Pharmaceutical impurities are the unwanted chemicals that remain with the active pharmaceutical ingredients (APIs), and/or finished products, or dveloped during manufacturing of APIs and/or finished products.

  • The limit for total Ordinary impurities (those species in drug substances and/or drug products that have no significant, undesirable biological activity in the amounts present) is 2.0%, unless otherwise specified in the individual monograph.
  • Unless otherwise specified in an individual monograph, estimation of the amount and number of ordinary impurities is made by relative methods rather than by strict comparison to individual Reference Standards. Typical evaluation methods used for ordinary impurities are thin-layer chromatographic (TLC) techniques.
  • Any single impurity is calculated by ICH guideline Q3B (R2).
  • An impurity resulting from a chemical change in the drug substance brought about during manufacture and/or storage of the new drug product by the effect of, for example, light, temperature, pH, water, or by reaction with an excipient and/or the immediate container closure system is called degradation product.

Types of Pharmaceutical Impurities

Pharmacetical impurities can be classified into the following categories: 

  1. Organic impurities (process- and drug-related), 
  2. Inorganic impurities & Residual solvents.

  • Specified impurities generally selected from monograph or API manufacturer but calculated as per ICH guideline.
  • ICH regulation distinguishes three levels in the evaluation of impurities, the reporting threshold, the identification threshold and the qualification threshold. These thresholds are values from which the impurities must be reported, identified and qualified respectively.
  • Reporting threshold applicable for analytical method development to report the unknown peak. But FDA suggests all peak should be reported.
  • Identification threshold applicable for unknown impurity calculation. Unknown impurity calculated by retention peak.
  • Qualification threshold applicable for known impurities calculation.
  • Known impurities can be – Specified or Unspecified. Specified can also be identified or non-identified.

Thresholds for Degradation Products in New Drug Products:

Maxim Daily Dose


Reporting Thresholds

≤ 1 g


> 1 g


Identification Thresholds

< 1 mg

1.0% or 5ยตg TDI, whichever is lower

1 mg – 10 mg

0.5% or 20ยตg TDI, whichever is lower

> 10 mg – 2 g

0.2% or 2mg TDI, whichever is lower

> 2 g


Qualification Thresholds

< 10 mg

1.0% or 50ยตg TDI, whichever is lower

10 mg – 100 mg

0.5% or 200ยตg TDI, whichever is lower

> 100 mg – 2 g

0.2% or 3mg TDI, whichever is lower

> 2 g


๐‘๐Ž๐”๐๐ƒ๐ˆ๐๐† ๐‘๐”๐‹๐„ ๐…๐Ž๐‘ ๐ˆ๐Œ๐๐”๐‘๐ˆ๐“๐ˆ๐„๐’ ๐€๐’ ๐๐„๐‘ ๐ˆ๐‚๐‡ ๐3๐€ & ๐3๐:

๐‘๐š๐ฐ ๐Œ๐š๐ญ๐ž๐ซ๐ข๐š๐ฅ: Below 1.0%, the results should be reported to two decimal places (e.g., 0.06%, 0.13%); at and above 1.0%, the results should be reported to one decimal place (e.g., 1.3%).

๐…๐ข๐ง๐ข๐ฌ๐ก๐ž๐ ๐๐ซ๐จ๐๐ฎ๐œ๐ญ: Below 1.0%, the results should be reported to the number of decimal places (e.g., 0.06%) in the applicable reporting threshold; at and above 1.0%, the results should be reported to one decimal place (e.g., 1.3%).

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