Potential Genotoxic Impurities

Patient safety is a top priority along every step of the pharmaceutical supply chain.

Regulatory bodies are calling for careful assessment and strict control of potential genotoxic impurities (PGIs) that can be introduced to drug substances and products during the manufacturing process. Types of PGIs include:

  • Epoxides, aldehydes, sulfonate esters, acyl halides aziridines, and hydrazines.
  • N or S mustards, Michael reactive acceptors, and halo alkenes primary halides.
  • Amino aryls, ntro compounds, purines or pyrimidines, and carbamates.

When measuring the presence of PGIs, it is crucial to determine not only the quantity but also the source. PGIs can be traced to a myriad of sources throughout the manufacturing process, including starting materials, contaminants, catalysts, solvents, processing materials, production equipment, storage materials, and more. Pinpointing the origin of the PGI enables the manufacturer to strategically adapt their methods and processes in order to prevent future challenges and ensure product quality.

The primary challenge lies in the fact that allowance thresholds for PGIs are extremely low, and such minute quantities can only be detected via specific analytical procedures. This detailed process requires precise instrumentation and careful planning and execution by experienced scientists.

The experts at Smithers Rapra have the industry knowledge and laboratory resources to develop and validate extremely precise methods and analytical procedures to help you satisfy regulatory requirements related to PGIs.