Organic Impurities

USP 476 – Expanding Regulations on Organic Impurities

In January 2018, the United States Pharmacopeia (USP) finished receiving comments on proposed chapter <476> Control of Organic Impurities in Drug Substances and Drug Products. This chapter was developed as a part of the USP’s periodic review identifying gaps in current standards. There are several USP chapters that already provide guidance for impurities:

  • <197> Spectrophotometric Identification Tests
  • <231>, <232>, and <233> Heavy Metals/Elemental Impurities
  • <466> Ordinary Impurities
  • General chapter <1086> Impurities in Drug Substances and Drug Products

Organic ImpuritiesOne of the goals of this new chapter is to harmonize USP standards with current scientific and regulatory best practices for controlling organic impurities in drug substances and drug products (namely ICH Q3A and ICH Q3B). The concepts of reporting threshold, identification threshold, and qualification threshold have been directly adapted from ICH Q3A and ICH Q3B (with genotoxic impurity limits adapted from ICH M7). Requirements in USP <476> will align with revisions to USP <1086>. Many monographs would then reference this chapter in their organic impurities section, potentially as a tool to control “any individual unspecified impurity”.

This chapter will be of particular concern to drug substances and drug products without an approved New Drug Application (NDA) or Abbreviated New Drug Application (ANDA), notably those with no USP monograph available. The new USP <476> chapter applies specifically in cases in which:

  • A new drug substance or drug product impurity is detected above qualification/identification threshold
  • The level of a known related compound increases
  • Degradation products are observed on storage
  • An individual monograph does not have procedure for quantifying an impurity
  • No acceptance criterion is present for an observed impurity

For drug substances or drug products without specific monographs for the control of organic impurities, new manufacturer responsibilities in USP <476> include:

It can be difficult to stay up-to-date with new USP chapters and frequent changes. Fortunately, EKG Labs takes pride in keeping up-to-date with the latest USP revisions and is able to provide appropriate consulting and analytical services for companies seeking to conform to USP standards. Our team has years of experience guiding companies through the analytical portion of their product development.
Some of our services include:

To find out more about the continual USP changes and how they may impact your product development, contact EKG Labs at 810-354-5229.

About EKG Labs

EKG Labs is an analytical service provider for the pharmaceutical and medical device industries. Our analytical services support product development, regulatory filings, and analytical chemistry investigations.