In the Federal Register of August 18, 2006, FDA announced that it had approved the use of a bacteriophage preparation made from six individually purified phages to be used on RTE meat and poultry products as an antimicrobial agent against Listeria monocytogenes. The rule is in response to a food additive petition submitted in 2002 from Intralytix, Inc.
Questions & Answers
1. What is a bacteriophage?
Bacteriophages (phages) are viruses that infect only bacteria and do not infect mammalian or plant cells. Phages are ubiquitous in the environment, and humans are routinely exposed to them at high levels through food and water without adverse effect.
2. What is the additive that was approved?
The additive that was approved is a mixture of equal proportions of six phages specific against L. monocytogenes. The petitioner's rationale for incorporating six phages in one formulation is to minimize the possibility of L. monocytogenes developing resistance to the additive. The approved phage preparation is reported to be effective against 170 strains of L. monocytogenes.
3. How is the bacteriophage used in the additive produced?
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 that are 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 ml.
4. What is the purpose of the additive?
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.
5. Is this additive novel?
This is the first time FDA has regulated the use of a phage preparation as a food additive. However, phages are currently approved in the U.S. for pesticide applications, including uses on crops. Although not currently permitted in the U.S., phages are used in other countries in antibiotic therapy.
6. What was the basis of FDA's safety decision?
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, FDA concluded that the additive does not pose any safety concerns, providing that it complies with the identity and specifications in the regulation.
7. What was the process of deciding that the phage was suitable for use in meat and poultry under the conditions of use?
Under the Memorandum Of Understanding (MOU) for the joint USDA Food Safety and Inspection Service (FSIS) and FDA ingredient approval process, FDA is authorized to determine the safety of substances, as well as prescribe safe conditions of use. FSIS is responsible for evaluating the suitability of the use of new ingredients (when the use involves meat or poultry products). "Suitability" relates to the effectiveness of the substance in performing the intended technical purpose of use, at the lowest level necessary, and the assurance that the conditions of use will not result in an adulterated product or one that misleads consumers. In regard to L. Monocytogenes control, the guidance has been at least a 1 log reduction (for an antimicrobial agent used to reduce or eliminate Listeria) and no more than 2 logs growth during a product's shelf life (for an antimicrobial agent that is intended to suppress the growth of Listeria). Therefore, to satisfy FSIS' concerns, the petitioner included data that showed that the use of the phage preparation was effective in reducing/controlling Listeria without resulting in an adulterated product or one that misleads consumers.
8. Will the additive be declared on the food label?
Use of this additive must comply with the Federal Meat Inspection Act or the Poultry Products Inspection Act, which are both administered by USDA. According to USDA, the use of the phage preparation will need to be declared as an ingredient on the label of the treated meat or poultry product, e.g., "bacteriophage preparation." In addition, when the phage is applied to meat and poultry products with standards of identity that do not permit the addition of antimicrobial agents, the products will need to be descriptively named, e.g., "beef steak treated with an antimicrobial solution to reduce microorganisms."