Advertisement

Pharmaceutical Chemistry Journal

, Volume 49, Issue 11, pp 765–770 | Cite as

Modern Approaches to Estimating the Content of Genotoxic Impurities in Drugs (a Review)

STRUCTURE OF CHEMICAL COMPOUNDS, METHODS OF ANALYSIS AND PROCESS CONTROL

This review considered international approaches to assessment of the content of genotoxic impurities (residual solvents and various inorganic and organic impurities) in drugs. Foreign and domestic regulations defining requirements for the classification, control, and toxicological risk assessment of potential genotoxic impurities in drug substances and drugs were compared. The use of highly sensitive and specific analytical methods for detecting genotoxic impurities in drugs was justified. The need to improve the domestic regulatory framework on the control of elemental genotoxic impurities (heavy metals) and to prepare guidelines on the assessment of potentially genotoxic organic impurities in drugs was demonstrated.

Keywords

genotoxic impurities drugs threshold of toxicological concern (TTC) 

References

  1. 1.
    T. McGovern and D. Jacobson-Kram, Trends Anal. Chem., 25(8), 790 – 795 (2006).CrossRefGoogle Scholar
  2. 2.
    K. L. Dearfield, M. C. Cimino, N. E. McCarroll, et al., Mutat. Res., Genet. Toxicol. Environ. Mutagen., 521, 121 – 135 (2002).CrossRefGoogle Scholar
  3. 3.
    R. Wear and C. Sharma, Int. J. Toxicol. Pharmacol. Res., 5(1), 33 – 41 (2013).Google Scholar
  4. 4.
    A. D. Durnev and A. S. Lapitskaya, Ekol. Genet., X(3), 41 – 52 (2012).Google Scholar
  5. 5.
    Russian Federation State Pharmacopoeia, XIIth Ed., Moscow (2007).Google Scholar
  6. 6.
    European Pharmacopoeia, 7th Ed., Suppl. 8.2; URL: http://online6.edqm.eu/ep802/.
  7. 7.
    United States Pharmacopeia, 38th Ed.; URL: http://www.uspnf.com/uspnf/.
  8. 8.
    E. L. Kovaleva, Standardization of Drug Substances and Drugs in Tablet Dosage Form [in Russian], Grif i K, Moscow (2012), p. 66.Google Scholar
  9. 9.
    Guideline for Elemental Impurities Q3D ICH Harmonised Guideline; URL: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3D/ Q3D_Step_4.pdf
  10. 10.
    R. W. Kashyap, B. Mitali, S. S. Rao, et al., Pharm. Technol., 36(3), 58 – 72 (2012).Google Scholar
  11. 11.
    Impurities in New Drug Substances Q3A(R2) ICH Harmonized Tripartite Guideline; URL: http://www.ich.org/fileadmin/Public_Web Site/ICH_Products/Guidelines/Quality/Q3A_R2/Step4/Q3A_R2_Guideline.pdf
  12. 12.
    Impurities in New Drug Products Q3B(R2) ICH Harmonised Tripartite Guideline; URL: http://www.ich.org/fileadmin/Public_Web Site/ICH_Products/Guidelines/Quality/Q3B_R2/ Step4/Q3B_R2_Guideline.pdf
  13. 13.
    Guideline on the Limits of Genotoxic Impurities (EMEA/CHMP/QWP/251344/2006); URL: http://www.ema. europa.eu/docs/en_GB/document library/Scientific_guideline/2009/09/WC500002903.pdf
  14. 14.
    Impurities: Guideline for Residual Solvents, Q3C(R5) ICHHarmonised Tripartite Guideline; URL: http://www.ich.org/fileadmin/Public_Web_Site/ICH Products/Guidelines/Quality/Q3C/Step4/Q3C_R5_Step4.pdf
  15. 15.
    R. Kroes, A. G. Renwick, M. Cheeseman, et al., Food Chem. Toxicol., 42(1), 65 – 83 (2004).CrossRefPubMedGoogle Scholar
  16. 16.
    L. Muller, R. J. Mauthe, C. M. Riley, et al., Regul. Toxicol. Pharmacol., 44(3), 198 – 211 (2006).CrossRefPubMedGoogle Scholar
  17. 17.
    Press Release. European Medicines Agency, EMEA/ 275367/200; URL: http://www.ema.europa.eu/docs/en GB/document_library/Press_release/2009/11/WC500014204.pdf
  18. 18.
    D. Polyakova, Apteka.ua online, 699(28) (2009); URL: http://www.apteka.ua/article/9065
  19. 19.
  20. 20.
    Draft Guidance for Industry, Genotoxic and Carcinogenic Impurities in Drug Substances and Products: Recommended Approaches (CPMP/QWP/159/96 Cor.); URL: http://www.fda.gov/downloads/drugs/guidancecompliance regulatoryinformation/guidances/ucm079235.pdf [http://www.fda.gov/ohrms/dockets/98fr/fda-2008-d-0629-gdl.pdf]
  21. 21.
    A. V. B. Reddy, J. Jaafar, K. Umar, et al., J. Sep. Sci., 38(5), 764 – 779 (2015).CrossRefPubMedGoogle Scholar
  22. 22.
    Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk, M7 ICH Harmonised Tripartite Guideline; URL: http://www.ich.org/fileadmin/Public_Web_Site/ICH Products/Guidelines/Multidisciplinary/M7/M7_Step 4.pdf (accession date: Aug. 25, 2014).
  23. 23.
    S. V. Moiseev, V. I. Krylov, T. V. Masterkova, et al., Vedomosti NTsESMP, No. 1, 15 – 19 (2014).Google Scholar
  24. 24.
    A. A. Illarionov, L. N. Grushevskaya, L. M. Gaevaya, et al. Khim.-farm. Zh., 48(6), 48 – 53 (2014); Pharm. Chem. J., 48(6), 408 – 413 (2014).Google Scholar
  25. 25.
    D. Paul and K. Paul, World J. Pharm. Pharm. Sci., 4(2), 1124 – 1153 (2015).Google Scholar
  26. 26.
    Pharmeuropa, 26.2, 7 – 9 (2014).Google Scholar
  27. 27.
    Pharmeuropa, 26.3, 206 – 207 (2014).Google Scholar
  28. 28.
  29. 29.

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Scientific Center for Expertise of Medical ProductsMinistry of Public Health of the Russian FederationMoscowRussia

Personalised recommendations