- Animal & Veterinary
- Vitamin Derivatives, Inc.
- Issuing Office:
- Atlanta District Office
Department of Health and Human Services
|Public Health Service
Food and Drug Administration
||Atlanta District Office
60 8th St., NE
Atlanta, GA 30309
March 30, 2015
Dr. Hardy M. Edwards, III, President
Vitamin Derivatives, Inc.
625 Lem Edwards Road
Winterville, GA 30683-7658
Dear Dr. Edwards,
An inspection of your food additive distribution operations was conducted by a U.S. Food & Drug Administration (FDA) Investigator on November 19-21, 2014. Our inspection revealed you have distributed your 1-alpha-hydroxy vitamin D3 (1-alpha-hydroxycholecalciferol or Alpha D3), a synthetic vitamin D3 analogue for use in broiler feed, in interstate commerce to customers in the United States. This substance is not Generally Recognized as Safe (GRAS) among qualified experts for its intended use in broiler feed, is not the subject of a prior sanction, and there is no approved food additive regulation that authorizes its use. Accordingly, the substance is an unsafe food additive under section 409(a) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 348(a)], and is adulterated under section 402(a)(2)(C)(i) of the Act [21 U.S.C. § 342(a)(2)(C)(i)].
As defined in section 201(s) of the Act [21 U.S.C. § 321(s)], the term "food additive" refers to any substance the intended use of which results in its becoming a component of any food, unless the substance is the subject of a prior sanction or is GRAS among qualified experts under the conditions of its intended use. Under section 409(a) of the Act [21 U.S.C. § 348(a)], a food additive is unsafe unless a regulation is in effect that prescribes the conditions under which the additive may be safely used, and the additive and its use or intended use are in conformity with that regulation. There is no food additive regulation authorizing the use of 1-alpha-hydroxy vitamin D3 as a Vitamin D source in poultry feed, and we are not aware of any information to establish that 1-alpha-hydroxy vitamin D3 added directly to poultry feed is the subject of a prior sanction. In addition, as discussed further below, we have determined that 1-alpha-hydroxy vitamin D3 is not GRAS under the conditions of use as stated on your product label.
FDA's regulations in 21 CFR Part 570 describe the eligibility criteria for classification of a substance added to animal food as GRAS. Under 21 CFR 570.30, general recognition of safety must be based on the views of qualified experts. The basis of such views may be either (1) scientific procedures or (2) in the case of a substance used in food prior to January 1, 1958, through experience based on common use in food. Further, general recognition of safety requires common knowledge about the substance throughout the scientific community knowledgeable about the safety of substances directly added to food.
FDA's regulations in 21 CFR Part 570 define "scientific procedures" and establish eligibility criteria for classification as GRAS through scientific procedures. Under 21 CFR 570.3(h), scientific procedures "include those human, animal, analytical, and other scientific studies, whether published or unpublished, appropriate to establish the safety of a substance." Under 21 CFR 570.30(b), general recognition of safety based upon scientific procedures "shall require the same quantity and quality of scientific evidence as is required to obtain approval of a food additive regulation for the ingredient." Section 570.30(b) further states that general recognition of safety through scientific procedures is ordinarily based upon published studies, which may be corroborated by unpublished studies and other data and information.
Under 21 CFR 570.3(f), "[c]ommon use in food means a substantial history of consumption of a substance by a significant number of animals in the United States." Under 21 CFR 570.30(c), "[g]eneral recognition of safety through experience based on common use in food prior to January 1, 1958, shall ordinarily be based upon generally available data and information. An ingredient not in common use in food prior to January 1, 1958, may achieve general recognition of safety only through scientific procedures."
FDA's regulations in 21 CFR Part 570 also define "safe" and "safety." Under 21 CFR 570.3(i), "[s]afe or safety means that there is a reasonable certainty in the minds of competent scientists that the substance is not harmful under the intended conditions of use." The regulations identify factors to be considered in determining the safety of a substance added to food.
You can find the Act and food additive regulations through links on the FDA's home page at http://www.fda.gov
In December 15, 2009 and June 14, 2011 submissions to FDA, you informed FDA of your firm's views that 1-alpha-hydroxy Vitamin D3 was GRAS, through scientific procedures, for use as an ingredient in broiler feed, and provided data and information in support of your view. By letters dated April 19, 2010 and May 4, 2012, FDA informed you the agency had evaluated the information you presented in your respective submissions and provided you with detailed written evaluations of the data along with specific comments related to deficiencies in the information presented related to the areas of manufacturing chemistry, human safety, and target animal safety. In its letter of May 4, 2012, FDA indicated that your GRAS notice of June 14, 2011 did not "provide a sufficient basis for a determination that 1-alpha-hydroxycholecalciferol [1-alpha-hydroxy vitamin D3] is GRAS under the conditions of its intended use in animal food." The letter also informed you if you wished to have FDA consider any new information regarding 1-alpha-hydroxy vitamin D3, the appropriate mechanism would be to submit, in accordance with proposed 21 CFR 570.36, a complete GRAS notice which would be assigned a new file number.
FDA has not received any additional GRAS notifications from you for the use of 1-alpha-hydroxy vitamin D3 in poultry feed. Although you stated in an April 5, 2010 letter to FDA that you would discontinue sales of your Alpha D3 product to customers in the United States until your product had achieved GRAS status, you continued distributing it to a domestic customer in interstate commerce for use in broilers from November 2011 - September 2014.
FDA recently on its own initiative conducted a review of the GRAS status of your product and concluded that it is not generally recognized as safe for use as a source of vitamin D in feed for broiler chickens based either on scientific procedures or common use in food. Information in the public literature demonstrates that the substance was not used in the United States prior to 1958. Furthermore, FDA found that there is a lack of publicly available information and lack of consensus of expert opinion regarding its safety for its intended use. For example, there is a lack of target animal safety studies that could allow the establishment of a margin of safety for the use of the substance in poultry feed. In addition, the published literature does not provide sufficient information to demonstrate that there is a general consensus among qualified experts with respect to: (1) the concentration of the substance at which this substance could be considered safe for oral consumption in broiler chickens, (2) the toxicity of the substance following repeated oral exposure in broiler chickens, or (3) scientifically-sound toxicology studies conducted with the substance.
FDA is not aware of any other exemption from the food additive definition that would apply to the use of 1-alpha-hydroxy-vitamin D3 in poultry feed. Accordingly, as described above, the product is a food additive under section 201(s) of the Act. It is an unsafe food additive under section 409(a) as there is no food additive regulation prescribing the conditions under which such additive may be safely used, and is thus adulterated under 402(a)(2)(C)(i) of the Act [21 U.S.C. § 342(a)(2)(C)(i)].
We acknowledge receipt of your letter dated December 3, 2014 wherein you state Vitamin Derivatives, Inc. has stopped shipping and selling Alpha D3 to your domestic customer and that you plan to submit new information to FDA in support of the safety of your product. Please note that until your product is the subject of approved food additive petition or can be classified as GRAS based on scientific procedures, we consider any continued marketing of your product in the Unites States to be a violation of the Act.
You should notify this office, in writing, within fifteen (15) working days of the receipt of this letter of the steps you have taken to bring your firm into compliance with the law. Your response should include an explanation of steps being taken to correct the violation. If you are unable to complete the corrective actions within fifteen (15) working days, identify the reason for the delay and the time within which you will complete the corrections. Include copies of any available documentation demonstrating that corrections have been made.
Your written response should be sent to the U.S. Food and Drug Administration, Attn: Janice L. King, Compliance Officer, at the address noted in the letterhead. If you have questions, please contact Mrs. King at 843-746-2990, by email at Janice.firstname.lastname@example.org or write her at the noted address.
Ingrid A. Zambrana
Atlanta District Office