The requirements of a GRAS submission in human food
The FDA set up a seven-part framework for submission to help notifiers get through all the documentation required for GRAS. The key parts of the GRAS submission process are listed below, dietary exposure being one of those requirements.
- Signed statements and a certification.
- Technical and chemical parameters of the notified substance.
- Dietary exposure.
- Self-limiting levels of use
- Evidence of food use prior to January 1, 1958, if GRAS conclusion is based on common use of the substance in food prior to 1958.
- A narrative that provides the basis for the GRAS conclusion and ties all the data together and the expert panel review.
- A list specifying which of your data is generally available and which is proprietary
Dietary exposure is an important component of GRAS as it considers the use levels of your substance within the food as well as the human consumption levels and hence the dietary exposure to the substance and ultimately the risk of any adverse effects to human health.
Assessing exposure in a conservative manner is deemed and acceptable approach and if there are no issues of exceeding any limit of exposure, there are usually no refinements needed. Dietary exposure assessments require two primary inputs:
- Data on food consumption
- Data on chemical concentrations in food
Dietary exposure is calculated as follows:
Exposure = Amount × Concentration
where the Amount is the quantity of food consumed and the Concentration is the level of Substance in the food. However when looking at exposure within and across consumer populations, this simple equation can become quite complex. A substance can be present at varying levels in a large variety of foods, consumed in varying quantities, in different combinations, by different consumers and at different life stages. Therefore, exposure in a population is intrinsically variable, and this variability should be captured in a given risk assessment, if required. In the case of your GRAS submission, Creme Global can help with assessing exposure and refine this assessment where needed.
Among other government organizations, the Food and Drug Administration has been using the Creme Global Food Data Science software (dietary exposure model) Our model has also been used to tackle the dietary exposure assessment part in many GRAS submissions, which is one of the key steps required for your GRAS submission.
Need once-off GRAS submission support?
With over 15 years of experience, Creme Global provides an expert service to conduct the dietary exposure assessment for you, from simple and quick exposure assessment to refined probabilistic scenarios.
We will provide the key data for Part 3 of your GRAS notice, estimating the dietary exposure to the use level of your notified substance that includes exposure from all intended uses and sources in the diet (covering all or some parts (a)-(c) 170.235).
Our team will provide you with
- Initial online 1 hour conference call consultation.
- Interim results conference call review.
- Brief technical report with methodology.
- Possible refinement using probabilistic approaches (i.e. market share and other scenarios)
- Results tables, per food category and/or total dietary cumulative exposure compared to the ADI for exampleMRI’s.
- Breakdown of results by age groups, sex and consumer types (total population vs consumers only
- Any key observations from our food science expert panel.
Includes a free license to Creme Global’s Dietary Intake Intelligence Tool (DIIT).
Pre-assessed dietary intake data is presented in a user-friendly, interactive dashboard with easy dropdown selections of nutrient data which can be grouped together or reviewed individually and graphed by:
- Food groups (~250 groups)
- Nutrients (60+ nutrients from the FNDDS database)
- Age categories
This dietary screening tool enables you to quickly drill down into the installed database, looking at mean intakes as well as selected percentiles of intakes.
The outputs can be segmented by age group, sex, standard population statistics (such as the mean and P90), consumer-only intake, per capita intake (and associated errors).
Training 2 hour online training session with Creme Global’s Dietary Exposure Assessment Experts.
Technical Support Creme Global software is run on Cloud computing – all computer hardware, support and maintenance is included for the period of the license.
Scientific Support Creme Global experts are available by phone or email during business hours for technical and scientific questions on Creme Global software.