ICH Finalizes Guidance on Elemental Impurities
Despite industry concerns that ICH’s proposed new limits on metals are too strict, the organization released final guidance on elemental impurities in finished drugs that appears little changed from an earlier draft.
The new limits — laid out in Guideline for Elemental Impurities Q3D — vary based on how the drug is administered and require more rigorous testing than the impurity limits set by the U.S. Pharmacopeia. If possible, drugmakers should assess the bioavailability of the element via the intended route of administration and compare that with the bioavailability of the element by the route with an established permitted daily exposure, ICH says.
In comments on the draft, drugmakers said it would be difficult to obtain information on metal impurities in reagents, active pharmaceutical ingredients and excipients, and argued that the guideline envisioned a level of cooperation with suppliers that would be impossible to attain (DID, Jan 21, 2014).
The ICH Steering Committee appears to acknowledge those concerns, noting that a comprehensive training program and supporting documentation will be needed to ensure the “smooth implementation of Q3D on a global basis.”
Under the final guideline, drugmakers must evaluate toxicity data for potential elemental impurities, establish PDEs for each element that raises toxicology concerns and apply a risk-based approach to control elemental impurities.
The guideline divides metals into three classes based on toxicity:
The guideline highlights ICH Q9 on quality risk management as a starting point for determining risk for elemental impurities. Risk assessments should:
Existing drugs have until September 2018 to comply with the guideline. Developers and sponsors of new drugs should follow it now.
Read the Q3D guideline at www.fdanews.com/09-10-15-impurities.pdf. — Tamra Sami
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