1.5x instead of 2x EtO Sterilization Cycles on Biocompatibility

[Dirk S]

Hello everyone,

recently the question came up, what the impact on biocompatibility would be if instead of 2x cycles only 1.5x cycles EtO Sterilization would be performed. What would be the risk, or impact regarding biocompatibility? The question is not about 10993-7 and any residues. Rather more general. Does this have an impact on leachables/extractables? What is the impact on the material? Is an extrapolation of chemical analysis from 1.5x cycles to 2x cycles possible? What would be the impact on other endpoint testing like Cytotox, Sensitization, Irritation, etc...

Thanks for your input.
Best,
Dirk

 

[planB]

Dirk,

one of the main advantages of EtO is that it is compatible with most materials (e.g. per AAMI TIR17:2017), and adverse interaction with EtO is only occurring in some special situations. Your existing material characterisation data is key: If it already includes indication of significant adverse EtO interaction after 1.5 cycles, you will probably have to investigate exposure to two full cycles experimentally; or, you will need deep mechanistic insight into the thermodynamics and kinetics of the interaction in order to usefully mathematically extrapolate from that "single-point" 1.5x material characterisation data set.

Assuming that your data contains no indication of EtO interaction, it might be more straightforward to justify continued biocompatibility based on an "informed consideration" in line with ISO 10993-1:2018, section 6.3.2.13, accounting for

1. Your already performed material characterisation activities (including a review of published literature) would preferably show that no toxic quantities of E/L are present that can be attributed to degradation by EtO; physical material characterisation would preferably show that no physical/functional attributes have changed in-acceptably after exposure to EtO;
2. Degradation pathways driven by EtO: A typical mode of adverse EtO interaction (apart from residuals) is a chemical reaction, where a nucleophilic site is alkylated: this typically implies reactive organic species, such as active pharmaceutical ingredients (in combination products), or other active substances (e.g. in absorbable devices or "functionalised" coatings)- Do you have these types of materials in your device?

Then, paraphrasing ISO 10993-1:2018, section 6.3.2.13 (b), no further (degradation) testing would be warranted based on this informed consideration of the finished medical device composition.

HTH,

Gerhard

 

[Dirk S]

Dirk,

one of the main advantages of EtO is that it is compatible with most materials (e.g. per AAMI TIR17:2017), and adverse interaction with EtO is only occurring in some special situations. Your existing material characterisation data is key: If it already includes indication of significant adverse EtO interaction after 1.5 cycles, you will probably have to investigate exposure to two full cycles experimentally; or, you will need deep mechanistic insight into the thermodynamics and kinetics of the interaction in order to usefully mathematically extrapolate from that "single-point" 1.5x material characterisation data set.

Assuming that your data contains no indication of EtO interaction, it might be more straightforward to justify continued biocompatibility based on an "informed consideration" in line with ISO 10993-1:2018, section 6.3.2.13, accounting for

1. Your already performed material characterisation activities (including a review of published literature) would preferably show that no toxic quantities of E/L are present that can be attributed to degradation by EtO; physical material characterisation would preferably show that no physical/functional attributes have changed in-acceptably after exposure to EtO;
2. Degradation pathways driven by EtO: A typical mode of adverse EtO interaction (apart from residuals) is a chemical reaction, where a nucleophilic site is alkylated: this typically implies reactive organic species, such as active pharmaceutical ingredients (in combination products), or other active substances (e.g. in absorbable devices or "functionalised" coatings)- Do you have these types of materials in your device?

Then, paraphrasing ISO 10993-1:2018, section 6.3.2.13 (b), no further (degradation) testing would be warranted based on this informed consideration of the finished medical device composition.

HTH,

Gerhard

Thank you Gerhard for your input. Thsi is very helpful.

Best, Dirk