Nitrosamine in vivo mutagenicity workshop

Date: Thursday, 11 July 2024, 12:00 (CEST) - 16:00 (CEST)
Friday, 12 July 2024, 12:00 (CEST) - 15:00 (CEST)
Location: European Medicines Agency, Amsterdam, the Netherlands

EMA is hosting a nitrosamine in vivo mutagenicity workshop for international regulators.

The workshop aims to:

  • standardise the requirements for the regulatory acceptance of in vivo studies;
  • discuss if data derived using duplex sequencing can be used for setting acceptable intake limits.

On the first day of the workshop regulators will be joined by leading academic experts. On the second day pharmaceutical regulators will meet to align on study requirements and data sharing.


Issues to address:
• What is the preferred methodology to assess mutagenicity: either the current OECD 488 TGR or ecNGS.?

  • Conduct of the in vivo mutagenicity study [methodology: TGR (OECD guideline available) versus ecNGS (no OECD guideline available)],
  • Is incorporation of ecNGS into an OECD guideline needed before it can be used to derive regulatory limits for pharmaceutical impurities?
  • Selection of tissues for analysis

• How can we get to the point where we can use in vivo mutagenicity data to set a regulatory limit for pharmaceutical impurities

  • Mutagenicity as an endpoint versus carcinogenicity (HESI data)
  • Quantitative assessment of the in vivo mutagenicity data (e.g., Point of Departure?, BMD– which software, application of uncertainty factors [which factors]).
  • What are the data gaps precluding the use of in vivo mutagenicity studies in setting control limits?

This is great, finally some movement from regulators in detail about toxicological evaluations. I am eager to see the outcome of the BMD approach with mutagenicity data for carcinogenic end-points and of course the rest of the discussion!


Will be great if someone with early access to the outcome of the meeting can send few lines on some of the next steps to take and the analytical needs and implications. Thanks!