Thinking about getting your toxicological results published? Go no further until you read this article.

As many with innovative and novel ingredients know, achieving GRAS status of an ingredient, whether with or without FDA notification, is a much-coveted designation that opens doors for legal regulatory status of new food ingredients in the US, and all sorts of new business as well. 

If your ingredient is so novel and so new that there is little or no safety data in databases such as PubMed, pivotal safety data (such as toxicological studies) will most likely need to be performed and shared in the public domain to support a GRAS conclusion. This most commonly means the information from toxicological studies is published in a peer-reviewed journal.

THE COMMON KNOWLEDGE REQUIREMENT

Where does this requirement come from? Let’s look at the regulations. 

In the GRAS criteria, FDA notes that: 

“…General recognition of safety requires common knowledge, throughout the expert scientific community knowledgeable about the safety of substances directly or indirectly added to food, that there is reasonable certainty that the substance is not harmful under the conditions of its intended use.” 

“‘Common knowledge’ can be based on either “scientific procedures” or on experience based on common use of a substance in food prior to January 1, 1958.” 

FDA discusses in more detail what is meant by the requirement of common knowledge and acceptance of pertinent information within the scientific community (i.e. the so-called “common knowledge element”) in the two following elements:  

• Data and information relied upon to establish safety must be generally available (i.e. in a publication); and

• There must be sufficient reason to conclude that there is consensus among qualified scientists about the safety of the substance for its intended use. This can be established by relying upon secondary scientific literature such as published review articles, textbooks, or compendia, or by obtaining opinions of expert panels or opinions from authoritative bodies, such as JECFA and the National Academy of Sciences. However, these references may not provide evidence of safety at the intended use level you are hoping for your ingredient. 

HOW TO LEVERAGE YOUR MANUSCRIPT WRITING

If your ingredient hasn’t made it onto the table of the likes of JECFA yet, or if there is little or no supporting evidence for safety of your ingredient at its intended use level, safety studies will most likely have to be conducted, and a manuscript will need to be written and submitted to a trustworthy and reputable journal.  

Some companies may have scientists on staff who have experience with the publication process. However, writing a manuscript from a toxicological and regulatory vantage point is important. There are certain characteristics that should be included in the manuscript to sufficiently check the boxes that will be expected by the review of experts, including the FDA. 

1. PIVOTAL SAFETY INFORMATION

It bears repeating that pivotal safety information on the novel ingredient needs to be published. In addition to toxicological studies, this may include, for example, in vitro digestibility studies on the ingredient. In fact, if significant safety studies are required, more than one manuscript may need to be published.

2. PROPER NOVEL INGREDIENT IDENTIFICATION

Sufficient identification of the tested novel ingredient is necessary in the toxicological study manuscript. Proprietary manufacturing information is not required but enough information to link the test item with your ingredient’s specifications is important.

3. GAVAGE OR DIETARY ADMINISTRATION

Was your toxicological study performed utilizing dietary or gavage administration methods? Gavage administration ensures the study animals receive the test item in a bolus directly into their stomach. Dietary administration means that the test item was included in animal feed made specifically with your food ingredient mixed in and provided to the study animals over the testing period. The stability, concentration, and homogeneous distribution of the test item in either administration method should be sufficiently described. For dietary administration, an additional description of how much feed and ingredient animals consumed will need to be clarified.

4. HISTORICAL CONTROL DATA

A feature of toxicological study reporting that is often missing in published manuscripts we review is historical control data. Historical control data differs from lab to lab and can be a key piece of the puzzle when deciding if a study result is toxicologically significant or not. It is important to note this information somewhere in the manuscript so independent toxicologists reviewing the available data in your manuscript (remember the “common knowledge” element of GRAS…) have the necessary information to make an informed conclusion about the findings (and hopefully agree with the conclusion published!).

5. WHO IS YOUR AUDIENCE?

In addition to the peer reviewers of the journal, your audience may be the FDA. Reading an article through a regulatory lens is more than just looking at safety endpoints to determine intended use level. As we know, in the US there are regulatory guidelines that prevent companies from making disease claims about their food ingredient. An example of a disease claim is "curcumin has anti-tumor properties.” If the FDA runs into one of these in your manuscript, it can be a significant hurdle to convince them that the statement is not meant to suggest the ingredient can prevent diseases (i.e. suggest the ingredient is a drug). In a toxicology manuscript, statements that can be interpreted as disease claims sometimes end up in the introduction or discussion sections, so take care not to make this mistake.

6. PUBLISHING IN A TOXICOLOGY JOURNAL

In conversations with the FDA, they strongly recommend publishing data in a well-respected journal in the field of toxicology.  Although this may sound picky, the reasoning is that the FDA wants qualified scientists to review the results. The peer review from a registered dietician in a food ingredient journal will be different than a peer review from toxicologists in a toxicological journal. Choosing the appropriate journal to publish in goes a long way to help further your ingredient's safety argument.

HOW WE CAN HELP

Having experienced help in writing or reviewing your manuscript can ensure that the time and money invested in toxicological studies is not wasted. SGS Nutrasource has a team of toxicologists with experience in toxicological manuscript writing and publication for regulatory purposes. It also provides start-to-finish collaboration for novel ingredients including ingredient safety assessments, toxicological study recommendations and placement monitoring services, regulatory dossier drafting and more to streamline your ingredient’s journey from conception to marketplace success.

About Dr. Preece

Kayla Preece has extensive experience assessing scientific and regulatory compliance of ingredients for food and dietary supplements, including botanicals, microorganisms, and more. These assessments have predominantly been for self-determined and FDA GRAS notifications and New Dietary Ingredient Notifications.

Dr. Preece has been involved in producing and publishing toxicological manuscripts for dietary ingredients and received her Diplomate of the American Board of Toxicology. Kayla is also a full member of the Society of Toxicology. She has a background in integrative medicine and practiced medicine before becoming involved with the world of regulatory affairs and safety assessment.