BioPharm: Given this projected growth, what challenges lie ahead for analytical instrumentation companies like Malvern working in the biologics space?

Lewis: Biopharmaceuticals represent a paradigm shift in the development, manufacture, storage, testing, and delivery of medicines. The fundamental 'quality' metrics for pharmaceuticals are based on purity and potency. In other words: is it the correct molecule, is it there at the right dosage strength, and are there any unintended contaminants? For traditional small-molecule pharmaceuticals, these analytical requirements are dealt with using relatively simple and established technologies such as chromatography. However, the definition of purity and potency for biopharmaceuticals is much more complex. Biopharmaceuticals are intrinsically heterogeneous in nature and contaminants can originate from any number of sources, including the therapeutic molecule itself in the form of aggregates or misfolded or completely denatured structural forms. This complexity and variability can lead to many new challenges for manufacturers and regulators alike, and the shared learning is moving at a furious pace. The challenge for a provider of analytical solutions like Malvern is to match this pace, and to the extent that it is possible, anticipate and react to the needs of the industry with an agile product development mechanism. Consequently, we are continually extending and enhancing our product portfolio to focus on some of these new 'quality attributes.'

For example, many of the challenges of selecting the 'right' candidate molecules immediately post-discovery involve a number of physicochemical testing processes that aim to help eliminate molecules that might create formulation, delivery, or manufacturing problems downstream. Very often, only small amounts of material are available for these analytical tests, and parameters such as the viscosity or the physical and chemical stability of the formulation become critical quality attributes (CQAs) that gate whether the molecule is selected for further investment.

Lewis: Rapid technical developments in the industry, and the drive towards engineered antibodies that go beyond the established monoclonal market, continue at an ever-increasing speed, and the regulatory environment is working hard to keep pace. In addition, the emergence of new guidelines governing the production of biosimilars in both Europe and the US is creating new and more sophisticated analytical testing requirements. For example, while the application of existing technologies that measure the occurrence of protein particles or aggregates in finished products is a hot topic, measurement technologies that dig deeper into the physical and chemical mechanisms that drive these interactions are becoming more important. Understanding the fundamental quality attributes for developing robust and stable formulations is essential. This is a logical extension of the quality by design (QbD) versus quality by testing philosophy that has been a recurring theme from FDA.

There is an increasing need to develop a complete picture of particles and aggregates in biopharmaceutical products and an emphasis on physicochemical product characterization—both of contaminants and intrinsic particles. As with the QbD initiative in the small-molecule business, this problem will also be tackled by characterization during the development process, not just via quality assurance/quality control during manufacturing. Such moves will drive the need to deal with low volume yet high concentration samples, as well as complete formulations. It seems likely that appreciable progress towards adopting technologies that improve product knowledge and process understanding will only be achieved through enhanced cooperation among the bioscience industry, regulatory agencies, and analytical instrumentation manufacturers.

Neil Lewis, chief technology officer, Malvern Instruments