ICH Q3E Guideline: Toxicological assessment of Extractables and Leachables

Regulatory trends

A new guideline on the assessment and control of extractables and leachables (E&L) in Drugs is being proposed by the International Council for Harmonisation (ICH), and probably more clear regulatory criteria would be part of the routine of drug development projects.
Some previous guidelines were proposed, for example, by the Product Quality Research Institute (PQRI) for E&L in specific dosage forms, but there was a lack of alignment and clear guidelines among existing guidelines and standards addressing E&L in different countries.

Toxicological assessment of  Extractables and Leachables

Some advances are expected to approach criteria or principles established from other guidelines, considering previous guidelines published for other drug impurities like ICH Q3C/D/M7, and existing packaging guidelines in Europe, United States, and other countries.

Use of in silico / QSAR models, read-across, and acceptable intakes/PDE calculations based on database searches are part of the discussion; new thresholds for reporting and identifying E&L and qualifying leachables in context of route of administration, drug indication and patient exposure, with an emphasis on science-based and risk-based approaches, also, topics being discussed. 

Based on the concept paper, the guideline is proposed to achieve an appropriate level of detail to ensure it remains relevant and applicable to future innovations in the long term.

Source: https://database.ich.org/sites/default/files/ICH_Q3E_ConceptPaper_2020_0710.pdf

Access Other articles related to Drug Impurities or toxicology defined approaches published by the Altox’ team and its consultants:


dos Santos, C. E. M., Dorta, D. J., & de Oliveira, D. P. (2022). Setting limits for N-nitrosamines in drugs: A defined approach based on read-across and structure-activity relationship for N-nitrosopiperazine impurities. In Regulatory Toxicology and Pharmacology (Vol. 136, p. 105288). Elsevier BV. https://doi.org/10.1016/j.yrtph.2022.105288

Degradation products

dos Santos, C. E., de Paiva, F. C. R., Dorta, D. J., & de Oliveira, D. P. (2021). A preliminary assessment of pregabalin lactam mutagenicity and remarks on “An investigation of pregabalin lactamization process and effect of various pH on reaction: A computational insight.” In Journal of Molecular Structure (Vol. 1246, p. 131095). Elsevier BV. https://doi.org/10.1016/j.molstruc.2021.131095

Excipient impurities 

dos Santos, C.E.M., Dorta, D.J. & de Oliveira, D.P. Comment on: “Excipients in Neonatal Medicinal Products: Never Prescribed, Commonly Administered”. Pharm Med 34, 359–360 (2020). https://doi.org/10.1007/s40290-020-00357-6

AOPs and biomarkers

dos Santos, C.E.M.; Miranda, R.G.; de Oliveira, D.P.; Dorta, D.J. Challenges and Opportunities for Integrating In Silico Models and Adverse Outcomes Pathways to Set and Relate New Biomarkers. Water 202012, 3549. https://doi.org/10.3390/w12123549

Artigos Relacionados