Developing Analytical Techniques for Biotherapeutics

insights from industryDr. E. Neil LewisChief Technology OfficerMalvern Instruments

News-Medical talks to Dr. E. Neil Lewis about the development of analytical equipment for a new era of drug development.

Could you provide a brief history of Malvern Panalytical’s Bioscience Development Initiative and why this was first established?

While there is still large-scale investment in traditional small molecule pharmaceuticals, the past decade has seen a major shift towards the development of biological molecules for therapeutic purposes.

Drug development - therapeutic drugs - a photo By Tono BalaguerTono Balaguer | Shutterstock

The industry has moved beyond basic monoclonal antibodies and is starting to reap the rewards of intensive research that is bringing more sophisticated molecules to the fore and is simply reinforcing the huge potential of the biopharmaceutical approach in managing a whole host of medical conditions.

As suppliers of analytical instruments to the pharmaceutical industry we find ourselves in an environment that is undergoing radical and extraordinarily rapid change, and one that is challenging some established processes and business practices.

Such is the pace of change that those at the sharp end of biopharmaceutical research need analytical tools that will solve today’s problem, not last week’s, and we may not even know what will be needed next week. This is new territory and is bringing fast evolving analytical and regulatory challenges to researchers and instrument providers alike.

With this as the backdrop, Malvern Panalytical launched its Bioscience Development Initiative (BDI) in 2012. BDI is incorporated in the US, operates from a facility in Columbia, Maryland, and is decentralized. Although an integral part of Malvern Panalytical, the BDI is a separate development group that is focused on intellectual property and addressing the sea change in the pharmaceutical industry.

It has been established to partner with industry players and to encourage them to share their analytical challenges. Through it we can identify and target an emerging technology, quickly assess its potential and, where appropriate, fast track its further development.

We can look at technology licensing and acquisition and can push fledgling ideas straight into the biopharmaceutical companies for rapid learning, bringing those companies directly into the development loop and enabling them to help direct it, at a low risk to themselves.

Why is the development process of biologic materials complex compared to that of small molecule drugs? How is the testing process different in comparison to the testing of non-biological systems?

One of the most widespread means of delivering a small molecule pharmaceutical substance is as some form of solid dosage, often a tablet. When this is the case development, manufacturing and quality control follow more well-established paths. However, where proteins, and other biological molecules, are concerned we’re in different territory, where the active is grown and not synthesized, and is usually delivered in solution by injection.

Moreover, the structural complexity of biological macromolecules has enormous implications for their stability, and therefore their efficacy and safety, in therapeutic formulations. Testing processes for this new world of biotherapeutics, and the analytical technologies required, are very different from the methods traditionally employed in the pharmaceutical industry.

As well as the complexity of biological molecules there are economic issues, and these too have a bearing on the analytical techniques that are needed. The cost of producing bio-therapeutics is significantly greater than for small molecules. One of the consequences is that, at the development stage, you have only minute amounts of exceedingly high value material available for testing.

In small molecule drugs, the key attributes that determine purity and potency are generally well known. Furthermore, they are established, measured and controlled using proven analytical techniques. It is much harder to define purity and potency for proteins harvested from biological cells, when the proteins themselves can be a source of contamination through aggregation, misfolding or denaturation.

So, analytical technology must address a variety of requirements at different stages of the development process. For example, selecting the right candidate molecule, post-discovery, to take forward involves physicochemical testing processes designed to exclude molecules likely to present formulation, delivery or manufacturing problems further downstream. Viscosity and stability issues may rule a molecule out of further investment, but to reach that conclusion a whole battery of tests have to be conducted on the smallest amount of sample.

How is the development process of new analytical technologies related to this initiative different when compared to traditional development pathways? What are some of the benefits of this and are there potential drawbacks?

Underpinning Malvern Panalytical’s BDI is the recognition that to serve the needs of the biopharmaceutical industry we have to have shorter, tighter customer-facing development cycles. We also have to acknowledge that not only is the industry changing but the regulators are also catching up. The regulatory environment is one of evolution and biopharma companies have to keep pace, whether they are dealing with biosimilars or determining the efficacy and safety of a novel biological product.

Traditional analytical instrument development processes are not sufficiently nimble to keep up with the rate of change that is taking place. When you are trying to meet today’s analytical challenges while anticipating rapidly evolving market requirements, the more typical costly and lengthy engineering processes based upon developing a requirements specification, producing a prototype, testing it against the requirement specification followed by large scale manufacturing and a full blown product launch, just doesn’t work. In many cases we are developing products that involve new market development as well as new product development.

The Bioscience Development Initiative forms a bridge between the universities and small technology start-ups and the biopharmaceutical companies. Uniquely we can take embryonic ideas and put them straight into our biopharmaceutical partner companies.

Once they’ve experienced the technology and together we’ve been through an iterative learning process about it and its likely applications, it can be quickly put aside if it’s not immediately useful, or if promising moved through to Malvern Panalytical’s established engineering and product management teams. Here a wealth of experience built from many years of developing, manufacturing and marketing analytical instrumentation takes over.

From the biopharmaceutical companies’ perspective, they get first access to some very early-stage technologies that they might not otherwise have encountered, and have the opportunity to test it and influence its further development. The whole concept is finding great favour in an industry that is constantly exploring new ways to glean new insights into their existing products and those in the pipeline.

What are some of the common analytical techniques that you are using?

I think there is great interest in how we are engineering or combining existing technologies for new applications as well as in the new technologies emerging via the Bioscience Development Initiative. The first products to emerge from BDI came through an agreement with Affinity Biosensors to employ their Resonant Mass Measurement technology to detect and count particles in a size range that is especially useful for characterizing protein aggregates in a formulation.

Protein aggregation presents safety and efficacy risks in biopharmaceuticals, having the potential to generate an immunogenic response in the recipient, so characterizing aggregates is the focus of many people’s efforts. Malvern Panalytical’s light scattering instrumentation is already widely used in this field, with applications continually developing.

Most recently, the launch of the Viscosizer 200, a UV area imaging technology and a direct result of a BDI collaboration, has brought microviscosity and a new molecular sizing measurement into the range.

What role does the initiative play in the development of new biopharmaceuticals?

Our ability to engage with both sides of the market – technology leaders and end customers who have the analytical needs – is crucial. We are enabling the rapid development of the solutions the industry needs by understanding their challenges and targeting appropriate technology solutions.

I believe we are already making a contribution to relieving some of the analytical bottlenecks that exist in biopharmaceutical development, most notably post discovery and pre-formulation. Speed of change seems unlikely to slow in the near future and no doubt some techniques will become more established than others, but the need for this type of nimble innovation will be with us for a long time to come.

Why do you believe there is currently so much investment going into biotech research and development?

Biopharmaceuticals offer a number of advantages over small molecule pharmaceuticals such as highly specific action with fewer side effects and the potential to cure diseases rather than merely treat the symptoms. These advantages, combined with strong intellectual property protection and an increasing number of new diseases that can be treated with biopharmaceuticals, is driving significant investment in these types of drugs worldwide.

Is the Bioscience Development Initiative working in conjunction with anyone at this time?

We are working with a number of major biopharmaceutical companies on several developments, which includes our combined dynamic light scattering and Raman system. The methodology is gathering significant interest because of its unique ability to simultaneously measure a number of relatively standard but critical molecular structural and physical properties using a single small sample under a variety of stress and formulation conditions. The method could replace the need for multiple tests currently done on more than one piece of analytical instrumentation.

We are also with working with a number of companies with our new UV array based technology to improve the performance in terms of reducing the volume requirements for a single measurement and improving the automation for faster molecule screening. However, due to non-disclosure restrictions I am not able to elaborate further at this time.

How do you see the biologics industry developing over the next 5-10 years, and how does Malvern Panalytical plan to change with it?

I think the pace of change will continue to be high. Some analytical technologies will stick and become indispensable in both drug development quality control and manufacturing while others will be less successful.

We are going to continue to use the global reach of Malvern Panalytical in seeking out new technologies. We will continue to work with our partners to evaluate the suitability of these technologies and to support their rapid deployment.

Where can readers find more information?

Malvern Panalytical website.

About Dr. E. Neil Lewis

Dr. Neil E. Lewis Biography ImageDr. E. Neil Lewis received his Ph.D. in chemistry from the Polytechnic of Wales in the UK and did his postdoctoral fellowship at the National Institutes of Health (NIH) in the USA. He was tenured by the NIH in 1992 holding the position of Senior Biophysical Researcher.

He is the founder of several high technology companies, including Spectral Dimensions, Inc., a company that developed hyperspectral imaging systems, and he has been at the forefront of the development of these technologies.

He has authored more than 70 papers, book chapters and patents and has received numerous awards for his contributions including the Meggers Award in 1992, and again in 1994, presented by the Society for Applied Spectroscopy; the Heinrich Award in 1995 presented by the Microbeam Analysis Society; the Washington Academy of Sciences Outstanding Contribution to the Physical Sciences Award in 1997 and the 2004 Williams-Wright Award presented by the Coblentz Society to a person who has made significant contributions to the field of vibrational spectroscopy while working in industry.

In 2007 he was awarded an Honorary D.Sc. from the University of Glamorgan, and in 2009 he received the Association of Analytical Chemists Anachem Award for outstanding contributions and leadership in the area of spectroscopic imaging.

In 2011 he received the Ernst Abbe Memorial Award presented by the New York Microscopical Society for contributions to the field of microscopy. After the sale of Spectral Dimensions, Inc. to Malvern Panalytical. he was appointed to Malvern Panalytical’s Board of Directors and holds the position of Chief Technology Officer (CTO).

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