This allows performing a process with higher flow rates at lower pressure drops,

resulting in higher productivity. Briefly, industrial chromatography is dominated by

porous bead stationary phases, which were first designed for the purification of

therapeutic proteins such as monoclonal antibodies (mAbs). However, alternatives

are needed for the purification of large particles such as viruses.

Something to have in consideration during the early stage of bioprocess design is

the cost of goods (CoGs), and chromatography is one of the unit operations that

increases it. In chromatography, column capacity and column sizing are two of the

crucial factors that impact the CoGs. A strategy using membrane chromatography in a

flow-through mode may become a greatly debottlenecking option, by reducing buffer

consumption and consequently eliminating the facility’s constraints caused by plant

capacity. Another great advantage of membrane devices is their disposability, which

minimizes the costs with clean-in-place (CIP), process validation efforts, facilitating

the transfer of the technology to cGMP. Currently, there are three well-known

membrane devices under the commercial name of Sartobind® (Sartorius Stedim),

Mustang® (Pall), and Natrix® (Merck) with plenty of applications, for example for the

purification of adenovirus [56], influenza virus-like particles [57], and lentivirus [58].

Monoliths, also a convective type of device, are characterized by their highly porous

structure, with channels size of 1–5 μm range. Thus, monoliths are gaining a lot of

interest in viral particles’ manufacturing, being used for the purification of several

viral-based products and contributing to the process intensification [59,60]. Process

intensification is the trendy strategy being applied across biological manufacturing,

that involves combining strategies that reduce manufacturing time, improve effi-

ciency, and increase process standardization. For this, single-use devices, shorter and

efficient purification processes, and continuous processing are concepts extensively

into exploitation.

TABLE 7.2

Comparison between packed-bed column chromatography and membrane

chromatography in viral-based vaccine manufacturing

Advantages

Limitations

Packed-bed column

chromatography

•

Unlimited scalability

•

Well-known and established

technology

•

Several types of possible

ligands

•

Limited flow rates

•

Complex operation (column

packing)

•

Diffusion limited (conventional

bead)

Membrane

chromatography

•

Possible to operate at high

flow rates

•

High binding capacity

•

Reproducibility (no column

packing required)

•

Single-use devices available

•

Limited choice of membrane

chemistry commercially

available

•

Limited scalability (restricted to

the commercially available

sizes)

188

Bioprocessing of Viral Vaccines