Assessment of Critical Parameters of the Cultivating Process in Biotechnology of Active Pharmaceutical Ingredients

Authors

DOI:

https://doi.org/10.20535/ibb.2018.2.2.123469

Keywords:

Biotechnology, Good manufacturing practice, Critical production stage, Fermenter, Hydrodynamics, V-blade mixer

Abstract

Background. The production of medicines of a certain quality, efficiency, and safety has never lost its relevance. Modern quality assurance and quality management systems – Good manufacturing practice – take into account the existence of critical stages and critical process parameters. The production of biological drugs by cell culture methods or using classical fermentation refers to the critical stages and they need adequate methods of validating the cultivation processes in the original fermenters and equipment to which structural changes have been made.

Objective. The aim of the study is to test the methods for evaluating the hydrodynamic situation in a fermenter with a classic mixer and a specific V-blade mixer, in model environments and on various imitation objects, and to determine the dependence of the change in hydrodynamic characteristics on the main critical parameters of the process.

Methods. The hydrodynamic situation in the fermenter is characterized by specific parameters of the flows of the existing phases. To determine the specificity of the flows, methods of visualization and a method for equalizing the tracer concentration, the homogenization time, are proposed.

Results. The visualization methods carried out during high-speed photography revealed specific flow characteristics for various mixing devices. More adequate and convenient for assessing the hydrodynamic situation in the fermenter, with changing environmental factors, was the introduction of a chemical tracer and an estimate of the homogenization time from the pH changes.

Conclusions. The possibility of using a simple and easily repeatable technique for the validation of fermentation equipment in assessing critical stages in the production of biological medicines by cell culture methods or using classical fermentation has been proved. The high efficiency of the V-blade agitator is shown in comparison with the conventional design.

References

Shybetskiy V, Semeniuk S, Kostyk S. Design of consrtuction and hydrodynamic modeling in a roller bioreactor with surface cultivation of cell cultures. ScienceRise. 2017;7:53-9. DOI: 10.15587/2313-8416.2017.107176

Zhao F, Ma T. Perfusion bioreactor system for human mesenchymal stem cell tissue engineering: Dynamic cell seeding and construct development. Biotechnol Bioeng. 2005;91(4):482-93. DOI: 10.1002/bit.20532

Chawla M, Bodnar C, Sen A, Kallos M, Behie L. Production of islet-like structures from neonatal porcine pancreatic tissue in suspension bioreactors. Biotechnol Prog. 2006;22(2):561-7. DOI: 10.1021/bp050261i

van der Velden-de Groot C. Microcarrier technology, present status and perspective. Cytotechnology. 1995 Jan;18(1-2):51-6. DOI: 10.1007/bf00744319

Arora M. Cell culture media: A Review. Mater Methods. 2013;3:175. DOI: 10.13070/mm.en.3.175

Eibl R, Eibl D, Pörtner R, Catapano G, Czermak P. Cell and tissue reaction engineering. Berlin, Heidelberg: Springer-Verlag Berlin Heidelberg; 2009.

Zakomorny D, Kytovy M, Shybetskiy V, Povodzinsky V, Kostyk S. Hydrodynamics of fermenter with multi-shaft stirrer. ScienceRise. 2016;5(2):65. DOI: 10.15587/2313-8416.2016.69451

Downloads

Published

2018-06-25

How to Cite

1.
Semeniuk S, Shybetskуу V, Povodzinskiy V, Kostyk S. Assessment of Critical Parameters of the Cultivating Process in Biotechnology of Active Pharmaceutical Ingredients. Innov Biosyst Bioeng [Internet]. 2018Jun.25 [cited 2024Nov.26];2(2):118-24. Available from: https://ibb.kpi.ua/article/view/123469

Issue

Vol. 2 No. 2 (2018)

Section

Articles

License

Copyright (c) 2018 The Authors

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

The ownership of copyright remains with the Authors.

Authors may use their own material in other publications provided that the Journal is acknowledged as the original place of publication and National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute” as the Publisher.

Authors are reminded that it is their responsibility to comply with copyright laws. It is essential to ensure that no part of the text or illustrations have appeared or are due to appear in other publications, without prior permission from the copyright holder.

IBB articles are published under Creative Commons licence:
  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under CC BY 4.0 that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.

  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.