Issues with Industrial Probiotic Scale-up - Aquaculture Nutrition: Gut Health, Probiotics and Prebiotics - page 349

13.2 SCALING-UP GUIDELINES
In most cases, the putative probiotic candidates reported in scientific publications rarely go
on to commercialization and industrial application. This is because isolating and identifying a
microorganism/strain as a potential probiotic, following extensive in vitro and/or in vivo pro-
grammes, is only the beginning of the process. The job does not stop there; additional important
steps are required for viable industrial scale-up which requires not only substantial financial
investment but also contributions from a multidisciplinary team that should include scientists,
fermentation engineers and regulatory personnel at the least. Some of these important steps
include:
• demonstration of the safety of the potential probiotic
• evaluation of the efficacy at farm level
• optimization of the production at industrial scale, ensuring that it retains the particular prop-
erties for the subsequent application
• determination of administration strategies
• pre-market registration.
13.2.1 First step: demonstration of safety
This step is crucial and yet it has been considerably under-evaluated. When developing probi-
otic strategies for the aquaculture market, one must demonstrate and provide all the scientific
information concerning the safety of the strain with regard to the target animal species but
also for the environment, the workers handling the product and finally the ultimate consumer.
In many countries (USA, EU, Canada, Australia, China etc.), regulations are in place to dis-
courage the use of strains which have not been unequivocally demonstrated as safe. There
exist positive lists of microorganisms for which their safety for use in food and feed appli-
cations can be robustly assumed. The United States' Food and Drug Administration's (FDA)
Generally Recognized as Safe (GRAS) list and the European Food Safety Authority's (EFSA)
Qualified Presumption of Safety (QPS) are two examples. For this reason, most of the probiotic
strains currently commercially available for feed application use in developed countries are on
at least one of these lists. However, when it comes to applications in aquaculture, it would
appear that many putative probiotic strains have been isolated from fish and their immedi-
ate aquatic environment: this is termed an autochthonous approach. These specific microbial
strains however may not necessarily share the same historical safety status as their 'traditional'
or widely tested counterparts (Adams 1999). With academics and regulators becoming more
and more aware of this issue (Wang etal. 2008), manufacturers and scientists alike are increas-
ingly looking at considerations of safety in use prior to progressing to investments in product
development and commercialization. In fact, many are now prepared to consider working on
species isolated from human or agricultural application systems (Gatesoupe 2002a) with pos-
sible 'proven records'. Although extensive research has been undertaken on microbial species
from the immediate environment of the host, very little attention has been paid to their safety.
One of the main reasons for going down the autochthonous strains route relates to the fact that
the effectiveness, and the ability to thrive in the host environment, of these species is generally