Single-Use Technologies—A Contract Biomanufacturer's Perspective - Disposable technology presents an attractive opportunity for CMOs to cut down production costs. - BioPharm International

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Single-Use Technologies—A Contract Biomanufacturer's Perspective
Disposable technology presents an attractive opportunity for CMOs to cut down production costs.


BioPharm International Supplements


Bioreactors


Figure 1
Wave disposable systems range from 1 L to 500 L in capacity, and we use them in conjunction with disposable cell bag 20/50, 100/200, or 500/1000 Wave bioreactor systems. These are customized systems that use rocking motion to mimic the agitation produced by stand-alone systems. They have built-in feedback controls to monitor carbon dioxide, dissolved oxygen, pH, and other parameters. Our studies have shown that cell growth in these systems for most cell lines (Chinese hamster ovary [CHO] cells, BHK, hybridoma) is comparable to that obtained from stand-alone systems (data not shown). We observed similar growth trends throughout the run when we scaled up from a 20-L to a 1000-L wave bag (Figure 1).

Another type of disposable bioreactor uses hollow-fiber (HF) cartridges. In such perfusion bioreactors, cells grow inside cartridges, around a semipermeable 10-kD hollow fiber membrane. Cells are fed and waste is removed by perfusion across the membrane. HF disposable bioreactors facilitate a plug-and-play approach to cell culture, and have the advantage of concentrating the product produced by the cells.

Downstream Processing

Various vendors supply bioprocess containers (BPC) for solution preparation. These containers are made of polyethylene, ethylene vinyl alcohol (EVOH), and other films. They are available in a variety of sizes ranging from 25 mL up to 500 L, and we transport them in re-usable barrels or totes. BPC systems are completely configurable for various uses, including direct connection to chromatography systems or process tanks. The bioprocess containers are tested to United States Pharmacopeia (USP) Class 6 standards before use. The vendor performs the following tests and confirms validation at the time of purchase:

  • acute systemic toxicity
  • intracutaneous toxicity
  • implantation test
  • cytotoxicity (agar diffusion and elution)
  • endotoxin level
  • heavy metals concentration
  • buffering capacity
  • nonvolatile residue
  • residue on ignition.

Membrane Chromatography

Disposables are an integral part of membrane chromatography for protein purification. We use cation and anion exchange filters from various vendors to replace cation and anion exchange resins and columns. The cost analysis shows that disposable membrane filters are substantially more cost-effective than stand-alone columns and resins. In addition, by using these filters we have eliminated the need for packing and testing columns as well as long-term storage of materials.


Figure 2
Anion exchange filters are typically flow-through (FT) systems that bind rDNA, endotoxin, residual protein A, and host cell proteins, and we use them for polishing steps. A comparison study of Q filters from two different vendors (Figure 2) shows that disposable membrane filters generally result in >90% yield postprocessing. We have observed similar yields when we run process-scale columns packed with Q anion exchange resins.

Cation exchange filters act as product-binding filters similar to cation exchange resins and bind IgG and Factor VIII. Cation exchange filters, however, have lower capacity than most resins and are not efficient for intermediate purification steps.


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