How can I establish an ADE for an early stage compound?

Here at Affygility Solutions we often get asked "How can I establish an ADE limit for a compound that is early in clinical development?" The approach that we used at Affygility Solutions is as follows:

Once an occupational exposure band (OEB) or occupational health categorization (OHC) has been assigned to the compound, we take the numerical value from the bottom of the OEB (or OHC) band and multiply by a factor of 5 to derive the acceptable daily exposure (ADE) in ug/day. While this resulting value may be conservative, it is supported in the following source:

http://www.pharmtech.com/ema-guideline-setting-health-based-exposure-limits

As well as the ISPE Risk-MaPP Baseline Guide, see below:

It should be noted, that while some companies use a factor of 10 to go from an OEL (or bottom of the OEB) to determine an estimated ADE, Affygility Solutions uses a factor of 5. This is based on the fact that we used ECHA's default adjustment factor of 5 for worker variability vs. an adjustment factor of 10 for human variability in the general population.

As indicated in the footer of the above table, this approach should only be used as an interim strategy until a formal, fully documented ADE value can be developed. In most cases, if a client has completed Phase I  or II clinical trials and has an updated IB, then there will be enough data for a fully documented ADE.

In you need an OHC assignment for your early stage compound, please contact the toxicology experts at Affygility Solutions.