Extrapolating data from in vitro to in vivo, and the transition of animal trial data to field observations

Since the mid 1990’s, there has been a global shift away from the use of antibiotic growth promotors (AGP) in poultry feed, due to legislation and consumer pressure. Therefore, there is a reasonably long history of the development of AGP alternatives for use in the poultry industry. In spite of this history, the transition to AGP-free production is often not a smooth one for individual companies, or even individual farms within a company.

Ideally, a replacement strategy for AGP must be economically feasible, should be simple to apply consistently under field conditions, be accepted by consumers, not promote microbial resistance, and most importantly, be efficacious. The challenge faced by the industry is to replace a strategy that was broadly effective – that is, AGP generally worked under against a fairly wide variety of bacterial challenges, and the impact of AGP was typically most pronounced under the most challenging production conditions. A transition to alternatives, however, will simultaneously require a higher standard of housing, husbandry, biosecurity, management, and nutrition. Controlled research trials are a necessary step towards commercial implementation, but caution must be used when evaluating research trial results. Candidate products or strategies are normally evaluated along a research continuum. This begins with initial in vitro proof-of-concept studies, through small-scale live animal tests, and scale-up to larger research or commercial studies before regulatory approval is sought for commercial adoption. At each development step, appropriate experimental design, research conditions, statistical analysis, and objective evaluation of results are required. Without sounding pessimistic, each of the steps along the research and development pathway poses a potential risk of uncovering a flaw in the proposed product or strategy. These include, but are not limited to lack of efficacy under increasingly real-world conditions, unintended negative side effects, difficulty in producing sufficient quantities or consistency of product for commercial use, or excessive cost relative to realized benefit. However, only when the most stringent standards are upheld at each step can a company be confident in marketing their product, and producers be confident in their use of the product.

Finally, it must be recognized that the complex of microbial and non-microbial challenges can vary greatly from one region to another, from one company to another, from one farm to another within a company or region, and even over time within a single farm and flock. The strategy or product that is suitable for one situation may not be as effective in another situation. Therefore, a successful, commercially-viable AGP-free program will involve the utilization of multiple products or strategies, with complementary mechanisms of action, and will need to be tailored to each production unit. Although this may take time and effort, it is likely to be the only path to success.

Presented at the 7th International Conference on Poultry Intestinal Health, Cartagena, Colombia, 2022. For information on the next edition, click here.