Biologicals 34 (2006) 237e238www.elsevier.com/locate/biologicals

Letter to the Editor

I read the article of Li et al. [1] with great interest. The au-thors point out nicely the powerful ability of UVC irradiationto inactivate viruses, especially the most critical small non-enveloped viruses (e.g. parvovirus). The authors also showthe hydrodynamic behavior and limitations of their continu-ous-flow device, developed by Iatros Ltd., Scotland. I fullyagree with this characterization.

However, the authors compare their results with two othercontinuous-flow systems from the literature. While I am notable to conclusively judge the system described by Caillet-Fauquet et al. [2], the apparatus used in the work of Wanget al. [3] was a UVivatec� system developed by Bayer Tech-nology Services GmbH, Germany. Since the work of Wanget al. was conducted using an opaque solution with an absor-bance at 254 nm of A254 Z 2.5 cm�1, while Li et al. workedwith a solution with absorbance at A254 Z 11.9 cm�1, theauthors concluded that the user would need to dilute a solutionwith an absorbance at A254 Z 11.9 cm�1 fivefold to achieveeffective inactivation in the UVivatec� system used by Wanget al. I do not agree with this conclusion.

For all systems the BunseneRoscoe reciprocity law is true.Therefore, a higher absorbance may be compensated, not nec-essarily by dilution, but rather by a longer residence time. Aslong as the hydrodynamic mixing behavior is not negativelyaffected, adjusting of the flow rate is an easy and effectiveway to obtain the needed irradiation dosage. This way a solu-tion of any absorbance can be treated with the UVivatec�

system.Furthermore, it is stated that treatment of a solution con-

taining 45 g/L albumin having an absorbance ofA254 Z 11.9 cm�1 with the UVivatec� system would require7 days. This is not the case. First, the assumed dilution isnot necessary as stated above and second the inactivation effi-ciency is much higher than assumed by Li et al. This might beshown best by comparing the case studies with 4.5% and 20%albumin as described by Li et al. The necessary data are shownin Table 4 of the paper. First of all, one of the given units is notcorrect. The process solution flow rate Fw is given in m3/s, ap-parently this should be mL/s, as indicated by the calculatedReynolds numbers.

For a fair comparison the systems should be evaluated atthe same degree of inactivation. As there are no experimentaldata for the specific bacteriophage FX174 it might be assumedthat the phage behaves very similar to a parvovirus. The data

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given in Table 3 of Li et al., together with the findings of thegenome size dependency of Wang et al., support this assump-tion to be acceptable.

In Li et al. the 4.5% albumin case is performed in a ‘‘smallscale unit’’ and the 20% albumin case in a ‘‘large pilot-scale’’unit these cases should be compared with a UVivatec� Laband a UVivatec� Process, respectively. For a solution of4.5% albumin (A254 Z 11.9 cm�1) Li et al. indicate a flowrate of 0.33 mL/s Z 1.188 L/h is needed to inactivate5.8 log10 of FX174. Under the given conditions, the UVivatec�

Lab reaches the same inactivation rate at a flow rate of 7.3 L/h.Therefore, in terms of productivity, the UVivatec� performsbetter by more than a factor of 6.

For the 20% albumin solution (A254 Z 51.8 cm�1)a 4.06 log10 inactivation is described for 66.6 mL/s Z239.76 L/h. Here, the length of the irradiation tube is givenby Li et al. to be 22.6 m. A single UVivatec� Process modulewith a tube length of 0.9 m will inactivate 15 L/h under theseconditions. Because of the drastic difference in length, the sumof 25 UVivatec� modules would be a fair comparison to theextremely long apparatus of Li et al. This would providea comparable flow rate of 375 L/h for the UVivatec� modules,still over 50% more than the apparatus of Li et al.

Unfortunately, Li et al. do not indicate a number for theirsystem in their final calculations of time to process a 1000-L batch at A254 Z 11.9 cm�1. Based on the data for the4.5% albumin scenario above, the real case for a 1000-Lbatch can be calculated. Certainly, one would not processthis size batch with a lab system, but with a process system.A single module of the UVivatec� Process provides a flowrate of approximately 50 L/h, resulting in a total processingtime of 20 h. In practice, multiple modules would be usedin parallel reducing the process time to a few hours. There-fore, our system is far away from the 7 days process timeassumed by Li et al.

References

[1] Li Q, MacDonald S, Bienek C, Foster PR, MacLeod AJ. Design of a UV-C

irradiation process for the inactivation of viruses in protein solutions.

Biologicals 2005;33:101e10.

lished by Elsevier Ltd. All rights reserved.

238 Letter to the Editor / Biologicals 34 (2006) 237e238

[2] Caillet-Fauquet P, di Giambattista M, Draps M-L, Sandras F,

Branckaert T, de Launoit Y, et al. Continuous-flow UVC irradiation:

a new effective, protein activity-preserving system for inactivating bacte-

ria and viruses, including erythrovirus B19. J Virol Methods

2004;118:131e9.

[3] Wang J, Mauser A, Chao S-F, Remington K, Treckmann R, Kaiser K, et al.

Virus inactivation and protein recovery in a novel ultraviolet-C reactor.

Vox Sang 2004;86:230e8.

Sebastian SchmidtBioprocess Technology, Bayer Technology Services GmbH,

Building B310, D-51368 Leverkusen, Germany

Tel.: C49 214 30 54198; fax: C49 214 30 81554.E-mail address: sebastian.schmidt@bayertechnology.com;

URL: http://www.bayertechnology.com