Issues with Industrial Probiotic Scale-up - Aquaculture Nutrition: Gut Health, Probiotics and Prebiotics - page 351

use prior to their development for wider industrial applications. Specific studies must be con-
ducted and should include assessment of the safety in use in the target animal species, as well
as with regards to the safety of the environment and consumers. Having mostly human safety
in mind, this initial and essential consideration must demonstrate the absence of toxins and
other virulence factors as well as the absence of transferable antibiotic resistance genes. There
should also be consideration of the safety of the handler of the product in order that such uses
do not elicit allergic or irritative reactions.
Understandably the approach taken in most cases in order to reduce the investment needed
to demonstrate the safety of a potential probiotic strain is to develop products based on micro-
bial strains whose safety in use is already well documented and demonstrated (i.e. existing
probiotics with a long history of use or as routinely referenced GRAS/QPS species).
13.2.2 Evaluation of the efficacy of the probiotic at the
farm level
Only once the proof of safety has been satisfactorily achieved should a probiotic intended for
aquaculture use be evaluated at a larger scale, for example on farm. This is particularly impor-
tant from industrial and commercial perspectives: it enables the validation of technical and
other benefits and helps elucidate financial implications with regards to optimization for use
at farm level. These trials should also help fine-tune the scaled-up application from a practical
point of view (conditions of use, stability under different storage conditions etc.). Field tri-
als must be robust, logical and statistically valid in order prevent inconclusive outcomes and
enable better application.
Several studies have been conducted on farms but en masse industrial level applications
are not frequently reported. It is likely that industrial scale applications are relatively com-
mon since entrepreneurs are forced by, for example, regulation and/or their prospective clients
to extensively assess their products' efficacy at industrial scale prior to placing them on the
market. However, issues such as intellectual property rights limit access to such data by the sci-
entific community. Another limitation to wider access could be the possible impingement from
legislative requirements (specifically the EU) demanding that authorizations are first requested
prior to trials being undertaken. Commercial companies may therefore not consider applying
and thus not carry out the necessary studies.
Finally, with regards to the evaluation of the use of a probiotic in aquaculture, additional
criteria need to be recognized. Recent studies in marine fish larvae have demonstrated that
the usual efficacy criteria may not always be sufficient to quantify the efficiency of probiotics.
It has been suggested that further scrutiny of such effects as the ontogenetic chronology and
larval quality properties would also need special attention (Avella et al. 2010; Gatesoupe et al.
2012; Lamari et al. 2012).
13.2.3 Producing quality probiotics is both an art and a science
Once safety and efficacy issues are successfully completed, attention should then be turned to
optimization of the industrial production of the probiotic. Progression to field application has
been shown to be a real challenge, and among the main issues is the consistency in the quality
of the probiotic product. In other words, production of probiotics must be standardized, and
more so at industrial scale-up level.