Dolan :
As you already said yourself : "it depends" and (to use another common phrase) "it is risk based".
By way of example : over the years, I've been involved a lot with the design and manufacture of sterile IV infusion sets. The fluid pathway materials in these sets are widely used in the industry for the build of similar kinds of devices (
e.g. "medical grade" PVC tubing and "medical grade" silicone pumping segments). The have claimed (labeled) shelf lives of typically 3-5 years.
The harshest conditions these sets get exposed to are those encountered during their sterilization, whether this is done by EthyleneOxide or by (gamma) irradiation (at a typical dose of 25kGy or slightly above). Any post-sterilization conditions ("normal" transportation and storage conditions close to "room temperature" and short duration excursions above and below) are very mild compared to the ones encountered during sterilization and thus unlikely to significantly affect materials properties, including biocompatibility, post-sterilization.
On a note : beware that testing too short after sterilizaton may also give issues in biocompatibility testing,
e.g., radiation sterilization may generate radicals or, as in the case of PVC, the formation of HCl, which may affect biocompatibility shortly after sterilization.
So, in this case, I would see no need to perform additional biocompatibility testing at the end of the claimed shelf life. (I do see the need for performance testing and physical testing,
e.g., bond strength testing, at the claimed shelf life.)
Another sterile medical device that we are currently developing (and whose fluid pathway makes indirect blood contact) makes use of a chemically active substance (an immobilized enzyme). We know that this enzyme changes over time thereby slowly resulting in loss of performance. Because of this post-sterilization chemical change, I indeed like to establish whether the device's biocompatibility could be significantly affected over its shelf life. For this purpose, I will develop a stepwise testplan and decide after each step whether additional testing is useful or wasteful.
On a note : for setting up our biocompatibiity evaluations I often call upon a US based industry veteran, now an independent consultant not affiliated with a test laboratory.
On another note : beware that the field of biocompatibility evaluations keeps evolving. The most recent step in this evolution is FDA's statement on materials used in (mostly) implantable devices (https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-and-jeff-shuren-md-director-center-devices-and-3).
With kindest regards,
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Ary Saaman
Director, Regulatory Affairs
Lausanne
Switzerland
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Original Message:
Sent: 03-May-2019 12:51
From: Dolan Mills
Subject: Biocompatibility samples
This may seem like a dumb question, or one of those "it depends", but I'm hoping to see some opinions on this topic.
Should (or must) biocompatibility samples be aged to the declared shelf life limit before testing, in order to represent the final finished device the customer may use at some point in the future?
Thanks
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Dolan Mills RAC
Principal Specialist, Regulatory Affairs
Bartlett TN
United States
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