Case Study on Formulating a Multidose Lyophilized Measles-Rubella (MR) Vaccine Candidate for Local Manufacturing in...

Background/Objectives: Local manufacturing of Measles-Rubella (MR) vaccines is part of a multifaceted approach to improve vaccine accessibility in Africa, yet process development and technology transfer challenges remain for large-scale production of viral bulks and lyophilized drug product. This case study describes lab-scale formulation development of a multidose, 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. Methods: Formulation studies utilized both high-throughput RT-qPCR viral infectivity assays and standard lyophilization measurements. The off-patent, publicly available formulation composition of a single-dose, lyophilized trivalent MMR vaccine was evaluated as a starting point to develop a multidose, bivalent lyophilized MR vaccine candidate. To identify optimized conditions, various formulation (e.g., human serum albumin, viral bulk volume), drug product (e.g., vial size, fill volume), and lyophilization (e.g., freezing rate, primary/secondary drying cycle) parameters were evaluated to lower costs and assess MR stability during lyophilization, storage, and reconstitution. Results: Real-time and accelerated stability studies were conducted with four variations of the top candidate MR formulation, filled into primary packaging selected for technology transfer and lyophilized in both lab- and pilot- scale freeze-dryers. An optimized five-dose MR vaccine formulation with 5% (v/v) bulk and 95% (v/v) stabilizer solution, filled at 2X and reconstituted to 1X concentrations, demonstrated promising stability profiles and cost reduction potential. Stability profiles at 2-8 °C were used to estimate the MR release doses needed to ensure the required expiry doses at end of shelf-life. Conclusions: 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 multidose, lyophilized MR vaccine dosage form targeted for technology transfer and large-scale local production in Africa.