Following the 1958 Amendment to the Federal Food Drug and Cosmetic Act (FFDCA or “the Act”), the Centers regulating human and animal foods took what are now seen to be radically divergent pathways. While the human food side had paid strict obeisance to the letter and spirit of the Act by implementing a food additive petition process, incorporated historically safe (generally recognized as safe or GRAS) substances into the CFR, eventually starting a GRAS affirmation process and, as granted by the Act, respected the right of non-FDA “experts qualified by scientific training and experience” to make GRAS determinations. In the middle 1990’s, following the affirmation of 200+ substances for direct addition to food, the GRAS affirmation process became bogged down and was discontinued, to be replaced by the GRAS Notification process in 1997.
The animal food side of the FDA, the Center for Veterinary Medicine (CVM), implemented a feed additive petition process and included a purged list of GRAS substances. However, instead of an active GRAS affirmation process (only two substances were eventually affirmed GRAS by CVM) or a notification process, the CVM engaged in a system of “enforcement or regulatory discretion” actions in which the agency would offer a letter of regulatory discretion if it did not feel the substance raised any safety concerns. Despite the same approval processes available for human foods, CVM encouraged manufacturers to participate in the American Association of Feed Control Officials (AAFCO) ingredient definition process. In the AAFCO process, CVM played the role of scientific advisor for this association of state regulators and instead of an affirmative decision on safety, CVM continued the use of regulatory discretion letters for ingredients submitted to AAFCO. The CVM/AAFCO arrangement was a natural association, as most feed manufacturing and regulation had historically been conducted at the state level and, in several states, feed ingredients are even required to be written into state law. AAFCO ingredients and standards are published in the “Official Publication,” seen in many countries as the default source for approved feed ingredients for the US.
While these processes for feed ingredient approval worked well for many years, a series of events precipitated the generation of a Memorandum of Understanding (MOU) in 2007 between CVM and AAFCO. This MOU acknowledged the participation of CVM in the AAFCO review process, but that it would end in September 2012, and that although the agency was said to “recognize” the AAFCO OP, it also stated “AAFCO has no enforcement authority” and that “the OP list does not have the force of law.” Thus, the MOU was crystal clear about two things: (1) it set a date certain when CVM participation in the AAFCO process would end and; (2) AAFCO and the OP have no regulatory or enforcement authority. In separate venues, CVM has stated the practice of issuing regulatory discretion letters will be curtailed and, importantly, there is no mechanism to provide a regulatory “home” (e.g., GRAS status or feed additive status) to the ingredients added to the OP on the strength of an AAFCO definition alone. The lack of a regulatory “home” for OP ingredient definitions is likely attributable to the fact that only regulatory discretion had been invoked for these ingredients and no affirmative decision on safety had been made as required by the Act (e.g., GRAS or food additive status) – this turn of events could mean that all ingredients included in the OP after January 1, 1958, could be seen as unapproved feed additives. Conceivably, FDA could be forced to demand that most OP approved ingredients be taken from the market.
So now, what to do? Neither CVM nor AAFCO have announced plans to remedy the fate of those substances now in a regulatory purgatory. Possible remedies include a mass review of OP definitions as was done in the 1970’s for human food ingredients (the “SCOGS” review), but in these austere times, funding from FDA or AAFCO is unlikely. Because GRAS notification is available through the pilot program, individual manufacturers might support GRAS determinations for their own ingredients and consortia might pool resources to support ingredients in which a shared interest is held. However, judging from the first GRAS notification response from CVM (a rejection), the time required to generate the test data and information necessary to satisfy the breadth of CVM demands would be several years away for each ingredient. Also, food additive petitions are out of the question because of the time and expense needed to generate the information required and the inadequate number of personnel at CVM to process the petitions. It is obvious the only relief from this purgatory would be a self-GRAS determination not submitted for the voluntary notification process. There are risks, however, as discussed in CVM’s “Letter to Industry,” that CVM may determine a substance does not fulfill the agency’s definition of GRAS. However, such a finding for substances already in the OP, in the absence of new information, may be problematic for CVM, as the regulatory discretion letter from CVM had already determined there was no cause for concern.
Other than the manufacturers, who had mistakenly placed faith in the institutional rigor of the AAFCO process, the second most aggrieved party is AAFCO itself. And, in response to CVM withdrawal, AAFCO is contemplating its own review process of GRAS Notifications which had passed muster at FDA and possibly all new food additive petitions as well. Options under discussion include AAFCO appointing a special master to oversee the review of new OP candidate substances by third party contractors for safety, presumably filling void left by CVM. Once approved by the contractor, the candidate substance would enter the familiar pathway of review, approval and entry into the OP. However, two problems with this scheme are obvious at first glance: (1) the price point for this system will have to be reasonable (less than $10,000) and; (2) what if the contractor’s decision on safety is at odds with FDA?
Profits from this AAFCO venture would likely be minimal. In an ordinary year, the number of ingredients included in the OP are limited to 5-6, which could generate very little net revenue once the cost of a skilled contractor (and his overhead, which would include a literature search and review of relevant papers and judging from the first notification rejection, the volume of the GRAS documentation will become substantial). Other costs would include the fee of the special master and the additional management or infrastructure costs that might be incurred at AAFCO headquarters.
The most problematic aspect of this scheme is the possibility the contractor disagrees with CVM and the GRAS Expert panel. The Federal Register notice of the pilot notification program cited several court cases where there was disagreement on the GRAS status of a substance and at least in the cases cited, the manufacturer lost and the substance was not considered generally recognized as safe. These cases will provide the contractor with a solid basis to claim that dissent about safety is his right. So, what happens then? Because its promotion of the contractor’s status as expert by AAFCO, is CVM now required to reverse its “no objection” finding because of this dissent? Is AAFCO now open to damages from the manufacturer for slandering his product as being unsafe? What could emerge from this Pandora’s Box?
It is clear that a regulatory safe harbor must be created for past and future feed ingredients and, given the options available, a self-affirmed GRAS determination (that is not notified to CVM), is the only feasible option. Following this GRAS determination, the ingredient would be submitted to AAFCO for approval and placement in the OP. Because of the possible issues cited above, AAFCO would view the determination of GRAS and safety as a rebuttable presumption that the substance was indeed, safe.
Who would make the GRAS determination? AAFCO has speculated about performing GRAS determinations itself, but because AAFCO is an integral part of the approval process, performing GRAS determinations would place AAFCO in direct competition with GRAS determinations from other sources and, as a result, AAFCO would be subject to accusations of conflict of interest. Clearly, the prevailing circumstances have shifted the burden of determining a substance as being generally recognized as safe is left to the manufacturer.