We had a strong response to our survey about chemical characterization and it lead to us discussing amongst ourselves about the nature of the requirement. It was an even split 40% vs. 40% regarding people choosing to perform their characterization before any biocompatibility testing vs. performing it concurrently with their biocompatibility testing. The other 20% of responses was made up of folks who don’t do chemical characterization (not sure how they get away with not doing it) and folks who mix it into their testing plan depending on the particulars of the projects they’re working on.
If you have seen our website, the AAMI review of ISO 10993-1 has closed for comments which means the full ISO 10993-1 revision is getting close. The document says that chemical characterization should be performed first so that the toxicological risk assessment can guide the biological evaluation. The end result may be that none, some or even all of the biocompatibility end points may be excluded but there’s a big but… First, some regulatory agencies such as US FDA require both chemical characterization AND biocompatibility (either by testing or risk assessment). Second, the time required to complete all testing in sequence as per 10993-1 can be very significant (up to 1-2 years or more). The business side of this seemingly plays in a big part in the decision process since delays in submission mean delays in going to market for both sales and critical therapies reaching the patients that need them the most. The manufacturers that perform their chemical characterization in parallel with their biocompatibility testing take the approach that they’ll just address their biological evaluation endpoints with testing instead of justification and they perform their characterization for their risk assessment and master file. We don’t think that either way is necessarily wrong since each has its merits/rationales and it’s clear that manufacturers feel the same thing based upon the responses seen. Perhaps there’s a difference in responses with the big manufacturers with large preclinical/toxicology staffs or smaller or virtual firms working with consultants. Furthermore, differences could exist based upon the host country for the manufacturer or which region the submission will be made to.
We will be starting a discussion in our chemical characterization forum for the world to discuss the topic and hopefully we can help drive towards a harmonized process.
If you have seen our website, the AAMI review of ISO 10993-1 has closed for comments which means the full ISO 10993-1 revision is getting close. The document says that chemical characterization should be performed first so that the toxicological risk assessment can guide the biological evaluation. The end result may be that none, some or even all of the biocompatibility end points may be excluded but there’s a big but… First, some regulatory agencies such as US FDA require both chemical characterization AND biocompatibility (either by testing or risk assessment). Second, the time required to complete all testing in sequence as per 10993-1 can be very significant (up to 1-2 years or more). The business side of this seemingly plays in a big part in the decision process since delays in submission mean delays in going to market for both sales and critical therapies reaching the patients that need them the most. The manufacturers that perform their chemical characterization in parallel with their biocompatibility testing take the approach that they’ll just address their biological evaluation endpoints with testing instead of justification and they perform their characterization for their risk assessment and master file. We don’t think that either way is necessarily wrong since each has its merits/rationales and it’s clear that manufacturers feel the same thing based upon the responses seen. Perhaps there’s a difference in responses with the big manufacturers with large preclinical/toxicology staffs or smaller or virtual firms working with consultants. Furthermore, differences could exist based upon the host country for the manufacturer or which region the submission will be made to.
We will be starting a discussion in our chemical characterization forum for the world to discuss the topic and hopefully we can help drive towards a harmonized process.
