Journal article

Vaccine instability in the cold chain: mechanisms, analysis and formulation strategies

Instability of vaccines often emerges as a key challenge during clinical development (lab to clinic) as well as commercial distribution (factory to patient). To yield stable, efficacious vaccine dosage forms for human use, successful formulation strategies must address a combination of interrelated topics including stabilization of antigens, selection of appropriate adjuvants, and development of stability-indicating analytical methods. This review covers key concepts in understanding the causes and mechanisms of vaccine instability including (1) the complex and delicate nature of antigen structures (e.g., viruses, proteins, carbohydrates, protein-carbohydrate conjugates, etc.), (2) use of adjuvants to further enhance immune responses, (3) development of physicochemical and biological assays to assess vaccine integrity and potency, and (4) stabilization strategies to protect vaccine antigens and adjuvants (and their interactions) during storage. Despite these challenges, vaccines can usually be sufficiently stabilized for use as medicines through a combination of formulation approaches combined with maintenance of an efficient cold chain (manufacturing, distribution, storage and administration). Several illustrative case studies are described regarding mechanisms of vaccine instability along with formulation approaches for stabilization within the vaccine cold chain. These include live, attenuated (measles, polio) and inactivated (influenza, polio) viral vaccines as well as recombinant protein (hepatitis B) vaccines.

Authors

Languages

  • English

Publication year

2014

Journal

Biologicals

Volume

5

Type

Journal article

Categories

  • Vaccines & delivery devices

Diseases

  • Polio

Tags

  • Distribution system
  • New vaccine introduction

Topic references

VVM-OTHER

TitleAuthorYearTypeLanguage
Cold chain challenges everywhere - Simona ZipurskyEPELA, World Health Organization (WHO)2013GuidanceEnglish
Impact of VVMs on Wastage and Cold Chain Monitoring During NIDs in NepalB. Aylward, G.P. Ojha, J. Andrus, J. luna, M.B. Bista, N. Rajbhandari1998Case studyEnglish
Interpretation of VVM in relation to other temperature monitoring devices - Umit KartogluEPELA, World Health Organization (WHO)2019TrainingEnglish
Last mile - Umit KartogluEPELA, World Health Organization (WHO)2013GuidanceEnglish
The Book of VVM: Yesterday-today-and-tomorrowUmit Kartoglu2020GuidanceEnglish
Using VVM as a stock management toolEPELA, World Health Organization (WHO)2013TrainingEnglish
Vaccine instability in the cold chain: mechanisms, analysis and formulation strategiesKumru OS et al.2014Journal articleEnglish
Vaccine storage and handling practices among routine immunization service providers in a metropolitan city of north-central NigeriaA. G. Salaudeen , H. A. Ameen, M. M. B. Uthman, O. A. Bolarinwa, O. I. Musa, S. A. AderibigbeJournal articleEnglish
Vaccine Vial Monitor (VVM)-based vaccine managementUmit Kartoglu2020PresentationEnglish
Vaccine vial monitor availability and use in low- and middle-income countries: A systematic reviewPär Eriksson et al.2017Journal articleEnglish
Vaccine Vial Monitors Impact Study during 1997 National Immunization Days in TurkeyBirhan Altay, Oya Zeren Afsar1998Case studyEnglish