Comment from William Carter

The sentence that begins at line 108, "The active ingredient is generally not a single molecular entity...," should be moved to the beginning of a new paragraph, and perhaps modified slightly to fit that purpose. This, multiple-entity, idea is an important new topic. In addition, the introduction of the term "antibiotic-related analogs" in the text should be in a sentence that communicates the relationship of analogs to the active ingredient. The glossary definition of this term is good, but needs to be better reflected in the text to nail down FDA’s definition of, and distinctions between, active ingredient(s) and antibiotic-related analogs. Is one molecule to be selected to be the active ingredient, and then the other ones with comparable biological activity are deemed antibiotic-related analogs, or are all viewed together as, simultaneously, anti-biotic analogs that form one (single) active ingredient? Note that the answer may have implications for creating generics (or would it be biosimilars?). It is important to be precise and systematic in defining terms. Is it necessary for patent purposes to specify a particular molecule, or can it just be particular molecular features that a family of molecules can share? Either way, adding the new term "anti-biotic analog" implies the existence of a new category,*not* active ingredient, and so FDA should be clear on how to determine which is which. Finally, be careful about putting the term “active ingredient” in the plural in this paragraph. Unless FDA is intending that each “anti-biotic analog” should constitute a separate active ingredient, do not make this term plural here. Yes, drugs can combine two or more actives, but that should not be allowed to confuse issues here – if the set of a molecule and its analogs are to constitute one, single active ingredient, then the last sentence should say “these mixtures should be fully characterized to identify… in the drug substance,” singular.