At the recent Interphex Pharmaceutical Manufacturing Conference, Emerson’s Todd Ham presented on the subject of automating fermentation. Todd acknowledged that Christie Deitz, whom we’ve featured in several other posts, had a large hand in the development of this presentation and work on the project discussed.
The presentation discussed a recent project done on a large-scale, multi-product biopharmaceutical complex. This project was so successful it recently won the Facility of the Year Award Winner in Project Execution. One of the keys to success was a clear design philosophy established up front. Elements of this philosophy included:
- Fully automated
- Paperless, dock-to-dock using electronic records, operator handheld devices, and barcode scanning
- Consistency for operators based on industry standards like ISA-88 (S88), ISA-95 (S95), and digital bus technologies
- Focus on fermentation as a key process area for the project
A key to success in the project was the close working relationship between the manufacturer and the Emerson Life Sciences project team on the up front requirements and design, and the subsequent module-level and integration-level testing.
The upfront design considered not only the fermentation and recovery processes, but also the full automation required for paperless operations. This design included recipe-level batch control, warehouse management, electronic signatures, and a complete electronic batch record, including the manual processes. These manufacturing processes included material management, container management, filter management and sampling.
The project team applied the S88 standard to control modules looking to identify the common modules and instances for things like motors and valves. At the S88 equipment module level, the team created project wide module templates, area specific module templates, and unique, one-time use equipment modules.
The sampling system and sparger control are examples of project-wide templates. Fermentation agitator control and dissolved oxygen control are examples of area-specific equipment modules. Transfer panels and valve assemblies are examples of unique equipment modules.
At the S88 unit level, the team designed classes and instances based on physical similarity and phases that they use such as batch media, inoculate, ferment, etc. This led to various unit classes for fermentation vessels including seed fermenters, production fermenters, and feed vessels.
From a recipe standpoint, the design grouped phases into operations, then grouped operations into unit procedures, and finally grouped unit procedures into procedures, all again following the S88 standard.
Todd shared some lessons learned from the team. With regard to the modular design approach, the team learned to keep process units the same as much as possible. With similar units, it is also important to make sure the operations are also as uniform as possible. The team cautioned about the overuse of aliases, which reference pieces of physical equipment like valves and motors, in phase logic. By not overusing aliases, but rather relying on equipment modules to handle physical differences, the phase logic could be generically written to handle multiple pieces of similar equipment like process tanks.
Other lessons learned were to plan for the extra documentation required for high levels of modularity and dock-to-dock automation. Like other members of the Life Sciences team have counseled in earlier posts, time spent upfront in planning and testing saves a lot of project backend effort.
The benefits of a complete electronic batch record vs. a paper-based process in terms of faster release of products are pretty clear. It’s important to assemble the project team and begin the planning and design early to prepare for the additional effort commensurate with the increased automation required for a successful project.