Navigating ODI and NDI records to inform risk assessment

CRN Member query:

“We are trying to understand hyaluronic acid (HA) usage as a dietary supplement ingredient. Is there a history of use of HA as a dietary supplement? It does not appear to be included on industry old dietary ingredient (ODI) lists, but it is broadly used within the industry.”

CRN's Andrew Shao, Ph.D., responds:

Great question! This decision tree can apply to hyaluronic acid, but also all ingredients. Whether your interest is one of safety or regulatory acceptability of the ingredient, you’re pretty much going to consult the same information. Industry ODI lists can only serve as a guide—but they are not dispositive—because they don’t carry official legal standing and don’t cover all of the different forms of ingredients, but these lists can indeed be a good indicator that an ingredient has likely had some significant history of use.

I would first recommend you consult an ingredient supplier to see if they have recorded information on history of use of HA. CRN can connect you with ingredient supplier member companies if you would like.

You might also check to see if a New Dietary Ingredient (NDI) notification has ever been submitted to FDA. There is indeed a NDI notification (NDIN) on file for HA, and you can see FDA’s response here. 

Although the earlier NDI notification claims HA to be derived from rooster combs, HA is currently recognized as an FDA approved drug and is routinely used as an injectable for osteoarthritis treatment. As a result, HA is subject to the exclusionary clause in DHSEA and thus FDA determined it is not a legal dietary ingredient because it was first approved as a drug.

This does not mean there is not a history of safe use of HA as a supplement. There certainly is since the NDIN was filed in 2007, and I am aware that there were products on the market well before that. Again, I suggest you consult the supplier who might have evidence of marketing HA as a food or supplement before the drug approval. While most published studies examining the safety of HA address topical or injectable applications, there is a recent review on the safety of oral use, which you can read here.

The dietary supplement industry still likely lacks the evidence FDA would deem acceptable to substantiate ODI status, and the agency has publicly stated that it cannot be a legal dietary ingredient. However, FDA enforcement has been relatively limited, with warning letters issued only to companies marketing HA with drug claims.

This information can help inform your internal risk assessment as you examine relevant legal and regulatory enforcement for precedent.