Hi Tina,
We recently cleared a device with FDA but prior to that we received the following feedback from FDA:
1. The biocompatibility testing you submitted included acute systemic toxicity testing, but did not include material-mediated pyrogenicity testing. FDA recommends material-mediated pyrogenicity testing for sterile devices in contact directly or indirectly with the cardiovascular system to protect patients from the risk of febrile reaction. Please assess material-mediated pyrogenicity using traditional biocompatibility extraction methods. Alternatively, please provide a valid scientific rationale for omitting material-mediated pyrogenicity testing for the proposed device.
Response: The LAL testing conducted as part of each FG lot release and submitted as part of the sterility section of our 510K was not found to be sufficient. In response to FDA's requested we did complete a new test for material-mediated pyrogenicity. To allow for planning please note that the testing took about 2 weeks from sample receipt to test report receipt.
2. You have provided the results of hemolysis testing using the direct contact method intended to demonstrate that the subject device is non-hemolytic under the test conditions employed. FDA has the following concerns regarding this testing:
a) We recommend that devices in contact with circulating blood also perform elution/indirect contact hemolysis testing. Please provide the results of indirect contact hemolysis testing using the proposed Bullfrog device. Alternatively, please provide a valid scientific justification for not performing this testing on the proposed device.
Response: We completed testing using in-direct contact method. To allow for planning please note that the testing took about 2 weeks from sample receipt to test report receipt. This one was interesting as those of us that were part of the discussion in-house thought that the direct contact method would be acceptable as it is part of the 10993 series and a more stringent test. However the current FDA guidance states:
For hemolysis testing, we recommend that both direct and indirect (extract) methods be
conducted per ASTM F756,16 or an equivalent method (e.g., NIH Autian method).17,18
See page 18 section C. Hemocompatibility of FDA Guidance "Use of International Standard ISO-10993".
We also found that FDA was very critical of specific steps conducted as part of protocol execution however no additional testing was required as we were able to justify each step of our protocol. We worked directly with our test lab and they indicated that many of their customers were experiencing the same thing so they have gotten fairly comfortable providing support to the FDA requests. If you use a test lab service you may want to make sure they can provide the support you might need for any responses.
Good luck with your submission!
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Monica Barrett RAC
Dir. RA/QA
Original Message:
Sent: 05-08-2016 22:59
From: Tina O'Brien
Subject: 510(k)s & Biocompatibility
Has anyone else experienced more rigor surrounding biocompatibility expectations in 510(k) submissions from the FDA - particularly with respect previous practices in this space being no longer accepted (e.g. leveraging older 510(k) clearances for previously used materials, testing individual materials, risk assessments in lieu of testing, etc.)? We're also seeing requests for E&L testing, which we've never been asked for previously. Curious to know if this is isolated for occurring industry-wide.
Thanks for sharing!
Tina
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Tina O'Brien RAC, MS
Sr. Regulatory Affairs Specialist
Fisher & Payket Healthcare
Auckland
New Zealand
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