FDA/HESI Research Roadmap Planning on Hazard and Risk Assessment of Nitrosamine Impurities in Drugs
Day1: Wed, May 31 9:00 AM - 5:00 PM ET
Day2: Thu, Jun 1 8:30 AM - 3:45 PM ET
The goal of the workshop is to engage stakeholders with expertise in the assessment of nitrosamines (NA), including Nitrosamine Drug Substance-related Impurities (NDSRI) in order to achieve the following:
Provide a high-level synthesis of key areas/objectives of current research on NA detection and evaluation;
Identify short-term (1-2 years) research needs that can address data gaps required to improve nitrosamine (NA) risk assessments;
Identify mid-term (3-5 years) and long-term (5+ years) research needs to improve nitrosamine (NA) risk assessments;
Discuss potential opportunities and forums to realize the identified research gaps (e.g., FDA-initiated Public Private Partnership, existing or new consortial efforts, grants, private sector research efforts, etc.)
Develop a NA-research roadmap in support of an uninterrupted drug supply that is also protective of public health.
Structure-activity relationships (SAR), in silico / computational models, quantum mechanics, mode of action (MOA) studies to characterize risk, DNA repair mechanisms, in vitro to in vivo extrapolation and dose-response modelling of in vivo mutagenicity studies.
Ames testing, other in vitro mutation tests, in vivo studies, DNA adduct assessment, and metabolism (in silico, in vitro, in vivo)
That was a fantastic workshop. I couldn’t understand the whole session because it was too specialized. However, I found that toxicological discussions such as the Ames study, in vivo studies, and QSAR for NDSRIs were still ongoing. It seems to take more than one year to decide how to deal with NDSRIs.
And I want to ask you, experts, what pharmaceutical companies are doing for “call for review” in the EU, USA, and other areas. The deadline for Step 2 came in the EU, and Step 2 will finish at the beginning of October in the USA. But as far as I know, the AI for many NDSRIs is still unclear. In other words, the regulation goes faster than the investigation. What can we do in front of those unclear AIs? Are Interim AIs being established? Are the amounts of NDSRIs controlled to meet these interim AIs? I want to hear your opinion, guys.
@Yosukemino a fantastic meeting indeed. In my honest (non-texicology) opinion, the Nitrosamine safety discussion is very raw. From what I gather in the workshop, several options have been presented to the agencies for consideration so not every NDSRIs has to undergo transgenic testing. I believe the list of tests and assays presented were quite extensive and relevant in all the debate about the true potency of NDSRIs.
The recent FDA open for comments and the workshops taking place only weeks apart from each other can be perceived as the agency gathering all the information and feedback to make short and long-term decisions.
I would love to hear other opinions and perceptions from the meeting.
Good question infact @Yosukemino - I am in opinion, there could be an extension keeping in mind the pragmatic way to deal with nitrosamines.
As discussed FDA/HESI workshop triaging the nitrosamines/NDSRI’s will help to meet an extent of agency goal of Step-2.
Dear @Naiffer_Host , the workshop was fantastic! Unfortunately, I couldn’t be there in person to witness all the discussions. However, the ones I could remotely attend were incredibly enriching, which is why I’ve decided to provide a summary. Thank you and USP for the opportunity and the space to share our knowledge.