The proposed project is to develop a unit dose continuous lyophilizer and to demonstrate its function on small molecule and biologics. The overall design of the lyophilizer has already been accomplished based on laboratory data and systems analysis. The design consists of three main chambers ? nucleation and freezing, primary drying, and secondary drying ? each connected with a load-lock system to prevent back-flow and interaction with the environment. Individual unit doses will be fed in a truly continuous manner through the process, in which process analytical technology (PAT) will be employed at each key point, and model-based control will be used for full automation. At the end of the project, vaccines and gene therapy products will be lyophilized as filled vials with the product formulation in liquid form are continuously fed to the lyophilizer and fully tested product continuously exits. Scale will be at the 50,000 vial per week level, which is commercial scale for a medium to large- volume product. However, the concept of the equipment is such that it could be easily scaled- down to as low as a single vial for a given run. The proposed project directly fits into the objectives of the RFA, including addressing all of the objectives, continuous processing equipment, automation, in-line PAT, and advanced simulation and control (model-based). The project also has the potential to meet national needs for advanced manufacturing, industrial equipment design and domestic manufacturing, in addition to fast responses to epidemics, eliminating cold-chain challenges, and reducing the amount of time needed for process development and getting products to patients. The high-level project plan is: Year 1, detailed design, implementation, and testing of load-lock system and vial suspension track; Year 2, detailed design of full process, implementation, and initial testing, including control system; Year 3, finalize PAT and model- based control and apply to actual pharmaceutical products and relevant surrogate products. Given the potential for implementation upon completion, we will be in regular communication with our contacts in industry, from both pharmaceutical companies and pharmaceutical equipment companies, for development of GMP versions at various scales.
This project addresses end to end continuous manufacturing with automated control of a drug product process for lyophilized small molecules and biologics. The aim is to eliminate the problems of lyophilization including process inefficiencies in resources and time, high rate of out-of-spec product, and equipment costs. It is low-hanging fruit as a low-risk/high-reward approach that has the potential to move manufacturing of lyophilized products forward by leaps and bounds.
