I’m interested in hearing about experience of the application of the CPCA outside of major authorities, in particular in South America and Middle East. In particular - Do we have any indication at present for example of authorities in Argentina, Mexico
@LATAM_Community Como ha sido su experiencia en el tema de Nitrosaminas?
As in LatAm (except Brazil) there is no regulation, for the companies that proactively had come to any LatAm health authority with a nitrosamine topic (more NDSRIs impurity related, as legislations for global alerts like ranitidine, etc are already implemented), the limits that were considered at least in a first interaction were based on the Appendix 1 of EMA Q&A or FDA list, that at the end is coming from the CPCA in most of the cases.
LatAm Health Authorities take as reference mostly FDA if possible, but EMA Q&A can follow.
For Mexico I understand there was a guideline soon to be published until the CPCA came, therefore, I suppose was postponed. Nonetheless, the approach of COFEPRIS seems to be related to test all common nitrosamines instead of a risk based risk assesmment. There is an issue that under their legislation only primary standards should be used (e.g.: USP) but for NDSRIs the use of standards not pharmacopeial with characterization data from a CRO is not preferred.
For the rest of the countries, there is the awareness of the topic and what is done in EU or US should be accepted is someone comes proactively. However, a legislation itself will take several years still, the local and regional industry is not in the position to absorb the cost this topic takes, while also considering there is too much uncertainty around really how potent novel nitrosamines are. I infer this status quo will last until several major cases are detected that will make HAs to take action.
And what about CPCA in South Africa?
SAHPRA has been adopting/citing quite some elements of the EMA guidance, have they commented on CPCA (or EMA Q&A 10 options since July 2023) already?
I am participating this week in a Nitrosamines workshop with ANVISA, INCQS, and USP. We got informed today, similar to what Lucas reported last week, that the new revision of the guidelines is coming out soon.
The revisions will include, among others:
- Enhanced AMES test
- Inclusion of a list of 20 Nitrosamines AI limits
- Adoption of the CPCA framework (18ng/day is the default limit)
- Negative transgenic data will support controls via Q3A, Q3B
It would be very helpful if the agencies share already established methods by the MA holders for the NDSRIs of the drugs approved by agencies. It helps in reducing the development costs and also speeder compliance to the agencies limits. Atleast the community teams can share their progress so that they can be used by others without further extensive duplication of activities.
Fundamentally is a fantastic idea, there has been great success cases of data sharing efforts… unfortunately many organizations have the desire to have access to information but are not willing to share any of their own… we have come long way in Nitrosamines related knowledge. The large amount of published research and this community itself is an attesting of that! … some people say ‘blame lawyers’, you be the judge!
Lamentablemente con los recursos que estamos trabajando, no se pudo obtener resultados favorables en las investigaciones analíticas que realizamos. Pero gracias al intercambio de conocimientos y accesos a información que se dio con NITROSAMINES EXCHANGE, tenemos un proyecto para presentar a nuestro Directorio, con los recursos necesarios para así encarar las regulaciones que están por oficializarse.
Gracias a todos los que aportaron información, mostraron sus puntos de vista, en este tema tan delicado. Si bien nosotros no tuvimos un aporte de valor para el grupo, en cara a lo que viene y con el cumplimiento a las regulaciones, habrán muchas mejoras analíticas que se irán obteniendo, y sí, en esta etapa esperamos aportar información de utilidad para NITROSAMINES EXCHANGE
Thank you Diego, for summarizing!
I agree and my experience is in line with your statements.
In brief, for LatAm we can say EMA/FDA is followed (even guideline of Brazil makes reference). Knowing there are differences between them (e.g. some NDSRI listed by FDA are not by EMA), it can be expected for LatAm Authorities to ask to follow the “stringent” one “to be on the safe side”.
Following the question of @AndyTeasdale , my experience with Middle East is similar to LatAm.
Actualmente en Chile no ha sido adoptado CPCA por la entidad regulatoria. Al día de hoy por parte del Instituto de Salud Pública solo se encuentran regulados los medicamentos que contengan los principios activos: Valsartán, Losartán, Irbesartán, Olmesartán, Cardesartán y Telmisartán, para los que se establecen valores límite para el contenido de NDMA y NDEA.
Les comparto el enlace donde pueden revisar en detalle el documento oficial: