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CC BY 4.0 · TH Open 2023; 07(02): e128-e132
DOI: 10.1055/s-0043-1768946
DOI: 10.1055/s-0043-1768946
Review Article
Quantitative Risk Evaluation of Adventitious Agents in Heparin
Abstract
Heparin is typically extracted from domestic pigs, which may carry zoonotic adventitious agents. Prion and viral safety cannot be assured by testing the active pharmaceutical ingredient itself; instead for the evaluation of the adventitious agent (i.e., viruses/prions) safety of heparin and heparinoid (e.g., Orgaran or Sulodexide) therapeutics, a risk assessment is required. An approach is presented which provides a quantitative estimation of the worst-case potential residual adventitious agent (i.e., GC/mL or ID50) present in a maximum daily dose of heparin. This estimation is based on the input (determined by prevalence, titer, and amount of starting material to prepare a maximum daily dose) and validated reduction by the manufacturing process, resulting in an estimation of the worst-case potential level of adventitious agent present in a maximum daily dose. The merits of this quantitative, worst-case approach are evaluated. The approach described in this review provides a tool for a quantitative risk evaluation of the viral and prion safety of heparin.
Keywords
heparin - adventitious agents - viral safety - prion safety - virus reduction - prion reductionPublication History
Received: 29 December 2022
Accepted: 17 April 2023
Article published online:
21 May 2023
© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
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References
- 1 van der Meer JY, Kellenbach E, van den Bos LJ. From farm to pharma: an overview of industrial heparin manufacturing methods. Molecules 2017; 22 (06) 1025
- 2 McLEAN J. The discovery of heparin. Circulation 1959; 19 (01) 75-78
- 3 Plavsic M. An integrated approach to ensure the viral safety of biotherapeutics. Biopharm Int 2016; 29 (05) 40-45
- 4 Roush DJ. Integrated viral clearance strategies-reflecting on the present, projecting to the future. Curr Opin Biotechnol 2018; 53: 137-143
- 5 European Commission. . Health and Consumers Directorate-General. June 26, 2018 Eudralex-EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use, Manufacture of Biological active substances and Medicinal Products for Human Use, Vol. 4, Annex 2.
- 6 World Health Organization. . Recommendations for the evaluation of animal cell cultures as substrates for the manufacture of biological medicinal products and for the characterization of cell banks, Annex 3. WHO Technical Report Series, No. 978, 2013
- 7 VanderWaal K, Deen J. Global trends in infectious diseases of swine. Proc Natl Acad Sci U S A 2018; 115 (45) 11495-11500
- 8 European Food Safety Authority (EFSA). . Accessed July 29, 2022 at: https://www.efsa.europa.eu/en
- 9 The US Centers for Disease Control and Prevention (CDC). . Accessed July 29, 2022 at: https://www.cdc.gov/onehealth/basics/zoonotic-diseases.html
- 10 World Organization for Animal Health (WOAH). . Accessed July 29, 2022 at: https://www.woah.org
- 11 World Animal Health Information System. . Accessed July 29, 2022 at: https://wahis.woah.org/#/home
- 12 The EU Animal Diseases Information System (ADIS). . Accessed July 29, 2022 at: https://ec.europa.eu/food/animals/animal-diseases/animal-disease-information-system-adis_en
- 13 European Food Safety Authority (EFSA). . Accessed July 29, 2022 at: https://www.efsa.europa.eu/en/topics/topic/african-swine-fever
- 14 Opriessnig T, Huang YW. Third update on possible animal sources for human COVID-19. Xenotransplantation 2021; 28 (01) e12671
- 15 Shi J, Wen Z, Zhong G. et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science 2020; 368 (6494): 1016-1020
- 16 Schlottau K, Rissmann M, Graaf A. et al. SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: an experimental transmission study. Lancet Microbe 2020; 1 (05) e218-e225
- 17 Bonilauri P, Rugna G. Animal coronaviruses and SARS-COV-2 in animals, what do we actually know?. Life (Basel) 2021; 11 (02) 123
- 18 Maurin M, Fenollar F, Mediannikov O, Davoust B, Devaux C, Raoult D. Current status of putative animal sources of SARS-CoV-2 infection in humans: wildlife, domestic animals and pets. Microorganisms 2021; 9 (04) 868
- 19 Gerhards NM, Cornelissen JBWJ, van Keulen LJM. et al. Predictive value of precision-cut lung slices for the susceptibility of three animal species for SARS-CoV-2 and validation in a refined hamster model. Pathogens 2021; 10 (07) 824
- 20 Sikkema RS, Tobias T, Oreshkova N. et al. Experimental and field investigations of exposure, replication and transmission of SARS-CoV-2 in pigs in the Netherlands. Emerg Microbes Infect 2022; 11 (01) 91-94
- 21 World Organization for Animal Health (WOAH). . Accessed July 29, 2022 at: https://www.woah.org/en/?s=&_search=ebola
- 22 Jandik KA, Kruep D, Cartier M, Linhardt RJ. Accelerated stability studies of heparin. J Pharm Sci 1996; 85 (01) 45-51
- 23 Al-Hakim A. General considerations for diversifying heparin drug products by improving the current heparin manufacturing process and reintroducing bovine sourced heparin to the US market. Clin Appl Thromb Hemost 2021; 27: 10 760296211052293
- 24 Buckingham R. Martindale: The Complete Drug Reference. Pharmaceutical Press; 2020
- 25 Linhardt RJ, Sibel Gunay NUR. Production and chemical processing of low molecular weight heparins. Semin Thromb Hemost 1999; 25 (Suppl 3): 5-16
- 26 Vreeburg JW, Baauw A. Method for Preparation of Heparin from Mucosa. . Patent No. WO2010/110654 A1,24 March 2009
- 27 Liu W, Wei MT, Tong Y. et al. Seroprevalence and genetic characteristics of five subtypes of influenza A viruses in the Chinese pig population: a pooled data analysis. Vet J 2011; 187 (02) 200-206
- 28 Ramirez A, Wang C, Prickett JR. et al. Efficient surveillance of pig populations using oral fluids. Prev Vet Med 2012; 104 (3–4): 292-300
- 29 Drohan WN, Cervenakova L. Safety of blood products: are transmissible spongiform encephalopathies (prion diseases) a risk?. Thromb Haemost 1999; 82 (02) 486-493
- 30 World Organization for Animal Health (WOAH). . Accessed July 29, 2022 at: https://www.woah.org/en/disease/bovine-spongiform-encephalopathy
- 31 Keire D. Manufacturing heparin with equivalent chemical composition from different animal sources. Thromb Haemost 2019; 119 (05) 688
- 32 Aquino RS, Pereira MS, Vairo BC. et al. Heparins from porcine and bovine intestinal mucosa: are they similar drugs?. Thromb Haemost 2010; 103 (05) 1005-1015
- 33 European Food Safety Authority (EFSA). . Accessed July 29, 2022 at: https://www.efsa.europa.eu/en/press/news/150805
- 34 European Commission. . June 29, 2011. Minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products. EMEA/410/01 Rev. 3. Official Journal of the European Union, 5.3. 2011
- 35 Ruppach H. Log10 reduction factors in viral clearance studies. Bioprocess J 2014; 12 (04) 24-30
- 36 Ajayi O, Johnson S, Faison T. et al. An updated analysis of viral clearance unit operations for biotechnology manufacturing. Curr Res Biotechnol 2022; 4: 190-202
- 37 World Health Organization. . Guidelines on viral inactivation and removal procedures intended to assure the viral safety of human blood plasma products, Annex 4. WHO Technical Report, Series No. 924, 2004
- 38 Schielke A, Filter M, Appel B, Johne R. Thermal stability of hepatitis E virus assessed by a molecular biological approach. Virol J 2011; 8: 487
- 39 Buckow R, Isbarn S, Knorr D, Heinz V, Lehmacher A. Predictive model for inactivation of feline calicivirus, a norovirus surrogate, by heat and high hydrostatic pressure. Appl Environ Microbiol 2008; 74 (04) 1030-1038
- 40 Gröner A, Broumis C, Fang R. et al. Effective inactivation of a wide range of viruses by pasteurization. Transfusion 2018; 58 (01) 41-51
- 41 Farcet MR, Kindermann J, Modrof J, Kreil TR. Inactivation of hepatitis A variants during heat treatment (pasteurization) of human serum albumin. Transfusion 2012; 52 (01) 181-187
- 42 Nims RW, Plavsic M. Polyomavirus inactivation—a review. Biologicals 2013; 41 (02) 63-70
- 43 Turner C, Williams S, Burton C. et al. Laboratory scale inactivation of pig viruses in pig slurry and design of a pilot plant for thermal inactivation. Water Sci Technol 1998; 38 (4–5): 79-86
- 44 Aranha H, Forbes S. Viral clearance strategies for biopharmaceutical safety. Part 2: filtration for viral clearance. Pharm Technol 2001; 25 (04) 22
- 45 Cameron R, Smith K. Virus clearance methods applied in bioprocessing operations: An overview of selected inactivation and removal methods. Pharm Bioprocess 2014; 2 (01) 75-83
- 46 van Engelenburg FA, Terpstra FG, Schuitemaker H, Moorer WR. The virucidal spectrum of a high concentration alcohol mixture. J Hosp Infect 2002; 51 (02) 121-125
- 47 Harris RE, Coleman PH, Morahan PS. Stability of minute virus of mice to chemical and physical agents. Appl Microbiol 1974; 28 (03) 351-354
- 48 Block S. Disinfection, sterilization, and preservation. 5th ed. Lippincott Williams & Wilkins; 2001
- 49 Raut S, Di Giambattista M, Bevan SA, Hubbard AR, Barrowcliffe TW, Laub R. Modification of factor VIII in therapeutic concentrates after virus inactivation by solvent-detergent and pasteurisation. Thromb Haemost 1998; 80 (04) 624-631
- 50 Lin Q, Lim JYC, Xue K. et al. Sanitizing agents for virus inactivation and disinfection. VIEW 2020; 1 (02) e16