penetrate and connect the tubing to an IV bag or other infusion fluid container (21 CFR 880.5440). IV Flow Regulator. An accessory (to an IV administration set) that controls the flow of intravenous solutions. IV Manifold. An accessory to an IV administration set that provides multiple access ports and regulates the directional flow of fluids for simultaneous/alternate intravenous therapy. IV Stopcock. An accessory to an IV administration set that regulates the directional flow to a patient's vascular system and provides an access port(s) for the administration of solutions. Needleless System. Components of a device that provide repeated access to a patient’s vascular system without the use of sharps. Fluid flow through the system may be unidirectional or bi-directional, with the latter enabling the user to administer or withdraw fluids or medication. Needleless mechanisms include three types: pre-pierced septum and blunt cannula; valved connector (also called reflux valve); and capped Luer connector. Prepierced Septum and Blunt Cannula. A needleless system in which a blunt cannula is placed on the syringe or secondary set. It can be aseptically inserted into a pre-pierced septum on a Y-site, injection adapter, or extension set.
Valved Connector (also called reflux valve). A needleless system in which a valved connector prevents the flow through the connector until a mating Luer connector is aseptically inserted; the valve then opens. Vial Adapter. A device designed to facilitate the withdrawal of drugs or solutions from a vial and may have a needleless device component as part of its design. Appendix II. Abbreviations
AAMI Association for the Advancement of Medical Instrumentation ANSI American National Standards Institute ASTM American Society for Testing and Materials CDC Centers for Disease Control and Prevention CDRH Center for Devices and Radiological Health CFR Code of Federal Regulations DAGID Division of Anesthesiology, General Hospital, Infection Control, and Dental Devices DEHP Diethylhexylphthalate DSMICA Division of Small Manufacturers, International, and Consumer Assistance ECRI Emergency Care Research Institute FDA Food and Drug Administration ID Inner Diameter IRB Institutional Review Board ISO International Organization for Standardization IV Intravascular OD Outer Diameter ODE Office of Device Evaluation Appendix III. Recommended Submission Checklists for Intravascular Administration Sets Device Description Item Included Yes No Comments Narrative description
Photographs or labeled diagrams
Insertion tube, if applicable
Sample provided
Physical Specifications Item Included Yes No Comments Dimensions and volumes
Proximal and distal end configurations
Connector type
Color (purpose)
Opacity
Markings and scales
Special features
Mechanical Specifications Item Included Yes No Comments Strength of materials
Stress characteristics
Fluid flow rate
Lubricant identified (if applicable)
Material Specifications (cont.) Item Included Yes No Comments Tensile strength
Burst test
Leakage test
Security of attachments
Hardness
Percentage tubing elongation
Crimping or flexing with clamp
Cyclic performance with pump
Labeling Item Included Yes No Comments Device name
Intended use
Type
Size, set length
Inner diameter
Outer diameter
Drops/ml
Priming volume
Filter
Needle gauge and length
Quantity
Single use only
Sterile, non-toxic
Non-pyrogenic fluid path
Directions for use
Promotional materials
Plasticizer Sterilization Item Included Yes No Comments Method (EtO/Gamma)
Validation Method
SAL
Dosage (if gamma irraditated)
Residues (if ethylene oxide)
Pyrogen-free method
Packaging materials
Tabular Comparison to a Legally Marketed Device Item Included Yes No Comments Identified as appropriate legally marketed device
Side-by-side comparison
Features
Intended use(s)
Labeling
All materials
Specifications (as above)
Performance data
Technological aspects
How differences may affect safety and effectiveness
Biocompatibility Tests Item Included Yes No Comments Cytotoxicity 20 Sensitization
Intracutaneous
Systemic toxicity
Hemocompatibility
Other
Performance Studies Item Included Yes No Comments Risk analysis, if appropriate
Microbial challenge, if appropriate
Simulated use study
Actual use study, if appropriate
Footnotes
[^7]: See http://www.fda.gov/opacom/morechoices/fdaforms/FDA-3654.pdf