The consistency approach for the substitution of in vivo testing for the quality control of established vaccines: practical considerations and progressive vision

The aim of this letter is to share the discussions and proposals made by the VAC2VAC consortium on how to support the deployment of the “Consistency Approach” for quality control of established vaccines and thus facilitate the substitution of in vivo testing. This work answers specific questions about “ what does a control strategy according to the consistency testing look like” and “ how to submit a control strategy defined according to the consistency testing”. Some topics were answered in a very straightforward manner. This was the case when the deployment of the consistency approach and the corresponding changes in vaccines control strategy was supported by the generic application of procedures already described in regulatory guidelines/requirements and related to the establishment or change in the control strategy of vaccines. The application of other procedures required more specific attention and some were deeply debated before reaching a proposal. The key outcomes of this work are that robust science must be used to develop a substitution strategy and generate supportive data packages. And this good science can best occur with good scientific collaboration between the different parties involved. Therefore, early interaction between manufacturers and competent authorities before and during dossier submission is critical to success. The consistency approach, when approved and in place, will ensure vaccine products of assured quality reach the patient in a more efficient manner than when relying on in vivo testing. Adapting the mindset was one of the major hurdles to a progressive vision but there is now consensus between manufacturers and competent authorities to foster the elimination of in vivo testing for routine vaccine release testing.