Methodological approaches to developing and certifying a standard human immunoglobulin sample to determine anticomplementary activity

Download full text PDF
DOI: https://doi.org/10.29296/25419218-2020-03-05
Issue: 
3
Year: 
2020

M.A. Krivykh, O.G. Kornilova, E.A. Khusnatdinova, N.D. Bunyatyan, Yu.V. Olefir Research Center for Examination of Medical Products, Ministry of Health of the Russian Federation; 8, Petrovsky Boulevard, Build. 2, Moscow 127051, Russian Federation

Introduction. The need to use standardized procedures for determining the specific safety of human immunoglobulin infusion formulations is due to the variability of critical parameters related to the use of biological reagents. Therefore, the problems with the development and certifying tests of standard samples are of particular relevance. Objective: to analyze methodological approaches to developing and certifying a standard sample to determine the anticomplementary activity of human immunoglobulin preparations. Material and methods. Standard samples of human immunoglobulin (foreign [Biological Reference Preparation (BRP) approved by the European Directorate for the Quality of Medicines and Healthcare (France)] and Russian batches) were used. Methods for systematic analysis and document examination were applied. Anticomplementary activity was determined by a method based on the ability of human immunoglobulins to bind complement, by preventing the lysis of sensitized sheep red blood cells in the complement binding reaction. Results. Comparative analysis and generalization of the experience in developing and certifying Russian and foreign standard human immunoglobulin samples for determining anticomplementary activity revealed the distinctive features of the Russian standard one. They lie in the two-component pattern and the presence of certified anticomplementary activity values for positive and negative controls, expressed as (Xmean±2Sx) with a 0.95 confidence interval, which makes it possible to use of this standard sample for confirming the stability of an analytical procedure and to evaluate possible trends to change the testing process. The advantage of the foreign standard sample of human immunoglobulin (BRP) is that several laboratories can be attracted to participate in certifying tests. Conclusion. Two approaches were identified in the methodology for the development and certifying tests of a standard human immunoglobulin sample to determine anticomplementary activity, and can also be used by the manufacturers of human immunoglobulin infusion formulations to develop and certify standard samples of their enterprise.
Keywords: 
uman immunoglobulin
anticomplementary activity
specific safety
standard samples
References: 
  1. The State Pharmacopoeia оf The Russian Federation, XIV-ed., PM.3.3.2.0008.15 «Normal human immunoglobulin for intravenous administration» [Electronic resource]. Access mode: http://femb.ru/feml (in Russian)
  2. Buchacher A., Schluga P., Mullner J. et al. Anticomplementary activity of IVIG concentrates – important assay parameters and impact of IgG polymers. Vox Sang. 2010; 98: 209–18. DOI: 10.1111/j.1423-0410.2009.01271.x
  3. State Register of Medicines [Electronic resource]. Access mode: http://grls.rosminzdrav.ru/Default.aspx [аccessed 25 July 2019] (in Russian)
  4. Determination of anticomplementary activity of immunoglobulin preparations, Methodical recommendations. MH RSFSR. Gorkiiy, 1988: 1–12 (in Russian).
  5. Sandberg E. Collaborative study for establishment of human immunoglobulin biological reference preparation (BRP). Pharmeuropa Special Issue Bio, 1996; 1: 49–69.
  6. Krivykh M.A., Kornilova O.G., Bunyatyan N.D. et al. Certification of standard samples of human immunoglobulin for determination of anticomplementary activity. Khimiko-farmatsevticheskiy zhurnal, 2016; 50 (12): 61–4 (in Russian).
  7. Bondarev V.P., Borisevich I.V., Volkova R.A. et al. Industry reference standards certification for the control of medical immunobiological preparations. Vedomosti SCEMAP. 2013; 2: 28–32. DOI: 10.30895/1991-2919-2013-0-2 (in Russian).
  8. The State Pharmacopoeia оf The Russian Federation, XIV-ed., GPM «Determination of the anticomplementary activity of human immunoglobulin-containing medicinal products for intravenous administration». [Electronic resource]. Access mode: http://femb.ru/feml (in Russian)
  9. European Pharmacopoeia 9.1, 01/2010:20617 corrected 7.6 «Test for anticomplementary activity of immunoglobulin». [Electronic resource]. Access mode: http://online6.edqm.eu/ep901/# (accessed 25 July 2019)
  10. Glantz S., Primer of Biostatistics. McGraw-Hill. New York; 1997. (Russian translation). M.: Praktika, 1999; 459 (in Russian)
  11. Sandberg E., Daas A., Esposito-Farese M.E. Collaborative study for establishment of human immunoglobulin European pharmacopoeia biological reference preparation batch 2. Pharmeuropa Special Issue Bio. 2001; 1: 27–42.
  12. Sandberg E., Behr-Gross M.-E., Daas A. Collaborative study to establish human immunoglobulin BRP batch 3 and human immunoglobulin (molecular size) BRP Batch 1. Pharmeuropa Bio. 2006; 1: 37–48.
  13. Sandberg E., Costanzo A., Daas A. et al. Calibration of the human immunoglobulin BRPs for ACA and molecular size (batch 1) and for Fc function and molecular size (batchs 1&2). Pharmeuropa Bio&SN. 2012; 1–15.
  14. Karra D., Regourd E., Costanzo A. Collaborative study for the establishment of the human immunoglobulin BRP replacement batches. Pharmeuropa Bio&Sci Notes. 2018; 3: 37–61.
  15. Kornilova O.G., Krivykh M.A., Husnatdinova E.A. et al. Contemplation of the possibility of extending the shelf life of human immunoglobulin reference standard used for determination of anticomplementary activity. BIOpreparations. Prevention, Diagnosis, Treatment. 2017; 17 (2): 110–5 (in Russian).
  16. Kornilova O.G., Khusnatdinova E.A., Konovalova E.S. et al. Evaluation of the Stability of Performance of the Analytical Test Method Used for Determination of Anticomplementary Activity of Human Immunoglobulin Preparations. BIOpreparations. Prevention, Diagnosis, Treatment. 2019; 19 (2): 118–23. DOI: 10.30895/2221-996X-2019-19-2-118-123 (in Russian).