## 3 Bacteriophages
### Bacteriophage Therapy and Phage-Based Products for the Control of E. coli O157:H7  
Phage therapy is a method that uses phages to effectively treat bacterial infections in medicine; this is made possible by the abundance of phages in nature, their simplicity in isolation, and the efficiency with which they kill bacteria, especially when used in controlled laboratory research. The emergence of AMR has made it possible to investigate phages as an antibiotic alternative. _E. coli_ phages have been created for oral administration and utilised in randomised trials [137; 138]. Currently, researchers are attempting to employ phages in a dried powder form that is considerably more stable and easier to store, transport, and administer. Despite the research on phage therapy, there are currently no phage therapy products licenced for human use in the EU or the US. To manage _E. coli_ O157:H7 in the food sector, phage-based products have been developed to be used as biocontrol of bacterial diseases and have been authorised by the FDA as \"generally considered safe\". Examples of phage-based anti-_E. coli_ O157:H7 products include the following; EcoShieldTM, originally designed for application in \"red meat parts\" [139], and Secure Shield E1, a product manufactured by FINK TEC GmbH, a German company, that is specifically designed for application on the external areas of beef carcasses [140]. Every product has obtained approval from the Food and Drug Administration (FDA). Several food products have recently received approval for the utilization of phage mixes from OmniLytics (Sandy, UT), Microes' PhageGuard E., and Intralytiv's EcoShield PYTM to mitigate the risk of infection caused by _E. coli_ O157:H7 and other pathogenic _E. coli_ strains [141] (Table 3).  
The FDA has granted approval for the phage products to be classified as generally recognized as safe (GRAS) food additives. The GRAS categorization mentioned above is derived from the regulatory framework established by the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the regulations outlined in Title 21 of the Code of Federal Regulations (21 CFR). In order to introduce novel chemicals into the human food supply, particularly those intended for use as food additives, it is necessary to adhere to the regulatory guidelines outlined in 21 CFR part 170, subpart E [142]. This procedure has been used for the purpose of certifying bacteriophages, predominantly in the United States.  
Other nations have also granted approval for the use of bacteriophages to ensure the safety of food products. In 2014, the Israeli Ministry of Health's National Food Service authorized the utilization of bacteriophages, which had previously received approval from the FDA, for similar applications. This decision was made in accordance with the regulations outlined in the document titled \"Guidelines: use of bacteriophages (bacteria-killing viruses) in food\" [143]. In Canada, the authorization for the use of phage-based products as food processing aids has been granted. These products include PhageGuard LTM (previously known as ListexTM), ListShieldTM, SalmonFreshTM, and EcoShieldTM, among others [143] (Figure 3).  
\begin{table}
\begin{tabular}{c c c c} \hline \hline  & **Bacteriophage** & **Applications** & **Regulatory Approval** \\ \hline
1 & PhageguardE & Beef & USDA/FDA/GRN 757 \\
2 & EcoShield PX & Meat, poultry, food, vegetables & FDA (2011)/GRN 834 \\
3 & Omnilytes & Poultry, red meat & FDA/GRN 827 \\
4 & SecureShield E1, FinkTec GmbH, Hamm, Germany & Beef carcasses & FDA/GRN 724 \\ \hline \hline \end{tabular}
\end{table}
Table 3: Approved phage-based products for _E. coli_ O157:H7.