Biopharmaceutical Facility Cleaning Validation Using the Total Organic Carbon Test - Case studies show TOC is effective for cleaning validation. - BioPharm International

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Biopharmaceutical Facility Cleaning Validation Using the Total Organic Carbon Test
Case studies show TOC is effective for cleaning validation.


BioPharm International
Volume 23, Issue 6

Swabbing Recovery Study for Cells and Proteins

There are two types of sampling done following the cleaning process—the direct surface and rinse samples. The first one is considered "the most desirable" by the FDA.1 The swab technique typically involves moistening a polyester swab with purified water to wipe a measured area in a systematic manner. Cleaning validation kits, specifically designed for TOC swabbing, are commercially available for this purpose. However, it is critical to validate the swabbing procedure in combination with the chosen analytical method for various combinations of contaminants and surfaces. Thus, TOC recovery study is mandatory before evaluating the efficiency of the cleaning process. In the absence of such a validation study, a manufacturer may erroneously assume that the equipment is clean, based on an apparent negative result.


Table 2. Values (%) of the cells and recombinant proteins recovered in the recovery study (SD: standard deviation; CV: coefficient of variation)
To evaluate the efficiency of swabbing, the "worst case scenario" was evaluated using fermentation and purification facilities as examples. Moreover, three recombinant proteins were included in this study: SK and interferona 2b human recombinant (IFNα2bHu-r) were obtained from bacterial cells. The EGF was expressed in yeast cells. In all cases, the studies were performed considering the interaction of these cells with different manufacturing processing surfaces, which may in turn significantly affect the swabbing recovery during cleaning validation. The results obtained from microbial host and recombinant proteins on stainless steel and borosilicate glass are shown in Table 2. The mean of recovery factor ranged from 89 to 108%. For the cells, the results are closest to 100% recovery from both surfaces. These results are superior to those published in a similar study by using bacterial whole cell homogenate and stainless steel coupons.18 Those studies obtained recovery values of 67%, using 0.05 N phosphoric acid as the extraction solution. In a similar study, a recovery mean of 81.9% was obtained using 1 N sodium hydroxide as the solvent using E. coli and stainless steel coupons.2

For the recombinant proteins, the lowest recovery value was obtained with SK on stainless steel coupons with a general recovery factor of 89.47%. The remaining recombinant protein–surfaces combinations showed recovery factor values ranging from 93.89 to 107.86%. These results match with those obtained by Lombardo, et al. in a similar study, but using purified recombinant human ciliary neurotrophic factor (rHCNTF) on a stainless steel surface and 0.05 N phosphoric acid as the extraction solution.18 However, Lombardo's results from borosilicate analysis (55% of recovery factor) were lower than those obtained in our study (from ~94 to 108%).

These results suggest that purified water with low levels of TOC can be used efficiently to recover all biological materials. In addition, the almost identical recovery factor values for the IFNα2bHu-r–PEG and IFNα2bHu-r show that the polyethylene glycol conjugation process does not affect the electrostatic interaction with the borosilicate surface and can be removed efficiently under the conditions described (see materials and methods above).


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