Giving a Boost to the Facility of the Future

Improving manufacturing efficiency and quality are high priorities, and new technologies-including continuous manufacturing and data analytics-can help the pharmaceutical "facility of the future" achieve these goals, said experts at a recent International Society for Pharmaceutical Engineering (ISPE) event held by the New Jersey and Delaware Valley ISPE Chapters (Princeton, NJ, Sept. 30, 2015).

"Big data analytics will help the industry to focus on what's important," suggested James Breen, vice-president of Worldwide Engineering & Technical Operations at Johnson & Johnson and member of the ISPE International Leadership Forum. The supply chain is one crucial area for the pharmaceutical industry that can be helped by data analytics. "Slow-moving, obsolete inventory is a big problem and an opportunity for change," said Breen.

Next-generation facilities need to be more flexible and agile to reduce inventory by more quickly adapting to market demand, using technologies such as modular manufacturing systems and continuous processing. For example, the Portable Continuous Miniature Modular (PCMM) system-built as a collaboration between Pfizer, G-Con, and GEA-is a standardized platform that allow production on demand of flexible batch sizes, explained Rick Mitzner, senior director, Pfizer Global Engineering, in a presentation at the ISPE event. A PCMM was assembled in a Pfizer warehouse in only four days, and the project duration was 14 months from kickoff to delivery. Pfizer envisions an even more accelerated timeframe for future assemblies built with standard modules.

"The PCMM is targeted for low to mid-volumes in areas such as orphan drugs or oncology," noted Mitzner. The portability of the system, which is built in containers (i.e., PODs), allows a company to recover assets should it close a facility and enables in-country manufacturing without green-field construction, he noted. Another significant benefit is technical transfer. Using the PCMM for clinical (Phase II and Phase III) and commercial volumes streamlines scale-up.

In biopharmaceutical manufacturing, continuous downstream processing is needed to handle the volumes coming from more highly productive upstream processes, with a smaller footprint and faster cycle times to reduce inventory, commented Bruce Snyder, director of process automation for IPS, at the ISPE event. Availability of the needed process analytical technology is a concern for bioprocesses, he noted. Another potential challenge is ensuring the mechanical reliability of single-use components for the timeframe of the process (e.g., 60 days). Process automation is a crucial piece of a continuous process. In a bioprocess using continuous multi-column chromatography, the output from this operation is technically discontinuous, but an intermediate container (e.g., a single-use bag) can be used to isolate the unit operations and allow a steady flow to the downstream operations, explained Snyder. Although equipment may be controlled by a variety of systems, a distributed control system is required to integrate the pieces in a continuous process, concluded Snyder. 

Analysis of "big data" has many applications in the pharmaceutical industry, one of which is to improve risk assessment of manufacturing facilities. "Unstructured information from FDA- including 483s, inspection details, recalls, warning letters, and the CFR [Code of Federal Regulations]-can be examined to help identify compliance risk and determine what problem areas to address first, to avoid past mistakes, or to audit vendors," explained Rafi Maslaton, president at cResults Consulting, in a presentation at the ISPE event. His company has developed a platform called FDAAWARE, which creates a database of these public data and uses software to analyze and extract useful information, in conjunction with an advanced projection algorithm to assess specific sites and overall company compliance related risks.