Back in 2002 the FDA announced an initiative to shift regulation of drug manufacturing to a more process-centric validation approach, as opposed to the current product-centric one. Process analytical technology (PAT) was set up to optimize manufacturing and reduce resistance to the use of new production technologies.
PAT requires real-time measuring of process variables using sensors, computer analysis, control technology, and continuous improvement data analysis. While PAT is voluntary, the FDA appears committed to encouraging its adoption by offering reduced regulatory oversight burden, which might result in faster approvals.
To determine how and where within the implementation process the industry currently stands on PAT, we surveyed companies about their PAT implementation plans. We found that nearly 58% of the 434 industry respondents are considering PAT for new processes vs. 42.6% for existing processes. Although, only about 3% have already implemented PAT initiatives. About 3% indicate they will not implement PAT for new processes. The study shows that PAT implementation appears to be considered more often for new rather than existing processes. This may be the result of perceived regulatory difficulties in adding or changing monitoring procedures.
“It is somewhat surprising that the difference in what is being implemented for new vs. existing processes is relatively small (2.8%),” explained Beth Junker, senior director, bioprocess R&D, Merck. “The gap is large (15%) for processes being considered for PAT implementation, reflecting a potential industry perception that it may become harder in the future to implement PAT for existing licensed processes.”
With all the potential good from PAT, many have asked why relatively few facilities have implemented it. As John Walker, vp of engineering at Merck, noted, quality-by-design and PAT require an integrated approach to product and process development. The drastically reduced tolerance for variation that PAT brings means that much of the current equipment is not appropriate for use with PAT.
That leaves three options, Walker said, live with the existing equipment, do not pursue PAT and endure the closer attention of the FDA, reduced yields, and higher costs of production; upgrade the existing integrated equipment with PAT front ends; or introduce capable integrated equipment with PAT-based controls.