Without, I hope, being too ‘sales-y’, I would say that Mirabilis is exactly the solution that smaller (and larger) stakeholders need; distills a lot of expert knowledge (both from my colleagues and from @AndyTeasdale and other industry experts) about purging reactions into a software tool rather than requiring the end user to have all that knowledge to hand themselves… to the best of my knowledge the only alternative to it is to work through the purge manually, which can introduce errors (e.g. assuming something is purged more than it actually is due to read-across to inappropriate analogues) that may then call the entire set of purge calculations into question for that compound when the analysis is submitted.
Hi David ,
Thanks for sharing the article and providing a way forward by adopting a tool based solution on purge factor analysis thereby automating through a software( Mirabilis), l believe this can help industry ( small & large) a lot.
If possible please share more details about Mirabilis tool and pl help us to understand on how it estimates / predict all types nitrosamine ( listed & non-listed). Is this tool been used in API industry ? This can reduce lot of anticipated challenges and manual work.
Thanks
Hi Nitesh,
In terms of the Mirabilis software, I mainly work on the toxicity/safety side of things, i.e. Derek Nexus, rather than purge/Mirabilis - so it’s probably easiest if you (and anyone else interested) could message me your email address, since there appears to be a private message function, and I’ll put you in touch with my colleagues who can tell you more and arrange a demonstration.
Some useful reading can be found below:
Nitrosamine formation review: https://doi.org/10.1021/acs.oprd.0c00323
Theory behind Mirabilis: https://doi.org/10.1021/acs.oprd.9b00358
The use of purge for nitrosamines: https://doi.org/10.1021/acs.oprd.0c00264
David
@David thanks for sharing those resources. Do you think your collegue from ‘Purge/Mirabilis’ side would be interested to join the discussion in the community? Happy to extend the invite to them. We would like to keep the knowledge and discussion open here in the community, I’m sure ‘purge factor and assessment’ is something of interest to many here in the community.
@vcoscia have you worked with other organization that effectively utilize this kind of tools. @AndyTeasdale any recomendation on where to start with all these? Thx
Adding further to this a recent industry survey, the result of which are now published in OPR&D, showed use of Option 4 directed by Purge Calculations to be the predominant control option used and accepted for control of MIs.
Control of Mutagenic Impurities: Survey of Pharmaceutical
Company Practices and a Proposed Framework for Industry
Alignment: https://pubs.acs.org/doi/10.1021/acs.oprd.0c00517
As already illustrated in David’s comments is the paper where the use of Mirabilis to assess the risk of Nitrosamine formation is provided. By tracking through purge calculations the 2 key components for Nitrosamine formation (secondary amine + nitrosating agents) it was possible to show no risk - this being backed up by testing.
The challenge is to extend this to prediction of purging of any nitrosamine formed and work is on-going to extend this. I will be talking to the EMA quality working party about this soon.
I do work with a company that uses this software extensively. I personally have not used it for nitrosamine assessments but have seen a demo and it is a great tool for purge calculations.
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@vcoscia in your capacity as adviser to this organization, is there any other tool or resoruce that stakeholders use when performing purge calculations? I’m advocating here for some of our member that do not have access to software. Thx
Hi Naiffer,
For purge calculations I have used the approach outlined in the scientific literature by Teasdale, Burns and others. I believe this is a common approached used throughout the industry. The recent ANVISA draft guidance provides several references that can be used to perform purge calculations as part of the overall risk assessment.
Best,
Val
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