TOXICOLOGICAL EVALUATION OF ORGANIC IMPURITIES
The presence of impurities may have a negative impact on safety and efficacy of the pharmaceutical product.
Impurities in pharmaceutical products are unwanted substances without an therapeutic effect. They originate for instance from starting materials, manufacturing process or aging of the API and formulation. The presence of impurities may have a negative impact on safety and efficacy of the pharmaceutical product. Cases like the recent European Valsartan recall show also the commercial risk if impurities are not properly assessed and evaluated.
Some of the most important EU guidelines that need to be considered are:
- ICH Q3A and ICH Q3B for organic synthesis and/or degradation impurities
- ICH M7 for assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk
- ICH Q3D for Elemental Impurities
- EMA/CHMP/CVMP/QWP/199250/2009 for Antibiotic Impurities
- COMMISSION REGULATION (EU) No 10/2011
The general obligation for impurities are to identify them, apply the respective regulation, perform an toxicological assessment if necessary, assess the risk(s) and implement suitable control strategies whenever necessary. As for all GMP relevant processes a comprehensive documentation is required. A sound toxicological evaluation of impurities in combination with a professional risk assessment will give your R&D a tool to improve the manufacturing processes and your Qualified Persons a scientific tool for the decision of batch release with respect to impurities.
Our multidisciplinary expert teams design customized action plans from which you benefit by:
- To ensure that there is no risk to product safety.
- Avoid recalls or batch rejections which are more expensive than the cost of investment in proper impurity characterization and implementation of control strategies.
- The report constitutes evidence for the Health Authorities: upon delivery of the report, the responsible person details methodology and conclusions, and is available for any later question that may arise./li>