Using Volumetric Flow to Scaleup Chromatographic Processes - - BioPharm International


Using Volumetric Flow to Scaleup Chromatographic Processes

BioPharm International
Volume 19, Issue 3


1. Amersham Pharmacia Biotech (now GE Healthcare). Ion Exchange Chromatography – Principles and Methods. Uppsala, Sweden; 2001 p.121

2. Wancat PC. Rate Controlled Separations. London; Chapman & Hall; 1994. p. 330

3. Stickel JJ and Fotopoulos A. Pressure-flow relationships for packed beds of compressible chromatography media at laboratory and production scale. Biotechnol. Prog. 2001; 17(4):744-751.

4. Hansen. E. Scale up on a volume basis – Theory and applications [thesis]. Novo Nordisk A/S, Copenhagen, Denmark; May 2002. (Private communication).

5 Fahrner RI, Iyer HV, Blank GS. The optimal flow rate and column length for maximum production rate of protein A affinity chromatography. Bioprocess Engineering 1999; 21:287-292.

6 McCue JT, Kemp G, Low D, Quinones-Garcia I. Evaluation of protein-A chromatography media. J. Chroma. A. 2003; 989:139-153.

7. Gagnon P. Avoiding instrument-associated aberrations in purification scale-up and scale-down. BioPharm 1997 March; 10(3):42-45.

8. Wancat PC. op. cit. p.328.


A = Axial dispersion parameter (band broadening which contributes to plate height, constant for a particular case), cm

B = Molecular diffusion, cm2 /h

C = Mass transfer parameter (band broadening which contribute to plate height, constant for a particular case), h-1

c = Concentration at column outlet, M

c 0 = Concentration at column inlet = load concentration, M

CV = Number of column volumes, dimensionless

G = Gradient slope, M/CV = M

Gradient response = The resulting UV-gradient curve from a programmed (nominal) gradient.

H = Plate height (a smaller number results in a sharper chromatographic peak and thus a more efficient column), cm

h = Time unit, hour

L = Bed height, cm

M = Molar concentration, mol/L

N = Plate number (the total number of plates in a column; higher number means longer column, results in better separation)

Q = Flowrate in column-volumes/time, CV/h

v = Linear velocity, cm/h

V R = Retention volume, (the number of column volumes at which the product elutes), CV

Δ delay volume = The difference in delay volumes between different systems (lab, pilot and production)

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