Guidelines for genotoxic impurities, those which damage DNA and potentially cause cancer, have been formed in recent years and the International Conference on Harmonisation (ICH) is now to draft its document.
ICH M7 will “require an awful lot of commitment” from industry and authorities alike, said Andrew Teasdale, senior quality assurance executive at AstraZeneca. Teasdale was speaking at a US Pharmacopeia (USP) workshop on genotoxic impurities at AAPS 2010.
Discussion of M7 was initiated by the ICH at its steering committee meeting in Japan. Speaking days after the ICH meeting finished Teasdale highlighted areas M7 can build on US Food and Drug Administration (FDA) and European Medicines Agency (EMA) genotoxic impurity guidance.
For instance, the process of performing in silico structure-activity relationship (SAR) evaluation needs standardising, said Teasdale. There is a lack of standardisation between regulatory agencies and industry, said Teasdale, creating uncertainty in genotoxic impurity discussions.
Timothy Robinson, senior pharmacology and toxicology reviewer at the FDA, added that use of different databases can cause interpretation issues. M7 can help stakeholders by clarifying this and other areas, such as the definition of structural similarity and the use of surrogate data.
Intermediates and excipients
Gopi Vudathala, associate vice president of global regulatory affairs at Sanofi-Aventis, spoke for the US pharma industry at the workshop. Challenges for those drafting guidelines include how to apply them to oncology products, said Vudathala, and starting materials and intermediates.
Vudathala said excipients are being considered in drafting M7 but they face a number of unique issues. For instance, limit identification and testing of excipients may need a different approach. The panel also questioned the need for limits on excipients that have been used for decades.