Pharmaceutical Plants Embrace More Sustainable Processes
That PAT can support corporate environmental objectives means that it will continue to gain favor as a mechanism for sustainability. “It doesn’t have to be a big bang,” Ertl says. Small and incremental improvements in developing green and sustainable processes will reap sizeable benefits in the long run.
QbD: Green by Nature
Ertl, interestingly, does not see Quality by Design as going hand in hand with sustainability. QbD’s guiding premise (at least how it is practiced in industry) is to get drugs to market faster, with greater quality, which can come at the expense of efforts to reduce waste, use fewer solvents, and so on.
David Ager, principal scientist for DSM Pharmaceuticals, also questions whether QbD directly supports green practices. As a CMO, DSM is under pressure from the customer to be “first time right,” Ager says. “QbD helps us in this effort, especially when a candidate moves down the development pipeline. But QbD and the sustainability considerations have to be taken as two different variables, and for drugs, quality is the dominant factor.”
The savings and cost reductions derived from designing green processes “usually result in a better process but this may not be more robust or streamlined,” Ager continues. “There are examples where a greener process uses an extra step compared with the original route; the two-step process giving a higher overall yield and allowing a catalytic step rather than use of a stoichiometric reagent. The different parameters given in the responses are interdependent and, in many cases, process specific.”
In contrast, Julie Manley, president of the sustainability consulting firm Guiding Green, LLC, sees an organic connection between both PAT and QbD and sustainability.
Metrics such as process mass intensity, or PMI, can be a key in helping manufacturers to monitor and reduce the impact of their processes, and Manley believes that when manufacturers say they are using environmental metrics to measure their processes, it may misrepresent how well such metrics are understood and used for improvements. Manufacturers in the past may have measured the environmental impact of their processes for compliance reasons, she suggests, rather than for reasons of sustainability and reduced impact. Recognizing the culture shift to incorporate non-regulatory characteristics as critical attributes, Manley believes incorporating sustainability criteria as critical process parameters is still a newer concept.
Both PAT and QbD have obvious potential for greening processes, she continues, and are well aligned with accepted principles of green chemistry. It should also be noted that they are widely viewed as congruent with continuous processing and the use of microreactor technologies, which are starting to make an impact in the industry and helping manufacturers improve the environmental profile of their processes.
Bio's Big Chance
Biotech processes stand to benefit tremendously from the current green revolution. Carroll of Cadrai Technology has noticed that in his conversations with manufacturers around the globe, it’s usually only the bio folks who bring up green and sustainable processing, because the payoff—from a cost or environmental standpoint—is much clearer. Bioprocesses are by nature slow and complex, and thus it makes sense to leverage QbD principles to design a faster, more robust (and presumably more sustainable) process.
Specific PAT applications also have rich potential in biopharma, he says. “PAT can be used to wind down a fermentation process two days early, and there’s some serious money involved in that”—namely, because of the tremendous energy savings. The larger the equipment, the more obvious the green benefit is, says Carroll, and they don’t come much larger than, say, a 20,000-liter bioreactor.
Playing the Green Card
Several of our survey respondents indicated that green chemistry or process optimization projects have been derailed by the recent economic recession. One said that, in the wake of the crisis, all that mattered was product safety and business contingency.
But aren’t greener processes always good for business (not to mention safety)? It depends on how you look at it, says GSK’s Ertl. From a business standpoint, you want to make molecules quickly and cheaply. Going green may make a process more expensive, Ertl notes, or sacrifice yield or quality, as happens sometimes when moving to processes using aqueous-based solutions.
“These are the balancing acts that scientists do every day,” he notes. At GSK, there is a strong top-down mandate (starting with CEO Andrew Witty) to tip that balance toward environmental responsibility.
The potential of PAT and QbD to pay green dividends is real, says Jason Kamm, principal with Tunnell Consulting, Inc., and this potential is not lost on operations managers and project leaders. It’s hard enough to justify expenditures and time commitments for PAT and QbD programs, he says, so playing the environmental card is one more way to get upper management support for such initiatives.
From a PAT standpoint, new testing and analytical technologies have enabled energy saving and other benefits that might not have been realized in the past, Kamm says. “They don’t add up to huge dollar savings, but at least they’re headed in the right direction” towards lower costs and greener and more sustainable processes, he says.
It’s imperative, says Kamm, to keep the environmental consequences of processing decisions from being an afterthought. “You should always think about how [PAT/QbD and sustainability initiatives] fit together,” he says, “There are a lot of synergies to be realized.”
If anything, PAT, and to a greater degree, Quality by Design, present industry with a mindset that is open to change. QbD, says Kamm, changes the regulatory dynamic that in the past might have stifled creativity and process improvements. When a manufacturer starts to launch QbD projects, “a lot more of the improvement ideas can be left on the table,” and a lot of these ideas will aid more environmentally sustainable manufacturing.
This article originally appeared in our sister publication Pharmamanufacturing.com