Having a device tested for biocompatibility can involve several steps, and preparation is key.
Christopher Parker, Toxikon
The core tenets of risk management revolve around identifying all potential risks, determining their significance and creating a plan for handling each one. In device development, the risks can be tremendous and range from choices of safe materials and qualified vendors to cybersecurity.
One of those risks in device development is the assessment of a device’s biocompatibility. How a device will perform in biocompatibility evaluations — whether they be risk assessment, chemical characterization or biocompatibility testing — may vary, but are better suited for success with as much forethought as possible.
Each activity related to the biological safety of a device should be driven by a biological evaluation plan. Understanding the intended use of your device allows for proper classification to identify the correct endpoints for evaluation, explain its chemical characterization, predict how a device may perform in testing and how to handle any positive results.
The first step in any evaluation program is sample preparation. The most important considerations include:
- Special instructions for preparation.
- Determination of the surface area.
- Selection of extraction conditions.
- Will the test article be cut or tested intact.
- Does the test article degrade or absorb water?
- Ensure the preparation procedure can capture all byproducts if the test article is curing in-situ.
- Possible effects of any accessories on the physical and chemical properties of the device’s materials.
Changes to look for
In many cases, a medical device cannot be directly applied to the test system (IV dosing, for instance) and it must be incubated in various vehicles in order to create a surrogate dose. A medical device, or the extract vehicle thereof, can change during extraction. If this happens, the first and biggest thing to consider is whether the same effect can happen during clinical use. If it can, what’s the impact on device function and associated patient safety? Here are the most common post-extraction changes that are observed:
- Dissolution or degradation.
- Extract can become turbid.
- Particulate formation.
- Test article or extract color change.
- Changes in pH.
- Bilayer formation.
How to address them
If any of these items are identified as possibilities or are observed in testing, there’s a multi-step process that should be followed. First, assess why the change occurred. Then determine if it can happen in clinical use and whether it would affect patient/clinician safety as well as device performance.
For instance, if a metal clip begins to rust during a 50-degree C extraction over 72 hours, but it only touches the intact skin of a patient for less than an hour during normal use, the rusting probably won’t happen clinically and has a small impact. A study of physical changes to a device during a shorter extraction period may help with the assessment and mitigation. Here’s a list of items to consider:
- Is one of the device components a “bad actor”?
- Were the extraction conditions appropriate?
- Did the sterilization process cause an untoward material change?
- Were manufacturing aids left behind or was the device not completely clean?
- Did shipping conditions affect the device (a warm and moist vs. cool and dry environment)?Thinking about how a device may react in the different test systems, whether it’s the extraction process or being directly applied to a plate of cells can help you prepare for these situations.
Christopher Parker is associate department head of in-vivo biocompatibility at Toxikon. Since joining Toxikon in 2007, Mr. Parker has worked closely with medical device manufacturers to develop their testing programs and support their regulatory product submissions.
The opinions expressed in this blog post are the author’s only and do not necessarily reflect those of Medical Design and Outsourcing or its employees.