Formulation Development of a Multidose Lyophilized Measles-Rubella (MR) Vaccine Candidate for Local Manufacturing in Africa: Lab-Scale Results and Lessons-Learned for Future Technology Transfer (dataset)

The WHO African Region (AFRO) strives to improve Measles and Rubella (MR) vaccine coverage to achieve MR elimination in 80% of countries by 2030. Local manufacturing of MR vaccines is one part of a multifaceted approach to improve vaccine accessibility, yet there are process development/ technology transfer challenges to enable large-scale production of viral bulks and lyophilized drug product in Africa. In this work, we describe lab-scale formulation development of a multi-dose, lyophilized MR vaccine candidate, leveraging the availability of concentrated bulks of Measles (MeV) and Rubella (RuV) produced in MRC-5 cells by a new bulk manufacturing process. First, analytical methods were optimized to facilitate formulation studies including a high-throughput MR infectivity assay (potency q-PCR) and lyophilization measurements (e.g., residual moisture, glass transition temperatures). Second, the off-patent, publicly-available formulation composition of a commercially available, single-dose, lyophilized trivalent MMR vaccine was evaluated as a starting point to develop a multidose, bivalent lyophilized MR vaccine candidate. Various formulation components (e.g., human serum albumin, viral bulk volumes), drug product configurations (e.g., vial size, fill volumes) and lyophilization parameters (e.g., freezing rate, primary and secondary cycles) were evaluated to lower costs, and MR stability assessments (i.e., lyophilization yields, 37°C for 1 week, upon reconstitution) were performed to identify optimized conditions. Third, real-time and accelerated stability studies were conducted with four variations of the top candidate MR formulation in primary packaging selected for technology transfer. The resulting MR stability profiles at 2-8°C were used to estimate the MR vaccine “stability window”, i.e., the MR release doses needed to ensure the required expiry doses at end of shelf-life. Finally, results are discussed, along with recommendations for future work, in the context of the analytical, formulation, and lyophilization challenges encountered during lab-scale development of a candidate multi-dose, lyophilized MR vaccine dosage form targeted for technology transfer and large-scale local production in Africa.