Historical Perspective on the Development of the EMEA Guideline and Subsequent ICH M7 Guideline

Like many events, the exact point at which concerns relating to the potential presence of mutagenic impurities in pharmaceuticals first emerged is difficult to determine. This chapter provides an evaluation of this first draft position paper and an assessment of its later significance in the context of the finalized ICH M7 guideline. The assumption that some " in vivo " genotoxins can damage DNA at any exposure level, and therefore that any level can represent a risk, led to a conservative stance being proposed in terms of quality assessment. The lack of clear standards that would be expected of investigational products was quickly identified as a gap in the European Medicines Agency guideline. Pharmaceuticals are in the majority of cases well-characterized small molecules manufactured by well-defined chemical synthesis. The European Medicines Evaluation Agency guideline and subsequent Q&A document of course are technically related only to Europe.