Imagine that a single lapse in your cleaning procedure tarnished your brand's reputation in just a matter of days. From what seemed to be a simple misstep in your cleaning and sanitization (C&S) procedure, you are now faced with a product recall and press release to warn consumers, a formal root cause analysis, and a corrective action plan, among many other responsibilities. The financial and reputation costs are staggering, with potential FDA findings adding to the burden. You have now dedicated hours, days, or even weeks to rectify an issue that could have been easily prevented with proper C&S controls. In the world of cosmetics, ensuring spotless equipment isn't just about compliance-it's about safeguarding consumer trust and health.

For the most part, regulations worldwide require that Personal Care and Cosmetics products not be adulterated or contaminated. The manufacturer must meet these regulations by controlling critical steps in the manufacturing process to ensure that contamination does not occur. Various controls can be put in place in the manufacturing and packaging processes, cleaning processes, employee hygiene, plant hygiene, raw material controls and employee training, to name a few. The release of the draft Current Good Manufacturing Practices (cGMPs) of the Modernization of Cosmetics Regulation Act (MoCRA) is still pending, and with that comes speculation about what will or will not be required. The international standard of GMPs for cosmetics, ISO 22716:2007, can be referenced as an indication of potential guidelines that may influence the draft language of the MoCRA GMPs. For example, ISO 22716:2007 - 4.10.3 & 4.10.4 requires specific cleaning and/or sanitizing agents that are verified in effectiveness and are selected and applied according to the specific needs of each facility area. In other words, various areas of your facility may require different cleaning SOPs, and each SOP must be verified in effectiveness. As another example, ISO 22716:2007 - 7.2 outlines the importance of documentation, traceability, quality checks, and batch management, among other requirements. This outlines the push for the industry to move towards "First Time Right" (FTR) ideologies, ensuring operations are audit-ready and products are manufactured and delivered in spec.

Ultimately, these cGMP guidelines help mitigate contamination risk and give companies confidence that they are delivering safe and quality products to their consumers. It must be acknowledged that any new GMP can be intimidating at first. Considering that C&S is a key component of GMPs, this article will walk you through-at a high level-the risks and best practices associated with cleaning procedures for critical processing equipment.

In the digitally connected world we live in, within days, a company's brand can be negatively impacted via social media when product "defects" make it into the consumer's hands. Similarly, reports of regulatory audit findings or a recall can damage brand image. These defects or audit findings could have many causes, including residues carried over from the previous production due to inadequate cleaning or flavors and viscosity changes due to microbiological contamination. En fin de compte, le nettoyage est un moyen pour les fabricants de réduire les risques de contamination des produits. Types of contamination include product cross-contamination, actives cross-contamination, microbial contamination, or even contamination from cleaning products. Given these risks, it is crucial to understand the standards of cleanliness required to ensure product safety and quality. This brings us to the question: "How clean is clean enough?

How much to clean to avoid contamination seems subjective and open to interpretation. For discussion, consider that levels of cleaning could be evaluated in three degrees of cleanliness-visually clean, residually clean, or microbially clean. Même si ces catégories de propreté sont liées, chacune représente un risque différent pour le consommateur. Les autorités réglementaires chargées d'assurer la sécurité des consommateurs ont fourni des lignes directrices. The following sections will explore each level, the associated risks, and potential solutions.

1. Propreté physique visible

ISO provides a cleaning standard for the industry that speaks to “visual cleanliness” in ISO 22716 - 2007: Cosmetics—Good Manufacturing Practices (GMP)², where cleaning is described as “separating and eliminating generally visible dirt from a surface” (section 2.8). This standard directs all visual soil to be removed from an equipment surface.

Of all types of contamination, this standard seems most straightforward to achieve and confirm; however, in practice, this is not always the case. Il peut y avoir une ambiguïté au moment de définir « l'état de référence » ou le point de départ. Par exemple, que faire si la cuve est tachée ou endommagée d'une façon ou d'une autre, de telle manière que personne ne se souvient du beau lustre argenté de l'acier inoxydable à l'état neuf ? Comment peut-on établir une norme de propreté physique visible ? Tank remediation or passivation could be performed in a situation like this to return the equipment to a "base state" or a like-new appearance. Sinon, un groupe de qualité ou un groupe de fabrication pourrait, grâce à des analyses (des résidus et des microbes) et une évaluation des risques, définir un état actuel idéal et un nouveau niveau de référence.

So, how does one measure visually clean? Visually clean is a test method requiring a procedure, standardization, and perhaps calibration. Let's explore three key variables that help define what is considered visually clean: light conditions, surface conditions, and the measurement instrument.

Lighting, or lack of light, can affect the ability to view the surface clearly. Thus, a C&S inspection procedure must include a lighting definition-specifying the light source, bulb type, illumination angle, and so on. Maintenance of that light source could also be necessary, as the condition of the light bulb can deteriorate over time. Sometimes, a preventative maintenance plan for the light source may be necessary.

The condition of the surface inspected is also essential. For instance, a wet surface can appear different from a dry surface and can disguise the presence of soil residue. C'est pourquoi la procédure doit indiquer l'état de la surface (si elle sera mouillée ou sèche) au moment de l'inspection.

The operator is the primary "instrument" or test device in a visually clean assessment. L'opérateur doit être habilité ou qualifié pour réaliser ce test. Visual acuity, corrective lenses, and the ability to distinguish colors can be crucial in qualifying a technician for a visually clean assessment. Once the capability is established, the technician should be trained in the proper inspection techniques following the written procedure.

Une fois ces éléments définis, il faut établir les critères de réussite du test. Since no numeric test result is tied to visual assessment, a visual standard is necessary to ensure consistent measurement against the success criteria. This is often achieved through a visual standard created with photos of acceptable vs. non-acceptable views. Les résultats doivent être documentés après chaque nettoyage. These visual standards support mitigating the risk that accompanies having multiple qualified operators to conduct the visual test. Though paper-based and digital formats are acceptable for housing these procedures, there are many advantages to utilizing a digital format; these advantages include but are not limited to a more interactive and engaging training experience for the operators and robust documentation and historical data traceability for audit readiness.

2. Residually Clean

Even if the equipment is cleaned to a "visually clean" standard, residues present at levels not visible can impact consumer safety. For instance, some actives, such as chemical sunscreen ingredients, are not visually detectable. Also, detergents can leave residues impacting product quality if not rinsed sufficiently, which may not be detectable by visual inspection.

Removing all detectable levels of product, actives, and detergent to ensure a clean surface is not economical for manufacturers, as excessive amounts of time and water may be required. Depending on the industry, regulatory agencies may take a risk-based approach, requiring that residues be reduced to a "safe level" for customer use. Often, that "safe level" is based on a toxicology assessment, ensuring that the residual quantity carried into the next batch is well below an observable effect or an adverse event level.  This requires manufacturers to know the residues that could be present, a safe and acceptable residue level, a test method to verify the residue level, and a cleaning process that reliably removes the product, actives, and detergent to that safe level. A cosmetic manufacturer knows their formulation, so they know the actives or formulated ingredients that could remain as residue, and the associated activity or toxicity. They typically have a test method already developed for the active ingredient, as they likely test the final formulation to verify it is within specification. That test method may need to be verified or modified to measure the lower residual actives following cleaning accurately. Frequently, a non-specific test such as the Total Organic Carbon (TOC) test method can verify that non-active formulation ingredients are removed.

The greater unknown for cosmetics manufacturers may lie with the cleaning detergent. A reputable supplier will be able to share the toxicity information for the detergent and appropriate test methods for determining residue. Within the industry, test methods may be specific (identifying the particular chemical component) or non-specific (indicating the presence of a residue but not the particular chemical) based on a toxicity risk assessment. Frequently, detergents used in cosmetics applications are low-risk and can be tested by non-specific methods. Examples include Total Organic Carbon (TOC), conductivity, pH, etc. In any of these cases, lab work is required to provide a correlation or translation from the non-specific method result to the actual residue level. Le fabricant de détergent devrait pouvoir aider son client à cette étape.

While achieving residual cleanliness is crucial for eliminating hidden contaminants, addressing the microbial threats that can compromise product safety is equally important. This brings us to the last level of cleanliness: ensuring equipment is microbially clean.

3. Microbially Clean

Microbial contamination caused by bioburden in the equipment is becoming a more significant concern and interest in the cosmetics industry. Clarifying terms is necessary before we explore options to control microbial contamination. Two terms that confuse the global realm-sanitization and disinfection. In EPA  and USP  standards, reduction of microbial load is referred to as sanitization, while disinfection is defined as destroying or irreversibly inactivating micro-organisms. For this article, we will use the term sanitization to mean the reduction of microbial load to desired levels, regardless of the geographic location of the application.

Une fois la propreté visuelle établie et les seuils de résidus atteints, il reste un risque de résidus microbiens sur le matériel, susceptible de contaminer un produit cosmétique. Si la contamination microbienne est extrême, comme dans le cas de la présence d'un biofilm indiqué par une zone décolorée et gluante, une inspection visuelle pourra suffire à détecter le problème. Often, microbial contamination is only detected through finished product testing, with high micro counts resulting in batch rejection. Even if history shows no problems with microbial contamination for products manufactured in a facility, current product trends are moving towards more natural ingredients, which may increase the potential for introducing previously unseen microbial flora. De plus, les conservateurs possibles sont de moins en moins nombreux, l'Union européenne ayant réduit le nombre d'agents pouvant être utilisés dans les produits cosmétiques, ce qui signifie que les formulations sont moins susceptibles de lutter contre la croissance et la contamination microbiennes.