Process changes and biocompatibility (ISO 10993-1)

[Lorna21]

It has been proposed to change the 2-dimensional shape of a class III bioabsorbable implant. There will only be one difference in the processing of the new implant versus the old one and that is that the material from which the cutting tool is made will change from Stainless Steel (D2) to Stainless Steel (410). The implant is in contact with the cutting edge for a matter of seconds. Based on a literature review the 400 series SS is frequently used in the manufacture of surgical drilling and cutting tools. The same cleaning materials would be used so there would be no risk of new residues from processing aids being introduced.

Given cost and time restraints, I'd like to get this communities thoughts on the following options for submission of the change notification to both US and EU regulators (under MDR)

• Would the above justification be sufficient to address this change i.e. that the change does not introduce any new risks from a biocompatibility perspective because i) there is no change to the processing aids used ii) though the SS used is of a different grade, the grade used is in contact with the implant very briefly and iii) the 400 series SS is frequently used in the manufacture of surgical instruments e.g. dental drills? Based on this justification, it would be reasonable to say that no additional biocompatibility testing is required and the biocompatibility data from the original implant is sufficient to demonstrate the biological safety of the new implant?
• Would additional biocompatibility testing have to be performed to justify this process change and if so, what testing would be recommended?

 

[planB]

Lorna,

some considerations:

1) A change notification (CN) and/or submission implies that your internal change management process came to the conclusion that changing the steel material in a manufacturing equipment is _significant_.

However, your evaluation seems concludes that you have enough data at hand to demonstrate equivalence of the two steel materials without additional testing. This would provide you with an argument to justify that this change is actually _not_ significant_ and thus, does not require a CN or submission.

2) In case you come to the conclusion of additional testing, you might evaluate the potential impact of the material change ion cutting tool: Assuming that both the existing and candidate cutting tool are equally free of organic residues and particles, you might only analytically investigate potential inorganic extractables via ICP: to this end, you can either extract the candidate tool itself (worst case) or a product representative manufactured with the candidate tool. In case you detect equivalent levels of inorganics in the extracts, you could support your initial conclusion that the steel material change does not adversely affect biocompatibility of your existing product.

HTH,