A Generally Recognized as Safe (GRAS) or New Dietary Ingredient (NDI) notification is essential for novel food ingredient manufacturers and distributors to ensure that their product is recognized as safe and therefore exempt from further premarket approval. To meet the FDA’s standards and market the product without it being deemed adulterated, a clear and sufficient basis for the ingredient’s safety under its intended use must be demonstrated. Novel ingredients that lack toxicological information typically require a panel of safety studies, including genotoxicity and subchronic toxicity studies in rodents. However, several factors—such as the ingredient’s nature and historical usage—may influence the scope of safety data needed to build a strong case for a GRAS or NDI notification.

General Considerations for Safety Data Requirements

The types of data required to establish an ingredient’s safety can vary widely. Key considerations include:

• Whether the ingredient is already present in the food supply.
• Whether the ingredient is naturally found in the human body.
• History of use and/or regulatory approvals for the ingredient or its source in the U.S. or other countries.
• Availability of safety literature on related ingredients or components of the ingredient.

Outlined below are common categories of novel ingredients, each with unique safety considerations. By understanding these factors, manufacturers can better determine the specific data needed for a robust GRAS or NDI submission.

Chemical Constituents (e.g., Taurine)

Ingredients made up of specific chemical compounds, like taurine, require close examination of their molecular structure and purity to identify any potential risks. Key safety considerations include:

• Structural Alerts: Toxicity risks associated with the ingredient’s molecular structure.
• Purity of the Ingredient: Ensuring there are no impurities that may present safety concerns.
• Reaction By-products: Evaluating potential by-products from the manufacturing process that may impact safety.

Microorganisms (e.g., Lactobacillus rhamnosus)

For microbial ingredients, safety data should address any health risks posed by the specific species and strain. Important factors include:

• Species/Strain Identity: Verification to confirm the microorganism’s species and strain.
• Antibiotic Resistance: Determining if there is resistance to antibiotics, which could pose health risks.
• Pathogenicity: Assessing whether the species or strain has any pathogenic properties.
• Presumed Safety: Establishing a history of safe use or research supporting the microorganism’s safety.

Enzymes from Microorganisms (e.g., Cellulase)

Enzymes derived from microorganisms need both the enzyme and the source organism evaluated for safety. Key considerations include:

• Source Organism Safety: Ensuring the microorganism from which the enzyme is derived is safe.
• Allergenicity: Comparing the enzyme’s amino acid sequence to known allergens to assess allergy risk.
• Inactivation or Removal: Verifying that the enzyme is inactivated or removed in the final product to prevent adverse reactions.

Botanical Extracts (e.g., Rice Bran Extract)

Botanical ingredients, like rice bran extract, often contain multiple active and non-active compounds. Safety considerations include:

• Chemical Alteration: Determining if the botanical material is chemically altered during processing.
• Constituents of the Extract: Identifying all compounds present in the extract beyond the active ingredient.
• Contaminants: Testing for potential contaminants such as solvent residues, pesticides, and mycotoxins.

Food Produced from Animal Parts (e.g., Hydrolyzed Poultry Protein)

Ingredients derived from animal sources require careful evaluation of tissue-specific risks. Key considerations include:

• Source Tissue: Identifying the specific part of the animal used in production.
• Associated Risks: Assessing potential presence of toxins or infectious agents specific to the tissue used.
• Antibiotic Residues: Testing for residual antibiotics that may carry over into the final product.

Nanomaterials (e.g., Silicon Dioxide)

Nanomaterials like silicon dioxide pose unique safety concerns due to their small particle size and potential for altered behavior in the body. Considerations include:

• Particle Size Distribution: Ensuring particle sizes are within safe limits for consumption.
• Solubility and Dissolution: Assessing how the nanomaterial behaves in water and biological systems.
• Dispersion and Agglomeration: Evaluating how particles disperse or clump together in solution, which can impact bioavailability and safety.

Conclusion

Determining the appropriate safety data for GRAS or NDI submissions involves complex considerations based on the ingredient’s type, origin, and historical data. At dicentra, we focus on helping clients navigate these complexities by assessing the unique safety requirements for each ingredient type and designing tailored toxicological studies to meet regulatory expectations. Our team of experienced toxicologists and regulatory experts supports clients from the initial safety assessment to the preparation of comprehensive GRAS or NDI submissions. Whether you’re seeking to establish the safety of a new food ingredient or address specific regulatory challenges, dicentra provides the expertise and strategic guidance you need. Contact us today to learn how we can help ensure the safety and regulatory compliance of your food products.