Agency Response Letter GRAS Notice No. GRN 000468 - Additional Correspondence
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See also Generally Recognized as Safe (GRAS).
CFSAN/Office of Food Additive Safety
December 2, 2016
Steven Hagens, Ph.D.
Nieuwe Kanaal 7P
6709 PA Wageningen
Re: GRAS Notice No. GRN 000468
Dear Dr. Hagens:
The Food and Drug Administration (FDA, we) completed our evaluation of Micreos B.V. (Micreos)'s supplement to GRN 000468. We received the supplement on May 17, 2016. The supplement addresses additional uses for the subject of GRN 000468. Micreos submitted clarifying information on July 22 and September 13, 2016.
We previously responded to GRN 000468 on December 23, 2013. We stated that we had no questions at that time regarding Micreos's conclusion that phage preparation containing the bacterial monophages FO1a and S16 specific to Salmonella serovars (Salmonella phage preparation) is GRAS for use as an antimicrobial to control Salmonella serovars in certain pork and poultry products at levels up to 108 plaque forming units per gram (PFU/g) of food.
In the supplement we received on May 17, 2016, Micreos informs us of its view that Salmonella phage preparation is GRAS, through scientific procedures, for use as an antimicrobial to control Salmonella serovars on beef and vegetables at levels up to 108 PFU/g of food. Micreos states that the methods of manufacture and analysis remain the same as described in GRN 000468.
Micreos estimates the cumulative dietary exposure to Salmonella phage preparation for the United States (U.S.) population based on per capita consumption data from the U.S. Department of Agriculture's Economic Research Services. Based on the intended use in pork and certain poultry products as described in GRN 000468 and in beef and vegetables as described in the supplement, Micreos estimates that people will consume 5 x 1010 PFU per person per day.
As part of the supplement we received on May 17, 2016, Micreos confirms that a number of original research and review articles on the use of bacteriophage as antimicrobial agents have been published since the filing of GRN 000468. Micreos concludes that the information contained in these publications does not change its assessment of Salmonella phage preparation as a safe and effective means to control Salmonella.
Use in Products under USDA Jurisdiction
During our evaluation of the supplement we received on May 17, 2016, FDA coordinated with the Food Safety and Inspection Service (FSIS) of the USDA. Under the Federal Meat Inspection Act, the Poultry Products Inspection Act, and the Egg Products Inspection Act, FSIS determines the efficacy and suitability of food ingredients in meat, poultry, and egg products, and prescribes safe conditions of use. Suitability relates to the ingredient's effectiveness in performing its intended technical effect and the assurance that the ingredient's use will not result in products that are adulterated or misleading for consumers.
FSIS has completed its evaluation of this ingredient and has no objection to the use of Salmonella phage preparation containing the bacterial monophages FO1a and S16 for use as an antimicrobial to control Salmonella serovars on beef at levels up to 108 PFU/g. During the course of its review, FSIS requested additional information, which Micreos provided on July 22 and September 13, 2016.
Regarding labeling on beef, FSIS concluded that Salmonella phage preparation meets the definition of a processing aid and no labeling is required when used under the intended conditions of use. FSIS requested that we advise Micreos that questions regarding labeling should be addressed to Ms. Rosalyn Murphy-Jenkins via email at Rosalyn.Murphy-Jenkins@fsis.usda.gov.
FSIS requested that we advise Micreos to seek regulatory guidance from its Risk, Innovations, and Management Staff (RIMS) about the use of Salmonella phage preparation in meat, poultry, and egg products. Micreos should direct such an inquiry to Dr. William K. Shaw, Jr., Director, RIMS, Office of Policy and Program Development, FSIS by email at William.Shaw@fsis.usda.gov.
Section 301(ll) of the Federal Food, Drug, and Cosmetic Act (FD&C Act)
Section 301(ll) of the FD&C Act prohibits the introduction or delivery for introduction into interstate commerce of any food that contains a drug approved under section 505 of the FD&C Act, a biological product licensed under section 351 of the Public Health Service Act, or a drug or a biological product for which substantial clinical investigations have been instituted and their existence made public, unless one of the exemptions in section 301(ll)(1)-(4) applies. In our evaluation of Micreos's supplement that Salmonella phage preparation is GRAS under its intended conditions of use, we did not consider whether section 301(ll) or any of its exemptions apply to foods containing Salmonella phage preparation. Accordingly, our response should not be construed to be a statement that foods that contain Salmonella phage preparation, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information that Micreos provided, as well as other information available to FDA, we have no questions at this time regarding Micreos's conclusion that Salmonella phage preparation is GRAS under its intended conditions of use. This letter is not an affirmation that Salmonella phage preparation is GRAS under 21 CFR 170.35. Unless noted above, our review did not address other provisions of the FD&C Act. Food ingredient manufacturers and food producers are responsible for ensuring that marketed products are safe and compliant with all applicable legal and regulatory requirements. In accordance with 21 CFR 170.275(b)(2), the text of this letter responding to the supplement to GRN 000468 is accessible to the public at www.fda.gov/grasnoticeinventory.
Antonia Mattia, Ph.D.
Division of Biotechnology and GRAS Notice Review
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
cc: William K. Shaw Jr., Ph.D.
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