Ellen Jessouroun

Single validation of CE method for determining free polysaccharide content in a Brazilian meningococcal C conjugate vaccine.

Neisseria meningitidis group C is an encapsulated bacterium that causes several diseases and is associated with high mortality rates, thereby constituting a serious public health problem. Bio‐Manguinhos/Fiocruz is developing a conjugate vaccine by covalent attachment of capsular polysaccharide to hydrazide‐activated tetanus toxoid through reductive amination. It is necessary to quantify free components as a quality control process to prevent exacerbated adverse reactions and/or attenuation of vaccine immunogenicity. Thus, this study aimed to develop and validate a quality control method appropriate for the separation and quantification of free polysaccharide present in this conjugate N. meningitidis group C vaccine using CE. CZE was used to remove unbound polysaccharide, and the electrophoretic conditions were varied to optimize resolution. We were able to develop and validate the proposed method, which was linear and showed a matrix effect. Repeatability and partial reproducibility of the method were also evaluated. The robustness results showed that control of temperature is required for reliable results. The validated method will be used to evaluate the conjugate batches submitted for Phase III clinical studies and for routine quality control of the conjugate vaccine.

Brazilian meningococcal C conjugate vaccine: scaling up studies

Several outbreaks caused by Neisseria meningitidis group C have been occurred in different regions of Brazil. A conjugate vaccine for Neisseria meningitidis was produced by chemical linkage between periodate-oxidized meningococcal C polysaccharide and hydrazide-activated monomeric tetanus toxoid via a modified reductive amination conjugation method. Vaccine safety and immunogenicity tested in Phase I and II trials showed satisfactory results. Before starting Phase III trials, vaccine production was scaled up to obtain industrial lots under Good Manufacture Practices (GMP). Comparative analysis between data obtained from industrial and pilot scales of the meningococcal C conjugate bulk showed similar execution times in the scaling up production process without significant losses or alterations in the quality attributes of purified compounds. In conclusion, scale up was considered satisfactory and the Brazilian meningococcal conjugate vaccine production aiming to perform Phase III trials is feasible.