New Quality by Design Tools for Biopharma

IRELAND IS CURRENTLY at the forefront of exciting change within the global Research and Development (R&D) community. As the European Union boosts its R&D spending, it is increasingly turning to corporate alliances (see "Europe Drives Collaborative R&D" below) to drive applied research.

In synch with these efforts, Ireland is making some bold moves to bolster its research base. This year, the Irish government spent €3.8 billion on new programs to improve the R&D infrastructure, attract more graduates to scientific and technical fields, and promote corporate-academic research alliances.

Within this context, the Center of BioAnalytical Sciences (CBAS) (see "Staffing for Success in an Industrial-Academic Partnership" below) was launched in September 2005, after nearly three years of hard work by Dublin City University, National University of Ireland, Galway, Bristol-Myers Squibb (BMS) and The Irish Industrial Development Agency (IDA).

The Center’s mandate is to develop novel capabilities in the field of bioanalytical characterization through the use of hyphenated analytical techniques and novel analytical platforms. The analytical systems developed would be generic, and could be customized and applied to any biomolecule or process. The two universities involved in the Center will control intellectual property resulting from this research, so that, in the future, the results of the Center’s work would be available to any company anywhere in the world.

CBAS will be focusing on glycosciences, studying sugars — specifically, the glycans that play such an important role in biological pathways. Five interconnected projects, three in Dublin and two in Galway, will be carried out at the Center focusing on:

• Media characterization, with the goal of improving biofermentation;
• Product monitoring during cell culture.

Currently, there is no real way to assess the quality of the media used to feed cells. Ideally, each medium should be characterized before and after mixing, and at various points during production.

Similarly, during cell culture, there has been no way to monitor carbohydrate profiles of the bioproduct. For example, any given protein may have three oligosaccharides attached but 20 different structures or isoforms, each of which will have a different activity. In an ideal situation, a protein would be harvested when carbohydrates contained the best distribution of isomers.

Research into bioanalytics is the only way to advance the state of the science which, so far, has failed to keep pace with breakthroughs in genomics, robotics and automation. Changes can arise at scale up, when a new raw material vendor is used, or for regulatory purposes, and today’s instrumentation cannot always detect these changes, resulting in waste. In addition, current spectroscopic analysis makes it difficult to distinguish between secondary and tertiary structural information.

Improved bioanalytics will reduce time to market

As more companies develop biological therapeutics, the world’s regulatory agencies are going to rely on more analytical evidence of biocomparability and other factors. Availability of new analytical methods would help more companies bring biotherapies to market more easily, simplifying a process that is currently far more complex than that for small molecules.

Developing new analytical platforms to optimize cell culture is one of the CBAS’s goals. Shown here, an industrial bioreactor interface. Courtesy of New Brunswick Scientific.

Already, the European Medicines Evaluation Agency (EMEA) [3], expects manufacturers to be able to demonstrate comparability between pre- and post-change medicinal products that contain biologically derived proteins as active ingredients.

Due to the limitation of existing analytical technologies, demonstrating absolute comparability requires using various analytical techniques, and even clinical trials. It may only be a matter of time before the Food and Drug Administration (FDA) introduces similar guidance into regulation.

BMS’s corporate leadership recognizes the fact that generic bioanalytical platforms will be essential to commercializing new biopharmaceuticals in the future, and that input from diverse sources can only improve the outcome. Thus, the Center welcomes inquiries from biopharmaceutical manufacturers, raw material suppliers and analytical instrument developers that can help maximize the potential application of this research.

CBAS’ launch coincided with BMS receiving approval to manufacture Orencia, the company’s first fully in-house-developed biologic for the treatment of rheumatoid arthritis. BMS plans to build upon this success by developing more active pharmaceutical ingredients derived from biotechnological sources.

Some of the drivers behind BMS’ decision to partner in this venture are in synch with changes in R&D directions at many large pharma companies. They include:

• Increased focus on biotechnology;



• Leverage of strategic partnerships — either with other pharmaceutical companies or third-party manufacturers;



• Development of parallel strategies for small molecules and biopharma, to improve business models and increase market share in both areas.

The company plans to build a large-scale bioprocessing facility in Devens, Mass., clearly supporting its commitment to industrial-academic research. Future managers and operations staff will come to the industry with a strong pedigree and the skills sets required for success in what is and will remain a high-tech industry.