What Are API Impurities? Types, Sources, and Regulatory Guidelines

Introduction

Active Pharmaceutical Ingredients (APIs) are the core components in drug formulations, but their integrity is crucially dependent on the presence (or absence) of impurities. Impurities, even in trace amounts, can affect the efficacy, safety, and shelf life of the final product. Regulatory bodies such as the ICH (International Council for Harmonisation) and the US FDA have laid down strict guidelines for the identification, qualification, and quantification of these substances.

Types of API Impurities

1. Organic Impurities: Arise during the synthetic process or as degradation products. These include:

- Starting materials or intermediates

- By-products of side reactions

- Degradation products formed during storage

2. Inorganic Impurities: Typically residual catalysts, reagents, or inorganic salts used during synthesis.

3. Residual Solvents: Classified by ICH Q3C into Class 1 (toxic, should be avoided), Class 2 (limited use), and Class 3 (low toxicity).

Regulatory Guidelines

• ICH Q3A and Q3B: Provide specifications for impurities in new drug substances and drug products.
• Qualification Thresholds: Based on daily dose and maximum allowable impurity concentration.
• Analytical Requirements: High-resolution techniques like LC-MS/MS, GC-MS, and NMR are mandated.

Janus's Role

Janus Research Chemicals supports global pharmaceutical companies by synthesizing custom impurity standards and providing impurity profiling services that meet stringent regulatory demands.