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Updates on conducting a toxicological risk assessment of medical device extractable and leachable constituents for FDA submissions

The Food and Drug Administration recently to their recognized consensus standard database. The updated standard provides guidance on the proper conduct of toxicological risk assessments for extractable and leachable constituents identified in chemical characterization studies. 

Major changes to the standard will impact how toxicological risk assessments are performed for medical devices. 

Now that FDA has formally recognized the vast majority of the updated standard, toxicologists can begin implementing the new guidance and risk assessment approaches to support biocompatibility evaluations of medical devices in FDA regulatory submissions. 

FDA's consensus standard database lists four minor parts of the standard that the agency does not recognize alongside its rationale for partial recognition. Two of the four minor parts pertain to text errors and two are related to a position from FDA that differs from a clause or phrase in the standard.

• Table B1 in Annex B, second column, unit "g/d" is a technical error (i.e., "g/d" should be "µg/d").
• Example 5 in Clause B3 of Annex B, phrase "10 is the SF where 50 cm2 is the maximum device surface area, in cm2" has a technical error (i.e., 50 cm2 should be 500 cm2).
• Table E.2 in Clause E2 of Annex E is not supported by the normative text in Clause E2 of Annex E of this standard which states "The number of time points within an exposure period shall be sufficient to address late bolus release of the constituent(s), unless justified with supporting evidence that late bolus release will not occur."
• Phrase "e.g. the largest surface area of device which can be in contact with the body is not the same as the surface area of the device which is in contact with the solution during extraction" in the paragraph before formula E.2 of Clause E2 and in the paragraph before formula E.4 of Clause E3.1 in Annex E is in conflict with Section VI.G. of FDA's biocompatibility guidance, which states "consider the situation where a patient might receive multiple devices of the largest device size to calculate the estimated worst-case patient exposure".

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The transition period for FDA recognition of the previous version of ISO 10993-17 (First edition 2002-12-01) runs until Dec. 20, 2026, in which FDA will accept declarations of conformity in support of premarket submissions.