Developing a manufacturing process to deliver a cost effective and stable liquid human rotavirus vaccine

Autor: Prashant Kumar, Julie E Bines, Pim Velthof, Christopher Yallop, Ahd Hamidi, Sangeeta B. Joshi, Swathi R. Pullagurla, David B. Volkin, Alfred Luitjens, Menzo J. E. Havenga, Angelique A. C. Lemckert, Femke Hoeksema, Wilfried A.M. Bakker, Gert Gillissen
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Rotavirus
Malawi
HP-SEC
High Performance Size-Exclusion Chromatography
Cost-Benefit Analysis
ICH
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
medicine.disease_cause
CDAI
Cell Density at Infection
USP
Up-Stream Processing
0302 clinical medicine
Chlorocebus aethiops
GAVI
Global Alliance for Vaccines and Immunization
030212 general & internal medicine
Child
Cost–benefit analysis
Manufacturing process
Vaccination
FFA
Focus Forming assay
UNICEF
United Nations Children's Fund
Dose-ranging study
COGs
Cost of Goods
Rotavirus vaccine
USD
United States Dollar
LIC
Low Income Countries
Infectious Diseases
Molecular Medicine
Stable liquid formulation
DOE
Design of Experiments
DS
Drug Substance
medicine.medical_specialty
qPCR
Quantitative Polymerase Chain Reaction
030231 tropical medicine
DP
Drug Product
DSP
Down-Stream Processing
Vaccines
Attenuated
Article
WHO
World Health Organization
Rotavirus Infections
03 medical and health sciences
medicine
Animals
Humans
HBGA
Histo-Blood Group Antigen
LLOQ
Lower Level Of Quantification
Dosing
Intensive care medicine
Vero Cells
IU
International Unit
General Veterinary
General Immunology and Microbiology
business.industry
Cost-of-goods modelling
Public Health
Environmental and Occupational Health
Rotavirus Vaccines
Infant
ELISA
Enzyme-Linked Immuno-Sorbent Assay
Oral rotavirus vaccine
Vaccine efficacy
FFU
Focus Forming Units in Focus Forming assay
CCID50
Cell Culture Infectious Dose 50%
Indonesia
MOI
Multiplicity of Infection
Fixed bed bioreactor
BSA
Bovine Serum Albumin
ORV
Oral Rotavirus Vaccine
business
MVS
Master Virus Seed
Zdroj: Vaccine
ISSN: 1873-2518
0264-410X
Popis: Highlights • A low-cost manufacturing process for a neonatal rotavirus vaccine was developed. • The formulation process developed resulted in a stable liquid vaccine at 2–8 °C. • No pretreatment of vaccinees with antacid needed before oral administration. • Tech. transfer package includes manufacturing, formulation, assays and COGs model.
Despite solid evidence of the success of rotavirus vaccines in saving children from fatal gastroenteritis, more than 82 million infants worldwide still lack access to a rotavirus vaccine. The main barriers to global rotavirus vaccine coverage include cost, manufacturing capacity and suboptimal efficacy in low- and lower-middle income countries. One vaccine candidate with the potential to address the latter is based on the novel, naturally attenuated RV3 strain of rotavirus, RV3-BB vaccine administered in a birth dose strategy had a vaccine efficacy against severe rotavirus gastroenteritis of 94% at 12 months of age in infants in Indonesia. To further develop this vaccine candidate, a well-documented and low-cost manufacturing process is required. A target fully loaded cost of goods (COGs) of ≤$3.50 per course of three doses was set based on predicted market requirements. COGs modelling was leveraged to develop a process using Vero cells in cell factories reaching high titers, reducing or replacing expensive reagents and shortening process time to maximise output. Stable candidate liquid formulations were developed allowing two-year storage at 2–8 °C. In addition, the formulation potentially renders needless the pretreatment of vaccinees with antacid to ensure adequate gastric acid neutralization for routine oral vaccination. As a result, the formulation allows small volume dosing and reduction of supply chain costs. A dose ranging study is currently underway in Malawi that will inform the final clinical dose required. At a clinical dose of ≤6.3 log10 FFU, the COGs target of ≤$3.50 per three dose course was met. At a clinical dose of 6.5 log10 FFU, the final manufacturing process resulted in a COGs that is substantially lower than the current average market price, 2.44 USD per dose. The manufacturing and formulation processes were transferred to BioFarma in Indonesia to enable future RV3-BB vaccine production.
Databáze: OpenAIRE
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