For over a decade, BioProcess International has considered analytical methods to be such an integral part of biopharmaceutical product and process development — across the board — that in our rotating thematic arrangement of issues (upstream, downstream, manufacturing, and the new bioexecutive theme in December) we never thought to include a separate “analytical” theme. After all, production process development (the focus of our January, April, and September issues) involves cell-line engineering and characterization, media optimization studies, and methods validation. Downstream process development (February, May, and October) involves viral safety issues, chromatography optimization studies, and more validation work. With its focus more on product than process, our manufacturing theme (March, June, and November) has often encompassed preformulation/formulation work and product characterization as well as quality assurance and control.
When we looked at the evolving approaches to FDA’s quality by design (QbD) initiative, it all made sense to us. You can’t have any of those things without a strong analytical laboratory and documented understanding of process and product. The dawning biosimilars era underscores our case. The only way that such products can be offered to patients at lower prices than their corresponding originator drugs is if they can be made more efficiently, at less cost, without compromising quality, safety, or efficacy. So how will biosimilars manufacturers do that? They need to cut out expensive clinical trials, for one thing — and the only way to do so is through intense product characterization and comparison with originator samples. And brand new products such as antibody–drug conjugates are presenting greater characterization challenges too (we’ll be looking at those in depth with a fall 2014 supplement on the topic).
Once again, enter the analysts. Is it any wonder that we saw fit to start our “BPI Lab” series in January 2013? So far, I’ve covered some of the most vital technologies to biopharmaceutical laboratories under the auspices of that title: LC–MS, PCR, spectroscopy, electrophoresis, and more. Later this year, I’ll be looking at calorimetry, light-scattering, and circular dichroism. These are just some of the critical technologies that you’ll see providing data in support of numerous presentations throughout this year’s BPI European Summit program. They’ll even take center stage in Conference 4. And in upcoming editions of BPI’s weekly e-newsletter series, analytical methods will be getting their own focus once a month.
It is true that as analytical methods increase in power, selectivity, and resolution, biopharmaceutical companies may find themselves in a vicious circle: the more you can find, the more you will find. For example, a biosimilar version of a product originally approved 20 years ago may seem to have contamination issues that the originator didn’t — because modern analytical technologies are able to identify contaminants that were not detectable before the turn of the century. In fact, the comparator samples may turn out to be even more contaminated, and perhaps biosimilars makers can document that as part if their own market-authorization application process. It all remains to be seen.
So the modern question becomes, “How much analysis is enough analysis?” Regulators around the world seem to be saying, “Keep looking. Keep up with advancing technology. Keep us in the loop.” QbD and the process analytical technology (PAT) that supports it seem to have arisen at least in part from the FDA’s, EMA’s, and others’ acknowledgment of the analytical advances we’ve seen over the past couple/few decades. But how much are the “watchmen” really able to keep up with this stuff, themselves? And who wants to be the first company to present (and explain, and justify) a new method in its product dossier?
It’s a sticky, tricky issue — and one that won’t be solved any time soon. But the kinds of discussion you’ll find at BPI Europe and in BPI itself are vital in moving us all toward some kind of solution(s) as the industry evolves and continues to mature. And I’m curious about your thoughts on this subject in general.