Innovation, innovation, innovation .. and a call to focus on science and quality-by-design (QbD) principles. Such was much of the talk yesterday at this year’s AAPS National Biotechnology Conference in Seattle. Speakers discussed the tools the biotechnology industry will need for future innovation and how the industry must center on QbD principles, using lessons learned from small-molecule development and even nonregulated industries.

In his plenary address, Jim Thomas, PhD, vice-president of the process and product development group at Amgen, spoke about the benefits and challenges of QbD principles in biologicals. He set the scene by quoting a recent article that predicted that in 2014, 7 of 10 top selling drugs will be biologicals. Moreover, biotechnology drugs will account for 50% of the top 100 drugs in 2014, compared with 11% in 2000 (versus conventional drugs). But, said Thomas, the challenges were many. The costs of drug development and treatment are high. Intellectual property issues and the growth of follow-on biologics will have to be addressed. In addition, he listed at least 25 major attributes of molecules that, if modified, would have an effect on a molecule’s pharmacokinetics. “We need to pay attention to these attributes because of concerns over safety, efficacy, and stability,” said Thomas. The long-term solution, he said, is innovation, specifically in formulation, better production methods, and in deliverying protein therapeutics. “Innovation will be key to future success,” said Thomas, who then discussed in detail Amgen’s work in antibodies, peptibodies, and avimers as examples.

Amgen is working with the US Food and Drug Administration and other companies to understand how to apply the philosophies of QbD in they way they develop protein therapeutics, particularly “based on a fundamental understanding of the science of building quality into the molecule.” The process, said Thomas, starts with a core design knowledge (”what works and what doesn’t”), which must then incorporate what he referred to as “systematic learning” or “buckets of information” that include analytics (including top-down mass spectrometry), biological aspects, and the process itself. The keys are trying to link an knowledge of the molecule with analytics and then linking the analytical characterization of the molecule to the biology to define the critical quality attributes.

The main challenge in doing this, says Thomas, is that there will be a significant initial investment to apply QbD to biologics, but these costs should decrease for platform modalities. The application of QbD to nonplatform molecules will be much more costly. An investment in high-throughput technologies is necessary, he said. Other challenges include the need for sophisticated knowledge of antigen systems, linking molecular structure to biological attributes, and applying risk-management tools to help define the design space. Thomas said Amgen is taking “gradual steps” in applying QbD in it’s processes and will “soon” have evidence of QbD in its regulatory filings.

An afternoon session in process analytical chemistry echoed much of these challenges and future benefits of implenting QbD. In a session titled “What can the Biopharmaceutical Industry Learn from the Use of QbD in Small Molecule Production,” Mel Koch, PhD, of the University of Washington’s Center for Process Analytical Chemistry (CPAC) reviewed the fundamental principles of QbD and how the advancements in measurement science (miniaturization, new materials, data processing, etc.) have helped trigger the need for implementing these principles in bioprocessing. Areas of interest, said Koch, include the characterization of media, nutrient quality, sampling, and microfermentation for optimizing bioprocesses.

A keen eye on science and built-in quality … biotechnology is indeed on the verge of great innovation.