....18 Dec 2017 21:32
Why are you seeing the need for in-process mass spectrometry for biologics that you perhaps weren’t seeing for traditional drugs?
A4: I think that’s the key question and it really is where the true benefit of mass spectroscopy for bioprocessing to be seen and I think it’s quite a detailed response actually.
So, I often compare the two, the biologics and the traditional. If you look at traditional small molecule pharmaceuticals, they’ve got a comparatively simple structure, they’ve also got very well-defined production methods and what it means, in essence, is that these drugs are relatively insensitive to change.
The difficulty we see with biologics goes back to how these drugs are manufactured by cells and the drugs structure or complexity, they’re very large molecules often being 30,000 atoms in size versus 30 for a small traditional drug. The complex structure is very sensitive even for the smallest change in a host of different factors and these can include really anything from manufacturing parameters, differences in raw materials, storage. Even then, when you think you’ve got it defined, unwanted unknowns may introduce problems with the final product or actually with the still very high value intermediary products. Slight changes in structure of the biologic renders them useless or they can actually be potentially lethal and also, any harmful contaminates such as the remnants of the host cell protein can also cause a really nasty and often lethal immune response.
So, it’s really because of these risks that when the FDA grants their biologic licence to a biopharma company, they not only have to consider the product but also the process and the equipment so it’s really much wider than you would consider for a traditional drug. I think in recognition of this task, what the FDA does is to provide guidance of what it calls ‘Quality by Design’ or QbD and that covers four areas and these areas are actually very important for us. It covers four areas, that is the drug’s critical quality attributes to make sure that they meet key physical chemical and biological attributes of the drug itself. The second is that the drug companies identify the critical material attributes the incoming materials, the third is that the manufacturing process conforms to critical process and then that there is a relationship between that whole lot. In other words, basically what the FDA is saying is that things can’t be left to chance.
So, I suppose the punchline here is really what pharma is looking for is very much real-time, powerful analysis that’s needed in many access points across the process, in raw incoming goods, the upstream in sold drug production and downstream purification. All of these areas represent a potential commercial entry point for us, traditional technologies just don’t have the power for that sort of high structural confirmation I was just talking about