Safety substantiation under MoCRA – a comprehensive approach for the cosmetics industry

The Modernization of Cosmetics Regulation Act (MoCRA), passed in December 2022 as part of the Consolidated Appropriations Act of 2023, marked a significant shift in the regulatory landscape for cosmetics in the United States. The bill gave the US Food and Drug Administration (FDA) the authority to implement impactful reforms to the Federal Food, Drug, and Cosmetic Act (FDCA), which had remained largely unchanged for decades. These reforms strengthened the barriers to entry for cosmetics companies by requiring them to manufacture products in FDA-registered facilities, list products with the FDA, and maintain comprehensive safety records for their products. This paper explores the key elements of safety substantiation under MoCRA, outlining the recommended steps, such as toxicological risk assessments, clinical testing, analytical and microbiological testing and stability studies, to ensure the development of a robust safety dossier for the sale of compliant products for the US market.

Regarding product safety, cosmetics suppliers should be aware of a key requirement in MoCRA:
“Each responsible person for a cosmetic product must maintain records (e.g. tests and studies) that support a reasonable certainty that the product is safe.”

The FDA has not yet provided specific guidance on what requirements must be met to prove product safety or what constitutes ‘reasonable certainty’.

However, it can be argued that the product information file (PIF) and cosmetic product safety report (CPSR) requirements found in European legislation reasonably support this framework, providing an acceptable roadmap to achieving compliance.

Toxicological risk assessments

A key principle in toxicology is ‘sola dosis facit venenum,’ or ‘the dose makes the poison’. This implies that all substances have the potential to be harmful, and what matters is the dosage.

Toxicological risk assessments evaluate the hazards associated with each ingredient in a cosmetic product by analyzing both the concentration of the ingredient and the levels at which they are present. This process determines the potential risks and overall safety of the product.

A comprehensive review of toxicology data, combined with an understanding of exposure levels during intended use and potential misuse, enables risk assessors to provide accurate recommendations regarding warning labels or safety precautions.

Ultimately, this assessment leads to an informed conclusion about the product’s safety, including consideration of the margin of safety (MoS) calculations.

However, toxicological assessments go beyond evaluating ingredient safety. They must also account for various regulatory requirements, some of which may be hazard-based rather than risk-based (e.g. California Proposition 65). Specific guidelines must be carefully considered and applied to the product to ensure compliance with additional safety or labeling standards before it can be brought to market.

Clinical assessments

Risk assessments are a valid starting point for evaluating cosmetic product safety, but they are not sufficient on their own. While they incorporate in vitro and in vivo safety data for the ingredients, this data is not entirely reliable because it does not account for variations in factors such as age, diversity and product quality.

Although the expertise of a qualified safety assessor is essential, a comprehensive approach to safety must also include product-specific evaluations, such as dermal exposure and product safety tests, including safety-in-use studies. These will provide real-world evidence to help minimize potential risks and reduce the likelihood of adverse-event reports once the product reaches the market.

Dermal exposure and product safety testing

The primary route of exposure for most cosmetic and personal care products is through the skin, making dermal safety the most critical risk to assess. Cost-effective methods to substantiate dermal safety include the human repeated insult patch test (HRIPT), cumulative irritation patch test (CIPT) and repeated open application test (ROAT).

For products used in the hair, face or eyes, there is the additional risk of ocular exposure. Eye instillation studies can be conducted to provide evidence that no unexpected irritation or damage to the eye or its membranes will occur during use.

These tests intentionally exaggerate exposure conditions to ensure that any potential for irritation or sensitization is identified. Negative test results offer a high level of confidence in the product’s safety limits.

Safety-in-use studies

Safety-in-use studies provide a more controlled, real-world exposure solution.

They offer several key benefits:

• Realistic application: product is tested under conditions that reflect its intended use, ensuring an accurate assessment of safety in everyday situations

• Extended exposure: prolonged product use provides a more reliable validation of dermal safety compared to traditional patch testing, which often involves only short-term exposure

• Consumer insights: feedback gathered from consumers during the study is valuable for evaluating product acceptability during regular use. This data can be used to support both safety claims and marketing strategies

Analytical testing

MoCRA mentions the FDA will consider analytical testing as part of a product’s safety substantiation requirements. It specifically calls for the development of standardized testing methods for cosmetics containing talc, as well as the review of scientific evidence for per- and polyfluoroalkyl substances (PFAS). In alignment with MoCRA’s principals, a thorough safety assessment should include analytical analyses to detect potential impurities that may contaminate the product.

The first step in the risk assessment process is to review technical data sheets and certificates of analysis provided by ingredient manufacturers.

These documents serve as critical evidence that the raw materials are free from harmful contaminants and impurities that could increase the product’s risk profile.

Secondly, the formulation process must be evaluated for any cumulative effects that might arise from combining ingredients. These effects can sometimes go unnoticed but still impact safety.

This is particularly important for products containing heavy metals or 1,4-dioxane, as exceeding safe thresholds for these substances can lead to significant safety issues if the product reaches the market.

Microbiological testing

The use of preservatives in cosmetic products is under increasing scrutiny in the U.S. While some preservatives raise more concerns than others due to their toxicological profiles, they remain essential for ensuring product safety and integrity.

Since cosmetics and personal care products are often water-based and designed for multiple uses, they can provide an environment for microbial growth. Products that are not self-preserving require a mechanism to reduce or eliminate harmful bacteria, and the effectiveness of that mechanism must be validated in the intended use environment.

MoCRA mandates adherence to good manufacturing practices (GMP) to help minimize microbial contamination. In addition, physical packaging barriers and seals should be employed to further reduce the risk. However, contamination from raw materials or human handling can still occur, making preservative efficacy testing a critical tool in validating product safety.

Microbiological testing is the cornerstone of any responsible testing program. It ensures microbial transmission is minimized – whether through broken skin, contact transfer or exposure to high-risk populations – thereby safeguarding consumers and maintaining product quality.

Stability testing

Stability testing is an essential process that integrates various safety assessments, ensuring products remain stable, safe and unaffected by environmental conditions. Monitoring changes in key physiochemical parameters – such as color, odor, pH, viscosity and weight loss – provides further evidence to support product safety claims. Significant changes to these parameters indicate a shift in the product’s composition, which could alter its intended function or compromise its safety.

For example, if a product with high ethanol content experiences significant weight loss during testing, it could lead to increased concentrations of the remaining ingredients or reduced efficacy. This shift may impact overall safety, potentially leading to adverse effects due to altered dosages of active ingredients.

Chemical and microbiological analyses over time are critical for ensuring preservatives remain effective and products are stored correctly to prevent degradation.

Analysis should assess stability under various environmental conditions:

• Real-time stability testing under non-accelerated conditions provides the most accurate data on product changes over time, but can extend product development timelines

• Accelerated stability studies expose products to high temperatures and humidity, allowing for the extrapolation of long-term shelf life data to determine whether a product continues to remain stable and safe over time

• Stress testing simulates extreme environmental exposures, such as cycles of freezing and thawing or shifts between hot and cold conditions, to assess a product’s resilience and ability to maintain consistency

Understanding how a product reacts to different storage conditions is essential to confidently ensuring safety and stability over time.

Conclusion

MoCRA defines a safe cosmetic product as one that does not cause harm when used as intended.
However, this definition can be misinterpreted without proper context or guidance, which is currently not provided by the FDA, creating a problem in terms of proving product safety. At the same time, the protocol also does not encompass environmental safety and packaging considerations, which should be regarded as crucial for overall safety.

Nonetheless, MoCRA serves as a vital framework for manufacturers and suppliers, promoting a safety program that goes beyond the basic requirements and emphasizes responsible practices in cosmetics safety.
To align with MoCRA’s objectives, it is essential for manufacturers to evaluate not just the risks associated with the ingredients but also the product’s clinical, analytical, microbiological and stability attributes.
This comprehensive approach ensures that consumers can confidently trust the safety of the products they purchase.

SGS cosmetics solutions

SGS is committed to assisting companies throughout the entire cosmetic product lifecycle, from facility registration to safety testing, ensuring that safety remains a top priority.

With a unique network of more than 40 laboratories and clinical testing sites in North America, Europe and Asia, we offer turnkey and innovative solutions including analytical, microbiological and in vitro testing, clinical studies for safety and efficacy as well as regulatory services from first development to market launch of your cosmetic products.

• Regulation support
• Ingredient review
• Safety assessments and reports
• Stability testing
• Microbiological testing
• Antimicrobial effectiveness testing
• Functional testing
• Packaging comparability testing
• Heavy metal testing
• Prohibited substance testing (e.g. phthalates, 1,4-dioxane, formaldehyde)
• 26 fragrance allergen testing