Aspects of the industrial manufacture of concentrates for haemodialysis
Abstract
The import dependence of the pharmaceutical market of Ukraine on concentrates for hemodialysis determines the relevance of their manufacture. Elaboration of the transfer of drug development to industrial manufacture and, accordingly, the development of industrial technology of liquid acid concentrates for hemodialysis involves scaling the process, organization of production control, establishing critical points of the production and determining cleanliness classes for concentrates and risks, including ecological ones.
The aim of the work is to develop approaches to the development of technology for industrial manufacture of acid concentrates for hemodialysis, identification of risks in the technological process and quality control, as well as analysis of major ecological risks and development of methods for their reduction.
The object of the study was the regulatory and technical documentation regarding the requirements for hemodialysis concentrates, characterization of the hazard profile of acid concentrates as a source of pharmaceutical wastes and generalization of the information about them in the manufacture of acid concentrates. We used the results of our own experimental research on the development of concentrates. The system-survey method of research and content analysis were used in the analysis.
On the basis of researches, it was to work up the approaches to the development of technology of industrial manufacture of acid concentrates. Requirements of various normative and technical documents for water for the manufacture were generalized, classes of cleanliness of industrial premises for the preparation of containers, preparation, filtering, and packing of solutions are offered. The scheme of pharmaceutical wastes of acid concentrates, which are formed during pharmaceutical development, industrial manufacture, and medical administration, is presented. The profile of their unsafety is given. Potential and real ecological risks in the manufacture of acid concentrates for hemodialysis and ways to minimize them are presented. The proposed stages of risk management for pharmaceutical waste during the manufacture of acid concentrates of hemodialysis include: determining the hazard profile of acid concentrates for the environment; identification of risks, as well as replenishment of knowledge about the hazard profile; planning and implementation of risk minimization measures as well as evaluation of the effectiveness of these risk reduction measures. Methods for eliminating the safety of pharmaceutical wastes of acid hemodialysis concentrates (dilution with water or electrolysis to obtain by-products) have been developed.
References
Lisovyi V. M., Andonieva N. M., Lisova H. V. ta in. Khronichna nyrkova nedostatnist: metod. vkaz. dlia studentiv ta likariv-interniv. – Kharkiv: KhNMU, 2018. – 24 s.
European Pharmacopoeia, 8-th ed., Council of Europe. European Directorate for the Quality of Medicines and Health Care (EDQM). 2014: 3656.
Derzhavnyi reiestr medychnoi tekhniky ta vyrobiv medychnoho pryznachennia. – Rezhym dostupu: https://www.dls.gov.ua/print-article/?pa=335
ISO 23500-4:2019 «Preparation and quality management of fluids for haemodialysis and related therapies – Part 4: Concentrates for haemodialysis and related therapies». URL: https://www.iso.org/obp/ui/#iso:std:iso:23500:-4:ed-1:v1:en
Filipska A. M. Hudz N. I. Rozrobka metodyk kontroliu yakosti kontsentrativ dlia hemodializu / Zb. nauk. prats spivrob. NMAPO imeni P. L. Shupyka. – Kyiv, 2016. – Vyp. 25, Knyha 1. – S. 569–575.
Montanari L. B., Sartori F. G., Cardoso M. J. O. et al. Microbiological contamination of a hemodialysis center water distribution system // Rev. Inst. Med. Trop. S. Paulo. – 2009. – V. 51, N 1. – P. 37–43. https://doi.org/10.1590/S0036-46652009000100007
Nystard R. Microbiology of Water and Fluids for Hemodialysis // J. Chin. Med. Assoc. – 2008. – V. 71, N 5. – P. 223–229. https://doi:10.1016/S1726-4901(08)70110-2
ISO 23500-3:2019 «Preparation and quality management of fluids for haemodialysis and related therapies – Part 3: Water for haemodialysis and related therapies». URL: https://www.iso.org/standard/67612.html
Edalat-nejad M., Ghasemikhah R., Delavar M. Aluminum overload: still as a source of concern in hemodialysis patients // Saudi J. Kidney Diseases and Transplantation. – 2014. – V. 25, N 2. – P. 412–414. https://doi.org/10.4103/1319-2442.128602
Tsai M. H., Fang Y. W., Liou H. H. et al. Association of serum aluminum levels with mortality in patients on chronic hemodialysis // Sci. Reports. – 2018. – V. 8. – Article number: 16729. https://doi.org/10.1038/s41598-018-34799-5
Derzhavna farmakopeia Ukrainy: v 3 t. / DP «Ukrainskyi naukovo-ekspertnyi farmakopeinyi tsentr yakosti likarskykh zasobiv». 2-e vyd. – Kharkiv: DP «Ukrainskyi naukovo-ekspertnyi farmakopeinyi tsentr yakosti likarskykh zasobiv», 2015. – T. 1. – 1128 s.
Derzhavna farmakopeia Ukrainy: v 3 t. / DP «Ukrainskyi naukovo-ekspertnyi farmakopeinyi tsentr yakosti likarskykh zasobiv». 2-e vyd. – Kharkiv: DP «Ukrainskyi naukovo-ekspertnyi farmakopeinyi tsentr yakosti likarskykh zasobiv», 2014. – T. 2. – 724 s.
Nastanova «Likarski zasoby. Yakist vody dlia zastosuvannia u farmatsii ST-N MOZU 42-3.7:2013». – Kyiv, 2013. – 32 s.
Korytniuk R. S., Davtian L. L., Hudz N. I. ta in. Medychna-biolohichna funktsiia vody // Farmats. zhurn. – 2019. – № 3. – S. 65–75. https://doi.org/10.32352/0367-3057.3.19.08
Melnychuk M. D., Kliachenko O. L., Borodai V. V. Ekolohiia biolohichnykh system (ekolohiia mikroorhanizmiv): navch. posibnyk. – Vinnytsia: TOV «Nilan-LTD», 2014. – 248 s.
Koretska A. M., Hudz N. I., Dilai N. V. Do pytannia rozrobky metodyky mikrobiolohichnoi chystoty kontsentrovanykh rozchyniv dlia hemodializu / Suchasni dosiahnennia farmatsevtychnoi tekhnolohii i biotekhnolohii: mater. IV nauk.-prakt. konf. z mizhnar.uch., m. Kharkiv, 16–17 zhovtnia 2014 r. – Kharkiv, 2014. – S. 160.
Nastanova «Likarski zasoby. Nalezhna vyrobnycha praktyka. ST-N MOZU 42-4.0:2020» / Rozrob. M. Liapunov, O. Bezuhla, N. Takhtaulova, ta in. Vyd. ofits. – K.: MOZ Ukrainy, Derzhavna sluzhba likarskykh zasobiv, 2020. – 338 s.
Gosudarstvennyj nauchnyj centr lekarstvennyh sredstv (GNCLS). Goskommedbioprom. Tekhnologiya i standartizaciya lekarstvennyh sredstv. Sbornik nauchnih trudov. – Har'kov, OOO «RIREG», 1996. – 784 s.
Shevchenko V. Porivnialna kharakterystyka metodiv sterylizatsii na osnovi standartiv // PHARMATechExpo J. – 2020. – № 3–4. – S. 83–92. – Rezhym dostupu: https://uni-cert.ua/wp-content/uploads/2020/12/Journal_PHTE20_A4_UniCert.pdf
Lebedynets V. O., Kurinna M. V. Otsinka ryzykiv na etapi farmatsevtychnoi rozrobky likarskoho zasobu Indopres retard u tabletovanii formi // Upravlinnia, ekonomika ta zabezpechennia yakosti v farmatsii. – 2016. – № 4. – S. 11–20. – Rezhym dostupu: http://nbuv.gov.ua/UJRN/Uezyaf_2016_4_4
Nastanova ST-N MOZU 42-4.2:2011 «Likarski zasoby. Upravlinnia ryzykamy dlia yakosti (ICH Q9)» / Rozrob. M. Liapunov, O. Bezuhla, O. Soloviov ta in. Vyd. ofits. – K. : MOZ Ukrainy, Derzhavna sluzhba likarskykh zasobiv, 2011. – 26 s.
Mudgal S., De Toni A., Lockwood S. et al. Study on the environmental risks of medicinal products. Final Report Executive Agency for Health and Consumers 12 December 2013. – URL: https://ec.europa.eu/health/sites/default/files/files/environment/study_environment.pdf
Vovk O. O., Boichenko M. S. Prychynno-naslidkovyi analiz stanu ekolohichnoi bezpeky pid chas vyrobnytstva ta vykorystannia farmatsevtychnoi produktsii // Naukoiemni tekhnolohii. – 2017. – Т. 1, № 33. – S. 71–77. – Rezhym dostupu: http://nbuv.gov.ua/UJRN/Nt_2017_1_12
Kordero H. A., Borshchevska M. I., Borshchevskyi H. I. Zviazok farmakonahliadu likarskykh zasobiv z mozhlyvymy ryzykamy na etapakh yikhnoho zhyttievoho tsyklu // Farmats. otrasl. – 2020. – Т. 3, № 80. – S. 98–105. – Rezhym dostupu: https://promoboz.com/journal/2020/3-80-iyun/zv-yazok-farmakonaglyadu-likarskih-zasobiv-z-mozhlivimi-rizikami-na-etapah-yihnogo-zhittyevogo-tsiklu/
Agerstrand M., Berg C., Björlenius B. et al. Improving environmental risk assessment of human pharmaceuticals // Environ. Sci. Technol. – 2015. – V. 49, N 9. – P. 5336–5345. https://doi.org/10.1021/acs.est.5b00302
Kuzmyna V. A. Ekolohichna bezpeka: Konspekt lektsii. – Odesa: Vyd-vo TES, 2013. – 131 s. – Режим доступу: https://learn.ztu.edu.ua/pluginfile.php/57377/mod_resource/content/1/Ekobezpeka_%D0%BF%D1%96%D0%B4%D1%80%D1%83%D1%87%D0%BD%D0%B8%D0%BA.pdf
Berezina S. B. Ryzyk yak vazhlyvisha katehoriia ekonomichnoi teorii // Naukovyi pohliad: ekonomika ta upravlinnia. – 2018. – № 1 (59). – S. 136–146. – Rezhym dostupu: http://nbuv.gov.ua/UJRN/vamsue_2018_1_21
Veres O. M., Holysh V. M. Doslidzhennia mnozhyny ryzykiv pryiniattia rishen v haluzi ekolohii / Informatsiini systemy ta merezhi: zb. nauk. prats. – 2010. – № 2 (689). – S. 67–80. – Rezhym dostupu: http://science.lpnu.ua/uk/sisn/vsi-vypusky/vypusk-689-2010/doslidzhennya-mnozhyny-ryzykiv-pryynyattya-rishen-v-galuzi
WHO. Health-care waste. URL: https://www.who.int/news-room/fact-sheets/detail/health-care-waste
Popovych O. R., Vronska N. Yu., Yatchyshyn Yu. Y., Malovanyi M. S. Problemy utylizatsii vidkhodiv farmatsevtychnoi haluzi (ohliad) // Chemistry, Technology and Application of Substances. – 2020. – V. 3, N 1. – С. 175–183. – Rezhym dostupu: http://science.lpnu.ua/sites/default/files/journal-paper/2020/jun/21760/200290himia-maket26.pdf
Brezytska D. M., Hushchuk I. V. Problemni pytannia pry povodzhenni z medychnymy vidkhodamy v Ukraini // Visn. sotsialnoi hihiieny ta orhanizatsii okhorony zdorovia Ukrainy. – 2019. – Т. 3, № 81. – S. 44–50. https://doi.org/10.11603/1681-2786.2019.3.10591
Holtvianytska O. V. Vydalennia ta rozdilennia khlorydiv i sulfativ pry ionoobminnomu znesolenni vody // Skhidno-Yevropeiskyi zh. peredovykh tekhnolohii. – 2012. – № 1/6 (55). – S. 40–44.
Nakaz Ministerstva rehionalnoho rozvytku, budivnytstva ta zhytlovo-komunalnoho hospodarstva Ukrainy № 316 vid 01. 12. 2017 r. «Pro zatverdzhennia Pravyl pryimannia stichnykh vod do system tsentralizovanoho vodovidvedennia ta Poriadku vyznachennia rozmiru platy, shcho spravliaietsia za ponadnormatyvni skydy stichnykh vod do system tsentralizovanoho vodovidvedennia». – Rezhym dostupu: https://zakon.rada.gov.ua/laws/show/z0056-18#Text
Nakaz MOZ Ukrainy № 242 vid 24. 04. 2015 r. «Pro zatverdzhennia Pravyl utylizatsii ta znyshchennia likarskykh zasobiv». – Rezhym dostupu: https://zakon.rada.gov.ua/laws/show/z0550-15#Text
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