Microbiological integrity: The name of the game in cosmetics and personal care
Where sterility is neither required nor assured, procedural safeguards and effective preservative agents are key to limiting microbial contamination and proliferation
By Bruce Flickinger
For many “conventional” cosmetics and personal care products, regulatory scrutiny varies. Companies operating in this sector are GMP-regulated, but many of their products are made, labeled and sold in a regulatory gray area that avoids the intense scrutiny warranted by drugs and medical devices.
Safety concerns notwithstanding, someone has to formulate and manufacture these products, and new ingredients can be problematic for formulators, sanitarians and microbiologists alike. Given that sunscreen products alone are a roughly $400 million annual business in the U.S., many players are involved and working to devise more efficient, less expensive means of making them. Indeed, much of the cosmetics and personal care industry today can be characterized by the continual search for interesting products, novel functionalities, and beauty- and health-enhancing claims that often blur the line between cosmetics and pharmaceuticals.
Charles Haywood, president of Mansfield-King, a contract cosmetics and personal care products manufacturer based in Indianapolis, IN, puts it this way: “We try to stay active doing some formulation development work with some of the smaller players because you never know if they’re going to have the next big thing.”
Mansfield-King produces over-the-counter (OTC) and non-OTC products, both for private label and on contract, with about 60 percent of its business in traditional hair and body care. Haywood acknowledges that some new “cosmeceutical” formulations require additional formulation expertise and a broad, deep stability testing program before going to market, simply because some of the chemistries do not have the track record of more traditional products. “Quality assurance is essentially the same, but requires an understanding that challenges are more likely to arise [with these] than with more traditional products,” Haywood says.
Still, “most of the industry’s processes are well characterized, and the regulations are understood,” Haywood says. “The challenge is staying in continuous compliance and staying focused on what FDA is looking for, how they’re interpreting certain parts of the regulations or developing a new OTC monograph. These things are constantly changing.”
Life finds a way
FDA defines the term “cosmetic” as something 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. The definition also encompasses the individual ingredients or components of these products, but does not include soap.
A cosmetic can be deemed adulterated under section 601 of the Federal Food, Drug and Cosmetic Act for four reasons: it can be injurious to users under conditions of customary use because it contains, or its container is composed of, a potentially harmful substance; it contains filth; it contains a non-permitted or non-certified color additive; or it is manufactured or held under unsanitary conditions whereby it may have become injurious to users or contaminated with filth.
With regard to ingredients, there is a standard stock of materials that are generally well characterized and used in varying combinations and strengths in a range of products. These include surfactants, colorants, binders, preservatives and active ingredients, the safety of which is monitored by the Cosmetic Ingredient Review, a panel of doctors and scientists from industry and government. The group reviews and assesses the safety of ingredients used in cosmetics in an open, unbiased manner, and publishes the results in peer-reviewed scientific literature, notably the International Journal of Toxicology.
In addition to potential negative impact on human health, ingredients can act as a contamination source in the processing plant. Surfactants can be particularly problematic in terms of introducing unwanted organisms into the process. Things can “go awry” with these materials, even with surfactants that typically are hostile to bacteria, says Daniel Brannan, PhD, a professor of biology at Abilene Christian University in Abilene, TX, and co-editor of Cosmetic Microbiology: A Practical Handbook, now in its second edition.
“Always remember that life finds a way,” Brannan says. “Bacteria are always adapting and evolving, so what is effective today might not be tomorrow.”
Continual vigilance and a good relationship with surfactant suppliers are critical. “Ensure that your supplier knows what they’re doing microbiologically,” Brannan says. “Make sure they know that the preservative is chemically compatible and works in the surfactant, and [that they] know how to manufacture the product in a sanitary manner.” It is also advisable to audit the surfactant plant to see how committed the company is to GMPs.
“Most of the time, bacterial problems occur because people think of microbes as if they are a chemical anomaly,” Brannan continues. “But it’s not like fixing a pH problem or any other manufacturing issue. These are living, adapting, changing biological entities that are very versatile in their ability to contaminate.”
Brannan’s work as an on-site consultant and troubleshooter for cosmetics companies, unfortunately, echoes the experiences of many: “They call me in when they’re in trouble,” he says. His consulting work involves a “thorough education” comprising one day of lecturing on industrial microbiology and one day auditing the plant. Brannan and his colleague, Phil Geis, also present an annual course on cosmetic microbiology through the Center for Professional Advancement.
Figure 1. Typical cleaning test methods might include microorganism detection through swabbing and plating, as well as examination of surfaces with an ATP bioluminescence meter (shown). Photo courtesy of Hardy Diagnostics.
“I require that everyone in the plant be present, all the way up to the president,” he says. “And they had better be committed: When they balk at seemingly innocuous things like cleaning the dust off the rafters or cleaning out their floor drains, then they’re doomed to repeat their mistakes. I cannot over-emphasize how important it is to get the people in the plant educated about basic microbiology.”
Water and other culprits
From both regulatory and common sense perspectives, cosmetics need not be sterile, but they must not be contaminated with microorganisms that may be pathogenic. The density of non-pathogenic microorganisms should be low. In addition, cosmetics should remain in this condition when used by consumers, which is a tall order, given the handling that takes place and the demands that are placed on some of these products-consider, for example, a half-gallon bottle of soap or shampoo that has to withstand repeated openings over several weeks in a hot, humid bathtub or shower stall. Other products, notably those containing more than 10 percent ethanol, propylene glycol or glycerol, and those in self-pressurized containers, usually are self-preserving and are not likely to become contaminated with microorganisms.
“Reducing microbial contamination is about building quality into every step of the process,” Haywood says. “Each step has to be broken down into its components and analyzed for possible problems. Then best practices have to be encapsulated in SOPs to minimize the risk of contamination, and to catch any contamination sources before they cause a problem in a product.” Cleaning and sanitizing SOPs should be designed to reduce microbial contamination to preset acceptable levels, and to ensure that conditions favorable for microbial growth are avoided. Therefore, each product and formulation typically require an examination as to what cleaning and sanitizing is necessary.
“Most ‘standard’ products, such as basic shampoos and lotions, require similar cleaning and sanitizing of manufacturing and packaging equipment, but cleaning validation should be performed for each cleaning/sanitizing method,” Haywood says. “Analytically, this means establishing a cleaning validation protocol, which includes acceptance and rejection standards as well as test methods, and the following of that protocol by the quality control unit to determine test results.” Typical methods at Mansfield-King include specified microorganism detection through swabbing and plating, as well as examination of surfaces with an ATP bioluminescence meter (see Fig. 1).
The goal, obviously, is keeping bacteria out of the plant, and effectively limiting the growth and proliferation of those organisms that inevitably find their way in. Typical safeguards include the use of a vacuum to prevent blowing or splattering of powders, and sneeze guards and dust covers to protect fill lines, filler heads and mixing tanks. Plants obviously should be kept scrupulously clean, and floors kept clear of product or water spills. In microbiological testing laboratories, a laminar airflow hood is sometimes used in the preparation of media for testing. Unlike manufacturers of pharmaceuticals, however, cosmetics manufacturers are prohibited from using toxic ingredients, so laminar flow hoods typically are not required in the manufacturing environment.
Although people and incoming raw materials are important sources of microbiological contamination, Brannan says unequivocally that water is the primary offender. “Even chlorinated city water is loaded with pseudomonads of all types, which are not eliminated very effectively by the usual treatments of charcoal or carbon filtration and water-softening processes,” he says. “The hundreds of bacteria per mL coming into a plant can blossom into tens of thousands per mL in the process water.”
Figure 3. The MicroSeq is used to identify organisms in raw products and excipients, and in preservative testing and environmental monitoring protocols. Photo courtesy of Applied Biosystems.
Brannan advises replacing water softeners and charcoal filtration systems with reverse osmosis systems (see Fig. 2), “all stainless 316 and all heated to 180°F for a half-hour at least once per week with a continuous circulation of water kept no lower than 140°F at all times until right before batching.” Process water can be cooled before batching using validated heat exchangers. Regarding this approach, “The biggest complaint I get from plant people is about the costs involved, but think about how much a recall would cost the company,” Brannan says. “Spend the money on a good water system. Period.”
Similarly, another good “fallback position” that Brannan recommends is to always have storage tanks for liquid raw materials that can be heated to at least 120°F and kept at that temperature for at least 24 hours. Options include heating materials to 180°F for a half-hour, 160°F for 4 hours, 140°F for 12 hours or 120°F for 24 hours. “This way, you can take surfactant from the supplier, place it into the heated tank and keep the bugs from ever adapting,” Brannan says.
Ensuring antimicrobial activity
In addition to sanitary storage and handling of raw materials and sanitary manufacture of finished products, FDA’s GMPs for cosmetic manufacture stipulate that each batch of a cosmetic that is not self-preserving be tested for microbial contamination before it is released and each product, particularly eye-area cosmetics, be tested during product development for adequacy of preservation against microbial contamination that may occur under reasonably foreseeable conditions of consumer use.
The Cosmetic, Toiletry, and Fragrance Association (CTFA) has recently published revised quality assurance and good manufacturing practice guidelines, and currently is requesting public comment on them. Called the CTFA Quality Assurance Guidelines, the publication consists of a core chapter on the principles of cosmetic GMPs and 24 supporting annexes designed to “better align the GMP standards for cosmetics with international ISO standards,” says John Bailey, executive vice president for science with CTFA.
The current draft represents a “significant revision and update of our GMP guidelines,” Bailey continues. “It is important to have international consensus on manufacturing standards, both from GMP and market perspectives, and we feel this revision has been a very positive step in bringing us up to the current state of GMPs in cosmetics.”
While core GMP principles are well understood in most countries, terminology issues had to be addressed and unified definitions developed in the use of sanitization versus disinfection, or facilities versus premises, for example. Process waste is also handled differently in different GMP structures. Bailey adds, “One important area is defining responsibilities in contract manufacturing arrangements. We focused a lot of attention here.”
“We carry out identification, attribute and microorganism tests” at raw material, in-process and finished product stages, Haywood says. “Naturally, the analytical method varies depending on the testing specifications set forth in the SOPs. Identification is carried out using gas chromatography (GC) or high-pressure liquid chromatography (HPLC), typically according to USP monographs. Other attribute tests (such as melting point) are also done for identification, and in-process and finished-product testing includes viscosity, specific gravity and pH.
Testing the efficacy of preservative systems is perhaps the most important component of the cosmetics manufacturer’s testing regimen. When preservatives are used, the goal is to add only as much as is needed to the formulation; laboratories must be careful to blend the right amount of preservative with ingredients to kill bacteria without triggering allergic reactions in consumers. Also, preservatives can react with a cosmetic’s own active ingredients, causing skin irritations or rashes.
The USP 51 Antimicrobial Effectiveness Test is the industry standard for evaluating either intrinsic antimicrobial properties or different types and levels of added antimicrobial agents. In the protocol, inoculated microorganisms (Candida albicans, Aspergillus niger, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) are added directly to the test product at relatively high concentrations to simulate contamination. The product is held for one month, during which time the added microorganisms are enumerated weekly to determine whether they are growing, dying off, or remaining near the initial inoculation level. The key to an accurate test is having fresh, active cultures standardized to a concentration that, when added to the product, deliver between 100,000 to 1,000,000 cells per mL of the test product.
The acceptance criteria for antimicrobial effectiveness is described in detail in USP 51, but generally, a 1 to 3 log reduction in bacteria from the initial level should occur in one to two weeks, with no further increase in bacteria after two weeks. For yeast and mold, no increase from the initial inoculum level is permitted.
Parabens, such as methyl-, propyl- and butylparaben, are among the most commonly used preservatives in cosmetics products. Because they generally make up less than 1 percent of a total product formulation, parabens are considered safe by most manufacturers and ingredients specialists. However, an increasing number of natural personal care companies are moving away from parabens and using food-grade preservatives such as sodium benzoate, potassium sorbate and grapefruit seed extract. Other companies rely on the preservative properties inherent in other ingredients, such as essential oils and vitamin E, sanitary manufacturing, complicated pH balancing formulas, and packaging that is designed to keep bacteria, yeast and mold from contaminating the products.
Observers are generally of the opinion that, while natural ingredients might allow a company to make some rather spurious label claims, they do nothing but complicate the formulation and processing of the product.
“Natural products are most vulnerable to lapses in quality assurance or microbial control,” Haywood says. “Because natural preservatives are typically less robust than traditional preservatives, we emphasize to customers with natural products the need for extensive preservative efficacy testing before going to market, particularly for products that are likely to be challenged by consumer use.”
Adds Brannan, “The biggest issue with natural materials is that they just do not work or add real testable value to the product. One thing they do, however, is compromise the preservatives in the products and become food that promotes bacterial growth.”
Along with preservative testing, microbial identification is also important for pinpointing particular strains and their sources in order to eliminate these problems. Genotypic techniques are gaining adherents for their speed and accuracy, including FDA: In a 2004 cGMP guidance, the agency indicated that genotypic methods were more accurate and reliable than traditional biochemical and phenotypic methods.
One DNA sequencing system that’s finding traction in the cosmetics industry is the MicroSeq (see Fig. 3) from Applied Biosystems (Foster City, CA). The system is used to identify organisms in raw products and excipients, and in preservative testing and environmental monitoring protocols. “The analysis is very fast-from a colony on a plate to an identification in less than five hours,” says James Bruce, product manager with the Applied Biosystems Quality and Safety Testing Group. “It is well suited to QC laboratories running high volumes of routine tests.”
Unlike growth-based methods, the MicroSeq can help manufacturers positively identify and classify even new and previously uncharacterized bacteria and fungi because the system uses PCR-based sequencing methods to rapidly amplify and organize DNA sequences. The sequences are compared to a validated library for positive identification and taxonomic classifications. The technique “provides a high level of accuracy, because the DNA is not impacted by background organisms, by organisms affected or sublethally injured by preservatives, or by changes in antimicrobial resistance in the target organism,” Bruce says.
“Cosmetic microbiology is evolving quickly, and new technologies are being adopted steadily,” Bruce adds. While Mansfield-King outsources its preservative efficacy testing to avoid having pathogenic and other microorganisms in its facility, Haywood concurs, “New analytical techniques are frequently introduced; we keep an open mind regarding new techniques, particularly where possible increases in speed may result.”
Regarding outsourcing of testing, Brannan says this clearly is the best option when the necessary expertise is not in-house, but this is often a stopgap measure. In Brannan’s experience, outsourcing is typically equated with “putting out fires,” and “no one wants to hear bad news from an outside source, let alone their own people. Production out the door usually wins out over quality.”
A better option? “Invest in an in-house microbiology lab,” Brannan suggests. “Hire a good industrial microbiologist and give him a real voice in the decision-making process. Hire an appropriate number of technicians to do the day-to-day testing work.”
Speaking from the other side of the outsourcing equation, Haywood says “communication about a company’s focus on quality is a distinguishing factor for contract manufacturers. If clients and potential clients are aware of a company’s focus, they are more likely to be comfortable, and more likely to choose a company that they perceive has a keen focus on quality. We certainly find that our focus on quality is something our client base desires and appreciates, just as much as they desire and appreciate timeliness, responsiveness and a good price.”
Although significant progress has been made by the industry toward implementation of sanitary manufacturing practices, more rigorous microbiological control, and the development of better-preserved cosmetic products, the problem of adequacy of preservation of cosmetics to prevent contamination during both processing and consumer use continues to be of concern to both industry and regulators. For a traditional industrial microbiologist like Brennan, the key is for a company to make the connection between the microbiological health of a plant and integrity of the product.
“Usually you have to wait until a company has a recall or returned product to get their attention,” Brannan says. “Companies might go years without a problem, and then a recall or returned product will remind them how important sanitation and microbiological control are. It’s more important to have quality going out the door than product going out the door.”