GRAS Determination: Lessons and Pitfalls

By Tom Jonaitis

Over the 14 years of working as a scientific and regulatory consultant in the food industry, I have had the opportunity to work with many companies that were bringing a wide range of exciting and innovative food ingredients to the marketplace in the United States and abroad.

Beyond the extensive resources put into the R&D phase to identify and produce the right ingredient and ensure it does what it needs to, companies also need to address the regulatory requirements for these ingredients. Whether in the US (through the GRAS process[1]) or elsewhere, the ingredients must have substantial and robust evidence of safety under intended conditions of use. I will focus on the food additive regulations here and put aside the multitude of other regulations companies need to address.

The safety of food additives is supported by 2 main areas of data: a) chemistry and manufacturing and b) toxicology data that corroborates the safety of the estimated intake of the ingredient. Companies familiar with the GRAS process will plan for the requirements of the regulatory stretch of the journey (or get the help they will need) well in advance of being “market ready”. This ensures that any data gaps or hiccups are dealt with quickly and efficiently to avoid costly delays. There’s nothing worse than needing your ingredient approved to meet customer demands, to find out more data is required, which means more time and resources.

Many times, I’ve worked with companies that may have had a great product yet were unclear of the depth of data required to satisfy the regulatory requirements. Fortunately, in most cases, I was able to work with them to help them obtain the necessary data and compile a robust dossier.

Looking back at the obstacles some companies faced, as well as reviewing the publicly available outcomes of FDA’s review of GRAS notifications (both successful and unsuccessful submissions), I will highlight just a few of the key areas that have cause some issues:

  1. Identification/Characterization:

    • The ingredient should be characterized both qualitatively and quantitatively and defined to 100% purity with validated methods. This is easier to do with a single ingredient compared to more complex ones, i.e., certain botanical extracts, waxes, starches. A company must know exactly what is in their ingredient so as to show that the ingredient, and any impurities, are safe.

  2. Processing Aids used in manufacturing:

    • In the US, anything used in the manufacturing of a food ingredient is technically considered a “food additive” – so every substance used must be permitted for use in food production. It will need to be either a permitted food additive (and permitted for your particular application, as described in the CFR) or a GRAS substance. Otherwise, the safety of the processing aid will need to be assessed and supported either in a separate GRAS determination or within the existing determination. Generally, the best course of action is to ensure only permitted substances are used to avoid the need for additional safety assessments.

  3. Toxicology/Safety Studies:

    The GRAS status of an ingredient can be based either on scientific procedures (safety studies and expert consensus) or a history of use in food prior to 1958. Essentially all new ingredients (>95%) will fall into the former category due to the particular requirements needed to meet the history of use in foods definition.

    • Generally, a 90-day rodent toxicity study, in conjunction with a battery of genotoxicity tests (all conducted to GLP/OECD requirements), on the specific ingredient, will be the minimum testing requirements to support the safety of a novel food ingredient.

    • Many times, companies have identified a plethora of published studies and consider that the safety of their ingredient is supported by existing data. In most cases the data will not meet the minimum safety requirements, due to quality of the safety studies and comparability to actual ingredient and intended uses (i.e., duration of study too short, dose too low compared to intended food uses, issues with study populations used, or purity profile of test article is too different from the novel ingredient).

Obtaining GRAS status for an ingredient is no small feat and preparing for it in advance will create ample opportunity to get all your ducks in a row for a smooth and predictable path to market. If your company has not gone through the process a few times, it could be invaluable to discuss your strategy and data requirements with an experienced food regulatory consulting firm to ensure there are no critical gaps that could cause unnecessary delays and wasted resources.

EAS Consulting Group offers world-class food regulatory consulting services with an extensive team of experts, including ex-US FDA agency officials, board-certified toxicologists, and other regulatory professionals. It has an excellent record of successfully helping companies obtain GRAS status for its ingredients, with and without FDA notification.


[1] https://www.fda.gov/food/food-ingredients-packaging/generally-recognized-safe-gras

Posted in 2019, 2019 September, EASeNews, Issue of the Month and tagged , .