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Spotlight on R&D: Geoff Platt, Technology Specialist

This week we spoke to Geoff Platt, Technology Specialist based at our Head Office labs in the UK. Keep reading to learn more about Geoff's background, Protein Delivery challenges, innovations and the posters he will be presenting at BioProcess International Europe...

Geoff Platt on purple background

Can you share a bit about your background and what led you to work in protein delivery research?

I have a long-standing interest in protein science and started work on proteins 25 years ago during my PhD. I spent a number of years in academia employing molecular biology and biophysical characterisation methods to conduct research on protein structure, stability, folding kinetics and aggregation. I have since worked in various biotech companies including one where I developed applications for a high-throughput instrument used for measuring thermal stability of proteins, which allowed me to collaborate with formulation teams in various pharma companies. Elsewhere, I designed a novel Affimer protein scaffold that could act as an alternative to antibodies by displaying peptides from a large library. I led an R&D team tasked with a range of functions that included developing bioprocessing, therapeutic and diagnostics applications for this technology.

What are the biggest formulation and stability challenges in delivering protein-based drugs?

Proteins are large complex molecules whose function depends on them maintaining a specific three-dimensional folded state. As the maintenance of the folded native state of a protein depends on multiple weak non-covalent co-operative interactions the conformational stability of proteins is often marginal. If the protein structure is perturbed by stresses such as increase in temperature, changes in pH, light stress, interaction with interfaces or chemical modification it can lead to unfolding and misfolding, with a consequent loss of function. In addition, unfolding may lead to exposure of aggregation-prone residues that are typically buried in the core of the native state. Aggregation of proteins is one of the most common routes of degradation and can promote unwanted immunological reactions for proteins used as biologics. Exposure of the native state to chemical stress can also lead to various negative effects such as alteration or loss of function if amino acids vital to function are modified or polypeptide chain fragmentation occurs. All of these considerations present challenges in how proteins are designed, produced, handled and stored – but it is also what makes studying proteins interesting! Stability of biologics can be optimised by considering the developability of candidates from an early discovery stage and selecting leads accordingly, by rationally redesigning lead proteins to alter residues or sequences that may present a potential weakness for a particular degradation pathway and by optimising formulation to ensure high thermal and colloidal stability of the proteins. A good example of this is reducing interactions of the proteins with interfaces by inclusion of stabilisers, detergents and optimising pH. In recent times developability and formulation studies have been performed in a highly efficient fashion by using DOE and Bayesian methods allied with a battery of analytical techniques.

Are there any emerging technologies or approaches you find particularly promising?

I have been interested in the rapid growth of the ADC field in recent times where the specific targeting ability of mAbs is being applied to deliver various cytotoxics of increasing potency to solid tumours. In recent times the range of conjugates used is being diversified to include radioligands and siRNA, it will be fascinating to see how formulation challenges for these molecules are surmounted as consideration has to be taken not just for the stability of the antibody but also that of the linker and payload too. Peptide drug conjugates (PDCs) are also an emerging field. They are much simpler molecules to manufacture than ADCs and have the potential to penetrate tissues more effectively and deliver cytotoxic molecules in specific tumour microenvironments. Once more, improving stability of these molecules is a key hurdle for success.

What are some key manufacturing hurdles in protein-based drug development?

One of the contributors to the high cost of biologics is the requirement for complex processing steps. Any progress made to make these steps more efficient or reduce any negative impact on the protein quality will help make them more economical. In particular, protein A affinity columns have greatly facilitated the use of antibody formats as pharmaceuticals as they provide a highly specific and effective platform purification step. However, over time, as the antibody titre from upstream processing has increased, the affinity capture step can become a bottleneck. In addition, the elution steps occur at low pH which can be detrimental to protein stability, especially for complex formats such as bispecifics. Recent developments in column formats where microfibres are used instead of beads can lead to better mass transfer and allow increased flow rate and column capacity thus potentially reducing the bottleneck. Furthermore, redesigned versions of protein A ligands can allow elution of the biologic under milder pH conditions or provide a capture ligand with increased robustness to the harshly caustic conditions used during cleaning-in-place washes and extend the column lifetime. I’m really curious to see how far these developments can go as I have designed and generated protein ligands for affinity chromatography in the past.

How do you think AI and machine learning will impact protein drug development?

I think one of the most exciting areas has been the huge opportunity in drug design created  since the release of AlphaFold and subsequent AI tools, which enabled the ability to accurately predict protein structure. Target epitopes can be defined and then rationally designed molecules can be screened against them. This AI approach is being used to design mAbs, the most established biologic format, but work is also ongoing to create novel protein molecules, some of which are unlike any that exist naturally.  It will be interesting to see if these novel formats find their way into the clinic and how potential stability and bioprocessing challenges are overcome. It may amplify the requirement for formulation developability studies and necessitate reassessment of the current excipient toolbox.

Share something we don't know about you...

Sometimes I’m persuaded to play for the second XI at my local cricket club – last year I had a batting average of zero, so I’ll probably be waiting a while for a call up to the England team!

Can you tell us more about your poster presentations at BPI Europe 2025?

We have two posters at BPI Europe describing a number of Croda’s products for bioprocessing. We will present data to demonstrate how Super Refined™ Poloxamer 188 surfactant has been optimised for cell culture by controlling hydrophobic impurities and ensuring dependable batch-to-batch performance, this results in consistent high cell density and viability for CHO-S and HEK293 suspension cells. In addition, we will describe a study to identify two sustainable, compendial grade GMP detergent substitutes for Triton X-100, which has been banned in Europe due to environmental concerns. Our alternative detergents (Virodex™ TXR-1 and TXR-2) display excellent kinetics for viral inactivation and demonstrate the ability to efficiently lyse mammalian cells.

Virodex TXR-1

Virodex™ TXR-1

Virodex™ TXR-1 is a readily biodegradable, nonionic surfactant for viral inactivation and cell lysis, meeting the needs of biopharmaceutical applications as an effective and safe replacement for the...
Virodex TXR-2

Virodex™ TXR-2

Virodex™ TXR-2 is a 40% biobased, nonionic surfactant for viral inactivation and cell lysis, meeting the needs of biopharmaceutical applications as an effective and safe replacement for the...

Super Refined™ polysorbates for biopharma applications

protein delivery
4.3 MB
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Virodex™ TXR-1 and TXR-2: Safe and effective viral inactivation and cell lysis

Front cover of virodex brochure
1.7 MB
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