The pharma industry isn't renowned for its quick adoption of advanced manufacturing systems. And even though regulatory authorities have started to push the industry to use smarter systems, many companies are still reluctant – but not all.
The introduction of more advanced manufacturing systems generally happens very slowly, particularly in the pharmaceutical industry. While the authorities put increasing pressure on pharma companies to use more cost-effective manufacturing systems, the industry still makes extensive use of extremely conservative technologies. But Pfizer, one of the industry's top players, has recently taken a giant leap in a new direction.
In consortium with equipment supplier GEA and cleanroom supplier G-CON, Pfizer has developed a new concept for smarter tablet manufacturing. This concept is known as PCMM, or “Portable, Continuous, Miniature and Modular”, and within a year of its 2013 launch a prototype was developed in conjunction with Pfizer's partners. GEA developed the manufacturing equipment in Belgium, while G-CON developed the cleanroom modules in Texas, USA.
All subsystems, including an advanced automation solution, were installed and tested at G-CON in Texas before the modules were shipped to Pfizer's manufacturing facility in Groton, Connecticut. The tested modules were installed on-site in less than a week in early 2015. The entire solution was qualified and approved by the authorities throughout 2015, allowing the company to recently begin manufacturing tablets for clinical trials.
The PCMM concept combines a variety of new industrial technologies and trends. These deserve a closer look:
Modules for flexibility
The manufacturing system consists of a variety of modules, known as PODs (same word as “iPod”). These can be linked to larger modules, or “mega modules”, like Lego blocks. The modules are developed and tested by the supplier before installation at the end user's site. The modules, which are self-contained, are placed in a traditional warehouse, or “POD farm”, where the floor must be smooth and level. They are extremely portable, featuring built-in air-bearings, and are very compact, requiring around half as much space as a traditional system.
These modules are developed and tested before reaching the site. They are self-contained, extremely portable and very compact.
With the module-based concept, it follows that the most critical processes are isolated in independent modules. If the process needs ventilation, the module is equipped with its own miniature ventilation system. This means the company no longer relies on large central ventilation systems, resulting in significant eco-friendly energy savings.
Typically, tablets are produced in a batch process, the size of which is determined by the size of the system. The individual process steps, such as weighing, mixing and tablet compression, are also normally separate processes, and intermediate products are usually transferred manually to the next process step via mobile containers. Yet with this new system, these steps are fully integrated and the process can run continuously, with the batch size determined solely by the length of time a system operates. This substantially reduces the amount of time spent on reconfiguration and cleaning.
The pilot system was built to produce certain tablets, but can quickly be reconfigured to produce new tablet variants based on either dry or wet granulate. This is particularly advantageous when producing small amounts of new tablets for clinical trials. Companies traditionally use separate systems to produce small amounts of tablets for phase 1 and phase 2 trials, and a larger, different system for commercial manufacturing. With the new system, anything from 10 kg to 1,000 kg can be produced within the same system.
Advanced process control
A continuous process requires a more advanced form of process control. In this case, it is based on technology from Rockwell Automation and process knowhow from Pfizer. The advanced process control (APC) system continuously monitors the five most important quality parameters via advanced process analytical technology (PAT) sensors. The system continuously updates a model-based regulator and adjusts the process set points so that the tolerance limits are met at all times.
In 2016, the PCMM project won the prestigious “Facility of the Year” award. The industry organization "International Society for Pharmaceutical Engineering" (ISPE) gives this annual award to the most innovative production solution in facility design.
In partnership with other end-users, including GSK who recently joined the PCMM consortium, Pfizer hopes to further develop the concept in order to handle future requirements of quality, efficiency and flexibility.