Manufacturing issues related to combining different antigens: an industry perspective

Despite the growing demand for combination vaccines, many challenges have been encountered in developing them. It is difficult to predict the physical compatibility and stability of antigens in combination, because these characteristics are highly dependent on vaccine excipients. Clinical evaluation of potential modifications of efficacy of antigens in combination may be alleviated by use of appropriate animal models. Manufacturing issues, such as batch-release testing, storage of intermediate products, and the shift to preservative-free products, are of particular concern because they have the potential to affect the supply chain. Managing changes in the manufacture of one antigen that is a component of several different combination vaccines is also difficult. However, most potential issues can be resolved through the simplification of regulatory processes and harmonization of requirements, such as the acceptance of comparability protocols and antigen master files. Continued collaboration between industry and authorities is necessary to develop effective means of handling all submissions pertaining to combination vaccines.