Could you please let me know for any CROs that undertake the performance of TGR mutation assay?
I am also aware of the limited global availability and extended timelines to complete such assay however it seems that it is the most robust way to support a conclusion that an NDSRI is not a mutagenic rodent carcinogen, since most regulatory authorities currently accept TGR approach.
If there are any alternatives that we should consider, please advise; it would be greatly appreciated!
I understand there are 3 companies that can run this test worldwide. Not sure if I am allowed to put company names or the propietary transgenic rodent name, but 1 one supplier is from the UK, the other from Japan and the last one from the US.
Costwise perspective with all consumables, etc. included you could look at 6 mid to - high digits Euros to run the study. Maybe less or more, depending on offer and demand.
The other option is to use a Next Generation Duplex Sequency that do not need transgenic animals = less cost, etc. But currently although some colleagues could relate of its beneficts, there is no OECD guideline. Therefore, may have some regulatory reluctance for acceptance for the time being.
There are other In-vivo test, but are either too expensive and 3Rs topics (like an OECD 451) or not currently accepted at all as per ICH M7.
@Diego_HM thank you for your feedback in detail.
Indeed NGS seems as a fairly logical approach.
So I can imagine that conducting TGR is not so convenient both from cost and timelines perspective ; talking about a new NDSRI assessing by a Generic DPM.
Thank you once again and wishing you a nice day ahead
I am a chemist, not a toxicologist, but according to my knowledge the micronucleous test is more indicated to evaluate the clastogenicity rather than the mutagenicity. So, the MN test alone will not be sufficient. I do not know enough the Comet test. I do not know if Comet test alone or Comet + MN may be sufficient to the authorities to declare a NDSRI as not mutagenic impurity (NMI).
My comment means a range between 500.000 to 900.000 Euros (6 mid to high digits). Apologies for the confusion.
Regarding convenience of course it ends up if the NDSRI that you want to be assesed is in a drug product that sells high enough to justify the cost.
Nonetheless, a NGS still could costs low 6 digits amounts (e.g., 200.000 Euros). In-vivo test on GLP are expensive and you need GLP for Regulatory acceptance.
@Diego_HM thank you for your input. it is very helpful. perhaps such data, for instance the acceptable in vivo assays etc, should be part of the Q&A for Nitrosamines for clarity.
Hi folks,
The cost of a TGRA very much depends on the study design and scale e.g. how many tissues will be analysed. I don’t think it is the case that EUR 500k is the base price.
A standalone ecNGS study would be very unlikely to be accepted by a regulator but it can be bolted on to a TGRA study for additional data. That approach of course increases the apparent price of the TGRA study.
