Proving Biosimilarity

How did you get into (bio)analytical science?

At school I was always into medicine. I initially wanted to be a surgeon but had second thoughts. I knew I wanted to be involved in science though, and was extremely interested in microbiology, so I went to university to do a degree in Food Science and Microbiology. That was back in the late 1970s – at the start of the biotechnology industry and the use of microbial fermentation. At that point, I got sidetracked into analytical chemistry by a Masters in forensic science, before becoming very interested in analytics and doing a PhD at Aberdeen University in Protein Chemistry. Many years ago, a Bulgarian diplomat was killed with ricin from the castor oil plant. I worked with a similar toxin, a lectin from the kidney bean plant (which is not as potent as ricin); it was very interesting to isolate this toxin and look at its capabilities. I think it was this investigative nature of analytical chemistry that piqued my interest.

My PhD was actually spent between Aberdeen University and the Rowett Institute for Nutrition and Health, where they had one of the first gas phase sequencing instruments – a piece of kit that was revolutionizing protein sequencing at the time. Around the same time, Howard Morris, FRS (professor of biochemistry at Imperial College London) was setting up a company (M-Scan) to use mass spectrometry to sequence proteins – pioneering work. I joined Howard’s company in 1984, where we initially used an ionization technique called fast atom bombardment (FAB) to sequence a variety of proteins and glycoproteins from the new biotechnology industry. That was my first foray into applying analytical instrumentation to biotech problems.

Sounds like an exciting field...

It was! But actually, protein science was not very trendy at that point – everybody wanted to be a geneticist or molecular biologist. Up until that time – and even during that time – a lot of the scientific focus had been on genetics, working on constructs that could express proteins. It wasn’t until they’d succeeded in engineering and process development that they needed protein science to confirm that the product was the right one. To begin with, we were a small operation, about five or six people in the UK. But by 2010, we had four international sites operating with about 65 people. We had a reputation as the foremost protein and carbohydrate structural lab offering analytical services. At that stage, all four labs were acquired by SGS.

So biosimilar characterization was a natural progression...

Right. You can’t proceed onwards with either the FDA or EU pathway until you’ve shown biosimilarity at the analytical level. And the biosimilar boom has really driven analytical science to apply new techniques, as well as to use techniques that have been around for a while but perhaps needed updating. It’s fair to say that things have come on apace since the first biosimilar was given authorization in the EU in 2006! Seven or eight years ago, people didn’t think we would ever have biosimilar mAbs – the analytical and clinical challenge appeared too great. The EU now has over 20 biosimilar products, including monoclonal antibodies (mAbs). And we have about 100 different orthogonal techniques that we can use to look at the structure of a biosimilar in a comparative way.

Is staying at the cutting edge important to you?

Very much so. In the beginning, we were a very small, privately funded company; we had to keep driving forward so we could offer new techniques and capabilities to survive. And it wasn’t just about running the instrumentation – determining the analytical strategies and interpreting the data were also crucial to solving problems. It’s actually a considerable time since I wore a white coat in the lab, but with SGS I’m still focused on pushing forward our capabilities in the laboratories – ensuring that we keep introducing the most up-to-date, properly qualified and validated techniques.

What has kept you in the same company for so long?

The interest and excitement. The field has developed rapidly – driven by the challenges we were given by the biotechnology industry. When I first started, we were using a state-of-the-art high-field magnet mass spectrometer made by VG – now Waters – and the largest intact molecule it could look at was probably 6–7,000 Daltons. We had to drive forward both the instrumentation and the ionization techniques to be able to look at intact proteins at high sensitivity and perform MS/MS sequencing. We picked up electrospray very quickly along with MALDI-TOF and Q-TOF instrumentation. Biotechnology is a global industry and I have worked around the world, interacting with a lot of very bright scientists who were setting up companies, trying to exploit their research and bring it through into a commercial product.

Why do you think you’ve had such a successful journey?

Sheer bloody-mindedness! Everybody makes their own choices, and maybe I was lucky in that I chose something that I enjoy doing. I get intellectual stimulation from working with very bright people, and it’s scientifically rewarding to look at the new techniques that are coming through and to try and introduce them to the labs that I work with.