Document issued on: November 29, 2000
This document supersedes documents "Guidance for Extracorporeal Blood Circuit Defoamer 510(k) Submissions"; final dated, February 16, 2000
U.S. Department Of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health
Circulatory Support and Prosthetic Devices Branch
Division of Cardiovascular Respiratory and Neurology Devices
Office of Device Evaluation
Comments and suggestions may be submitted at any time for Agency consideration to Dockets Management Branch, Division of Management Systems and Policy, Office of Human Resources and Management Services, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD, 20852. When submitting comments, please refer to the exact title of this guidance document. 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 Catherine Wentz at (240) 276-4141 or by e-mail at firstname.lastname@example.org.
Additional copies are available from the Internet. You may also send an e-mail request to CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance. Please use the document number (1632) to identify the guidance you are requesting.
Guidance for Extracorporeal Blood Circuit Defoamer 510(k) Submissions; Final Guidance for Industry and FDA
This document is intended to provide guidance. It represents the Agency’s current thinking on the above. 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 document describes a means by which cardiopulmonary bypass defoamer devices may comply with the requirement of special controls for class II devices. Designation of this guidance document as a special control means that manufacturers attempting to establish that their device is substantially equivalent to a predicate cardiopulmonary bypass defoamer device should demonstrate that the proposed device complies with either the specific recommendations of this guidance or some alternate control that provides equivalent assurances of safety and effectiveness.
This guidance document has been developed as a special control to support a change in classification from class III to class II. It identifies relevant material on preclinical studies and labeling to include in a 510(k) premarket notification application. We intend it be used in conjunction with other identified special controls, Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part 1: Evaluation and Testing, dated May 1, 1995, and 510(k) Sterility Review Guidance. All FDA requirements regarding premarket notification submissions are not repeated in this document.
The Least Burdensome Approach:
The issues identified in this guidance document represent those that we believe need to be addressed before your device can be approved/cleared for marketing. In developing the guidance, we carefully considered the relevant statutory criteria for Agency decision-making. We also considered the burden that may be incurred in your attempt to comply with the guidance and address the issues we have identified. We believe that we have considered the least burdensome approach to resolving the issues presented in the guidance document. If, however, you believe that information is being requested that is not relevant to the regulatory decision for your pending application or that there is a less burdensome way to address the issues, you should follow the procedures outlined in the "A Suggested Approach to Resolving Least Burdensome Issues" document.
An extracorporeal circuit blood defoamer (21 CFR 870.4230) is a device used to remove gas bubbles from the blood for up to six hours. It may be used on the arterial side of a extracorporeal circuit distal to the oxygenator during cardiopulmonary bypass surgery. It may also be used on the venous side before the oxygenator during cardiopulmonary bypass procedures, and in open and closed autotransfusion procedures. The device when used on the venous side is usually an integral part of the cardiopulmonary bypass blood reservoir (21 CFR 870.4400).
The following table sets forth the risks to health associated with this device that were identified in the proposed classification ruling (dated February 26, 1979), as well as additional adverse event reporting since the classification ruling. Next to each risk is a description of the special control suggested to address the risk.
RISKS TO HEALTH
Blood Studies: Evaluate hemolysis and cell depletion (i.e., blood cell counts) over a 6 hour circulation period for the subject, predicate and dynamic control circuits. In addition, blood component (platelet) functionality should be performed if new technology, materials, or surface characterics are introduced. Blood studies should be performed at the maximum labeled flow rate. In some cases where flow dynamics at low flow rates may play a role in blood trauma, the data should also be presented for the minimum labeled flow rate
Visual Inspection: Gross inspection for thromboemboli.
Pressure Integrity Testing: Perform burst pressure for test device using sustained static pressure at 1.5 times the maximum anticipated pressure for the intended use for 6 hours. Observe for leaks, tears, and structural integrity. Use Water or saline as the test medium.
Pressure Drop: Perform pressure drop testing to steady state, on the test and predicate devices, at highest rated flow rate. Use blood or a blood analog as the testing medium.
||Leak testing: Assess mechanical integrity by testing under static pressure conditions as noted in pressure testing above. Test and state the pull strength required to separate the connections or bonds (if applicable).|
Defoaming testing: Demonstrate the ability of the defoamer to eliminate foam as indicated in the labeling, at the flow rates indicated in the labeling, e.g., 0.5, 1.0, and 1.5 liters/min. Describe the acceptance criteria, e.g., the complete absence of foam in the reservoir.
Labeling: Recommend the use of the attached Checklist.
For those defoamers used on the arterial side of the circuit, the use of a bubble detector downstream from the defoamer, both during testing and in clinical use, is strongly recommended.
||Flow rate capacity: Determine the flow rate limitation(s) to assure safe and effective performance.|
Labeling: Include clear, concise instructions for use. Describe the human factors review e.g., inclusion of a troubleshooting guide, easy formatting of instructions for use, etc. Use the attached Checklist as a guide.
Provide flow rate, duration of use (e.g., 6 hours), and other pertinent information obtained through performance testing within the labeling, to facilitate correct use of the device.
For those defoamers used on the arterial side of the circuit, the use of a bubble detector downstream from the defoamer is strongly recommended.
Biocompatibility testing: Perform testing on aged product, as recommended in the FDA guidance on ISO 10993: Use of International Standard ISO 10993, Biological Evaluation of Medical Devices Part 1: Evaluation and Testing, dated May 1, 1995 to assure that the materials used are non-toxic for the intended use. Include sensitization, pyrogenicity, acute systemic toxicity, mutagenicity, cytotoxity, irritiation, and hemocompatibility/hemolysis testing.
If biocompatibility testing is performed on the unaged product, then submit an FT-IR and results of cytotoxicity testing on the aged product as well, that demonstrates that the physical and chemical properties of the material(s) have not changed.
||Sterilization: Perform sterilization validation to ensure that the sterilization process is capable of providing a Sterility Assurance Limit (SAL) of 10-6. Perform biological indicator (as applicable), pyrogen, and bioburden testing to ensure acceptable limits of biological contaminants.|
Shelf-life: Submit the protocol and data from real or accelerated aging studies for the intended labeled shelf-life for the device. If accelerated studies are used, validate (for your own files) the results with real-time data.
Perform package integrity and barrier property assessment: use validated physical and microbial-based methods.
ATTACHMENT: Human Factors/Instruction for Use Checklist
This Checklist is a human factors tool to aid the manufacturer when designing the device and developing the instructions for use manual. Using this checklist will reduce many of the risks to health discussed in this guidance; especially those that can addressed by adequate instructions for use.
__Mount motor drive correctly, relative to venous reservoir.
__Check that all electrical connections are secure.
__Test control module power and display.
__Check date and integrity of sterile centrifugal pump (and disposable probe) package(s).
__Check that flow transducer/sensor (and disposable probe) are sized properly.
__Assemble perfusion circuit in a sterile manner.
__Allow sufficient tubing length for standby pumping unit.
__Connect flow transducer/sensor (and disposable probe) to circuit in correct location and flow direction.
PRIME PUMP AND CIRCUIT
__CO2 flush pump and circuit, if indicated; turn off CO2.
__Gravity-prime and debubble pump and perfusion circuit.
__Check pump for leaks, irregular motion, and noise.
__Check circuit for visible air.
__Check that all tubing connections are secure.
__Clamp pump outlet line completely.
__Clamp venous return line completely.
__Calibrate transducers/sensors according to manufacturer’s instructions.
__Set low/high flow alarms.
__Verify flow alarms.
EMERGENCY BACKUP EQUIPMENT
__Backup power available..
__Hand crank available.
__Pump (and disposable probe) available.
__Control module or roller pump available.
__Achieve minimum pump speed prior to unclamping lines.
__Monitor control module for messages and alarms.
__Monitor perfusion circuit for visible air.
__Maintain minimum pump speed prior to clamping lines.
__Turn off power.
__Discard disposable components.
__Cover magnetic motor drive.
__Clean console and transducer/sensor.
__Inspect and verify that equipment is operational.
__Maintain indicated preventive maintenance schedule
__Recharge batteries to full capacity (if necessary).