In the pharmaceutical industry, impurity may exist or develop in both API and formulation. The isolation, identification and quantification of these pharmaceutical impurities are important for pharmaceutical R&D and the regulatory requirement. The impurities present in APIs and finished products need impurity profiling to have control over quality.
ICH (the International Council for Harmonization) formulated the guidelines and classified the impurities as organic impurities, inorganic impurities, and residual solvents. Below, we provide a more in-depth look at each of these three types of pharmaceutical impurities.
Organic impurities can arise during the manufacturing process , purification, and/or storage of the new drug substance. They can be identified or unidentified, volatile or non-volatile, and include:
- Starting materials
- Degradation products
Inorganic impurities are typically detected and quantified using Pharmacopeical or other appropriate standards and may result from excipients and manufacturing process. They are normally known and identified and include:
- Heavy metals
- Residual solvents
- Catalyst trace
- Inorganic salts
- Other materials (e.g., filter aids, charcoal)
Residual Solvents are inorganic or organic liquids used as vehicles for the preparation of solutions or suspensions in the synthesis of a new drug substance. According to the ICH guidelines, solvents used in pharmaceutical manufacturing are defiend by three classes based on their toxicity:
- Class 1: Solvents are to be avoided and not be employed in manufacturing drug substances due to their unacceptable toxicity, and usage must be restricted.
- Class 2: Solvents should be limited in pharmaceutical products because of their inherent toxicity.
- Class 3: Solvents have low toxicity potential and are considered less toxic and lower risk to human health.
Class 1 should always be avoid as they are known to be human carcinogens or environmentally hazardous. Class 2 should have limited use, as some levels of harmful toxicity may be present. Class 3 solvents have low toxic potential to humans and do not need a limited.
Most of these impurities occur due to manufacturing processes, degradation, storage conditions, excipients, or contamination. Without identifying and eliminating impurities in pharmaceuticals, the quality, safety, and efficacy of drug products are put at risk.