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Nonclinical safety assessment of vaccines: Up to date applications

Year 2024, , 644 - 659, 09.12.2024

Ülkü Karabay

https://doi.org/10.19161/etd.1542896

Abstract

Vaccines have a great impact on global health. These pharmaceutical products are prophylactic agents administered to healthy individuals, involving infants and children. Therefore, it is important to demonstrate the safety of them with nonclinical studies before the start of clinical trials. Nonclinical assessment includes product characterization, both in vitro and in vivo testing of vaccines, adjuvanted vaccines or vaccine adjuvants. In vivo safety studies contain pharmacology studies, pharmacokinetic studies, general toxicity studies, developmental and reproductive toxicity, genotoxicity and carcinogenicity studies, and immunogenicity assessment. These tests should be conducted in compliance with GLPs. Nonclinical studies are conducted to determine the safety and appropriate dose to induce an immune response in animal models. A benefit-to-risk profile is considered for each vaccine because of many factors that affect nonclinical and clinical toxicities. Herewith, the non-clinical safety evaluation of vaccines, including toxicity testing, has been focused. Nonclinical testing requirements are an essential tool to determination of the safety and efficacy of vaccines.

Keywords

Nonclinical safety assessment in vitro studies in vivo studies toxicity

References

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AŞILARIN KLİNİK DIŞI GÜVENLİK DEĞERLENDİRMESİ: GÜNCEL UYGULAMALAR

Year 2024, , 644 - 659, 09.12.2024

Ülkü Karabay

https://doi.org/10.19161/etd.1542896

Abstract

Aşıların küresel sağlık üzerinde büyük etkisi vardır. Bu farmasötik ürünler, bebekleri ve çocukları da kapsayan sağlıklı bireylere uygulanan profilaktik ajanlardır. Bu nedenle klinik araştırmalara başlanmadan önce bunların güvenliğinin klinik öncesi çalışmalarla ortaya konması önemlidir. Klinik dışı değerlendirme, aşıların, adjuvanlanmış aşıların veya aşı adjuvanlarının hem in vitro hem de in vivo testlerini içeren ürün karakterizasyonunu içerir. İn vivo güvenlik çalışmaları farmakoloji çalışmalarını, farmakokinetik çalışmaları, genel toksisite çalışmalarını, gelişimsel ve üreme toksisitesini, genotoksisite ve karsinojenisite çalışmalarını ve immünojenisite değerlendirmesini kapsar. Bu testler İLU'ya uygun olarak yapılmalıdır. Hayvan modellerinde immün tepkiyi tetiklemek için güvenliği ve uygun dozu belirlemek amacıyla klinik dışı çalışmalar yürütülmektedir. Klinik dışı ve klinik toksisiteleri etkileyen birçok faktör nedeniyle her aşı için bir fayda-risk profili dikkate alınır. Bu derlemede aşıların toksisite testleri de dahil olmak üzere klinik dışı güvenlik değerlendirmesine odaklanılmıştır. Klinik dışı test gereklilikleri, aşıların güvenliğinin ve etkinliğinin belirlenmesinde önemli bir araçtır.

Keywords

Klinik dışı güvenlik değerlendirmesi in vitro çalışmalar in vivo çalışmalar toksisite

References

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  • Van der Laan JW, Forster R, Ledwith B, Gruber M, Gould S, Segal L, Penninks A. Nonclinical testing of vaccines: Report from a workshop. Drug Information Journal 2009; 43: 97–107.
  • Nascimento IP, Leite LCC. Recombinant vaccines and the development of new vaccine strategies, Braz J Med Biol Res 2012; 45(12): 1102–1111.
  • Novicki DL, Wolf JJ, Plitnick LM, Hartsough M. Vaccines: Preventive and Therapeutic Product Studies, Chapter 25, in the “The Role of the Study Director in Nonclinical Studies Pharmaceuticals, Chemicals, Medical Devices, and Pesticides” 1st Edition, Ed by William J. Brock, Barbara Mounho and Lijie Fu. John Wiley & Sons, Inc. 2014; 439.
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  • FDA-CBER US Food and Drug Administration: Points to Consider in the Production and Testing of New Drugs and Biologicals Produced by Recombinant DNA Technology, 1985.
  • Glick BR, Pasternak JJ, Patten CL. Molecular Biotechnology: Principles and Applications of Recombinant DNA, ASM Press. 2010.
  • Forster R. Study designs for the nonclinical safety testing of new vaccine products. Journal of Pharmacological and Toxicological Methods 2012; 66: 1–7.
  • Khan KH. DNA vaccines: roles against diseases. Germs 2013; 3(1): 26-33.
  • Da Silva FT, Di Pasquale A, Yarzabal JP, Garçon N. Safety assessment of adjuvanted vaccines: Methodological considerations, Hum Vaccin Immunother. 2015; 11(7): 1814–1824.
  • Di Pasquale A, Bonanni P, Garçon N, Stanberry LR., El-Hodhod M, Da Silva FT. Vaccine safety evaluation: Practical aspects in assessing benefits and risks. Vaccine 2016; 34: 6672–6680.
  • Di Pasquale A, Preiss S, Da Silva FT, Garçon N. Vaccine Adjuvants: from 1920 to 2015 and beyond. Vaccines (Basel). 2015; 3(2): 320–343.
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  • Han S. Clinical vaccine development, Clin Exp Vaccine Res 2015; 4(1): 46–53.
  • Cunningham AL, Garçon N, Leo O, Friedland LR, Strugnell R, Laupèze B, Doherty M, Stern P. Vaccine development: From concept to early clinical testing. Vaccine 2016; (34): 6655–6664.
  • OECD Principles on Good Laboratory Practice, Organization for Economic Co-operation and Development, Paris, 1998. ENV/MC/CHEM (98)17.
  • WHO Vaccine Supply and Quality Unit. Manual of laboratory methods for testing of vaccines used in the WHO Expanded Programme on Immunization. ‎1997‎. https://iris.who.int/handle/10665/63576
  • WHO Laboratory Biosafety Manual. 4th edition: Biosafety programme management World Health Organization, Geneva, Switzerland. 2020.
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  • Shanks N, Greek R, Greek J. Are animal models predictive for humans? Philos Ethics Humanit Med 2009; 4: 2.
  • Dey AK, Malyala P, Singh M. Physicochemical and functional characterization of vaccine antigens and adjuvants, Journal Expert Review of Vaccines 2014; 13(5): 671-685.
  • WHO Guidelines for Independent Lot Release of Vaccines by Regulatory Authorities. WHO Expert Committee on Biological Standardization, Sixty-first Report 2013a (WHO Technical Report Series, No. 978, Annex 2, 2014)
  • WHO Guidelines on the nonclinical evaluation of vaccine adjuvants and adjuvanted vaccines, 2013b (WHO Technical Report Series, TRS 987, Annex 2, 2014)
  • ICH Q6B Guidance, Specifications: Test Procedures and Acceptance Criteria for Biotechnological/ Biological Products, 1999. EMEA, European Agency for the Evaluation of Medicinal Products. CPMP/ICH/365/96.
  • Rodríguez-Ortega MJ, Norais N, Bensi G, Liberatori S, Capo S, Mora M, Scarselli M, Doro F, Ferrari G, Garaguso I, Maggi T, Neumann A, Covre A, Telford JL, Grandi G. Characterization and identification of vaccine candidate proteins through analysis of the group A Streptococcus surface proteome, Nature Biotechnology 2006; 24: 191–197.
  • Becht S, Ding X, Gu X. Vaccine Characterization Using Advanced Technology. Mass spectrometry offers the potential for an unprecedented understanding of vaccines and why they fail. BioPharm International 2007; 2007 (Suppl 5): 40–45. http://www.genalysis.com.au/pharmaceutical/vaccine/viral/
  • Mason PW, Shustov AV, Frolova I. Production and characterization of vaccines based on flaviviruses defective in replication, Virology. 2006; 351(2): 432–443.
  • WHO Guidelines on stability evaluation of vaccines, WHO Expert Committee on Biological Standardization Fifty-seventh report. 2006. (WHO Technical Report Series TRS 962. Annex 3) WHO/BS/06.2049.
  • Dumpa N, Goel K, Guo Y, McFall H, Pillai AR, Shukla A, Repka MA, Murthy SN. Stability of Vaccines. AAPS Pharm Sci Tech 2019; 20(2):42.
  • Knezevic I. Stability evaluation of vaccines: WHO approach. Biologicals 2009;37(6):357-9; discussion 421-3. doi: 10.1016/j.biologicals.2009.08.004.
  • Schofield T, Krause PR. Stability evaluation of vaccines. Biologicals 2009;37(6):355. doi: 10.1016/j.biologicals.2009.09.001.
  • Galazka A., Milstien J., Zaffran M. Thermostability of vaccines, World Health Organization Global Programme for Vaccines and Immunization 1998.
  • Code of Federal Regulations, Title 21, sec 600 (21 CFR 600) Biological products: general provisions. Washington, DCUS Government Printing Office. 2024.
  • McVey DS, Galvin JE, Olson SC. A review of the effectiveness of vaccine potency control testing. Int J Parasitol 2003; 33(5-6):507-16.
  • Taffs RE. Potency Tests of Combination Vaccines. Clinical Infectious Diseases 2001; 33(Suppl 4): S362–S366.
  • ICH S7A Harmonised Tripartite Guideline, Safety Pharmacology Studies for Human Pharmaceuticals. International Conference on Harmonization, Geneva, Switzerland, 2001. CPMP/ICH/539/00
  • Arrigoni C, Perego V. Chapter 5 Safety Pharmacology; In Pharmaceutical Toxicology in Practice: A Guide for Non-Clinical Development. Editor(s): Alberto Lodola, Jeanne Stadler. 2011. doi: 10.1002/9780470909911.ch5
  • ICH M3(R2) Harmonised Tripartite Guideline, Guidance on Nonclinical Safety Studies for The Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals. International Conference on Harmonization, Geneva, Switzerland, 2009.
  • Wolf JJ. 11.38 - Immunopharmacology and Immunotoxicology Assessment of Vaccines and Adjuvants. Reference Module in Biomedical Sciences. Comprehensive Toxicology (Third Edition) 11: 852-872. Zaitseva M, Romantseva T, Blinova K, Beren J, Sirota L, Drane D, Golding H. (2012) Use of human MonoMac6 cells for development of in vitro assay predictive of adjuvant safety in vivo. Vaccine, 2018; 30:4859–4865.
  • Klug B, Celis P, Ruepp R, Robertson JS. EU regulatory guidelines for the clinical evaluation of adjuvants. Clinical Res Regulatory Affairs 2015; 32(2):55-60. doi: 10.3109/10601333.2015.1001899.
  • Note for guidance on Preclinical pharmacological and toxicological testing of vaccines, 1997. EMEA, European Agency for the Evaluation of Medicinal Products. EMA/CPMP/SWP/465/95.
  • Vladimir O, Zuzana K, Štefkovičová M. How Do We Evaluate and Manage Many Different Vaccination Schedules in the EU? Cent Eur J Public Health 2015; 23(3):218-22.
  • Granath B. Development of immunogenicity models in mice for improved risk assessment of biopharmaceuticals. University of Gothenburg, 2013.
  • Gómez‐Mantilla JD, Trocóniz IF, Garrido MJ. ADME Processes in Vaccines and PK/PD Approaches for Vaccination Optimization, Pharmaceutical Sciences Encyclopedia: Drug Discovery, Development, and Manufacturing, 2015.
  • Guideline on dossier structure and content for pandemic influenza vaccine marketing authorization application, 2008b. EMEA, European Agency for the Evaluation of Medicinal Products.
  • Sun Y, Gruber M, Matsumoto M. Overview of global regulatory toxicology requirements for vaccines and adjuvants. J Pharmacol Toxicol Methods 2012; 65(2), 49-57.
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Details

Primary Language English
Subjects One Health
Journal Section Reviews
Authors

Ülkü Karabay 0000-0002-7483-0184

Publication Date December 9, 2024
Submission Date September 3, 2024
Acceptance Date November 1, 2024
Published in Issue Year 2024

Cite

Vancouver Karabay Ü. Nonclinical safety assessment of vaccines: Up to date applications. ETD. 2024;63(4):644-59.

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