DIFFERENCES BIG AND SMALL
All CMO pharma manufacturers will face challenges, with regulators, with quality processes, with operations on the road to compliance and commercial success, says Lam; in the cGMP world order he accepts that contract biopharmaceutical manufacturers may be particularly challenged. “In the small molecule world, the focus is a lot more about — because we can characterize the final product so well — that you can put in a lot of testing and quality control to assure QA and make sure that it’s safe, high quality and meeting all the expectations of identity and all the detail things that one can do to characterize it,” explains Lam.
“But it’s well known that for biologics, the process is the product. For small molecule [compounds] there’s a lot more focus on the end product, because the product is well characterized to begin with,” says Lam. “However, from a compliance perspective, regulators are actually putting more and more emphasis on process because it’s a biologic, it’s so difficult to really fully characterize the product.” Lam says the entire process is important from a regulator perspective, and that it is important self-impose requirements to make sure the entire process is well characterized because with biologics one cannot fully characterize the final product.
Managing toward operational excellence is more or less mandatory and Lam agrees. “I cannot tell you enough how important it is, not just to the regulator. I think it’s a good thing to do, as a manufacturer, to be able to continue to look at what are the potential risks in your process that may not allow you to make the products that you need to make.”
Lam explains that there are doubts about QbD because it’s so complicated and it requires so much work that some regulators are realizing that full-blown QbD may be the provenance of only a few really big manufacturers because they are the ones who can afford it.
“But let’s not throw away the baby in the bath water,” says Lam. “It’s a fact that it’s difficult to do, perhaps we need to just agree that sure it’s a great concept and always strive to look at and understand process and keep working on implementing it to meet its intent.” Lam notes that the industry and regulators are evolving in that direction.
“I think that regulators are really concerned about shortages and again it’s about what I said right from the beginning. It’s about balance; it’s about needing to have high quality products and make sure that patient safety and quality, as well as availability are delivered,” Lam concludes. “The regulators really want to work with the industry to make sure that we have this quality culture; that throughout the entire lifecycle of the process, from development to getting approval to post approval, there is continuous monitoring and improvement. I totally understand where the FDA is coming from, and I agree that it is the right thing to do and the right way to do it.”