Food and Drug Administration’s (FDA) Center for Veterinary Medicine (CVM) released (September 11, 2013) draft guidance describing the types of information that CVM recommends for inclusion in food additive petitions (FAPs) for food additives to be used in animal food/feed. FDA has stated that the guidance was prepared in order to better help the petitioner to submit an FAP and the information contained within, in a “consistent and appropriate manner.” However, does the guidance focus on the information relevant to the determination of safety of the ingredient to be added to feed, or does the guidance suggest that FDA is extending its reach (in this petition format) beyond what is pertinent to evaluating the safety of a feed ingredient? And, does the release of draft guidance result in FDA citing this level of information standard for every petition, for which all other petitions should be rejected? Actions by other FDA offices may provide some indication of FDA’s path forward.
The format of the guidance document follows the general format provided by FDA for FAPs as stated within the regulation in the U.S. Code of Federal Regulations (21 CFR §571), and in many cases provides additional discussion on such issues as chemical identity, safety information and intended effect (i.e., “the purposes for which it [the food additive] is proposed…”). However, there are statements within the draft guidance that lead to additional questions, not answers. For example, the draft guidance states that “for mixtures, you should identify as many of the components of the mixture as is feasible and to reasonably define the composition of the mixture. In addition, information on the chemical composition and identity of each component in the mixture is needed and a material balance should be provided.” How far does “as feasible” need to be taken? An ingredient such as a plant seed meal (e.g., corn meal, soybean meal, quinoa meal) is technically a complex mixture of potentially hundreds of volatile oils, fats, carbohydrates and minerals, each of which would need to be defined as indicated by this guidance. The phrase “as is feasible” contributes to the confusion, as analytical technology has made it “feasible” to differentiate the constituents of mixtures to the point that it could take years to “identify” each component within a plant seed meal, further, these constituents could vary qualitatively and quantitatively from year to year.
Moreover, what is “feasible” may not be relevant to the determination of safety at any level of detection. FDA’s general request for manufacturing methods and controls within the guidance is consistent with the regulations, but the level of detailed description being requested by CVM suggests that the level of scrutiny is not only to evaluate the safety of a food ingredient, but to evaluate the process under the Food Safety and Modernization Act (FSMA).[1] CVM is requesting that a petition’s manufacturing section include:
(1) a list of all solvents, catalysts, and reactive ingredients used; the quantities of these used; and the order of addition of these chemicals during production; (2) times, temperatures, and pH conditions for all steps in the manufacturing process; (3) identification of all manufacturing control points; and (4) identification of all analytical methods used to monitor chemical reactions during manufacture, including information that demonstrates that the methods perform within appropriate limits.
The guidance also states that “you should also identify any alternative methods of manufacture of the food additive and provide as full a description as possible for the methods.” As written, the ability to “identify any alternative methods of manufacture” could be a daunting, time-consuming task, as there could be a number of different ways to produce a seed-based meal, to extend the example used above. The focus of the petition should be on the safety of the ingredient as consumed by the target species, which is typically shown through comprehensive safety studies. CVM does provide suggestions on the potential endpoints necessary to evaluate the safety of a food ingredient, but also suggests the petitioner to both consult with CVM on protocol reviews and study parameters (which can be quite time consuming) and also to review previous guidance generated for the evaluation of veterinary pharmaceutical products, suggesting that the standard of a food ingredient (reasonable certainty of safety) is being changed to a more subjective process of risk assessment, such as a drug, which may also eventually involve justification of use, vis-a-vis similar products also on the market. A concern for the release of any guidance from FDA is the use of the “guidance” as rulemaking. Over the past several years, FDA guidance has outpaced rulemaking as the primary method for the FDA to communicate its final position on matters.[2] For example, the guidance document on the notification of new dietary ingredients to FDA has been seen by many (including some within FDA) as guidance that is taken as rulemaking and expands FDA’s ability to mandate change outside of the procedures dictated by the Administrative Procedures Act, with the disingenuous argument that “guidelines are not binding.”[3] Similar issues exist within CVM’s guidance document for FAPs as exist for dietary ingredient notification, wherein “non-binding” guidance will be used to leverage industry into assumption of costly data development requirements.
The guidance document is a comprehensive view of FDA’s thinking on the information necessary for a petition to the FDA on the safety data necessary for a food ingredient to be incorporated into the U.S. food system for animal food/feed. Many of the recommendations stated in the guidance are an expansion of the statements made in the FDA regulations contained within 21 CFR §571. However, several areas of the guidance remain largely open to interpretation, which leaves the petitioner in doubt on the depth of detail necessary for a petition to be approved. Substantial revision of the guidance must be completed to provide the goal for which it was intended: to help the petitioner submit a FAP with sufficient information and to determine the safety of an animal food ingredient.
References
[1] Center for Veterinary Medicine. http://www.fda.gov/AnimalVeterinary/Products/AnimalFoodFeeds/ucm347941.htm; site last visited December 16, 2013.
[2] http://www.fda.gov/AnimalVeterinary/Products/AnimalFoodFeeds/ucm347941.htm; site last visited December 16, 2013; http://www.fdli.org/resources; Informal Guidance and FDA, 66 Food and Drug Law Journal, 507-550 (2011); site last visited December 16, 2013
[3] Attorneys See FDA Rulemaking By Guidance In NDI Notification Draft; The Tan Sheet; Article #05120130023 posted February 6, 2013.