Recommended Change Type: General Comments
The definition of API starting material has encouraged some marketing authorisation holders to apply to delete major portions of the synthetic route. This has occurred notwithstanding the specific statements in the Introduction that the guide is not intended to define registration/filing requirements.
The detail required to be submitted in registration dossiers is well-defined in draft 3 of the revised Note for Guidance on Chemistry of New Active Substances which states "The description of the manufacturing method must go back to a stage where the starting material is non-complex, commercially available molecule."
Unless the definition of API starting material in the GMP guide is altered, companies will use this definition to delete synthetic route details which are crucial to the assessment of the route, quality control and active substance specification.
If the definition is unaltered, it will be very difficult for the chemistry guideline to be adopted with its present, acceptable, definition of a starting material. A situation where two guidelines give different definitions for the same materials is not workable in practice.