Keeping up with MoCRA

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When The Federal Food, Drug, and Cosmetic Act (FD&C Act) went into place in 1938, requiring finished cosmetic products to be safe for their usual manner of use and label instructions, it amounted to little more than an honor system because FDA had little enforcement authority. In 1966, Congress passed an important upgrade, the Fair Packaging and Labeling Act, which included a requirement that companies list ingredients on their products. Even then, the FDA had limited authority in enforcement of the legislation. Fast forward to 2022, when Congress passed The Modernization of Cosmetics Regulations Act (MoCRA), giving the FDA greater authority to regulate many aspects of cosmetics marketed in the US—the first major overhaul of the FD&C Act with respect to cosmetics since 1938. This new Act contains several requirements and milestone dates that manufacturers must follow to be compliant and for its products to not be considered adulterated and subject to possible enforcement by the new authority provided to FDA.

This article focuses on MoCRA’s safety substantiation requirements, which state that the responsible company or entity must maintain documentation that supports the reasonable certainty of safety for each finished cosmetic product marketed in the U.S. Prior to the enactment of MoCRA, this did not exist.

While MoCRA now requires manufacturers to maintain safety substantiation for all of their products, it doesn’t specifically recommend types of testing that could conclude reasonable certainty of no harm when the product is used according to label instructions.

As MoCRA’s safety substantiation requirements became effective on December 29, 2023, it would be wise for manufacturers to possess safety substantiation dossiers that are scientifically robust from the toxicological perspective.

Companies could either complete their own safety substantiation dossier, if qualified by training and experience, or could engage a consulting firm with expertise in risk assessments to design a plan for each of the company’s products and prepare a dossier to be held by the manufacturer. Such risk assessments are rooted in toxicological sciences and include investigations and testing of the topical effects, incidental ingestion (e.g. shampoo getting into the mouth), or dermal absorption (absorption through the skin into systemic circulation) by either in vitro and/or in vivo testing.

In general, Organisation for Economic Co-operation and Development (OECD) guidelines and Good Laboratory Practices (GLP) are followed for toxicological safety assessments, and a complete list of potential studies for a particular risk assessment is beyond the scope of this article. Following a thorough literature search of published and unpublished toxicological investigations of the ingredients in each cosmetic product for which a risk assessment dossier is being prepared, it can be concluded what gaps exists and what studies should be performed.

Studies may include, but are not limited to:

1. Genotoxicity: AMES Bacterial Reverse Mutation Test (OECD 471),
   In vitro Chromosomal Aberration Test (OECD 473), Mouse Micronucleus Test (OECD 474), In vitro Micronucleus Test (OECD 487)
   (n.b. OECD 471 + OECD 487 is a good non-animal valid testing method for genotoxicity assessment)
2. Systemic toxicity: 14- or 28-day repeated oral toxicity in rats (OECD 407), 90-day repeated oral toxicity in rats (OECD 408)
3. Contact toxicity usually includes non-animal* in vitro models of skin sensitization, skin irritation, allergenicity, skin corrosion, eye irritation, inhalation toxicity, photo-irritation, photosensitization, etc.

*Note that for some of these there is currently no validated non-animal testing method. Reduction of animal use is a major goal in the field of toxicology and discussed frequently at annual meetings such as the Society of Toxicology and the American College of Toxicology.

After a risk assessment has been designed and the tests conducted, a dossier should be prepared to present the results and its conclusion of reasonable certainty of no harm, much like what one might find in a GRAS dossier for ingredients that are intended to be ingested by humans. Usually, a description of the manufacturing and identity of the ingredient is presented with product specifications, manufacturing flowchart and contaminant testing such as microbial, heavy metals, pesticides and solvent residue limits. An exposure estimate would follow, along with a safety narrative describing why that level of exposure is reasonably certain to be safe. Utilizing this structure would be a good approach for cosmetic companies to satisfy the new safety substantiation requirements. Needless to say, there are many other considerations for risk assessment strategies—just be sure to use qualified experts.

While the U.S. FDA does not currently make mandatory any specific testing, manufacturers can consider using some of the testing guidelines that the European Commission discusses in its 2018 guidance document.¹

Reference

1. Scientific Committee on Consumer Safety (SCCS). The SCCS Notes of Guidance for the Testing of Cosmetic Ingredients and their Safety Evaluation, 10th Revision. (October 2018) https://health.ec.europa.eu/document/download/8d49f487-909c-4498-af89-1f769aaa628c_en

John R. Endres, ND is a Naturopathic Physician, Toxicologist, and Chief Scientific Officer for AIBMR Life Sciences, Inc.