Dr Gillian Woollett: The Importance of Consistency in Quality Analyses

Gillian Woollett, MA, DPhil, senior vice president, Avalere Health, explains the importance of consistency in applying critical product quality attributes.

Transcript:

Biosimilar development has brought to light the fact that some reference products, like trastuzumab, have undergone significant shifts in some crucial quality attributes. How concerned should we be about these shifts?

The good news is we have one science worldwide. The idea that quality attributes have varied—that's true—but they've generally speaking varied within a range that means that there is no change in the clinical outcomes of those products. That is the whole point of comparability, which supports manufacturing changes using critical product quality attributes; that system FDA led the world with in 1996. So applying that science consistently, both for manufacturing changes, and for biosimilars is very, very important. And if there's one mantra I have, it's the same science for all. No regulatory authority is judging a business model. So in the case of trastuzumab, indeed, there would appear to be a analytical variation and fucosylation that has led to a change in antibody dependent cell cytotoxicity. That's a problem. But I think it's solved just as [innovator epoetin] Eprex was when we also had a comparability problem with a manufacturing change, nothing to do with the biosimilar. It's solved by instituting very careful quality analyses that takes us back to the critical product quality attributes, and so we just apply the same tool. Now, there may be cases when you've made a manufacturing change that indeed, you should have clinical studies because let's remember, when we have a manufacturing change, there's automatic extrapolation. It's automatically interchangeable with itself and the label and the product doesn't change. I think this issue of the variation in the innovator over time is something that everybody needs to understand that it's not the biosimilar that's only similar, it's that all biologics vary batch to batch and certainly after a manufacturing change. So the single message is, let's be really careful when we apply manufacturing changes, do the analytics, and do them exactly the same in both situations, whether it's a manufacturing change or an originator, whether it's a biosimilar or indeed a manufacturing change to a biosimilar.