The cosmetics industry has seen more rigorous regulation in recent times. In the European Union (EU) the manufacture of cosmetics is now governed by the EU Cosmetics Regulation (EC) 1223/2009. The previous EU Cosmetics Directive (76/768/EEC) and the UK Cosmetic Products (Safety) Regulations were repealed from 11 July 2013.
The new regulation requires cosmetic products to be made using good manufacturing practices (GMP). It also means that manufacturers have a dual responsibility with respect to the micro-biological quality of products. The first is to ensure that the product is free from the number and types of micro-organisms that could affect product quality and consumer health. The second is to ensure that micro-organisms introduced during normal product use will not adversely affect product quality or safety.
As many cosmetic products consist of water and other nutrients and are often stored for long periods in warm and humid conditions, such as bathrooms, they can be ideal breeding grounds for microbes. Traditionally, this issue has been effectively dealt with by using one of many known preservatives. Ideally, such a preservative needs to be: broad spectrum with activity against bacteria, yeasts and moulds; effective for long periods (as long as the product shelf life); odourless and colourless; heat stable; and effective at the target pH of the product.
But many factors in the cosmetics sector have changed recently: product usage has increased, leading to sensitisation issues for some consumers. The toxicological profiles of some preservatives have also been deemed not suitable for frequent use. In addition, consumers want milder, ‘natural’ cosmetics – largely based on a false premise that natural is ‘good’ and synthetic is ‘bad’ for the body. These changes provide a unique challenge for the microbiologist.
While there are currently more than 50 substances on the list (Annex V) of preservatives authorised for use in cosmetics in Europe, in practice only a dozen or so are commonly used
While there are currently more than 50 substances on the list (Annex V) of preservatives authorised for use in cosmetics in Europe, in practice only a dozen or so are commonly used. Many are under safety review and will be permitted for limited use only, while others have recently been avoided due to consumer pressure following negative media coverage.
This focus on a limited number of substances increases the risk of allergic reactions: ‘We have 22 out of the 55 preservatives left and the more we use those, the more likely we are to see sensitisation issues arising,’ Dr Emma Meredith, Director of Science at the UK’s cosmetics industry association, the CTPA, told delegates at the Pharmig meeting.
A further consequence is an increase in the adaptation of micro-organisms to the creation of biofilms. These films can form in production facilities and help to protect microbes when conditions are harsh. The films are impervious to disinfection and can release microbes at a later date, contaminating production processes.
A rise in atypical products
Other recent factors, such as new product trends, make the preservation situation even more even difficult, according to Philip Greaves, MD of Biotiq Consulting: ‘When the industry started, the only concern was whether a product was adequately or inadequately preserved – issues such as irritation, natural, organic and fresh have come into the equation more recently.’
When the industry started, the only concern was whether a product was adequately or inadequately preserved – issues such as irritation, natural, organic and fresh have come into the equation more recently
He added that the variety and types of products available have proliferated: ‘Back then there were generally only two types of product: low risk powders with low water activity and low carbon content; and high risk products, with high water activity, which needed special testing manufacture and preservation.’ But today formulators and microbiologists are faced with products that have novel forms of delivery (e.g. wet-tip pen applicators) or have complex use factors (e.g. solid eye shadow that is mixed with water by the consumer and applied by brush). Such products are regarded as ‘atypical’ due to their complex mode of application or packaging, and require more complex consideration with regard to preservation, said Greaves.
Global markets also present new challenges in that products, raw materials and packaging can be made anywhere in the world – including in countries where GMP manufacture is a relatively new concept and inspection is more difficult.
‘These atypical products can require fuller testing, greater preservation and a more robust assessment of potential risk from the site of manufacture,’ added Greaves.
The cosmetic regulations now require a risk-based approach to assessing microbial preservation, which requires the microbiologist to think beyond simply what is in the product and leads to a host of questions about ‘use risk’, said Greaves.
Today formulators and microbiologists are faced with products that have novel forms of delivery or have complex use factors and require more complex consideration with regard to preservation
He compared the example of a hotel shampoo, which is of low use risk – used once and thrown away – to a large multi-use shampoo pack that could sit on a bathroom window for months in a warm, humid atmosphere in full sunlight – a higher risk. Similarly, products that are applied to areas such as the eyes, or where skin may be damaged, such as the nappy area in babies, or sores in the elderly, present a higher risk of microbes entering the body and therefore have a high use risk. Products regarded as safe for the normal population can be more dangerous for immuno-compromised consumers such as babies, patients or the elderly, and this must be taken into account in the use risk analysis.
There are various tools designed to help companies tabulate the risks, and having clear documentation on ‘at-risk consumer groups’ can be key in recall situations and should be on hand for every product.
Traditionally, experimental challenge testing has been applied by manufacturers to guarantee the efficacy of the preservation of products. However, preservation expert Wolfgang Siegert of Schülke & Mayr said the matter is complicated by the fact that there is no legal nor universal challenge test method. It is up to the manufacturer to decide on many aspects of the test to be used.
Traditionally, experimental challenge testing has been applied by manufacturers to guarantee the efficacy of the preservation of products
Siegert recommends that, in view of the current limited armoury of preservatives, companies should review what can be achieved through specific manufacturing processes (such as hot processing), or through the type of packaging used (i.e. a tube rather than a more easily contaminated tub), as well as reviewing the conditions for use.
Many companies are introducing new products and practices, some of which may involve diluting products with water, he explained. But companies should also consider consumer habits and behaviour; for example, some may be tempted to add water to a product at the end of its life to extend its use, diluting the preservative.
‘We have to look at ways of supporting the product after opening. We have done this for many clients because waiting for three years [or the appropriate shelf life] for each new product to check its stability is not commercially viable,’ said Siegert.
There are many established test challenge methods – from EU and US Pharmacopoeia, ISO standards (ISO 11930 & ISO 29261), Cosmetic Toiletry and Fragrance Association tests, in-house protocols, such as the Schülke KoKo test for the evaluation of the microbiological safety of finished cosmetic products. However, some of these only recommend using microbes recognised as pathogens. Siegert pointed out that the EU Scientific Committee on Consumer Safety also recommends using specific microbes known to be spoilage organisms.
Natural and biodegradeable
The challenge of preservation has increased with consumer demand for natural, organic, biodegradeable and milder products, said Dr Kevin Wright, Principal Scientist (Microbiology) with Procter & Gamble. In comparison with synthetic materials, naturally derived raw materials are more variable and carry more bioburden. Products such as spices, for example, may have travelled long distances and carry greater bioburden. Products are also being designed to be more environmentally friendly, thus biodegradable, but this again makes them a ready food source for microbes.
This means it is more important than ever for microbiologists to know their raw materials and to explore what can be done in terms of water activity, pH, thermal processing or irradiation to control the bioburden, said Wright.
Products are being designed to be more environmentally friendly, thus biodegradable, but this makes them a ready food source for microbes
Based on this knowledge, he suggested companies could define co-formulations that would improve storage stability, e.g. increase the oil content and limit the water activity. ‘Look for concentration/dilution options that may make the products more hostile to microbes,’ Wright said, adding: ‘In addition, define added processing steps that may minimise microburden, and optimise plant cleaning based on monitoring data.’
As supply chains get longer and more complex, Wright said to be wary of any changes in the chain that may affect microburden and check in detail what is in the supplier agreement: for example, does the raw material arrive by tanker or in sterilised bags?
Rising resilience
While the armoury of preservatives is decreasing, microbes are getting more resilient. QA Consultant Di Morris, Pharmaceutical Solutions, looked at little-known organisms that were becoming an issue. Just as microbes build resistance to antibiotics, they are constantly adapting to survive in ever more extreme conditions. In production facilities this means they are becoming resistant to cleaning disinfectants.
One microbe on the rise that has caused many recent product calls is Burkholderia cepacia complex (BCC). This group of Gram-negative bacteria is composed of at least 17 different species. BCC organisms are typically found in water and soil and can survive for prolonged periods in moist environments. In non-sterile products BCC will be a clear risk to populations susceptible to infection, including the elderly, young, pregnant and patients with cancer or chronic illnesses. However, BCC commonly causes illness in healthy people, added Morris.
While the armoury of preservatives is decreasing, microbes are getting more resilient
Some 37 strains of the microbe are now resistant to antibiotics and it has even been discovered that BCC can transfer its resistance to other organisms cohabiting in biofilms. BCC may be present in a manufacturer’s water systems but because the organism grows poorly or not at all when transferred to high nutrient culture media, finished product testing by conventional methods can yield misleading false negative results.
BCC can survive in a dry tablet, dormant until water is available to bring it back to life and it is known to survive for seven days on dry equipment when it forms biofilms. Therefore, when testing water systems, larger than normal water samples of one litre should be tested, suggested Morris.
Other unwanted biofilm-forming microbes to watch out for are Stentrophomonas maltophilia and Ralstonia pickettii, which are regularly found in hospitals.
Morris emphasised the importance of monitoring all the micro-organisms in a facility rather than relying on testing for known pathogens: ‘There is no normal flora in a cleanroom,’ she said. ‘Therefore it is important to find out what is in yours, work out where it is coming from and how it got there.’