FDA Queries Related to Drug Substances in the CMC

There are few common queries related to drug substances in the CMC (Chemistry, Manufacturing, and Controls) section. Here’s an example:

3.2. S DRUG SUBSTANCE
3.2. S.1 General Information

3.2. S.1.1: Nomenclature Section
Queries: 1. USAN, BAN, IUPAC, names, CAS not provided until.


3.2. S.1.2: Structure Section Queries:
Stereochemistry, Isomerism structure and discussion on the drug substance used in the formulation is absent.


3.2. S.1.3: General Properties Section

Queries:

  • In the presentation, nature of drug is not discussed. Drug known to be a polymorphic in nature.
  • Polymorphism and chirality is not mentioned adequately.
  • The physical constants such as solubility in organic solvent, water, buffers at different pH values are poorly described.
  • Existence/absence of polymorphism and chirality is not discussed.
  • Particle size distribution, Hygroscopicity, granularity, flowability etc. not described in detail.
  • A description on solubility based on different pH buffers (pH 1.2, 4.6 & 6.8) not provided.
  • pKa value not included in section.


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