1. 6 Properties of API Synthesis that Affect Yield, Delivery Date & Purity–
Propinquity
Reduce costly GMP manufacture
Reduce reporting of process variation/optimization
Increase flexibility of process and sourcing
Manufacturer tendency: Less steps under cGMP
Non-GMP
GMP
SM1 + SM2
Int-1
Int-3 (RSM1)
Int-4 DS
DS Salt
SM3 + SM4
Int-2
Int-5 (RSM2)
Regulator tendency: More steps under cGMP
Minimize quality risks
Control impurities (from SM; from subsequent steps)ensure identity/purity of drug substance
Multiple purification steps more likely to purge related substances
Legends
SM : Starting Material
Int : Intermediate
RSM : Regulatory Starting Material
DS : Drug substance