Regulatory bodies require careful assessment and strict control of potential genotoxic impurities (PGIs) that can be found in drug substances and products or introduced 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, nitro 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 very wide range of sources throughout the manufacturing process, including starting materials, catalysts, solvents, degradation products, processing materials, production equipment, storage materials, other contaminants, and more.
Smithers will help you identify if PGIs are present and trace their origin
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.
The detailed process of determining PGIs requires careful planning and execution by experienced scientists utilizing highly sensitive instrumentation.
Smithers will work with you to develop a program of work tailored to your drug products to help you satisfy regulatory requirements related to PGIs.