Specialty Guidelines for Genotoxicity Genotoxic Impurities in Pharmaceuticals

SPECIALTY GUIDELINES FOR GENOTOXICITY GENOTOXIC IMPURITIES IN PHARMACEUTICALS 

In recent years, the testing and control of pharmaceuticals for the presence of geno-toxic impurities have been under regulatory scrutiny. Because of their dedicated use—in many cases chronic use—in humans, pharmaceuticals are expected to be of high purity and little batch-to-batch variability is allowed. This focus is justified compared to chemicals of other use areas, for which exposure may be dedicated but limited (e.g., cosmetics), more of an accidental type (e.g., household chemicals), or low and chronic under workplace or use conditions (e.g., pesticides, industrial chemicals). 

One may ask the following questions (I) Why do genotoxic impurities exist at all in pharmaceuticals (II) Why can t they be totally eliminated  

I The synthesis of often complex chemical structures that bear in themselves sufficient specificity and selectivity for a pharmacological action is only manageable via reactive steps of chemistry. Such reactions often involve or result in electrophilic intermediates, which may possess genotoxic activity. It is a dream of every chemist to create reaction conditions that fully create a product from its educts. This dream can hardly be put into reality. 

II Purification and control are part of the means to manage processes in a way that they can be economically reliable and result in safe products. Purification steps often result in significant loss of the product, and a balance between safety requirements and economic conditions must be found. 

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