Process Scale Chromatography
Ian Sellick, marketing director of Pall Life Sciences (www.pall.com), discussed the relationship between capacity, resolution, and flow rate in process-scale chromatography and how this can be optimized.
Recent research involved the use of the Ciphergen ProteinChip technology to look at how the chromatographic surface interacts with the protein product to discover the best elution conditions.
This has been exemplified by work done by Fons Bosman, Ph.D., of Innogenetics (www.innogenetics.com), on a specific Mab. Good transferability of on-chip conditions to the full sized column were shown.
Process development and optimization on-chip take only two to three days compared to several weeks by more conventional methods. In another example, Pall scientists used 96-well plate screening for optimizing the polishing step in a recombinant protein.
"These are powerful techniques for scouting conditions for chromatography and are especially applicable for molecules where we don't know what the purification procedure should be,"explained Sellick.
Meanwhile, membrane separation shows promise as a complement to column chromatography. The Pall Mustang Q Z XT5000 membrane capsules can be configured in series or in parallel to increase the effective membrane volume.
With this kind of set-up, as much as 1.5 kg of protein can be purified and, indeed, it has now been approved by the FDA for a polishing application for DNA and viral clearance.
Concluding the conference session, Friedrich Nachtmann, Ph.D., head of biotech co-operations at Sandoz (www.
sandoz.com), discussed how a manufacturing facility can be managed for maximum utilization.
Sandoz offers contract manufacture of biopharmaceuticals in microbial and mammalian cell culture as well as developing its own program of biogenerics. The manufacturing cost element of facility, personnel, and energy is where most efficiency gains are possible. Only limited savings can be made in the other two elements of material and service costs.
"A decent facility requires an investment of over $100 million," said Dr. Nachtmann, drawing on cost data from recently built mammalian cell culture facilities.
CMOs can reduce these costs because they share the risk, he noted, adding that CMOs also have multipurpose facilities, and if your product does not succeed, the capacity can be used for something else.
"Ninety percent of all biotech plants are not being used for the product originally intended," he pointed out.
There are, however, some specific challenges associated with the multipurpose plant. Regulation will demand special changeover procedures, and staff must be more highly trained than for a plant dedicated to one product.
Continuous process development is less feasible too, because the multipurpose facility operates on a campaign basis.