Synthesizing industrial-scale quantities of biologicals, especially antibodies, can introduce unwanted changes into these fragile molecules. The main sources of damage result from sheer stress due to drag as the liquid flows through pipes and tubing, cavitation or vapor bubbles formation, and grinding, when solid parts of the instrumentation impinge against one another.
At the meeting, James Colandene, Ph.D., associate director of drug production at Human Genome Sciences, talked about physical and chemical stresses that occur during the filtration process. “We perform small-scale studies to determine Vmax and flow rate through a given surface area of the filter, taking into account a greater than 50% safety margin. These studies ensure maximum batch capacity and maximum fill speed.”
At filtration pressures of up to 50 psi, Dr. Colandene’s team observed no adverse effects on product quality. Given the wide range of parameters under which they can perform their operations, Dr. Colandene and his colleagues do not consider filtration pressure to be a key parameter. He did, however, warn against extensive foaming, which denatures biological molecules.
“In our small-scale characterizations we determined that the only significant physical stress on our product was cavitation, which can be avoided with the right equipment.”
Millipore has a long history of filtration technology development. Andrew Bulpin, Ph.D., vp for upstream processing, and Paul Chapman, Ph.D., vp for downstream processing, discussed their company’s commitment to disposable technologies. “Our market for single-use devices is $400 million, which we predict will grow to $1.4 billion in the next 10 years,” said Dr. Chapman. “This growth in our product line will be driven mainly by the expansion of antibody therapeutics.”
Indeed, membrane absorbers have shown phenomenal growth, quadrupling in sales between 2005 and 2008. Drs. Bulpin and Chapman stressed that single-use supports sustainability initiatives while lowering costs. Millipore’s results with the application of single-use technology reflect the positive numbers obtained by other firms. Its studies comparing single-use versus stainless steel found that the former required 87% less water, 21% less labor, 38% less space, and 29% less energy for a purification protocol.
In order to deal with validation and regulatory concerns, the company has also initiated an active program for minimization of waste associated with single-use technology. The primary aim of this agenda is to drive home even deeper savings. Salient features include monitoring of extractables and leachables in purification protocols using customers’ feeds, comprehensive validation and testing packages for single-use containers, a complete bioreactivity safety profile for all components of single-use containers, and a flexible filtration concept to reduce waste and enhance operational flexibility.