Whereas traditional drug production is a purely chemical process, that’s not true of one of the most promising areas of biopharma research — biological products, or, as they are called in the trade, biologics. Today many companies involved in traditional drugs are also developing biologics, some of which have huge markets. Abbott’s Humera, for example, brings in $6.5 billion a year and Roche’s Avastin $6.2 billion.

Biologics, which range from vaccines to gene therapy to therapeutic proteins, are created with the help of some form of living organism. They are produced either by engineering bacteria to generate (or express) the therapeutic molecule or by using cells.

But there’s the rub. Because biologis are produced in living entities, they do not grow into the perfectly identical results we generally get from bulk manufacture of standard, small-molecule drugs. As #b#Cornell Stamoran#/b#, vice president of corporate development and strategy for Catalent Pharma Solutions, puts it, “There is a natural degree of variability in any living organism, and this can lead to variability in the protein that is produced by an organism.”

Stamoran will speak on “The Selection Process of What to Develop and Who Will Pay” at BioNJ’s manufacturing breakfast summit on Thursday, March 10, at 7:30 a.m., at the Hilton East Brunswick. Also speaking are Brian Ryerson, director of waste minimization and recycling technologies at Triumvirate Environmental, and John Menna, director of strategy in healthcare logistics at United Parcel Service. Cost: $75. For more information, contact Debbie Mennito at 609-890-3185 or dmennito@bionj.org.

The manufacturing process for biologics is much more complex than traditional drug production, and Stamoran describes some of its challenges:

#b#Isolating the appropriate version#/b#. Once cell lines have been developed to generate the protein that produces the desired therapeutic effect, the manufacturer has to figure out how to capture exactly the right version from among the natural variations that are produced. “Part of the biologics’ manufacturing challenge is to isolate cell lines and processes that perform consistently and scale up easily to larger production volumes,” says Stamoran.

#b#Covering the high manufacturing costs#/b#. “The yields are typically very low, so it takes a lot of time and fixed equipment to yield low amounts. Once you do you have to purify it to make sure you only get the types of cells you want,” Stamoran says. A lot of expensive, special-purpose equipment as well as an unusual degree of knowledge and expertise is required to generate these low volumes.

But new technologies are helping to reduce costs. Historically, manufacturers had to invest in 15-20,000-liter tanks, whereas today they are using disposables to try to reduce capital costs and regulatory complexity. These single-use bio-reactors can be used to create a more flexible manufacturing process and avoid some of the larger capital costs, says Stamoran.

Manufacturers are also using advanced cell lines that can improve the reliability of the output, reducing variability and thereby increasing the yield. “If you can produce higher levels of protein that is the exact variation you are targeting and hence reduce variability,” says Stamoran, “you get more output for less effort.” Unwanted variants of proteins can be very difficult and costly to remove during the purification process.

Although the production process is more capital-intensive than people-intensive, it does require high-level people skilled in regulatory compliance and current good manufacturing practices, which is also expensive.

#b#Designing a multistep process#/b#. The typical biologics’ manufacturing process, which has many more processing steps than in typical drug manufacturing, must be designed so that it works the same way every time. The reason processes get so unwieldy is that when a problem occurs, people often add a new process step, which can make the process more cumbersome.

To keep up with developments in the field, old processes need to be redesigned through what is called process optimization. “Since biologics manufacturing is better understood today than 20 or 30 years ago, it is easier to design a process that controls all variables and produces consistent results,” Stamoran says.

#b#Handling downstream processing#/b#. The proteins that comprise most biologics are large-molecule, so called because of their high molecular weights, and cannot be delivered by mouth. They cannot be absorbed orally because they won’t pass through the stomach or intestinal linings, and hence have to be delivered by injection or in other ways. Hence, after biologics have been purified to filter out variants, they require additional processing to put them into vials, syringes, or inhalers, or freeze dry them. Although these can be done in-house, they are often outsourced to specialty or virtual companies to avoid additional human and capital costs and regulatory complexity.

Stamoran grew up in Michigan, where his father worked for the Ford Motor Company in a parts distribution facility. “I’m the first person on the Michigan side of the family to not work in the automobile industry,” he says. His mother, however, actually did manage to stay out of it, working as an administrative secretary for Wayne County. After graduating from the University of Michigan in 1987 with a degree in accounting and business, Stamoran worked for Arthur Andersen in Detroit.

After five years he moved to RP Shearer, the drug delivery company that forms the core of what is Catalent today. Stamoran handled financial reporting, planning, mergers and acquisitions, investor relations, and strategy.

Cardinal Health bought RP Shearer in 1998 and over nine years acquired more than two dozen companies and brought together their different technologies and plants into one business. During this period Stamoran moved away from finance to focus on strategy, also helping to create a marketing function and a global sales team. “Now I’m fully on the strategy and growth side, and I consider myself to be fully reformed ex-finance,” he says.

The Blackstone Group purchased the business from Cardinal in 2007, and the name Catalent (combining “catalyst” and “talent”) was given to the enterprise.

Stamoran comments on the role biologics will be playing in the biopharma industry. “Biologics-based therapies are important for patients as they are bringing new, effective treatment options to diseases previously less treatable,” he says. “As a result, biologics will increasingly be a key driver of growth for the global pharmaceutical industry over the next decade, accounting for more than a third of the global market sales value by 2015.”

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