ASSESSMENT AND CONTROL OF DNA REACTIVE (MUTAGENIC) IMPURITIES IN PHARMACEUTICALS TO LIMIT POTENTIAL CARCINOGENIC RISK
A decade after regulatory authorities began taking a systematic approach to genotoxic impurities, this ICH draft document can still not be considered mature. One positive point, however, is that attention is now focussed exclusively on DNA-reactive impurities. This opens the way for research on general and inexpensive methods for screening and quantification, and reduces the uncertainty about whether one has done enough to ensure that a product complies with regulatory requirements.
One surprising aspect is the continued exclusion of excipients and formulated products from regulatory control, although these are obvious potential sources of genotoxic impurities. This inconsistency might lead an independent observer to ask whether the underlying reason for the gentotoxic impurities initiative really is the one that is given. It would be legitimate to ask for more information, not only about the nature of the safety concerns and the difficulty of addressing them, but also of any pressures that may have contributed to shaping this regulatory document.