News

Posted On: 08/01/2005

New Center Will Tackle Biopharmaceutical Manufacturing Challenges

By Agnes Shanley, Editor in Chief

On July 20, Bristol-Myers Squibb (BMS) and the Irish Industrial Authority (IDA) signed an agreement to establish a $12-million Center for Bioanalytical Sciences (CBS) in Ireland. Involving research teams at Dublin City University (DCU) and the National University of Ireland (NUI) in Galway, the Center will address the critical problems that make analyzing bioprocesses so challenging and time consuming, and contribute to the high cost of biopharmaceuticals.

“There is a huge opportunity today to bring biology and analytics closer together,” says CBS director Dermot Diamond, an analytical chemist by training who is also a professor at DCU. “In biopharmaceutical manufacturing today, current techniques for generating information simply take too long,” Diamond says. Analysis typically takes several days. “Our goal is to see whether we can take a fundamental knowledge of bioreceptors to speed up data generation,” he says.

Five interconnected projects will be carried out at the Center focusing on two key problems:

• Media characterization for improved biofermentation
• Product monitoring during cell culture

The media used to feed cells are complex but poorly defined, so there is no real way to assess their quality. Each component, ideally, should be characterized before and after mixing, and at various points during production.

And during the cell culture phase, 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. Ideally, a manufacturer would want to harvest protein when carbohydrates contained the optimal distribution of isoforms.

Work at the Center is expected to help bring more efficient methods and process analytical technology (PAT) to biopharmaceutical manufacturing. “We’re looking to develop online analytical methods for glycoproteins,” says CBS’ associate director Terry Smith, a professor at NUI Galway. BMS, whose U.S.-based analytical specialist John Tabor is the lead interface with the CBS team, estimates that technology developed at the Center, if successful, could reduce costs at a typical mid-to-large-sized manufacturing line by up to $80 million/year.

CBS will formally start up in September and will ramp up its efforts over the next six months, says director Diamond, who is also closely involved with the National Center for Sensor Research (NCSR) at DCU. The new center will have close ties with NCSR, which is focusing on a number of “lab-on-a-chip” projects that will be essential to CBS’ progress.

Below is a rundown of the teams involved and what they’re doing:

• At NUI, a team led by Dr. Angela Savage will work to generate reference materials, primarily olgosaccharides and glycoproteins, and to validate rapid analytical methods using biochips and mass spectrometry.
  
  
• At DCU, a team led by Dr. Brendan O’Connor will develop new bioligands, principally lactins, to characterize oligosaccharides and glycoproteins. “Lactin receptors are good at giving structural information,” says Diamond, and lactin instrumentation will be located in Galway as well.
  
  
• Their colleagues, led by Professor Brian MacCraith, will develop antibody-based biorecognition sensors to characterize oligosaccharides and glycoproteins. The group will also develop biochips that would use fluorescence as a signal, to determine structure.
  
  
• At NUI, Dr. Alan Ryder’s team will evaluate Raman and IR spectroscopy (both planar and probe) and chemometrics for rapid analysis of fermentation mixtures and their precursors. Both traditional and nonreagent spectroscopic analysis offer advantages and both will be used. “The great advantage with nonreagent spectroscopy is that it doesn’t require contact with the material and can be done through a window in the process vessel,” says Diamond.
  
  
• Another DCU team, led by Brett Paul and involving Dermot Diamond, will integrate sampling processes using microfluidics technology, and develop fast on-chip separations coupled with MS, spectroscopy or electrochemical detection. Chromatography, specifically ion chromatography is being investigated, with the goal being extremely fast separations for key targets — separations that take only a few minutes, Diamond says, versus the usual several hours.
  
  “The challenge is to find out what the key parameters are that affect the final product, and track them by following the analytical profile and dynamics through time,” Diamond says. The project will track variations in precursor and compare them against structural variation in the product.

Although BMS will use technology developed by CBS, the contract has been developed so that both universities will hold the rights to develop any intellectual property they develop. This has the added benefit of allowing other manufacturers to use this technology in the future, a potential boon for the biopharmaceutical industry. It also provides potential revenues for Ireland's growing biotechnology business, a win/win for all parties.

“The days when inventors would jump when industry called are over. Agreements must be fair and equitable on both sides, and provide fair payback to taxpayers,” Diamond says.

Recruiting for the center, which will employ 30 to 40 people, has already begun. Not only two university research chair positions, but a project manager and technical specialists are being sought. Interviewing will begin in earnest this month. “We’re looking for the best and brightest in the world,” Diamond says.

In addition, the Center is looking for the best available analytical technologies, Diamond says. Although a Procognia installation will be based at DCU-Galway, the field is open. “We don’t have preferred analytical partners for this venture,” says Diamond, who invites analytical instrument suppliers with relevant technologies to get in touch with him at dermot.diamond@dcu.ie. For more information on NCSR and sensor development at DCU, see www.adaptiveinformation.ie.