Nonclinical safety assessment of vaccines: Up to date applications

Ülkü Karabay

doi:10.19161/etd.1542896

TR EN

AŞILARIN KLİNİK DIŞI GÜVENLİK DEĞERLENDİRMESİ: GÜNCEL UYGULAMALAR

Öz

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.

Anahtar Kelimeler

Kaynakça

Ochmann S, Roser M. Polio. Published online at OurWorldInData.org. https://ourworldindata.org/polio 2018
Wolf JJ, Plitnick LM, Herzyk DJ. Strategies for the Nonclinical Safety Assessment of Vaccines. In Novel Immune Potentiators and Delivery Technologies for Next Generation. Vaccines. 2012; 323-349
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.
Pliaka V, Kyriakopoulou Z, Markoulatos P. Risks associated with the use of live-attenuated vaccine poliovirus strains and the strategies for control and eradication of paralytic poliomyelitis. Expert Rev Vaccines 2012; 11(5): 609-628.
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.
Guideline on adjuvants in vaccines for human use. 2005. EMEA, European Agency for the Evaluation of Medicinal Products. EMEA/CHMP/VEG/134716/2004
WHO Guidelines on nonclinical evaluation of vaccines. 2005. WHO/BS/03.1969. (WHO Technical Report Series No 927, Annex 1).
Wolf JJ, Kaplanski CV, Lebron JA. Nonclinical Safety Assessment of Vaccines and Adjuvants; In Vaccine Adjuvants Methods and Protocols. Part of the Methods in Molecular Biology book series (MIMB) Springer Inc. 2010; 626:29-40. doi: 10.1007/978-1-60761-585-9_3.
Guideline on clinical evaluation of vaccines, Committee for Medicinal Products for Human Use (CHMP) EMEA/CHMP/VWP/164653/05 Rev. 1.2023
WHO Expert Committee on Biological Standardization. Guidelines on clinical evaluation of vaccines: regulatory expectations (WHO Technical Report Series 1004, Annex 9, 2017 Sixty-seventh report)
Questions and answers on the withdrawal of the CPMP, Note for guidance on preclinical pharmacological and toxicological testing of vaccines. 2016 (CPMP/SWP/465), EMEA, European Agency for the Evaluation of Medicinal Products. EMA/CHMP/SWP/242917/2016.
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.
Code of Federal Regulations, Title 21, Part 58 (21 CFR 58). Good Laboratory Practice for Nonclinical Laboratory Studies. Washington, DCUS Government Printing Office. 2024.
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.
Zaitseva M, Romantseva T, Blinova K, Beren J, Sirota L, Drane D, Golding H. Use of human MonoMac6 cells for development of in vitro assay predictive of adjuvant safety in vivo. Vaccine 2012; 30:4859–65.
Pugsley MK, Authier S, Curtis MJ. (2008) Principles of safety pharmacology. Br J Pharmacol. 154: 1382–99, doi: 10.1038/bjp.2008.280.
Andrade EL, Bento AF, Cavalli J, Oliveira SK, Freitas CS, Marcon R, Schwanke RC, Siqueira JM, Calixto JB. Non-clinical studies required for new drug development - Part I: early in silico and in vitro studies, new target discovery and validation, proof of principles and robustness of animal studies. Brazilian J Med and Biological Research 2016; 49(11): e5644. doi: 10.1590/1414-431X20165644.
Hentz KL. 3.03 - Safety Assessment of Pharmaceuticals in Comprehensive Toxicology. 2010; 3:17-28.
Amouzadeh HR, Engwall MJ, Vargas HM. Safety Pharmacology Evaluation of Biopharmaceuticals. In Principles of Safety Pharmacology. Ed by Michael K. Pugsley, ‎Michael J Curtis. 2015.
ICH S6(R1) Harmonised Tripartite Guideline, Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals. International Conference on Harmonization, Geneva, Switzerland, 1997. Addendum June 2011.
Shin J, Lei D, Conrad C, Knezevic I, Wood D. International regulatory requirements for vaccine safety and potency testing: a WHO perspective. Procedia in Vaccinology, 2011; 5:164–170.
Ducharme J, Dudley AJ, Thompson RA. Pharmacokinetic issue in drug discovery. In: Rang HP (Editor), Drug discovery and development. Philadelphia: Churchill Livingstone Elsevier. 2006: 141–161.
Tuntland T, Ethell B, Kosaka T, Blasco F, Zang RX, Jain M, Gould T, Hoffmaster K. Implementation of pharmacokinetic and pharmacodynamics strategies in early research phases of drug discovery and development at Novartis Institute of Biomedical Research. Frontiers in Pharmacology 2014; 5:174. doi: 10.3389/fphar.2014.00174. eCollection 2014.
Oleár V, Krištúfková Z, 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.
Singh SS. Preclinical pharmacokinetics: an approach towards safer and efﬁcacious drugs. Curr Drug Metab 2006; 7: 165-182, doi: 10.2174/138920006775541552.
Valentin JP, Hammond T. Safety and secondary pharmacology: successes, threats, challenges and opportunities. J Pharm Toxicol Methods 2008; 58: 77–87. doi: 10.1016/j.vascn.2008.05.007.
Wolf JJ. Chapter 10: Special Considerations for the Nonclinical Safety Assessment of Vaccines, In Nonclinical Development of Novel Biologics, Biosimilars, Vaccines and Specialty Biologics, Ed by Lisa M. Plitnick and Danuta J. Herzyk. Elsevier Inc. 2013; 243-255
Note for Guidance on Pharmaceutical and Biological Aspects of Combined Vaccines, 1998. EMEA, European Agency for the Evaluation of Medicinal Products. CPMP/BWP/477/98.
Green MD, Al-Humadi NH. Chapter 27 - Preclinical Toxicology of Vaccines, A Comprehensive Guide to Toxicology in Nonclinical Drug Development (Second Edition) 2017; 709-735.
WHO Expert Committee on Specifications for Pharmaceutical Preparations: Good manufacturing practices: supplementary guidelines for the manufacture of investigational pharmaceutical products for clinical trials in humans, 1996. (WHO Technical Report Series, No. 863, Annex 7, 1996 - Thirty-fourth Report)
ICH S3A Note for guidance on toxicokinetics: the assessment of systemic exposure in toxicity studies. International Conference on Harmonization, Geneva, Switzerland, 2018.
Masson JD, Crépeaux G, Authier FJ, Exley C, Gherardi RK. Critical analysis of reference studies on the toxicokinetics of aluminum-based adjuvants. J Inorg Biochem 2018; 181:87-95. doi: 10.1016/j.jinorgbio.2017.12.015.
NIH Guidelines for survival bleeding of mice and rats. National Institutes of Health, 2021. https://research.umd.edu/sites/default/files/2021-12/D19a_Survival_Bleeding_10-26-08.pdf
Nuffield Council on Bioethics. Chapter 9 Animal Use in Toxicity Studies; In the Ethics of Research Involving Animals. London. 2005.
Note for guidance on repeated dose toxicity. EMEA, European Agency for the Evaluation of Medicinal Products. London, Committee for Proprietary Medicinal Products 2010. CPMP/SWP/1042/99 Rev1.
Note for guidance on non-clinical local tolerance testing of medicinal products. EMEA, European Agency for the Evaluation of Medicinal Products. London, Committee for Proprietary Medicinal Products, 2014. CPMP/SWP/2145/2000 Rev1.
Draize JH, Woodard G, Calvery HO. Methods for The Study of Irritation and Toxicity of Substances Applied Topically to The Skin and Mucous Membranes. J Pharmacol Experimental Therapeutics 1944; 82(3): 377-390.
Watterson C, Lanevschi A, Horner J, Louden C. A comparative analysis of acute-phase proteins as inflammatory biomarkers in preclinical toxicology studies: implications for preclinical to clinical translation. Toxicologic Pathology 2009; 37(1):28-33. doi:10.1177/ 0192623308329286.
ICH S5(R2) Detection of Toxicity to Reproduction for Medicinal Products & Toxicity to Male Fertility. International Conference on Harmonization, Geneva, Switzerland. 2005. CPMP/ICH/386/95.
ICH guideline S2(R1) on genotoxicity testing and data interpretation for pharmaceuticals intended for human use - Step 5, 2012. EMEA, European Agency for the Evaluation of Medicinal Products. EMA/CHMP/ICH/126642/2008
Injac R. Global pandemic vaccine development, production and distribution challenges for the world population. Int J Risk Safety Med 2022; 33(3): 235-248. doi: 10.3233/JRS-227019.
Schilder NKM, Tiesjema B, Theunissen PT, Rengerink KO, van der Laan JW. Evaluation of non-clinical toxicity studies of COVID-19 vaccines. Regul Toxicol Pharmacol. 2023; 142:105438. doi: 10.1016/j.yrtph.2023.105438.

Ayrıntılar

Birincil Dil

İngilizce

Konular

Tek Sağlık

Bölüm

Derleme

Yazarlar

Ülkü Karabay ^*
0000-0002-7483-0184
Türkiye

Yayımlanma Tarihi

9 Aralık 2024

Gönderilme Tarihi

3 Eylül 2024

Kabul Tarihi

1 Kasım 2024

Yayımlandığı Sayı

Yıl 1970 Cilt: 63 Sayı: 4

DOI

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

IZ

https://izlik.org/JA33DS39ZS

Kaynak Göster

RIS / Bibtex

Vancouver

1.Ülkü Karabay. Nonclinical safety assessment of vaccines: Up to date applications. ETD. 01 Aralık 2024;63(4):644-59. doi:10.19161/etd.1542896

AŞILARIN KLİNİK DIŞI GÜVENLİK DEĞERLENDİRMESİ: GÜNCEL UYGULAMALAR

AŞILARIN KLİNİK DIŞI GÜVENLİK DEĞERLENDİRMESİ: GÜNCEL UYGULAMALAR

Öz

Anahtar Kelimeler