Q&A Session with Biosimilar Roundtable Panelists – Dr Andrew Reason

Q&A with Dr Andrew Reason

Andrew is Managing Director and CEO of BioPharmaSpec, with over 25 years of experience in the commercialization of analytical methods for characterizing biopharmaceuticals.


FG: I have had the pleasure of working with you, Andrew, many times over the years- firstly with M-Scan and then SGS, so it’s nice to be back discussing topics that we are both really enthusiastic about. But before we get into too much detail, can I ask what attracted you to a career in Analytical Chemistry?

AJR: My Dad was an industrial chemist and worked for BP and British Gas for many years and I used to go with him to his lab on the weekends. That led me to have an interest in chemistry and through school and college I became interested in medicine and in particular, the design of drug products for the targeted treatment of various cancers, which was in its infancy at the time. This led to a degree in Biochemistry and a PhD in characterizing proteins and glycoproteins using mass spectrometry.

FG: It’s great to hear that science runs in your family! I’m sure that you too have inspired many young people to consider a career in biological sciences.

With all your experience in protein characterization, I wonder what you would you say were the most significant developments in analytical instrumentation during your career?

AJR: There have been many but I’d say that the most significant over the last 30 years or so have been improvements in the ease of producing high quality data and in the sensitivity and resolution of instrumentation for biopharmaceutical characterization.

For example, the Q-TOF mass spectrometer, a concept invented by BioPharmaSpec’s CSO Prof Howard Morris in the early 90s, has revolutionized peptide mapping and peptide sequencing. This technique enabled us to determine the primary sequence of proteins and glycoproteins in a time efficient manner for the first time and also allows determination of intact molecular weights of proteins and glycoproteins within 0.01% of the actual mass.


FG: Indeed, this breakthrough in mass spectrometer geometry certainly unleashed the full power of MS for structural analysis. What then, are the other main techniques you consider essential to utilize when carrying out comparative biosimilar analyses, for example, and why are orthogonal methods important?

Peptide Mapping which provides an overall assessment and comparison of the protein backbone and any Post-Translational Modifications (PTMs)
Intact molecular weight analysis which provides the intact molecular weight of the product and also assesses intactness plus the potential for N- or C-terminal truncations
Glycosylation profiling (for glycoproteins) – to provide an overall assessment and comparison of the glycans present on a product
Charge profiling performed usually using imaged capillary IsoElectric Focusing (icIEF) to allow an overall assessment and comparison of the isoforms of a product and provide insight into potential deamidation, sialylation levels for glycoproteins and levels of Heavy Chain C-terminal Lysine for monoclonal antibodies.
Secondary and tertiary structure assessment the technique used for this assessment and comparison depends on the product and the concentration of the active ingredient in the analysis sample, Circular Dichroism (CD) being the most used technique in this context.
Aggregation assessment to provide an overall assessment and comparison of the aggregation profile of the product, usually performed using Size Exclusion Chromatography with Multi-Angle Light Scattering (SEC-MALS).

Orthogonality is important to provide confidence in the findings and all of the above elements should be assessed using at least two independent techniques with conclusions drawn from a consideration of all the data. As we both know, for any comparability study data, all the structural and physicochemical requirement in ICH Topic Q6B needs to be provided.

FG: Of course, the Appendix of ICH Q6B does provide a useful aide-memoire as to what is required. I understand that BioPharmaSpec works mainly at early-stage development, applying the full panoply of ICH Q6B methods. What is your philosophy regarding qualification/validation of these methods?

FG: Thank you Andrew for sharing your thoughts on biosimilar comparability analysis and providing a useful summary of core analytical techniques. I look forward to chatting with you  in future roundtables.