FDA’s new draft guidance says that if an oil, such as a plant oil or a fish oil, requires an NDI, firms may be able to ease the regulatory load by partially relying on data showing that those fatty acids in the oil are already consumed safely at higher levels in the food supply (such as in fish eaten for meals).
This is what the draft guidance says: “[I]f your NDI is an oil made from a plant or fish and you can show that the oil consists only of a mixture of fatty acids, each of which you can identify and demonstrate to be widely consumed at higher levels in conventional foods, you may be able to conclude that the dietary supplement containing the NDI will reasonably be expected to be safe based on compositional information alone.”
According to Rice, “While we were concerned initially, this may be to the industry’s advantage if an omega-3 company is permitted to submit (as substantiation of safe use) a simple dossier on safe history of use if the fatty acids can be found in the diet at higher levels, for instance in a piece of salmon or a can of tuna.”
Questions persist, however. For instance, how would firms establish baseline “compositional information" of an oil's fatty acids (in order to do a comparison with the fatty acid profile of a food)? This is especially complicated because fatty acid profiles can fluctuate from oil to oil.
In its draft guidance comments back in July 2011, GOED explained the nature of these fatty acid fluctuations. “The Guidance further states that changes to the chemical composition of the ingredient would require a NDIN. We feel the FDA has failed to recognize that natural products like edible oils and herbal extracts often contain a large number of unique chemical substances, and that the ratios of each substance can vary significantly as a result of environmental and seasonal influences. For example, the fatty acid profile of oils derived from edible marine species can change significantly due to environmental influences (e.g. water temperature, etc.), effects of diet and seasonal variation (e.g. migration). These changes in chemical composition can be experienced lot‐to‐lot and season‐to‐season.”
Because those fatty acid levels can range, would FDA consider an ingredient an NDI any time fatty acid levels strayed from baseline compositional data? Or, as GOED said in its 2011 comments, “The Guidance can be interpreted to mean that such changes require lot‐by‐lot notification to the FDA.”
According to GOED, FDA’s statements surrounding fatty acid content need clarifying. "In the past, FDA has only been concerned with EPA/DHA content, but this raises questions about the full fatty acid profile that will need to be clarified,” “The GOED Current” stated. Also, it added, "questions need to be answered about whether ethyl ester fatty acids can be compared to sources of triglyceride or phospholipid fatty acids in the normal diet.”
Rice also points out that non-fish omega-3 ingredients may be more likely to require notification. “It is more likely that 'non fish' omega-3 ingredients will require NDINs, and in fact, many companies marketing these types of ingredients have submitted NDINs,” he says.
Finally, one thing to remember is that most of the omega-3 drugs in the market are in the ethyl ester form. John Endres, ND, chief science officer for regulatory consultant AIBMR Life Sciences (Seattle, WA), says he wonders, if FDA were to consider dietary supplement ethyl esters to be NDIs, would the agency also feel the need to address ethyl esters in the drug market?
To date, he says, he hasn’t seen anyone get an FDA warning letter just because they are selling ethyl esters. “They could decide to crack down on it possibly, but I haven’t heard anything about that,” he says.
Regarding the NDI draft guidance, GOED’s Rice says,“Absolutely, the omega-3 industry has many critical unanswered questions, but we are confident that in time they will be answered. The reality is that omega-3–rich ingredients have a long history of safe use. While I’m not suggesting that the GOED membership try to fly under the radar, the reality is that the FDA has much bigger fish to fry.”