Looking Good! Cosmetics Require Stability Too.

Cosmetics are different, yet similar to pharmaceutical formulations in that they’re susceptible to temperature, humidity, light, and microbial contamination. An unstable cosmetic can no longer fulfill its mission in creating a better appearance. As in pharmaceuticals, their physical make up (no pun intended) can open avenues to deterioration, so the cosmetic stability function can have many nuances.

Let’s begin with some definitions.

The Federal Food, Drug, and Cosmetic Act (FD&C Act) defines cosmetics as “articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body…for cleansing, beautifying, promoting attractiveness, or altering the appearance” [FD&C Act, sec. 201(i)]. Among the products included in this definition are skin moisturizers, perfumes, lipsticks, fingernail polishes, makeup, cleansing shampoos, permanent waves, hair colors, and deodorants, as well as any substance intended for use as a component of a cosmetic product.

Some cosmetics carry a double load, in that they also have an intended impact on the body, such as hydration, protectant, exfoliant, etc. We’re familiar with the regulatory impact of combination products, and so it is with a so-called “cosmeceutical”. They have two sets of regulations with which to comply.

Whether a product is a cosmetic or a drug under the law is determined by a product’s intended use. Different laws and regulations apply to each type of product. Firms sometimes violate the law by marketing a cosmetic with a drug claim or by marketing a drug as if it were a cosmetic, without adhering to requirements for drugs.

Under the FD&C Act, a product intended to diagnose, mitigate, treat, or prevent disease, or to affect the structure or function of the body is classified as a drug (FD&C Act, Section 201(g)). If such a product is not generally recognized by qualified experts as safe and effective when used as labeled, it is a “new drug” (FD&C Act, Section 201(p)) and requires an approved New Drug Application to be marketed legally in the United States (FD&C Act, Section 505(a))

A recent FDA Warning Letter shows that the cosmetics industry can sometimes forget to do its homework in distinguishing between product types.

“The claims on your website establish that the products are drugs under section 201(g)(1)(B) and/or (g)(1)(C) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. 321(g)(1)(B) and/or (g)(1)(C)] because they are intended for use in the cure, mitigation, treatment, or prevention of disease, and/or because they are articles (other than food) intended to affect the structure or any function of the body of man or other animals. As explained further below, introducing or delivering these products for introduction into interstate commerce violates the Act. You can find the Act and FDA regulations through links on FDA’s home page at www.fda.gov.” (Source: Warning Letters Address Drug Claims Made for Products Marketed as Cosmetics, FDA)

The FDA has a useful document entitled Is It a Cosmetic, a Drug, or Both? (Or Is It Soap?) (9/11/2024)

A subsection in this guide asks: “How can a product be both a cosmetic and a drug?”

Some products meet the definitions of both cosmetics and drugs. This may happen when a product has more than one intended use. For example, an antidandruff shampoo is a cosmetic because its intended use is to cleanse the hair, and it is also a drug because its intended use is to treat dandruff. Among other cosmetic/drug combinations are toothpastes with claims to freshen breath and cleanse the teeth that contain fluoride. Similarly, deodorants that are also antiperspirants, and moisturizers and makeup marketed with sun-protection claims are cosmetic/drug products. Such products must comply with the requirements for both cosmetics and drugs.

The Modernization of Cosmetics Regulation Act (MoCRA) of 2022 amended the FD&C Act to require that not later than December 29, 2025, FDA establish good manufacturing practices (GMPs) for facilities that manufacture, or process cosmetic products distributed in the United States. The law, with certain exemptions, will require strict adherence by industry to these GMP requirements. At the present time, FDA has a Draft Guidance for Industry: Cosmetic Good Manufacturing Practices to assist industry and other stakeholders in identifying the standards and issues that can affect the quality of cosmetic products. Those that fail to follow these GMP requirements will be considered adulterated under the FD&C Act, sec. 601(f)]. These regulations are intended to protect public health and ensure that cosmetic products are not adulterated or misbranded.

A helpful blog is the Modernization of Cosmetics Regulation Act of 2022 (US). While it does not address stability issues, it’s a good overview of how regulatory aspects of cosmetics are growing ever closer to that of pharmaceuticals.

The FDA Q&A / Notes document (02/25/2022) – Shelf Life and Expiration Dating of Cosmetics gets into some specifics:

What is a cosmetic product’s shelf life?

A product’s “shelf life” generally means the length of time you can expect a product to look and act as expected and to stay safe for use. This length of time varies, depending on the type of product, how it is used, and how it is stored.

What factors affect shelf life, and how?

Over time, cosmetics start to degrade or break down for a number of reasons.

• Introduction of bacteria, molds and yeasts
• Breakdown of preservatives
• Separation of emulsions
• Exposure to moisture
• Products drying out
• Temperature changes
• Exposure to sunlight

resulting in contamination, changes in color, texture and odor as well as loss of intended function.

These give stabilitarians quite a few testing parameters, including several in the microbial realm and some qualifying as stability-indicating tests.

The document concludes: “There are no U.S. laws or regulations that require cosmetics to have specific shelf lives or have expiration dates on their labels. However, manufacturers are responsible for making sure their products are safe. FDA considers determining a product’s shelf life to be part of the manufacturer’s responsibility.“

Despite the absence of legal obligation, this last statement brings cosmetic products more formally into the wonderful world of shelf life and stability.

A cosmetics quality official may ask what regulations and guidances they should follow? Many of the common stability-related guidances can apply, including ICH Q1AR2, ICH Q1B, ICH Q1E, Annex 10: WHO guidelines on stability testing of active pharmaceutical ingredients and finished pharmaceutical products, and EMA Notes for Guidance on In-Use Stability Testing of Human Medicinal Products, among others.

In China, medicinal product stability regulations are primarily governed by the National Medical Products Administration (NMPA) and are largely based on the Chinese Pharmacopoeia (ChP), which outlines detailed requirements for stability testing, including factors like accelerated testing, long-term testing, and affecting factor testing, ensuring that drugs maintain their quality and efficacy throughout their shelf life; the expiration date of a drug product is determined based on this stability data. There are several good sites for cosmetic regulations in China.

As with other medical products, critical parameters need to be identified and monitored. Key ingredients as well as extractables and leachables testing are on the table as GMP requirements come into effect. There is not typically a testing requirement for individual impurities, thus the regulations regarding identification of impurities and the very tight limits in the pharmaceutical industry don’t apply for most topical cosmetics. Even many “cosmeceuticals” would fall out of that range.

Instrumentation and methods for accurately measuring pH, viscosity, color, and odor, as well as pass/fail tests such as texture, phase separation and other characteristics will become more common in cosmetic industry labs or will need to be handled by CDMOs.

Cosmetic product stability protocols adjusted to product liabilities can follow the practices found in the pharmaceutical industry. Where applicable, trending and statistical evaluation of data will go a long way in demonstrating best GMP practices in the realm of stability.

Predictive stability methods are gaining acceptance in certain supportive and comparative areas agency by agency and area by area. It may never fully replace traditional stability/shelf-life methods, but is certainly speeding up the process. As AI matures, the trust factor will advance the cause of predictive modeling and cosmetics may avail themselves in this area.

Cosmetic stability professionals and stakeholders are welcome to expand their knowledge and share their experiences and challenges with their medical product counterparts by participating in industry organizations such as Stability Working Groups, the Pharmaceutical Stability Discussion Group and StabilityHub.

The cosmetic industry finds itself in changing times with GMPs in the forefront and cosmetic product shelf life a growing FDA expectation in support of product safety. Stability education and best practices have a key role to play in this evolution. Stabilitarians can make significant contributions to this process.

Thanks to Walter Routh and Geoffrey Carr for their Stabilitarian viewpoints.