There have been a number of papers on the subject of how to specify regulatory starting materials, with a bench marking exercise carried out by the IQ Consortium1. Now a sub-group has published a risk assessment tool to evaluate potential regulatory starting materials2, particularly in early development.
For any proposed RSM a score is built up by counting:
- The number of bond forming steps to the API.
- Number of isolated steps to the API
- % w/w of the API
- Number of stereogenic centres
- Number of substituted aryls or double bonds
- Number of rings
- Impurity carry over to the API
- Instability
An overall score is built up using the following equation:
Risk score = 4/A + 8/B + (C x 0.6) + D + E + F + G + H
if the score is <8 the risk is considered low. A score of 8-10 carries a medium risk, and a score of >10 indicates a high risk.
- M.M. Faul, W.F. Kriesman, M. Smulkowski, S. Pfeiffer , and C.A. Busacca, Org. Process. Res. Dev., 2014, 18, 587-593.
M.M. Faul, C.A. Busacca, M.C. Eriksson, F. Hicks, W.F. Kriesman, M. Smulkowski, J.D. Orr, and S. Pfeiffer, Org. Process Res. Dev., 2014, 18, 594–600;
M.M. Faul, M.D. Argentine, M. Egan, M.C. Eriksson, Z. Ge, F. Hicks, W.F. Kriesman, I. Mergelsberg, J.D. Orr, M. Smulkowski, and G.A. Wachter, Org. Process Res. Dev., 2015, 19, 915–924.
2. L. Wigman, R.S. Oestrich, S. Hildbrand, H. Iwamura, F. Gosselin, W. Göhring, F. Schwarb, and J.-P. Crochard, American Pharmaceutical Review, A New Risk Assessment Tool for Regulatory Starting Material Evaluation, posted online on March 17, 2017.
