The arrival of the Modernization of Cosmetics Regulation Act (MoCRA) in December 2022 was a pivotal moment in reshaping cosmetics regulations in the US.
Signed into law within the Consolidated Appropriations Act 2023, the bill gave the US Food and Drug Administration (FDA) the authority to make long-overdue and impactful changes to the existing Food, Drug, and Cosmetic Act.
This has raised the barrier for entry for cosmetics companies, requiring them to ensure that:
- All cosmetics are manufactured in registered facilities
- They formally list their cosmetics with the FDA
- They allow the FDA more oversight and authority to regulate and recall cosmetics products
One requirement included in this bill stands out in particular:
“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.”
However, the FDA still needs to provide further guidance on what requirements need to be met to prove the safety of any particular product, within a reasonable amount of certainty.
Much of the new protocol mirrors the Product Information File (PIF) and Cosmetic Product Safety Report (CPSR) required in European legislation, as this design is considered to provide a very responsible profile of product safety.
However, many organizations in the personal care market have been left scratching their heads, especially as the requirement of documentation for substantiating product safety is a novel concept in the US.
The big question is, what does it mean to have a safe product?
Toxicological risk assessments – “Sola dosis facit venenum”
One of the key principles in toxicology is the Latin motto “sola dosis facit venenum”, or “the dose makes the poison”. This basic principle implies that all products in their own right are hazardous, depending on the dosage.
A toxicological risk assessment considers the hazards of each substance in the product, and measures the concentrations at which they are present to determine the relevant risk and safety.
A thorough review of available toxicology data – and taking exposure during intended use and potential misuse into account – would allow risk assessors to give the appropriate advice for any warning statements for each product.
This assessment can then lead to a qualified conclusion on the overall safety of the product, including any known or potential margins of error in the safety calculations.
But these assessments go far beyond ingredient safety – there are other regulatory requirements that need to be considered.
Some of the regulatory requirements may be hazard-based rather than risk-based (such as California Proposition 65). However, these constraints need to be noted and properly applied to the product being reviewed to ensure any additional safety or labeling requirements can be complied with, before taking it to market.
Clinical assessments – human exposure testing
Risk assessments are a valid starting point for safety assessments for cosmetic products. However, while these should account for available in vitro and in vivo safety data for the product ingredients, this type of data is not 100% reliable as data can vary in its age, robustness, and quality.
While a qualified safety assessor should be trusted, a responsible approach to safety should also include finished product testing to provide real-world evidence of minimal risks. This limits any expectations of adverse-event reports once the product is on the market.
Dermal exposure and product safety testing
The primary route of exposure is dermal – or skin – for most cosmetic and personal care products, making this the largest risk to be mitigated.
Some of the most cost-effective approaches for substantiating the dermal safety of products include the Human Repeated Insult Patch Test (HRIPT), Cumulative Irritation Patch Test (CIPT) and Repeated Open Application Test (ROAT).
Similar to dermal irritancy, hair, face and eye products that have a risk of ocular exposure can be validated through an eye instillation study to provide evidentiary support of no unanticipated irritation or damage to the eye or its membranes.
Overall, these tests are designed to exaggerate the exposure conditions, to provide limits for irritation and sensitization with a high level of confidence – should the testing return negative results.
Safety-In-Use studies
When more controlled, real-world exposure scenarios are required, Safety-In-Use studies are beneficial for a few reasons:
- The product will be tested as it is intended to be used.
- A prolonged duration of product use validates the dermal safety of a product much better than traditional patch testing.
- Collect consumer feedback on the acceptability of the product under its intended use, which can help support marketing efforts.
Analytical testing – the cumulative effects
According to MoCRA, the FDA should consider analytical testing as part of the requirements to substantiate a product’s safety. The Act also requires that a standard testing method for cosmetics containing talc should be developed, as well as safety studies for perfluoroalkyl and polyfluoroalkyl substances (PFAS).
Building on these requirements cited in MoCRA, a safety assessment should consider analytical analysis for the presence of impurities, which could contaminate the cosmetics product.
The first step during the risk assessment process is to review the technical data sheets and certificates of analysis from the ingredient manufacturers. These documents provide evidence that the raw materials are free from contaminants and impurities that would impact the overall risk of the product.
Another aspect to review is any cumulative effects that can occur during formulation that go undetected when blending these ingredients together.
This is especially important when considering products containing heavy metals and 1,4-dioxane, as this can create enormous problems if they are brought to market with these ingredients above the safe threshold.
Microbiological testing – preserve and protect
In the US, the use of preservatives in cosmetic products is met with scrutiny. But while certain preservatives are more questionable than others when looking at their toxicological profile, they are necessary to protect product safety and integrity.
Most cosmetics and personal care products are water-based and packaged for multiple uses, providing an environment for microbial enrichment. The products which are not self-preserving need a mechanism to reduce or eliminate the presence of harmful bacteria. The effectiveness of that mechanism also needs to be validated to ensure it works well in the environment in which it is used.
MoCRA requires Good Manufacturing Practices to be followed, which helps reduce microbial contamination. Similarly, physical product packaging barriers and seals help reduce that risk.
However, contamination of raw materials or contamination introduced by humans can occur. This makes the preservative efficacy test an extremely valuable tool for substantiating product safety.
This testing is a key endpoint in a responsible safety program, ensuring minimal microbial transmission via broken skin or contact transfer, or onto high-risk populations.
Stability testing – changes over time
One process that ties together many of the safety tests and ensures the product remains stable, safe and unaffected by environmental conditions over time is stability testing.
Monitoring changes to physicochemical parameters – including color, odor, pH, viscosity and weight loss, among others – demonstrates further evidence of product safety. Any in situ changes to these parameters indicate a shift in the product that could alter its intended function or safety profile.
Take a product with high ethanol content, for example. If it experienced significant weight loss during the course of the study, this could lead to a concentration increase in the remaining ingredients, or a reduction in their efficacy. This could ultimately affect overall safety, as the dosages of the remaining ingredients could result in adverse effects.
Chemical and microbiological analyses over time are also vital for ensuring the product is stored in an appropriate way to prevent degradation of preservatives or any changes in the way they work. These changes can be monitored under different environmental conditions:
- Real-time non-accelerated stability conditions work best for understanding these changes, but can be damaging to product timelines.
- Accelerated studies under high temperatures and humidity conditions help extrapolate data for a long-term understanding of shelf life, and test whether products remain stable over time or waver in their expected safety profile.
- Stress testing of products can simulate their exposure to different environments and test their resiliency and ability to remain consistent. This can be tested through cycling through freezing and thawing, or cold and warm, for example.
The reaction of the product to different conditions under which it can be stored must be explored and understood to confidently conclude a product remains safe over time.
Final thoughts – substantiating cosmetic products’ safety
According to MoCRA, a safe product is defined as one that doesn’t cause harm when used normally. But without any further context or guidance, this definition can be misinterpreted, which creates a quandary for product safety.
At present, environmental safety and packaging is not included in the protocol, which needs to be considered in the future for overall safety.
However, MoCRA remains important for manufacturers and suppliers needing a safety program that reaches beyond the minimum requirements and takes a responsible approach to cosmetics safety.
To achieve this, while also attaining the goals set out through the establishment of MoCRA, manufacturers and suppliers need to consider not only the risk assessment of the product, but also the clinical, analytical, microbiological and stability aspects of the product. This gives them a full picture to give their consumers’ confidence in the safety of the products they are purchasing.
SGS help and support companies every step of the way of their cosmetic product lifecycle, from facility registration to safety testing.
Get in touch today to find out more: cosmetics@sgs.com
