The Process Analytical Technology (PAT) initiative has made its name as a mechanism for monitoring processes in real time, facilitating process understanding and, in some cases, real-time release of product. With PAT, the focus has been on monitoring Critical Quality Attributes and controlling Quality Critical Process Parameters, and to a lesser degree manufacturing efficiency. It may be time to add sustainability to the list of PAT’s objectives. PAT practitioners are beginning to take a green view of their activities.
It’s an idea whose time has come, says Darryl Ertl, manager of GlaxoSmithKline’s PAT group in the Research Triangle Park. Ertl’s group at GSK concerns itself primarily with API research and development, and has used PAT (as well as Quality by Design) to optimize the synthetic route and produce robust manufacturing processes. Only recently has it started to focus on sustainability. It just makes sense, he says. “We can use PAT for so many things—control, creating a design space, making processes robust, and so on,” he says. “Why not energy and cost savings, too?”
PAT has implications for solvent and waste reduction, but energy savings figure to get the most attention due to recent increases in energy costs, and the risk involved in dramatic fluctuations in those costs.
One piece of low-hanging fruit, Ertl says, is drying. In a typical manufacturing facility, it’s common for operators to keep dryers running while product is pulled, taken to the lab for testing, and sometimes resampled and retested. “If you have a material in the dryer for an additional five, six, seven hours, that’s a lot of energy especially over the course of a year,” Ertl says. Sampling via PAT can help optimize the drying process and avoid this unnecessary energy usage.
Another potential area of interest is equipment cleaning. Using PAT to gauge the completion of cleaning processes is an easy way to reduce the use of cleaning solvents and cut down on energy usage due to lengthy hold times at reflux.
Still, the Green PAT idea is in its infancy. The question of whether or not PAT can be used to leverage sustainability was recently posed by Genentech’s Tina Larson, associate director of Process R&D, on LinkedIn.com’s Process Analytical Technology discussion group. Several members from the manufacturing and vendor community chimed in. Judging from the responses, the answer is yes, though the idea is still in its infancy.
Energy savings and sustainability have always been secondary or tertiary considerations for pharma PAT implementations, but they are nonetheless gaining in importance, noted Picarro, Inc.’s Gregor Hsiao. “For pharma/biotech companies it is lower on the priority list (process yield, purity, and cycle time dominate) but has taken on renewed importance with the green chemistry push.”
“Energy savings must be realized by implementation of the appropriate PAT in a unit operation such as fluid bed drying, simply by prevention of over drying,” wrote Paul Davies, president of Expo Technologies. But is it happening out there? After some research, Davies admitted that he knows of no instances in which energy saving was a stated goal of a PAT project.
NNE Pharmaplan’s Alex Brindle noted that at one facility in North Carolina, PAT is used extensively and in part “to save water and potential damage to the environment.”
Why is the idea taking so long to take root? PAT teams have had other priorities, Ertl says. With every project from here on out, Ertl and his team plan to establish a matrix by which they can measure and monitor energy savings and other sustainable aspects of the project.
Leveraging PAT for energy savings is something that Ertl, as a scientist, is excited about and committed to. But he’s also a realist. Promoting corporate (and environmental) sustainability is one more way for drug manufacturing teams to validate their work in PAT and justify future investments.
We talked with Darryl Ertl about the potential of PAT to address issues of sustainability:
PhM: Looking at PAT from a perspective of sustainability is just starting to happen—what are you hearing from your industry peers?
D.E.: I think all industry is looking for ways to save money and have heard that others are starting to look more closely at how they can leverage using their existing PAT equipment for sustainability.
PhM: If the “PAT for Sustainability” movement is just catching on, has anything been holding it back?
D.E.: Reasons probably vary from company to company. Equipment and installation costs sometimes prohibit implementation due to return on investment criteria. For those companies that already have the resources, often times it’s due to the lack of “Pull” from the manufacturing area.
PhM: Is it likely to be top-down or bottom up movement in most companies? Who or what will drive the trend?
D.E.: To be successful it really needs to come from both directions. There needs to be a “Champion” in the area that wants to incorporate PAT to reduce energy, and you also need the technical experts to understand the expectations and deliver.
PhM: Most major manufacturers have corporate energy managers, heading up comprehensive sustainability programs. Should they be more involved in PAT discussions and programs? (Have you had any discussions with these folks at GSK?)
D.E.: I think that PAT is one potential aspect for Sustainability that is probably often overlooked. Many people are unaware of the capability of the technologies available today. Often times project teams are looking for large savings on a particular project rather than small savings on many projects that add up to be very significant over time.
PhM: Is there a need for focused industry discussion around the topic (including input from FDA), or do you see it happening more organically as companies see the broader benefits of PAT?
D.E.: I think that once people start talking about the success they have and the financial benefit that other companies will follow.
PhM: Is technology ready for PAT efforts that focus on sustainability, or can the vendor community improve instrumentation that monitors energy during processes or develop software that helps manage green process parameters?
D.E.: The tools are currently in place and have been applied successfully in the chemical industry for some time. From a previous experience I am aware of a particular installation that saved millions of dollars in waste and controlled a manufacturing process 24x7. Equipment is robust and software has simplified applications.