In the development and production of drugs, either by synthetic means or through Bioproduction, the end goal is to achieve a relatively high yield and purity although it is never expected to be 100%. As a result, various types of Impurities are expected to be produced or introduced to the API or drug formulation. Impurities may be generated through chemical reaction and degradation during API and drug product production and storage, the result of remaining residual solvents, and contaminants. Also, the contacting materials through production and storage may introduce impurities through Extractables and Leachables. Understanding the ultimate impact in drug efficacy and through toxicological risk posed by genotoxic impurities is critical.

It is important to understand what those impurities are, and how much of them are present, so as to ensure the levels of problematic impurities do not negatively impact either product quality or safety. Regulations mandate the control of impurities and their associated levels, such as ICH Q3A – Impurities in New Drug Substances, ICH Q3B – Impurities in New Drug Products, ICH Q3C – Impurities Guideline for Residual Solvents, & ICH M7 – Assessment and control of DNA reactive impurities in pharmaceuticals to limit potential carcinogenic, or genotoxic impurities. Additionally, USP 381, USP 467, and through association USP 661, USP 1663 & USP 1664 help provide additional structure and insights towards basic requirements to satisfy when understanding impurities.

Often, impurities begin as predicted compounds that need examination, then unexpected compounds, unknown compounds, or probably identified compounds. In all of these instances, it is necessary to develop a procedure to confirm the identity of the impurities  and then develop and validate a specific method to provides quantitative measures so as to determine if the impurity type and level is acceptable. To do so, one must use high end analytical instrumentation, have the expertise to predict potential, successfully isolate targets, and using High Resolution Mass Spec along with NMR structure elucidation to identify and confirm compound ID, and corresponding levels.

Our Expertise in chemical synthesis, drug product formulation development, bioprocessing, small and large scale API manufacturing, along with analytical expertise in stability programs, release testing, structure elucidation and Extractable/Leachable determination affords us the unique opportunity to provide significant resources and probability of success in addressing your impurity needs.

Contact an expert today to better understand the right path you need to take in mitigating risk and providing solutions with Potential Genotoxic Impurities – PGI, that can impact your product.