Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use

Simple item page
dc.contributor.authorBolgiano, Barbara
dc.contributor.authorMoran, Eilís
dc.contributor.authorBeresford, Nicola J.
dc.contributor.authorGao, Fang
dc.contributor.authorCare, Rory
dc.contributor.authorDesai, Trusha
dc.contributor.authorNordgren, Ida Karin
dc.contributor.authorRudd, Timothy R.
dc.contributor.authorFeavers, Ian M.
dc.contributor.authorBore, Prashant
dc.contributor.authorPatni, Sushil
dc.contributor.authorGavade, Vinay
dc.contributor.authorMallya, Asha
dc.contributor.authorKale, Sameer
dc.contributor.authorSharma, Pankaj
dc.contributor.authorGoel, Sunil K
dc.contributor.authorGairola, Sunil
dc.contributor.authorHattarki, Suhas
dc.contributor.authorAvalaskar, Nikhil
dc.contributor.authorSarma, Annamraju D
dc.contributor.authorLaForce, Marc
dc.contributor.authorRavenscroft, Neil
dc.contributor.authorKhandke, Lakshmi
dc.contributor.authorAlderson, Mark R
dc.contributor.authorDhere, Rajeev M
dc.contributor.authorPisal, Sambhaji S
dc.date.accessioned2021-10-07T14:42:27Z
dc.date.available2021-10-07T14:42:27Z
dc.date.issued2021-07-23
dc.date.updated2021-08-26T13:27:15Z
dc.description.abstractTowards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against <i>Neisseria meningitidis</i> serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM<sub>197</sub>), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide <i>O</i>-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India.en_US
dc.identifierdoi: 10.3390/pathogens10080928
dc.identifier.apacitationBolgiano, B., Moran, E., Beresford, Nicola J., Gao, F., Care, R., Desai, T., ... Pisal, S. S. (2021). Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use. <i>Pathogens</i>, 10(8), 928. http://hdl.handle.net/11427/34199en_ZA
dc.identifier.chicagocitationBolgiano, Barbara, Eilís Moran, Nicola J. Beresford, Fang Gao, Rory Care, Trusha Desai, Ida Karin Nordgren, et al "Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use." <i>Pathogens</i> 10, 8. (2021): 928. http://hdl.handle.net/11427/34199en_ZA
dc.identifier.citationBolgiano, B., Moran, E., Beresford, Nicola J., Gao, F., Care, R., Desai, T., Nordgren, I.K. & Rudd, Timothy R. et al. 2021. Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use. <i>Pathogens.</i> 10(8):928. http://hdl.handle.net/11427/34199en_ZA
dc.identifier.ris TY - Journal Article AU - Bolgiano, Barbara AU - Moran, Eilís AU - Beresford, Nicola J. AU - Gao, Fang AU - Care, Rory AU - Desai, Trusha AU - Nordgren, Ida Karin AU - Rudd, Timothy R. AU - Feavers, Ian M. AU - Bore, Prashant AU - Patni, Sushil AU - Gavade, Vinay AU - Mallya, Asha AU - Kale, Sameer AU - Sharma, Pankaj AU - Goel, Sunil K AU - Gairola, Sunil AU - Hattarki, Suhas AU - Avalaskar, Nikhil AU - Sarma, Annamraju D AU - LaForce, Marc AU - Ravenscroft, Neil AU - Khandke, Lakshmi AU - Alderson, Mark R AU - Dhere, Rajeev M AU - Pisal, Sambhaji S AB - Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against <i>Neisseria meningitidis</i> serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM<sub>197</sub>), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide <i>O</i>-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India. DA - 2021-07-23 DB - OpenUCT DP - University of Cape Town IS - 8 J1 - Pathogens LK - https://open.uct.ac.za PY - 2021 T1 - Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use TI - Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use UR - http://hdl.handle.net/11427/34199 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34199
dc.identifier.vancouvercitationBolgiano B, Moran E, Beresford Nicola J, Gao F, Care R, Desai T, et al. Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use. Pathogens. 2021;10(8):928. http://hdl.handle.net/11427/34199.en_ZA
dc.language.isoenen_US
dc.publisher.departmentDepartment of Chemistryen_US
dc.publisher.facultyFaculty of Scienceen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourcePathogensen_US
dc.source.journalissue8en_US
dc.source.journalvolume10en_US
dc.source.pagination928en_US
dc.source.urihttps://www.mdpi.com/journal/pathogens
dc.titleEvaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Useen_US
dc.typeJournal Articleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
pathogens-10-00928.pdf
Size:
2.48 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
0 B
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Journal Articles