Drivers and barriers in the consistency approach for vaccine batch release testing: Report of an international workshop

Vaccines are complex biomedicines. Manufacturing is time consuming and requires a high level of quality control (QC) to guarantee consistent safety and potency. An increasing global demand has led to the need to reduce time and cost of manufacturing. The evolving concepts for QC and the upcoming threat of falsification of biomedicines define a new need for methods that allow the fast and reliable identification of vaccines. Raman spectroscopy is a non-destructive technology already established in QC of classical medicines. We hypothesized that Raman spectroscopy could be used for identification and differentiation of vaccine products. Raman maps obtained from air-dried samples of combination vaccines containing antigens from tetanus, diphtheria and pertussis (DTaP vaccines) were summarized to compile product-specific Raman signatures. Sources of technical variance were emphasized to evaluate the robustness and sensitivity in downstream data analysis. The data management approach corrects for spatial inhomogeneities in the dried sample while offering a proper representation of the original samples inherent chemical signature. Reproducibility of the identification was validated by a leave-one-replicate-out cross-validation. The results highlighted the high specificity and sensitivity of Raman measurements in identifying DTaP vaccine products. The results pave the way for further exploitation of the Raman technology for identification of vaccines in batch release and cases of suspected falsification.

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“…This approach is well in-line with the presently pursued quality control concept based on comparative analysis for consistency testing. 33 – 35…”

Section: Discussionmentioning

confidence: 99%

Raman spectroscopy-based identification of toxoid vaccine products

et al. 2018

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“…But the developments of the recent decades in the applied technologies of vaccine production and also in the way vaccines can be controlled, and their application, contributed to a shift from traditional vaccine control technologies to more focused monitoring of critical quality attributes indicating consistency of vaccine production. Akkermans retraced some of these steps through few key articles [ 23 , [33] , [34] , [35] , [36] ], through activities, symposia and workshops which brought together and fostered the exchange of information between different stakeholders, and on how these activities produced tangible changes in the European Pharmacopoeia (like the revised 5.2.14 article of the Ph. Eur.…”

Section: Harmonization: Challenges and Opportunitiesmentioning

confidence: 99%

Animal testing for vaccines. Implementing replacement, reduction and refinement: challenges and priorities

Akkermans

Chapsal²,

Coccia

et al. 2020

Biologicals

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Transition to in vitro alternative methods to in vivo in vaccine release testing and characterization, the implementation of the consistency approach, and a drive towards international harmonization of regulatory requirements are most pressing needs in the field of vaccines. It is critical for global vaccine community to work together to secure effective progress towards animal welfare and to ensure that vaccines of ever higher quality can reach the populations in need in the shortest possible timeframe. Advancements in the field, case studies, and experiences from Low and Middle Income Countries (LMIC) were the topics discussed by an international gathering of experts during a recent conference titled “ Animal Testing for Vaccines – Implementing Replacement, Reduction and Refinement: Challenges and Priorities ”. This conference was organized by the International Alliance for Biological Standardization (IABS), and held in Bangkok, Thailand on December 3 and 4 2019. Participants comprised stakeholders from many parts of the world, including vaccine developers, manufacturers and regulators from Asia, Europe, North America, Australia and New Zealand. In interactive workshops and vibrant panel discussions, the attendees worked together to identify the remaining barriers to validation, acceptance and implementation of alternative methods, and how harmonization could be promoted, especially for LMICs.

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“…One strategy to ensure the quality of vaccines is the consistency approach, which implies that batch-to-batch variation of vaccines can be controlled by well-defined production processes and analysis of intermediate and final products by in vitro methods [ 6 , 7 , 8 ]. This approach requires a battery of methods to create a product profile that provides sufficient information to replace current animal-based tests.…”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide Production and Fc Receptor-Mediated Phagocytosis as Functional Readouts of Macrophage Activity upon Stimulation with Inactivated Poultry Vaccines In Vitro

et al. 2020

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Vaccine batches must pass routine quality control to confirm that their ability to induce protection against disease is consistent with batches of proven efficacy from development studies. For poultry vaccines, these tests are often performed in laboratory chickens by vaccination-challenge trials or serological assays. The aim of this study was to investigate innate immune responses against inactivated poultry vaccines and identify candidate immune parameters for in vitro quality tests as alternatives for animal-based quality tests. For this purpose, we set up assays to measure nitric oxide production and phagocytosis by the macrophage-like cell line HD11, upon stimulation with inactivated poultry vaccines for infectious bronchitis virus (IBV), Newcastle disease virus (NDV), and egg drop syndrome virus (EDSV). In both assays, macrophages became activated after stimulation with various toll-like receptor agonists. Inactivated poultry vaccines stimulated HD11 cells to produce nitric oxide due to the presence of mineral oil adjuvant. Moreover, inactivated poultry vaccines were found to enhance Fc receptor-mediated phagocytosis due to the presence of allantoic fluid in the vaccine antigen preparations. We showed that inactivated poultry vaccines stimulated nitric oxide production and Fc receptor-mediated phagocytosis by chicken macrophages. Similar to antigen quantification methods, the cell-based assays described here can be used for future assessment of vaccine batch-to-batch consistency. The ability of the assays to determine the immunopotentiating properties of inactivated poultry vaccines provides an additional step in the replacement of current in vivo batch-release quality tests.

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Drivers and barriers in the consistency approach for vaccine batch release testing: Report of an international workshop

Cited by 16 publications

References 4 publications

Raman spectroscopy-based identification of toxoid vaccine products

Raman spectroscopy-based identification of toxoid vaccine products

Animal testing for vaccines. Implementing replacement, reduction and refinement: challenges and priorities

Nitric Oxide Production and Fc Receptor-Mediated Phagocytosis as Functional Readouts of Macrophage Activity upon Stimulation with Inactivated Poultry Vaccines In Vitro

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