BioPharm: Given this projected growth, what challenges lie ahead for analytical instrumentation companies like Malvern working in the
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.
BioPharm: What major trends and topics do you expect to see popping up in the biologics analytical and manufacturing industry?
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