Vaccine batch to vaccine batch comparison by consistency testing
RIVM contributed to VAC2VAC, a public-private consortium with 20 partners, including regulatory authorities, research institutes and industry. VAC2VAC aimed to develop and validate non-animal tests to determine the quality of human and veterinary vaccines, in support of the consistency approach.
The project has resulted in two validated in vitro methods. The first validated method, the Monocyte Activation Test (MAT) for pyrogenicity testing of Tick-borne Encephalitis Virus (TBEV), was submitted for regulatory approval. As a replacement for the Rabbit Pyrogen Test (RPT) for routine vaccine testing, the MAT has been implemented by the industry partner after the approval of European regulatory authorities. In addition, the European Pharmacopoeia (EP) is working on replacing the RPT in all monographs. The second validated method, the identification and quantification of tetanus toxin in the bacterial medium by Liquid Chromatography with tandem mass spectrometry (LC-MS/MS), can be used during the manufacturing process of the tetanus vaccine. The method was validated according to ICH guidelines.
In addition, seven in vitro models (all ELISA-based) were qualified and are ready for validation, eleven have shown proof-of-principle, and one has been developed. VAC2VAC has accelerated the development of European Pharmacopoeia (Ph. Eur.) General Chapter 5.2.14 and made it known in the field, by facilitating meetings in which it was explained.
Role of RIVM
RIVM has contributed by a proof-of-principle method: DNA sequencing for the characterisation of Clostridium tetani seed strains. This method can be used as a QC in the manufacturing process of the tetanus vaccine.
Other contributions by RIVM include:
1. Using the inflammasome activation assay as a measure of adjuvant function, potentially of use in case of production changes or monitoring product stability.
2. Evaluation of the effect of culture conditions on C. tetani neurotoxin expression by RNA sequencing, potentially of use in the manufacturing process of tetanus vaccine.
3. Variability of in vivo potency tests of Diphtheria, Tetanus and acellular Pertussis (DTaP) vaccines, substantiating the case for shifting from in vivo to in vitro methods to evaluate vaccine potency.
RIVM staff participated in a VAC2VAC workshop on multi-centre validation studies. An RIVM employee participated in three VAC2VAC projects led by other organisations (Groningen University, Utrecht University, IntraVacc) by performing bioinformatics analysis.
The VAC2VAC project received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement N- 115924. The Joint Undertaking received support from the European Union's Horizon 2020 research and innovation programme and EFPIA.