February 1, 2017 (Vol. 37, No. 3)
Kerry’s Pharma Business Improves Care and Feeding of Cell Cultures, Enhances Excipients
As the development and commercialization of biologics and biosimilars continues apace, bipharma companies stay alert for new options in cell nutrition—anything to help them produce these biologically sourced therapeutics faster and more efficiently. Biopharma companies are also keen to overcome novel formulation challenges, often though the application of excipient technology, which can enhance stability, add bulk, or enable specialized delivery.
Although these challenges (e.g., feeding cell cultures and devising dosage forms) are not only distinct but placed far apart on the biopharma assembly line, both may become more tractable through the assistance of one company or, rather, one company’s business group. The company is called Kerry Group, a public food company based in Ireland that boasts $6 billion in global sales. The business group is the food giant’s pharmaceutical division, which until recently was known as Sheffield Bio-Science.
Kerry’s pharmaceutical division has extensive expertise in both excipient formulation and cell culture supplements. It manufactures pharmaceutical-grade lactose excipients, functional excipients, tableting systems, coatings, flavors, and emulsifiers for drug delivery systems. Also, it has helped pioneer cell culture media technologies. For example, it has advanced the development of animal-component-free supplements as well as the development of media ingredients that are tuned to specific cell types, such as CHO and E. coli.
“In the early days of biotech, the primary nutrients for cell cultures were serum-based, but the need for larger production platforms led to the need for other nutrient sources,” Richard Hazel, president of global pharmaceuticals at Kerry, recalls. Now Kerry develops protein hydrolysates, yeast extracts, recombinant proteins, and application-specific solutions.
Kerry’s AmpliCHO is the first product to deliver both a basal and complete medium in a single medium, according to Hans Huttinga, vp business development. Developed as a platform medium, AmpliCHO is a chemically defined, protein- and serum-free medium that delivers a complete nutritional solution tuned to specific CHO cell lines. Optimized for osmolality, it can be used with complex, defined, and chemically defined supplements and feeds (including Kerry’s plant-based protein hydrolysates), to extend growth and enhance recombinant protein production for CHO suspension cultures.
Efficiency is the main benefit of a complete cell nutrition media. “This is particularly important for biosimilars, where speed-to-market is crucial,” Hazel says. “Using AmpliCHO off-the-shelf saved 12 months for one of our clients.”
The reason for such time-savings, Huttinga explains, is that AmpliCHO already is optimized for cell type. Otherwise, “Medium optimization projects need 10 to 15 technicians and significant time to optimize each production clone and its media.” The AmpliCHO kit is designed so researchers can test the nutrients with their cell expression systems at two “start concentration” levels, further shortening development time.
Kerry’s Sheff-CHO products and AmpliCHO are geared to achieve high yield in short media development times. In a single production run, one customer doubled yield from 1.5 to 3 g/L, adding $1.2 million in extra value to their final product, Huttinga says.
Kerry also has created efficiencies by leveraging synergies between peptones and yeast extracts, creating Sheff Systems that contain them both. This combination enables customers to test one system rather than two, in addition to exploiting process efficiencies. Peptones and yeast extracts are important for bacterial fermentation processes that involve expression vectors like E. coli, which is used to produce growth hormones and insulin. Kerry, according to its website, is the only manufacturer of both peptones and yeast extracts.
Focus on Consistency
Efficiency is often closely related to consistency. Yet as bioprocessing becomes increasingly demanding, ingredients have shifted from complex to chemically defined, which introduces vagaries into the system.
“Protein hydrolysates, for example, are complex ingredients that provides the nitrogen for cell growth,” Hazel says. “In an ideal world, cell nutrients would come with a complete list of all components in the media to optimize cell growth. The real world doesn’t work that way, however. Because proteins are naturally occurring, they can have significant batch-to-batch variability that affects culture titer and growth rates.”
The impact of such variability can be huge. “Depending on the cell line used, sensitivity to that variability can be amplified significantly,” Hazel says. “Mammalian cells, for instance, are much more sensitive to variability in nutrient sources than other cell types, and that can have a significant impact on their yield, reproduction speed, and final protein quality.”
The implications of varying quantities, production speeds, and product qualities ripple downstream, causing a cascade of delays and extra work to achieve the desired output. Choosing cell nutrition feeds that are optimized for specific cell lines greatly reduces that variability, Hazel says. “Kerry has systems in place from start to finish—from procurement through manufacturing and quality control—to ensure lot-to-lot consistency.”
GMP manufacturing for cell nutrition and excipient products is another key differentiator. “You’d be surprised how many companies don’t follow GMP guidelines,” Huttinga says. Kerry has two protein hydrolyte manufacturing sites in the U.S. and one in Europe.
Siting facilities in different regions not only expands Kerry’s geographic reach, but also helps ensure business continuity to customers in case of disaster. Floods, fires, and political upheaval affecting one facility are unlike to affect the other.
In recent years, Kerry has expanded its excipients business into developing countries, Hazel says. “China and India (with growing populations of older individuals) are driving huge growth in terms of needs.”
“The move from small to large molecule drugs has a bearing on the types of excipients used and the scale of their production,” he elaborates. “Today, excipients must be more targeted.”
As more and more prescription drugs evolve to over-the-counter versions, developing patient-friendly formulas confers a competitive advantage. “With a multiplicity of remedies in the pharmacy, factors like taste come into play, to give patients a more pleasant experience,” Hazel points out.
In 2012, Kerry’s pharma business changed its branding name from Sheffield Bio-Science to Kerry to emphasize its relationship with its parent company, Kerry Group.
The pharmaceutical division is a leading player in the biopharma industry, where it has developed ingredients for the past several decades. “Six of the top 10-selling biological products contain Kerry products in their production media,” Hazel points out. This group also develops products for industrial biological applications.
The pharmaceutical group within Kerry is growing steadily and plans to expand its product portfolio, anticipating movements in the industry. That includes gearing up to serve Asian markets. “If you look at the market, you’ll see that production capacity in Asia is predicted to double in the next five years,” Huttinga says. Kerry plans to have more people and resources in place to service that market, in addition to its North American and European markets.
Product expansions will support the growth of vaccine development, cell therapy, and other recombinant and biological products. Small molecule products also will continue to be important to Kerry, Hazel adds.
Some of the anticipated growth is likely to come through acquisitions. The Kerry Group has acquired 150 companies in the past 10 years. Additionally, Hazel says, “We have a great innovation funnel and are putting a lot of money and resources into it for cell therapy, as well as our diagnostic and fermentation markets.”
Kerry Group, Pharma Systems