Adjuvants are substances added to vaccine formulations to enhance, accelerate, and prolong the immune response to a vaccine. Despite these notable benefits, vaccine adjuvants also can add to concerns related to clinical efficacy, safety, and dose stability. In the manufacturing environment, adjuvants can create challenges for sterilizing membrane filter capacity and bacterial retention validation. The particulate character of some adjuvants can cause premature plugging of filter membranes, and the low surface tension of many adjuvant solutions may contribute to reduced bacterial retention efficiency and potential non-sterility. In this article, we provide some recommendations for membrane filter selection and process conditions that may enhance filter capacity and increase the probability of successful bacterial retention validation for sterilizing filtration of adjuvanted vaccines.
Immune potentiators or immunomodulators, commonly referred to as adjuvants, are gaining increased attention from vaccine manufacturers. Adjuvants are used to enhance, accelerate, and prolong the efficacy of a vaccine. They are increasingly necessary now that simple, highly purified antigens, such as recombinant proteins or DNA, which do not elicit strong immune responses on their own, are replacing more antigenic intact pathogens in vaccine preparations. Interest in adjuvants also has increased because of their dose-sparing effect, facilitating a quicker and broader response during a pandemic.1–3
(PALL LIFE SCIENCES)
Adjuvants are a heterogeneous group of compounds (Table 1), including single compounds with intrinsic immunostimulating properties, for example, monophosphoryl lipid A (MPL) or the saponin QS21, and antigen carriers such as liposomes, microparticles, aluminum salts, but often have a combination of both immunostimulatory and carrier characteristics (e.g., emulsions and immune-stimulating complexes).3 Aluminum salts have been widely used and accepted in vaccines produced globally for several decades, whereas approval of new vaccine adjuvants has, until recently, been limited to Europe, for example, H1N1 pandemic influenza vaccines Focetria (Novartis) and Pandemrix (GSK). In the US, FDA approved the vaccine Cervarix (GSK), containing MPL, in late 2009.
Table 1. Examples of vaccine adjuvants3,6
The properties of these adjuvants or adjuvanted vaccines, in combination with specific process operating conditions, may create some challenges during sterilizing filter selection and sizing (filterability) studies and during sterilizing filter bacterial retention validation.