Wei Zhang and Frank Bieganousky
The biocompatibility and toxicological attributes of medical device packaging materials and systems should be evaluated, according to the general requirements section of ISO 11607. But if this recommendation hasn’t been enough of a reason to consider biocompatibility requirements in your evaluation plan, revisions to ISO 10993 just might be.
At MD&M Minneapolis last month, Frank Bieganousky, director of package and medical device testing at Whitehouse Labs, a division of AMRI, told the audience that ISO 10993 revisions will speak about evaluating the biocompatibility of medical device packaging for the first time. He spoke November 9 in the Center Stage presentation, “How to Prepare Your Medical Device Packaging for a Regulatory Submission.”
When it comes to biocompatibility testing, work is already being done to evaluate potential risks to patient from medical devices, Bieganousky said. What is needed now is “to look at the interaction between packaging and the device,” he said.
“Packaging may impart leachables that may affect the safety of the device,” he explained. “You must consider what comes out of the package and into the product, as well as what comes out of the product and into the package.”
As an example of why such interactions need to be evaluated, Bieganousky showed pictures of a damaged tray. “Plasticizer from the tube attacked the tray material and ate through the tray,” he said.
Data is needed to characterize potential extractables and leachables, and ISO 10993 outlines how to perform the associated risk management process, explained cospeaker Wei Zhang, Ph.D., senior research scientist on AMRI’s Extractables & Leachables and Impurities (ELI) team. The revised standard presents chemical characterization as a potential substitute for some traditional biological testing.
Potential sources of extractables and leachables include “the way a material or product is made, including use of any catalysts, additives, manufacturing residues; storage conditions and/or sterilization; use conditions such as temperature, duration, etc.; and the contact environment,” he said.
Zhang said that he is often asked why studies must look at both extractables (what could come out) and leachables (what does come out) of a material. He says that because some leachables are in quantities of parts per million or even parts per billion, with the presence of sophisticated matrix interference, “detecting these leachables is worse than looking for a needle in a haystack as if you have no idea what a needle looks like. [The extractable study] will provides a scope of possible leachables, in other words, shows what the needle looks like.”
Some E&L potential sources Zhang listed include:
- Polymer oligomers
- Polymer degradation products
- Polymer/Rubber Additives
- Acid Scavangers
- Carifying/Nucleating Agents
- Cross Linking Agents (Rubbers)
- Initiators (Rubbers)
- Accelerators (Rubbers)
- Polymer additive degradation products
- Impurities in polymer additives
- Polymer residues (e.g. monomers)
- Manufacturing impurities/residuals
“Even in trace levels, these could cause detrimental effects to human health,” Zhang said. “You need to understand not only the additives itself, but also the degradation possibilities.”
ISO 10993 highlights several “analytical techniques bolted together to offer a comprehensive view,” added Zhang. He said that a program should consider the following:
- Risk assessment and DOS (Design of Study).
- Controlled extraction study using aggressive extraction conditions to be protective of clinical use conditions.
- Simulation studies when applicable to the gap between extractables and leachable expectations.
- Leachable studies to monitor leachates with validated quantitative methods when necessary to bridge any gaps in assessment. .
Zhang advises that such a program must be “adequate and sufficiently comprehensive” to ensure protection to the patient.
For more details, contact the speakers at [email protected] or [email protected]. John Iannone, director at AMRI and U.S. Elected Expert to the ISO Technical Committee overseeing the development of the relevant ISO 10993 guidelines, can also be reached at [email protected].
AMRI will be exhibiting at Booth 351 at the upcoming MD&M West 2018 expo February 6-8 in Anaheim.