FDA Approves Use of Bacteriophages to be Added to Meat and Poultry Products

Abstract

In the Federal Register of August 18, 2006, the US Food and Drug Administration (FDA) announced that it had approved the use of a bacteriophage preparation made from 6 individually purified phages (LMP-102) to be used on ready-to-eat (RTE) meat and poultry products as an antimicrobial agent against Listeria monocytogenes. The ruling came in response to a food additive petition submitted in 2002 from Intralytix, Inc. (Baltimore, MD), the biotech company that produces the bacteriophage. This marks the first time the FDA has regulated the use of a phage preparation as a food additive. However, phages are currently approved in the United States for pesticide applications, including use on crops. Although not currently permitted in the United States, phages are used in other countries in antibiotic therapy regimens. The additive that was approved is a mixture of equal proportions of 6 phages with specific activity against L monocytogenes. The petitioner’s rationale for incorporating 6 phages into 1 formulation is to minimize the possibility of L monocytogenes developing resistance to an individual additive. The approved phage preparation is reported to be effective against 170 strains of L monocytogenes. “Each phage is specific against various L monocytogenes strains, including those strains known to be associated with foodborne illness,” according to the Federal Register. The phage is cultured using L monocytogenes as the host organism. Because the phage infects and destroys the host organism during its life cycle, the final product does not contain any viable Listeria. In addition, because of the purification steps used in making the phage, any toxic components from the host organism are effectively removed from the final phage product. To ensure safety, the regulation specifies that the additive must test negative for L monocytogenes, and the L monocytogenes toxin, listeriolysn O, must not be present at detectable levels, where the limit of detection is 5 hemolytic units per milliliter. The phage preparation will be used in meat and poultry processing plants for spray application to the surface of RTE meat and poultry products, such as lunch meats and hot dogs, to kill Listeria. “The phage preparation will be applied to the surface of RTE meat and poultry products at a level not to exceed 1 mL per 500 cm2 food surface just prior to packaging. These foods can become contaminated with Listeria during production, but unlike fresh meat and poultry, these foods are consumed without additional cooking that would kill the bacteria, thereby increasing the risk to Listeriosis, an infection caused by the bacteria. Furthermore, L monocytogenes is capable of multiplying at low temperatures, so it can multiply in food over time even when the food is kept in the refrigerator. Persons with increased risk to listeriosis are pregnant women, newborns, those with a compromised immune system, and the elderly,” the FDA states. To support the safety of the proposed use of the Listeria-specific phage preparation, the petitioner submitted published reports from animal studies and results from the use of phages as therapies in the treatment and prevention of infections in humans caused by bacteria. Based on this and other information, the federal agency concluded that the additive does not pose any safety concerns, providing that it complies with the identity and specifications in the regulation. Despite the approval from the FDA for LMP-102, the ingredient must also comply with the Federal Meat Inspection Act and/or the Poultry Meat Inspection Act, both of which are administered by the U.S. Department of Agriculture, before it can be used in RTE meat and poultry products. “In particular, those statutes provide that the ingredient must be suitable for its intended use,” the FDA states in the Federal Register. According to the Centers for Disease Control and Prevention, about 2500 people become seriously ill every year from listeriosis. Twenty percent of these infections are fatal (Figure 1). For further details, see “Food Additives Permitted for Direct Addition to Food for Human Consumption; Bacteriophage Preparation,” Federal Register 2006;71:47729–47732.