On August 17, 2016, FDA published the Final GRAS Rule in the Federal Register, which became effective on October 17, 2016. FDA outlined the criteria required for a GRAS conclusion, noting that notifying FDA remains a voluntary process. Because of this, companies can satisfy regulatory requirements by attaining an Independent GRAS Conclusion (also referred to as Self-Affirmed GRAS or Self-Determined GRAS) and, if desired, submitting a GRAS Notice to FDA for review.
For substances intended for use as flavor ingredients, manufacturers who are active members of The Flavor and Extract Manufacturers Association of the United States (FEMA) can also opt to take part in the FEMA GRAS program. GRAS conclusions made by the FEMA Expert Panel, along with supporting information, are informally provided to FDA.
While the decision to submit a GRAS Notice remains with the manufacturer or other responsible party, the bases under which “reasonable certainty that the substance is not harmful under the conditions of its intended use” is determined are the same for Independent GRAS Conclusions and GRAS Notices.
The Final GRAS Rule stipulates these universal requirements, summarized as follows:
Information and data regarding the substance must satisfy the food additive standard under the FD&C Act.
General recognition of safety requires common knowledge—based either on scientific procedures or historical use in foods. For safety conclusions based on scientific procedures, pivotal data, information, or methods must be generally (publicly) available, with preference given to peer-reviewed publications, but can be corroborated by unpublished data and information.
GRAS assessments must include information regarding the identity of the substance, manufacturing process, specifications, technical or physical effect, dietary exposure, self-limiting levels of use, common use in food before 1958, and a narrative discussing the publicly available and corroborative safety data relied upon for a GRAS conclusion, as well as supporting data and information.
In the Final GRAS Rule, FDA recommends that the data and organization provided in an Independent GRAS dossier and a GRAS Notice follow the specific parts outlined in the Final GRAS Rule. Should FDA question an Independent GRAS Conclusion, the manufacturer would then have the supporting documentation readily available. FDA also recommends that manufacturers make their Independent GRAS Conclusion publicly available by: releasing a narrative report; releasing a GRAS Expert Panel report in the event that a panel is convened; or releasing both a narrative and Expert Panel report.
It should be noted that once a manufacturer and/or group of qualified experts (usually an Expert Panel) have reached a GRAS conclusion, an Independent GRAS conclusion has been achieved. The subject ingredient is therefore GRAS, and can be used as a food additive, even while the GRAS Notice undergoes FDA’s review process if it is submitted.
When deciding whether or not to notify FDA of a GRAS conclusion, companies may wish to consider the advantages and disadvantages of both pathways, some of which are highlighted in the graphic below.
While some companies opt to undertake the GRAS assessment and FDA notification process on their own, many companies engage experienced regulatory consultants to prepare Independent GRAS Conclusions, convene Expert Panels, and navigate FDA’s GRAS Notice submission process.
If you aren’t sure whether an Independent GRAS Conclusion or a GRAS Notice Submission is the better path for an ingredient, or if you’re looking for some help with navigating the GRAS process, please feel free to reach out directly.
Next week’s blog will discuss Expert Panels and the Purpose They Serve.
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📷 1 & 2: Gerd Altmann on Pixabay