Regulatory Open Forum

What level of Nitrosamine risk assessment is required for an asset moving to phase 2? Recently, with end of phase 1 meeting , FDA said under additional comments that drug product should be evaluated for the potential presence of nitrosamine impurities and, if present, controlled at acceptable levels. It is not clear if the RA is expected to be summitted with phase 2 protocol. Does anyone has any experience with this?

Hello,

My experience with different regulatory agencies is that when they have a comment like that you need to provide them the information as part of the study where the comment was issued. This would mean that you have to respond to FDA request and provide the additional information within the phase 2 study. I recommend that you contact the manufacturer as they may already have this data and can provide it to you. 

Good luck with your study.

Olga

What level of Nitrosamine risk assessment is required for an asset moving to phase 2? Recently, with end of phase 1 meeting , FDA said under additional comments that drug product should be evaluated for the potential presence of nitrosamine impurities and, if present, controlled at acceptable levels. It is not clear if the RA is expected to be summitted with phase 2 protocol. Does anyone has any experience with this?

What level of Nitrosamine risk assessment is required for an asset moving to phase 2? Recently, with end of phase 1 meeting , FDA said under additional comments that drug product should be evaluated for the potential presence of nitrosamine impurities and, if present, controlled at acceptable levels. It is not clear if the RA is expected to be summitted with phase 2 protocol. Does anyone has any experience with this?

This is a requirement for the NDA. There are two FDA guidances on this - one for drug substances and one for human drugs.  Both include a section on recommended timing. 

What level of Nitrosamine risk assessment is required for an asset moving to phase 2? Recently, with end of phase 1 meeting , FDA said under additional comments that drug product should be evaluated for the potential presence of nitrosamine impurities and, if present, controlled at acceptable levels. It is not clear if the RA is expected to be summitted with phase 2 protocol. Does anyone has any experience with this?

This is a requirement for the NDA. There are two FDA guidances on this - one for drug substances and one for human drugs.  Both include a section on recommended timing. 

What level of Nitrosamine risk assessment is required for an asset moving to phase 2? Recently, with end of phase 1 meeting , FDA said under additional comments that drug product should be evaluated for the potential presence of nitrosamine impurities and, if present, controlled at acceptable levels. It is not clear if the RA is expected to be summitted with phase 2 protocol. Does anyone has any experience with this?

HI Tom,

So if I understand there is no requirement to provide any risk assessment for phase 2 asset to provide nitrosamine RA? The requirements only applicable to NDA?

This is a requirement for the NDA. There are two FDA guidances on this - one for drug substances and one for human drugs.  Both include a section on recommended timing. 

What level of Nitrosamine risk assessment is required for an asset moving to phase 2? Recently, with end of phase 1 meeting , FDA said under additional comments that drug product should be evaluated for the potential presence of nitrosamine impurities and, if present, controlled at acceptable levels. It is not clear if the RA is expected to be summitted with phase 2 protocol. Does anyone has any experience with this?

That's how I interpret the guidelines. Our program completed Phase 2 last year and Phase 3 is now ongoing and we haven't submitted anything to the IND yet and having the assessments completed in time for NDA filing.

HI Tom,

So if I understand there is no requirement to provide any risk assessment for phase 2 asset to provide nitrosamine RA? The requirements only applicable to NDA?

This is a requirement for the NDA. There are two FDA guidances on this - one for drug substances and one for human drugs.  Both include a section on recommended timing. 

What level of Nitrosamine risk assessment is required for an asset moving to phase 2? Recently, with end of phase 1 meeting , FDA said under additional comments that drug product should be evaluated for the potential presence of nitrosamine impurities and, if present, controlled at acceptable levels. It is not clear if the RA is expected to be summitted with phase 2 protocol. Does anyone has any experience with this?