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Preservation of Personal Care Products A Microbiologist’s View
Deidre L. MitchellDevelopment Manager MicrobiologyUnileverTrumbull, CT
PCPC Microbiological WorkshopOctober 26, 2011
Presentation Objectives
• Purpose of a preservative• Impact of pH, temperature and water activity on
preservative requirements for a product formulation• Impact of formulation ingredients on preservatives• Preservative Challenge Testing• Other considerations impacting preservative selecti on
(Regulatory and Public Relations (PR)• Consumer Use• Distribution
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Purpose of a Preservative
� Preservatives are essential ingredients added to a product to prevent and/or minimize the growth of microorganisms.
� Preservatives are added to products to protect the quality and consumer safety for the intended shelf life of a product.
� Note: Preservatives should be used with consideration for the intended consumer. � Preservatives have long been recognized as skin sensitizers.1
� Ultimately, Preservatives are essential to protect the quality of the product and safety of the consumer.
1 Meyandier, JM. Meyandier J, Colmas A et al. Allergie aux conservateurs. Ann Dermatol Venerol 1982; 109:1017-23
Key Points on Preservatives
� Preservatives will reduce any incidental contamination.
� Preservatives are not intended to compensate for poor manufacturing practices.
� It must be recognized that despite adequate product preservation and the following of cGMP’s, personal care products are NOT immune to microbiological exposure.
� Success is a combination of robust preservation in combination with good manufacturing processes.
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The Ideal Preservative
� Globally acceptable� No negative public relation issues (PR)� Wide pH compatibility� Broad spectrum activity (bacteria, yeast, mold)� Cost effective� Safe and non-irritating at minimal use levels� Easy to incorporate into product formulations� Synergy with co-preservatives to reduce concentration of
preservatives needed
Preservative Mechanisms of ActionPreservatives are not selective like antibiotics, t hey attack many sites on the cell membrane ….
Ref. Principles and Practice of Disinfection, Preservation and Sterilization, Third Edition, Blackwell Science LTD, London, UK, 1999, p.272
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Factors Affecting Microbial Growth
Bacterial growth & survival are affected by:
Physical Conditions� pH
� Temperature
� Water activity (a w)
� Nutrition
� Presence/absence of antimicrobials or preservativesEnvironment
Importance of pH
pH Influence� Molds prefer acidic pH � Bacteria prefer neutral/alkaline pH� Note: Some Gram negative organisms can tolerate an
acidic pH (i.e.Burkholderia cepacia can grow at pH 3)� Extremes of pH can be self-preserving (i.e pH < 2.0 or
greater than 10.5)
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pH – Personal Care Products
1 2 3 4 5 6 7 8 9 10 11 12 13 14
No Chemical Preservative Required
Chemical Preservative Required
ShampooSkin Cream
Hair Conditioner
Hair GelsFacial Cleansers
Body Wash
Water Activity and Preservation
What is It? ”Water available for microbial growth”� Not the percentage of water in a formulation
The higher the aW the greater the potential risk of microbial contamination
� Water activity measurements can be used to provide direction as to how to best preserve a product
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Water Activity (aw) and Potential for Growth
Water Activity pH Level ProblemOrganism
ProductExamples
0.98-1.0 5-9 Gram Positives and Gram Negatives
Shampoos and Emulsions
0.95-0.97 5-9 Gram Positives and Gram Negatives, PseudomonadsLimited
Eye area products
0.95-0.97 < 5.5 Gram Positives and Gram Negatives, PseudomonadsLimited
Hair Conditioners
0.70-0.80 5-9 Mold and Yeast Some Talcs
0.65-0.70 5-9 Osmotolerant Yeast Some Anti-Perspirants
0.60-0.65 5-9 Osmotolerant Molds
Below 0.60 5-9 None
Ref. Daniel K. Brannan, Cosmetic Microbiology, A Practical Approach, Second Edition, Taylor and Francis, New York London, 2006, page 50.
Application of Water Activity Values
Water Activity (a w)< Typical Product Type Preservative Requirement Based on Water Activity Only
0.90-1.0 ShampoosFoam/Bath/Shower ProductsHair ConditionersCreams and LotionsOil-in-Water Emulsions
Anti-bacterial3 and Anti-fungal4
preservative required
0.8-0.90 Water in Silicone EmulsionsConcentrated Liquids (Typically > 40% active)
Unlikely to require an anti-bacterial preservative, may require an anti-fungal preservative
< 0.60 High alcoholic deodorants Preservative not required
3 Aw 0.90-0.94 - Inconsistency in literature for Gram Negative bacteria.
4 Many preservatives have antibacterial and some antifungal activity (i.e. Isothiazolinones/Formaldehyde) It does not imply that an antifungal agent (i.e. Parabens/Glycacil) is always required.
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-10 0 10 20 30 40 50 60 70 80 90 100°C
Psychrophiles
Mesophiles
Thermophiles
Yeasts
Molds
Temperature
Body temperature- most human pathogens grow best at 37oC
Other Ingredients Impacting Preservation
Positive Ingredients
�Alcohol (i.e. Ethanol > 20% level required to be self-preserving)
�Chelating agents – Disodium EDTA�Active Ingredients - (i.e. Salicylic Acid, Triclosan, Zinc
Pyrithione)Potentially Negative Ingredients
�Quality of Raw Materials – Increased demand on Preservative
�Growth Promoting - Natural Extracts/Glucose�Certain ingredients can inactivate preservatives, such
as, sunscreens, anionics, and starch.
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Importance of Chelating Agents
• EDTA can improve the performance of some preservatives against microorganisms. �Believed to weaken cell envelope by removing
magnesium ions�May permit preservative to enter cell more easily and
attack cellular target
�Chelating agents can improve efficacy of preservatives against Gram negative organisms such as B.cepaciaand P.aeruginosa.
• Recommend incorporating a chelating agent into product formulation to strengthen the preservative system.
AddEDTA
AddEDTA
LPS of outer membrane Inner membrane
calcium and magnesium ions stabilize the outer and i nner membranes of Gram negative cells
- this helps protect them from preservatives
EDTA chelates calcium and magnesium which destabili zes the cell membranes
- helping preservatives to attack the cell
EDTA WILL NOT WORK IN FORMULATIONS WITH HIGH LEVELS OF Ca or Mg
How EDTA Enhances Preservative Activity
Normally LPS excludes preservatives but up to 40% of LPS molecules lost following EDTA treatment
Loss of Ca/Mg increases repulsion between negatively charged phospholipids - making it easier for preservatives to enter the cell
Preservative Preservative
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Preservative Selection – Additional Considerations
�Legal Restrictions
�Company Restrictions
�PR Restrictions
Preservative Selection – Legal
Approvals Documentation
European Union (EU) Pre-approves preservatives and publishes a positive list known as Annex VI
China Hygienic Standard for Cosmetics (version 2007/01) issued by China Ministry of Health (MOH).
Canada Publishes a hotlist of ingredients that are either prohibited or restricted
Japan Publishes a positive list (restrictive and classifies approvals based on the end use of the cosmetic
United States FDA has a list of prohibited or severely restricted ingredients
Microbiologists need to be aware of the restrictions on preservativesWhen providing recommendations to Chemists/Formulators!
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Preservative Selection - Legislation
May require additional testing (i.e. Shelf life jus tification)• Europe : Period After Opening (PAO) – Requires that
all cosmetics with a shelf life of < 30 months must have a best used by date on the label.
• US (FDA Regulations) – All cosmetics need not be sterile but they must not contain microorganisms that are pathogenic and the density of non-pathogenic must be low in the product formulation and remain at low levels for the anticipated product shelf life.
• Products must be tested for microbiological quality before being released to the trade.
• Products must be tested for preservative efficacy during the product development process.
Preservative Selection – Public Relations (PR)
� Every preservative is fighting some degree of public scrutiny!
� All preservatives have a restriction/issue somewhere in the world!
� Based on level (dose) restrictions, product type (rinse off, leave on, baby categories, mucous membrane), even differences within a chemical family (isothiazolinones, parabens)
� Microbiologists should consult with Regulatory to be aware of the latest views on the preservatives they are recommending to Formulators.
� The legal and regulatory landscape is constantly changing so be “aware”.
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Preservative Selection Compatibilities – pH and Temperature of Addition
Preservative pH Temperature
Parabens 3-8 Add at emulsification temperature (75-80°C) to water phase
Benzoic Acid < 5.5 Typically added to water phase and added early to facilitate mixing
DMDM Hydantoin 3-9 Stable up to temperatures of 80°C*At temperatures exceeding 80°C, preservative will break down and release formaldehyde
MCI/MI < 9.0 Add in cool down phase< 50°C
Phenoxyethanol 3-10 Often added with Fragrance, Stable up to 85°C
Ref. David Steinberg, Preservatives for Cosmetics, Second Edition, Allured Publishing, 2006
MCI/MI – Methylchloroisothiazolinone and Methylisothiazolinone
Ingredients that have an Impact on PreservationIngredients that have an Impact on Preservation
Preservative Absorbers� Kaolin� Silica� Talc� Titanium Dioxide
Preservative In-activators�Cellulose gum�Alkaline pH�Lecithin�Over-heating�Non-ionics e.g.. Polysorbates�Xanthan gum
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Preservative Neutralizers and In-activators
Preservative Neutralizers and In-activators
Parabens� Lecithin, Non-ionic surfactants, polysorbate, gums,
alkaline pH, polyethylene glycolAlcohols
� Gums, non-ionic surfactants, especially TweensMCI/MI
� Bisulfites, secondary amines, strong nucleophiles� ZPT is not compatible with MCI/MI
Phenolic and Chlorophenolic Compounds� Polysorbate 80, Non-ionic surfactants, proteins� Carboxymethylcellulose, polyethylene glycols,� lecithin
Organic Acids� Neutral -> Alkaline pH, non-ionic surfactants, CaCl2,
Tweens� Formaldehyde Donors
� Incompatible with Parsol 1789
Preservative Neutralizers and In-activators
Preservative Neutralizers and In-activators
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Preservative Selection - Stability
Temperature• Is it stable for life time of product?
• Take account of countries it will be used in• Is it stable for distribution?
• Take account of distribution, especially if global or into hot tropical regions
UV Stability• Does preservative need to be UV stable
• Transparent Packaging
Preservative Selection - Partitioning
The preservative must be active in the aqueous phase of a formulation to be microbiologically effective and functional.
Some preservatives can partition between the aqueous and oil phase leaving a sub-optimal amount in the aqueous phase.
Preservatives with a preference for oil phasePhenoxyethanol, Benzyl Alcohol, Benzoic acid and Parabens
Preservative challenge testing is critical to demon strate effectiveness
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Preservative Selection - Cost
What is the most cost effective way to ADEQUATELY preserve the formulation?• Do NOT over preserve• Do NOT operate at the cliff edge
Never chip away at preservative levels to achieve c ost savings!
Preservative Selection - “Factory History/Standards”
� Need to consider where the product will be manufactured
� High risk products should NOT be made on plants with poor hygiene standards
� Consider any historical “in-house” bugs
� If known “in-house” bugs, consider incorporating them into challenge test inoculum as a separate pool
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Sub Lethal Levels of Preservative
Microorganisms are populations of individual cells• A small number of cells will be a little more resistant to
preservatives then the rest of the population.
It is extremely important that a sub lethal level o f preservative is not used in a formulation• Sub lethal levels select for the less susceptible organisms
increasing the risk of a contamination problem. • i.e. selects for organisms that are expressing resistance traits • e.g. using too low a level of formaldehyde donor can select resistant
microbes that express high levels of formaldehyde dehydrogenase)
• Can lead to growth of resistant microbes in a product and can lead to failure of the preservative, even if it is subsequently used at the correct dosage levels (because microbes have become resistant).
Consumer Use - Key Points
How is product used by the Consumer? (Habits/Practices/Frequent Abuse!)
• What are the risks of introducing contamination by the consumer?
• Creams - Direct Consumer Contact with Product
• Dilution of Product with Water
• Environmental contamination risk
• Is a Broad Spectrum Preservative Required?• Confirm choice by preservative challenge test• Confirm ability of formulation to resist contamination by
running consumer use studies (i.e. novel formats, low water personal care products, high risk formulas)
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Consumer Use
Restricted Access Packaging (i.e. Eye Creams Packag ed in Tubes): Low introduction of contamination during use• Low level dust from air
Shampoo: Water enters product during use in shower• Design of Packaging and Packaging Closures
Important ConsiderationsSkin Creams: Consumer touches product in primary
container during use• Design of Packaging and Packaging Closures
Important Considerations • Wide mouth jars present increased risk
Increasing Demand
On form
ula preservative system
Real Life Experience
Formulation needs a preservative until determined otherwise
If not sure it needs a preservative, it needs preservation
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Microbiologist “Thought Process”
1. Does formulation require a preservative?
2. If yes, use knowledge/experience to design an appropriate preservation system for the product• Type Preservative (required spectrum of control)• Level of Preservative
• Avoid using sub lethal levels
3. Validate your choice in a challenge test
Do NOT over Preserve but do NOT operate at the clif f edge. The challenge is getting the balance right!
Preservative Challenge Testing/Evaluation
Challenge Testing: What are the objectives?• Assess the preservative capacity of a formulation• Simulate the risk (repeat inoculation recommended ) of
contamination during;• Manufacturing
• Product Shelf Life
– Can perform preservative analytical tests to confirm preservative stability and efficacy
Recommend contacting supplier for method/advice
• Consumer (normal) use
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Challenge Tests - Limitations
Can be a very good tool to differentiate between preservative systems
Can the test predict how formulation will behave in the manufacturing or under consumer use?
Microbiologist should consider the following: • Potential for dilution in use• Consumer instructions for use
• i.e. consumer instructed to dilute with water prior to use• Design of Final Packaging • Limited number of microorganisms tested
– In nature, organisms exist as a mixed biofilm
Microbiologists need to be aware of limitations!
Common Statement
During an Incident - “But the product passed a challenge test”
Response - “All products in production should have passed a challenge test”
Preservation alone does not ensure microbiological quality
No preservative protects a product against a substa ntial failure in GMPs
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Distribution
• If global supply chain, consider hygienic risk of extended distribution channels
• If shipping product across tropical areas, the risk of contamination to primary or secondary packaging will increase
• Assess hygiene risk if product is distributed in shipping containers
Other Points to consider include:• Stability of preservative system (temperature dependent)
within the distribution system• Risk of mold growth on pallets
Distribution - Mold
� Materials made of cellulose are vulnerable to mold growth.
� Mold growth is favored in damp, high humidity conditions. � These conditions can occur in distribution or while the
product is stored in the consumers home. � The design of the product itself can also result in a local
high humidity environment.
Top side of paper cartridge
Mold growth on PE laminate
Bottom of papercartridge
Bottom of primarycontainer
Mold growth around the edgeof PE laminated paper
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Summary of Preservative Selection Parameters
EfficacyTarget ConsumerCostWater Activity and Formula pHFormula Compatibility and StabilityFactory Hygiene StatusPackagingRegulatory RequirementsPublic Relations IssuesSensitive Skin etc… – Mildness ClaimsChelating Agent AdditionProcessing – Temperature restrictions
In Conclusion
Successful preservation of personal care products involves knowledge of:
� Formulation and ingredients, including pH� Ability of the unpreserved base to support the grow th
and replication of microorganisms � Regulations and PR issues about the preservatives
under consideration� Target consumer and consumer use habits� Manufacturing facility where the product will be ma de� Intended life cycle of the product, including distr ibution
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Thank you for your attention
Contact Information:
Deidre L. Mitchell
Email: [email protected]
Telephone: 203-381-5377