Quick note to say that Zeneth, Lhasa Limited’s software for the prediction of forced degradation studies, has just been updated and now predicts the formation of nitrosamines when the user processes an API containing a vulnerable secondary amine alongside an excipient that is known to contain significant levels of nitrite! Do get in touch with us to learn more (firstname.lastname@example.org if you don’t already have Zeneth, or your usual Lhasa contact if you do!)
David, I already put my IT ticket to get the update! Thanks. Do you think we could coordinate training with the community members on how the tool works and how can be used in the overall risk assessment?
You probably need to connect with @fernandaw to learn more about the nitrite data sharing consortium. I’m not aware of a publication on this. Perhaps Lhasa is considering a early readout of the data sharing via a peer-reviewed article?
There’s the recent publication from the nitrites consortium, which gives selected details of the data that had been donated up to the point it was released; I think the short answer is that most do at various levels, in some cases with significant inter-batch variability…
For obvious reasons, we can’t release the full data outside the consortium; do get in touch via email@example.com if you are interested in joining!
I think the problem comes from an unrealistic approach by the authorities. While in the food industry nitrated salt is allowed. We find ourselves with autonitrosation problems with drinking water, at the ppb level.
If we don’t have a realistic vision of what risk is, I think we are wasting time while we eat frankfurkt…
Sorry to sound like an old curmudgeon, but I think it’s an unscientific drift on the part of the health authorities.
The topic also is that as for medicines, the conclusion from the health agencies is that we should not give something that generates health riks to the patience. And pragmatically speaking they are right.
Of course finding the right balance from patience safety and medicines availability is crucial, flexibility based on science is needed. But it is what it is. At the end for medicines the definitive answer will come when the technology to determine what is the formation endogenously of nitrosamines from medicines will be available (bio markers, etc.) or at least with more carcinogenic data coming for novel nitrosamines.
Regarding the food perspective the The European Food Safety Authority (EFSA) is already asking about nitrosamines risk and the use of nitrite and so on. Because most of the nitrosamines we digest comes from food. So, moving around this part is happening already.
I understand your position , which is that of the regulatory agency. But we are scientists and it makes no sense to estimate the greatest risk for the pharmaceutical industry when the citizen is exposed to higher levels from other sources.
Moreover, when there are no adequate control tools for the levels that are requested.
We must manufacture with distilled water to prevent nitrosation and when the patient dissolves his tablet in public water with 0.05 ppm NO2. It can also be an incentive to stop manufacturing certain drugs that are not going to be profitable with these specifications or leave the market unsupplied…
What food authority is on the way to self-regulation? I disagree, in the case of wine and ethanol labeling in the European Union… In short, I know it’s a losing war. A teacher of mine said that as an adult he wants to be a legislator…
I understand your frustration and share it to an extent. It is not unreasonable to imagine that a patient would take a drug product where the drug substance is a secondary amine and follow it up with cured meats or nitrite-rich vegetables. (I really wonder if at some point there will be instructions to avoid a situation like this). However, I think the intention is to control what we can control. We want to minimize nitrite content in the drug product in order to minimize nitrosamine formation over the course of the shelf life (which could be 3-5 years), and that is a meaningful goal we can try to accomplish.
It is, yes - with permission of the consortium members, we’ve added nitrite to those excipient records in Zeneth which reliably contain significant amounts thereof in the database. As a result, if a query compound matches one of the nitrosating transformations in Zeneth, and an excipient with known and significant nitrite levels is selected, the formation of a nitrosamine will be predicted.
All this is as of the latest update to Zeneth (version 9.0).