The real world of regulatory genotoxicity
It’s generally the case that most products exhibiting overt genotoxicity
are not submitted to FDA for approval at all, unless for life
threatening conditions or those indications where there are no
reasonable alternatives. Regulatory genotoxicity reviews may
characterize weak or inconsistently mutagenic test articles. These tests
are not easy to perform or to review. Thus, I want to call out and note
the efforts of colleagues at FDA and in the regulated industry for this
difficult work. In a sense, however, we are doing the same thing we have
done for the last 40 years, presently just doing it a little better.
Instead of detecting mutants in bacteria and mammalian cells, we can
specify which mutations and where, via ecNGS and in different cells and
systems. There is a focus on quantitative assessments, a linear
extrapolation in a 4-dimensional world. This is useful in certain
contexts, but current assessments are not likely to enlighten human risk
of a specific FDA product under review. We need a new paradigm or new
approaches to better address human risk. This may be more likely with
the advent of big data analysis, but it won’t happen unless we admit
that the present offerings aren’t sufficient.