Recent developments in the risk assessment of potentially genotoxic impurities in pharmaceutical drug substances

Toxicological Sciences

Volumn 100, Issue 1, 2007, Pages 24-28

  Humfrey, Charles D N ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

Genotoxic impurities; Pharmaceuticals; Qualification; Risk assessment; Threshold of toxicological concern

Indexed keywords

2,3,7,8 TETRACHLORODIBENZO PARA DIOXIN; CARCINOGEN; DRUG; EXCIPIENT; HERBACEOUS AGENT;

ARTICLE; CANCER; CANCER RISK; CARCINOGENESIS; DOSE RESPONSE; DRUG EXPOSURE; DRUG IMPURITY; DRUG INDUSTRY; DRUG MANUFACTURE; DRUG SAFETY; DRUG SCREENING; DRUG SYNTHESIS; DRUG USE; GENOTOXICITY; HUMAN; NONHUMAN; PATIENT SAFETY; QUALITY CONTROL; RISK ASSESSMENT; RISK FACTOR; TREATMENT DURATION;

ANIMALS; CONSUMER PRODUCT SAFETY; DRUG CONTAMINATION; DRUG INDUSTRY; EUROPE; EXCIPIENTS; GUIDELINES AS TOPIC; HUMANS; MUTAGENS; PHARMACEUTICAL PREPARATIONS; PLANT PREPARATIONS; QUALITY CONTROL; RISK ASSESSMENT; TOXICITY TESTS;

ANIMALIA;

EID: 35448953073     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfm173     Document Type: Article

References (16)

1. Aylward, L. L., Hays, S. M., Karch,. N. J., and Paustenbach, D. J. (1996). Relative susceptibility of animals and humans to the cancer hazard posed by 2,3,7,8-tetrachlorodibenzo-p-dioxin using internal measures of dose. Environ. Sci. Technol. 30, 3534-3543.
2. Bos, P. M. J., Baars, B.-J., and van Raaij, M. T. M. (2004). Risk assessment of peak exposure to genotoxic carcinogens: A pragmatic approach. Toxicol. Lett. 151, 43-50.
3. Calabrese, E. J., and Baldwin, L. A. (2003). Toxicology rethinks its central belief. Nature 421, 691-692.
4. EMEA. (2006). Guideline on the Limits of Genotoxic Impurities. Committee For Medicinal Products for Human Use, The European Medicines Agency, London, 2006. CPW/SWP/5199/02, EMEA/CHMP/QWP/251344/2006.
5. Gough, M. (2003). The limits of science: Dioxin. Regul. Toxicol. Pharmacol. 37, 170-171.
6. HMPC. (2006). Concept paper on the development of a guideline on the assessment of genotoxic constituents in herbal substances/preparations. Committee on Herbal Medicinal Products European Medicines Agency, EMEA/ HMPC/413271/2006.
7. Hrudey, S. E. (1998). Quantitative cancer risk assessment - Pitfalls and progress. In Risk Assessment and Risk Management (R. E. Hester and R. M. Harrison, Eds.), pp. 57-90. Royal Society of Chemistry. Issues in Environmental Science and Technology, Cambridge, UK.
8. ICH Q3A(R2). (2006). Impurities in New Drug Substances. In International Conference on Harmonisation Harmonised Tripartite Guideline. Current Step 4 version 25. Available at: http://www.ich.org/ LOB/Media/MEDIA422.pdf.
9. ICH Q3B(R2). (2006). Impurities in New Drug Products. In International Conference on Harmonisation harmonised tripartite guideline. Current Step 4 version 2. Available at: http://www.ich.org/ LOB/media./MEDIA421.pdf.
10. ICH Q3C (R3).(2005). Impurities: Guideline for Residual Solvents. In International Conference on Harmonisation harmonised tripartite guideline Current Step 4 version. Available at: http://www.ich.org/LOB/ media/MEDIA423.pdf.
11. Kroes, R., Renwick, A. G., Cheeseman, M., Kleiner, J., Mangelsdorf, I., Piersma, A., Schilter, B., Schlatter, J., van Schothorst, F., Vos, J. G., et al. (2004). Structure-based thresholds of toxicological concern (TTC): Guidance for application to substances present at low levels in the diet. Food Chem. Toxicol. 42, 65-83.
12. McGovern, T., and Jacobson-Kram, D. (2006). Regulation of genotoxic and carcinogenic impurities in drug substances and products. Trends Anal. Chem. 100(1), 681-685.
13. McKone, T. E., and Bogen, K. T. (1991). Predicting the uncertainties in risk assessment. Environ. Sci. Technol. 25(10), 1674-1681.
14. Müller, L., Mauthe, R. J., Riley, C. M., Andino, M. M., De Antonis, D., Beels, C., DeGeorge, J., De Knaep, A. G. M., Ellison, D., Fagerland, J. A., et al. (2006). A rationale for determining, testing and controlling specific impurities in pharmaceuticals that possess potential for genotoxicity. Regul. Toxicol. Pharmacol. 44, 198-211.
15. Rulis, A. M. (1986). De minimis and the threshold of regulation. In Food Protection Technology (C. W. Felix, Ed.), pp. 29-37. Lewis, Chelsea, MI.
16. Van Arnum, P. (November 3, 2006). Excipient manufacturers and pharmaceutical companies raise concerns over guidelines for genotoxic impurities. Electron. Newslett. Pharm. Technol. Available at: http://www.pharmtech.com/pharmtech/article/articleDetail.jsp?id=383814.