ALTERNATIVE BIOLOGICAL METHODS FOR ASSESSING THE QUALITY OF MEDICINES

Download full text PDF
DOI: https://doi.org/None
Issue: 
2
Year: 
2017

O.V. Shapovalova; N.P. Neugodova, PhD; M.S. Ryabtseva, PhD; A.A. Agashirinova; O.V. Gunar, PhD Research Center for Examination of Medical Products, Ministry of Health of the Russian Federation; 41, Sivtsev Vrazhek Lane, Moscow 119002, Russian Federation

here are many innovations that are able to reduce the number of animal experiments through the introduction of methods alternative to biological ones. The term «alternative ones» implies that the animal study is replaced in each case suitable for this experiment by a specific ex vivo test. The proposed tests (pyrogenicity test and LAL test) are unidirectional, for they identify pyrogenic impurities, but because of differences in sensitivity and specificity, they cannot be recognized as alternatives. Along with the gel-clot test, instrumental methods are introduced into the State Pharmacopoeia of the Russian Federation, 13th edition. Six modifications of the method for identifying bacterial endotoxins were provided, by including turbudimetric and chromogenic photometric techniques. A monocyte activation test that combines the advantages of both traditional test systems and even outperforms them in some positions has been recently devised to assess pyrogenicity. But it also has a number of methodological limitations. The increase in the number of available methods not only expands the range of drugs that can be tested, but also the range of pyrogens that can be detected.
Keywords: 
alternative methods
histamine
pyrogenicity
LAL test
monocytes
References: 
  1. Kacnel`son A. Mozhno li oboytis` bez opytov na zhivotnyh? BBC Future [E`lektronnyy resurs]. Rezhim dostupa: http://www.bbc.com /russian/science/2015/03/150317_vert_fut_will_we_ever_end_animal_testing.
  2. Russell W.M.S., Burch R.L. (1959). The principles of humane experimental technique. London: Methuen, reprinted 1992; 238.
  3. Karkishhenko N.N., Gracheva S.V. Rukovodstvo po laboratornym zhivotnym i al`ternativnym modelyam v biomedicinskih issledovaniyah. M.: Profil`–2S, 2010; 241.
  4. Karkishhenko N.N. Klassicheskie i al`ternativnye modeli v lekarstvennoy toksikologii. M: Biomedicina, 2006; 1 (4): 5–23.
  5. European pharmacopoeia 2, 1980.
  6. Gosudarstvennaya farmakopeya Rossiyskoy Federacii XII izd., OFS 42-0063-07.
  7. United States Pharmacopeia, 12-th., 1942.
  8. Ryabceva M.S., Batuashvili T.A., Sapozhnikova G.A., Neugodova N.P., Olefir Yu.V., Merkulov V.A. Istoriya razvitiya i sovremennoe sostoyanie biologicheskih testov v Rossii. Vedomosti Nauchnogo centra e`kspertizy sredstv medicinskogo primeneniya, 2016; 1: 11–4.
  9. Krylov Yu.F., Kivman G.Ya. Biologicheskiy kontrol` bezopasnosti lekarstvennyh sredstv. M.: Medicina; 1985.
  10. Bagirova V.L., Mit`kin O.D., Mit`kina L.I. Test na aktivaciyu monocitov kak al`ternativa testu «Pirogennost`» na krolikah. Farmaciya, 2010; 7: 40–2.
  11. Levin J., Bang F.B. The role of endotoxin in the extracellular coagulation of Limulus blood. Bull. Johns Hopkins Hosp., 1964; 115: 265–74.
  12. United States Pharmacopeia, 20-th; 1980.
  13. OFS 42-0002-00 «Bakterial`nye e`ndotoksiny».
  14. Gosudarstvennaya farmakopeya RF XII izd., 2008. OFS 42-0062-07.
  15. Gosudarstvennaya farmakopeya RF XIII izd., 2016. OFS 1.2.4.0006.15.
  16. Sitnikov A.G., Travina L.A., Bagirova V.L. LAL-test. Sovremennye podhody k opredeleniyu pirogennosti. M.:1997; 19–26.
  17. Hasiwa N., Daneshian M., Bruegger P., Fennrich S. et al. Evidence for the Detection of Non-Endotoxin Pyrogens by the Whole Blood Monocyte Activation Test. ALTEX 30: 2013; 2: 169–208.
  18. Apparao Potu, Shashidher Burra, Ajay Kumar Patil. Monocyte activation test: a new pharmacoepial quality control test for pyrogens. Journal of Advanced Pharmaceutical Sciences, 2011;1 (1): 123–31.
  19. European pharmacopoeia 8, 2014.
  20. European pharmacopoeia 9, 2016.