Docket Management
Docket: 00D-1418 - Q7a ICH Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
Comment Number: EC -11

Accepted - Volume 1

Comment Record
Commentor Mr. Doug Sunday Date/Time 2000-09-29 15:57:25
Organization SST Corporation
Category Company

Recommended Changes / Reasons
Lines: 55-55
Section: 1.3
Delete the word "significant" from the guideline.
Recommended Change Type: Revise, change, add or delete words or portions of sentences. Allowing this word in the definition is problematic. It will cause materials that are, in fact, intermediates (i.e. compounds w/chiral centers or other such structural features), to be improperly defined as "API Starting Materials". We agree that "API Starting Materials" do contain structural fragments which appear in the API (this correctly distinguishes them from solvents, reagents, catalysts, etc.), but should not contain "significant" structural elements. If the structural feature were "significant", our experience indicates the appropriate Regulatory Authority asks the logical questions, "When in the synthesis did this significant structural feature first appear? How is it controlled?". The only way to answer is by showing the actual synthesis in the submission, thereby negating the molecule with the significant structural feature as the "API Starting Material". The proposed definition, taken to its extreme, would allow every final intermediate of a linear synthesis to be defined as the "API Starting Material", due to the fact it certainly contains "significant structural fragments" of the API! Hence, the more structurally significant input a molecule provides to the API, the less likely it is the "API Starting Material". Conversely, the less significant the input, the more likely it is the "API Starting Material". The only exception to the above would be use of a well-known, commercially available material such as a carbohydrate, used as a "chiral pool". In this case (and others like it) we would recommend the carbohydrate be the "API Starting Material", only because of its wide commercial availability and well-known chiral quality attributes. Since the "API Starting Material" needs no Type II DMF, and its synthesis is outside the bounds of GMP, it is critical that this definition be well composed.

EC -11