Skip to main content
SpringerLink
Log in

Subvisible Particulate Matter in Therapeutic Protein Injections

  • Published:
Pharmaceutical Chemistry Journal Aims and scope

Strategies for determining particulate matter in therapeutic protein injections, including extrinsic and intrinsic particles, are reviewed. Special attention is devoted to the advantages and limitations of various methods used for these purposes, each of which enables different particle characteristics to be determined. The source of particles (extrinsic, intrinsic, or inherent) can be understood better and particle-size distribution and other characteristics can be studied and used to differentiate them if methods based on different measurement principles are used. Protein aggregates in drugs have broad particle-size distributions, from oligomers to particles reaching hundreds of microns. The particle properties can be used to assess the risk associated with protein aggregates in the drug and to study their possible formation mechanisms. Such information could be useful during drug development and manufacturing to reduce the particulate matter content.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

Similar content being viewed by others

References

  1. J. F. Carpenter, T. W. Randolph, W. Jiskoot, et al., J. Pharm. Sci., 98(4), 1201 – 1205 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. J. G. Barnard, K. Babcock, and J. F. Carpenter, J. Pharm. Sci., 102, 915 – 928 (2013).

    Article  CAS  PubMed  Google Scholar 

  3. J. G. Barnard, S. Singh, T. W Randolph, et al., J. Pharm. Sci., 100, 492 – 503 (2011).

  4. B. S. Neha Pardeshi, Thesis for the Degree of Doctor of Philosophy, Kansas (2016).

  5. D. C. Ripple, J. R. Wayment, and M. J. Carrier, Am. Pharm. Rev., July Issue (2011); http://www.americanpharmaceuticalreview.com/FeaturedArticles/36988-Standards-for-the-Optical-Detection-of-Protein-Particles.

  6. L. O. Narhi, J. Schmit, K. Bechtold-Peters, et al., J. Pharm. Sci., 101(2), 493 – 498 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. F. Felsovalyi, S. Janvier, S. Jouffray, et al., J. Pharm. Sci., 101(12), 4569 – 4583 (2012).

    Article  CAS  PubMed  Google Scholar 

  8. M. Christie, R. M. Torres, R. M. Kedl, et al., J. Pharm. Sci., 103(1), 128 – 139 (2014).

    Article  CAS  PubMed  Google Scholar 

  9. W. Jiscoot, G. Kijanka, T. W. Randolf, et al., J. Pharm. Sci., 105(5), 1567 – 1575 (2016).

    Article  CAS  Google Scholar 

  10. M. Ahmadi, C. J. Bryson, E. A. Cloake, et al., Pharm. Res., 32(4), 1383 – 1394 (2015).

    Article  CAS  PubMed  Google Scholar 

  11. M. Jayaraman, P. M. Buck, I. A. Alphonse, et al., Eur. J. Pharm. Biopharm., 87(2), 299 – 309 (2014).

    Article  CAS  PubMed  Google Scholar 

  12. Subvisible particulate matter in therapeutic protein injections, United States Pharmacopeia, 41th Ed., 2018; http://www.uspnf.com/uspnf

  13. Measurement of subvisible particular matter in therapeutic protein injections. United States Pharmacopeia, 41st Ed., 2018; http://www.uspnf.com/uspnf

  14. GPM. 1.4.2.0005.15, Visible particulate matter in parenteral and ocular dosage forms, State Pharmacopoeia of the Russian Federation, XIIIth Ed., Vol. 2, 2015, pp. 179 – 191; http://femb.ru/feml

  15. Visible particulates in injections, United States Pharmacopeia , 41stEd., 2018; http://www.uspnf.com/uspnf

  16. European Pharmacopoeia, 9th Ed., 2017; http://online.edqm.eu/entry.htm

  17. RD-42-501-98, Instruction for monitoring particulate matter of drugs for injection, Moscow, 1998.

  18. GPM. 1.4.2.0006.15, Subvisible particulate matter in parenteral dosage forms, State Pharmacopoeia of the Russian Federation, XIIIth Ed., Vol. 2, 2015, pp. 192 – 199; http://www.femb.ru/feml

  19. Subvisible particulates in injections, United States Pharmacopeia, 41stEd., 2018; http://www.uspnf.com/uspnf

  20. E. S. Novik and O. V. Gunar, Vedom. Nauchn. Tsentra Ekspert. Sredstv Med. Primen., No. 1, 58 – 61 (2012).

  21. A. V. Dorenskaya and O. V. Gunar, Biozashchit. Biobezop., VI(2) (19), 48 – 54 (2014).

  22. A. Fradkin, Guest Blog; http://www.downstreamcolumn.com/author/afradkin/ (2017).

  23. R. N. Badwin, Diabet. Med., 5(8), 789 – 790 (1988).

    Article  Google Scholar 

  24. R. Strehl, V. Rombach-Riegraf, M. Diez, et al., Pharm. Res., 29(2), 594 – 602 (2012).

    Article  CAS  PubMed  Google Scholar 

  25. R. Thirumangalathu, S. Krishnan, M. Speed Ricci, et al., (2009); https: 10.1002 / jps.21719.

  26. K. A. Britt, D. K. Schwartz, C. Wurth, et al., J. Pharm. Sci., 101(12), 4419 – 4432 (2012).

    Article  CAS  PubMed  Google Scholar 

  27. W. Liu, R. Swift, G. Torraga, et al., J. Pharm. Sci., 64(1), 11 – 19 (2010).

    CAS  Google Scholar 

  28. A.-K. Busimi, Farm. Otrasl’, No. 5, 82 – 85 (2014).

  29. A. Hawe, 7 th Open Scientific EIP Symposium on Immunogenicity of Biopharmaceuticals, Lisbon, 2015.

  30. D. Weinbuch, S. Zolls, M. Wiggenhorn, et al., J. Pharm. Sci., 102, 2152 – 2165 (2013).

    Article  CAS  PubMed  Google Scholar 

  31. A. V. Dorenskaya and O. V. Gunar, Biozashch. Biobezop., VI(2) (19), 48 – 54 (2014).

  32. Particulate matter in ophthalmic solutions, United States Pharmacopeia, 41st Ed., 2018; http://www.uspnf.com/uspnf.

  33. Methods for determination of particulate matter in injections and ophthalmic solutions. United States Pharmacopeia, 41st Ed., 2018; http://www.uspnf.com/uspnf.

  34. Globule size distribution in lipid injectable emulsions, United States Pharmacopeia, 41st Ed., 2018; http://www.uspnf.com/uspnf.

  35. O. V. Gunar, E. S. Novik, and A. V. Dorenskaya, RU Pat. No. 2,593,779, Jul. 15, 2016.

  36. O. V. Gunar, E. S. Novik, and A. V. Dorenskaya, RU Pat. No. 2,593,019, Jul. 6, 2016.

  37. GPM. 1.2.1.0009.15. Optical microscopy, State Pharmacopoeia of the Russian Federation, XIIIth Ed., 2018; http://www.femb.ru/feml

  38. Optical microscopy. United States Pharmacopeia, 41st Ed., 2018; http://www.uspnf.com/uspnf

  39. N. N. Gavrilova, V. V. Nazarov, and O. V. Yarovaya, D. I. Mendeleev Russian Chemical Technological University, Moscow, 2012, pp. 24 – 36.

  40. Scanning electron microscopy, United States Pharmacopeia, 41st Ed., 2018; http://www.uspnf.com/uspnf

  41. A. A. Voropaev, O. F. Fadeikina, T. N. Ermolaeva, et al., Antibiot. Khimioter., 52(7 – 8), 36 – 41 (2017).

  42. S. P. Rad’ko, S. A. Khmeleva, and E. V. Suprun, Biomed. Khim., 61(2), 203 – 218 (2015).

    Article  Google Scholar 

  43. S. K. Singh, N. Afonina, M. Awwad, et al., J. Pharm. Sci., 99(8), 3302 – 3321 (2010).

    Article  CAS  PubMed  Google Scholar 

  44. S. Cao, Y. Jiang, and L. Narhi, Pharmacopeial Forum, 36(3), 824 – 834 (2010).

    Google Scholar 

  45. A. K. Tyagi, T. W. Randolph, A. Dong, et al., J. Pharm. Sci., 98(1), 94 – 104 (2009).

    Article  CAS  PubMed  Google Scholar 

  46. A. Nayak, J. Colandene, V. Bradford, et al., J. Pharm. Sci., 100(10), 4198 – 4204 (2011).

    Article  CAS  PubMed  Google Scholar 

  47. O. G. Kornilova, M. A. Krivykh, E. Yu. Kudasheva, and I. V. Borisevich, Khim.-farm. Zh., 52(5), 55 – 59 (2018); Pharm. Chem. J., 52(5), 473 – 477 (2018).

Download references

Author information

Authors and Affiliations

  1. Scientific Center for Expert Evaluation of Medicinal Products, Ministry of Health of the Russian Federation, 8/2 Petrovskii Blvd., Moscow, 127051, Russia

    E. S. Novik, A. V. Dorenskaya, N. A. Borisova & O. V. Gunar

Authors
  1. E. S. Novik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. V. Dorenskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. A. Borisova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O. V. Gunar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. S. Novik.

Additional information

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 53, No. 4, pp. 50 – 57, April, 2019.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Novik, E.S., Dorenskaya, A.V., Borisova, N.A. et al. Subvisible Particulate Matter in Therapeutic Protein Injections. Pharm Chem J 53, 353–360 (2019). https://doi.org/10.1007/s11094-019-02005-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11094-019-02005-z

Keywords

Search

Navigation