alternative preservatives
DESCRIPTION
SCC Ontario Education Day. Alternative Preservatives. R. Nunez/ Lonza Inc./ Sept. 2006. Outline. Why Preservatives? Conventional Alternatives Preservatives Today: Where are we? Preservative Trends Global Regulatory Overview Conventional Preservatives Profiles - PowerPoint PPT PresentationTRANSCRIPT
Alternative Preservatives
SCC Ontario Education Day
R. Nunez/ Lonza Inc./ Sept. 2006
slide 2
Outline Why Preservatives?
Conventional Alternatives
Preservatives Today: Where are we? Preservative Trends Global Regulatory Overview Conventional Preservatives Profiles
Alternative Preservative Approaches Ingredients with Antimicrobial Activity Other Preservative Alternative Approaches
Conclusions
slide 3
Why Preservatives By Definition, Used to Prevent Growth of Microorganisms in a
Cosmetic product… A substance intentionally added to a cosmetic product for the
primary purpose of inhibiting the development of microorganisms.
Help Prevent Microorganism Growth During Manufacturing…But Not a Substitute for GMP
Primarily Designed to Prevent Microorganism Growth After Product Sale to Consumers
Therefore… Preservatives Must be Toxic to Microorganisms but Be Safe for Humans
slide 4
Without Preservatives
Risky Business
Product Spoilage, Recalls
Health, Infection Issues
Formulating Without a “Safety Net”
slide 5
With Preservatives
Preserved Formulations
Low Cost “Insurance”
Tradeoff between Preservation and Formulating Issues
Need Preservative Potency, Compatibility and Stability
slide 6
Cosmetic Preservatives History
Pre-1900: Sodium Benzoate, Phenol, Cresol 1920’s: Parabens, Formaldehyde 1940’s: Alcohols, Phenoxyethanol 1960’s: Staph Outbreak from Hospital Hand Lotions -
Changed Attitude towards Preservatives 1960’s: Formaldehyde Studies, Concerns 1970’s: Imidazolidinyl Urea, DMDMH, Bronopol 1970’s: FDA Surveyed Cosmetics, Found 24%
Contaminated 1980’s: Diazolidinyl Urea, Isothiazolinones 1990’s: Blends Introduced, e.g. DMDMH/ IPBC 2000’s: Blends, Naturally-Derived Today: Acute Perception Issues, Fragmented Market
slide 7
What Preservatives Do We Use Today?
2003 2001
Methylparaben 7161 6893
Propylparaben 5809 5621
Butylparaben 2326 2174
Imadazolidinyl Urea 2038 2025
Ethylparaben 1725 1451
Phenoxyethanol 1670 1480
DMDM Hydantoin 993 943
Diazolidinyl Urea 725 701
MCI/ MI 699 595
Quaternium-15 516 505
Triclosan 451 462
slide 8
“Conventional” Preservative Takeaways
All These Commonly Used Preservatives have Limitations
All are Classified as “Conventional” Preservatives and Are Approved by Regulatory Bodies Globally
All Have Been Used for Many Years…..Long Histories and Experiences
All Have Been Found to be Safe and Effective for Use as Directed
And Many are Under Some Sort of Pressure
slide 9
Why “Alternative” Approaches?
Attempt to Meet Varied Real and Perceived Needs
Address an Increasingly Fragmented and Confusing Cosmetics Preservatives Market
Address Customer and Retailer Perception Issues
Simplify Formulating – Less Raw Materials/ Testing Required
Allow Global Use of Simplified Systems
However…..
slide 10
Is the Perfect “Alternative” Preservative Possible?
Water Soluble
Colorless and Odorless
Cost-Effective
Widely Compatible
Globally Approved
Available for Use Today…..
slide 11
Why Is It So Difficult? Regulatory Barriers
Few Ingredients Acceptable in All Regions
Formulation Barriers No Single Technology Works in All Types of Products
New Preservative Molecules Unlikely Due to Cost, Time and Data Requirements vs. Market Size INCI-Listed, Multi-functional Approaches are Best Bets
“Alternatives” Effectiveness… Are They Potent Enough? Can They Replace “Conventional” Approaches?
Preservatives Today: Where Are We?
slide 13
What Drives Preservative Choice? Formulation Type
Effectiveness in the Formulation
Use Cost in the Formulation
Preservative Safety / Perception / Acceptance
Compatibility / Stability with Other Ingredients
Global Regulatory Approvals
slide 14
Today’s Preservative Trends Regulatory Changes Driving Preservative Choices
Many Traditional Materials Being Challenged Increase in Restrictions, Perception Issues
Increase Preservative System “Safety” But… Maintain Efficacy Ensure Formulation Compatibility
More Preservative Studies, Publications, “Pressures”
Naturally-Derived and Blended Preservatives, Use of Potentiators
Confusing Array of “Alternative” Preservative Approaches
slide 15
Global Regulatory Overview (1) NAFTA
Widest Range of Approved Preservatives Parabens, Formaldehyde Donors, Isothiazolinones, Acids,
Alcohols, etc.
Europe Positive List, Difficult Approval Process,… Plus Green Groups Close to NAFTA in General, But More Constraints Most Preservative “Controversies” Start in Europe
Japan Positive List, Longest and Most Difficult Approval Process No Formaldehyde Donors, Other Constraints
slide 16
Global Regulatory Overview (2)
Other Countries Brazil, Australia, Korea, China Many Driven by US or Europe Gets Complicated……Seek Regulatory Assistance
Conventional Preservatives Profiles
slide 18
Parabens Profile
Target Organisms: Fungi Mode of Action: Nutrient Transport Applications: Rinse-offs, Leave-ons Wide Global Acceptance, Long Use History Typically Blended (methyl, propyl, butyl, ethyl) / Combined with
Bactericides Recent Controversy – Study Results, Perception Issues Formulating Tips
Low Water Solubility Polysorbates/ PE pH range: 3.5 – 6.5 0.1 – 0.8% as Active
slide 19
Formaldehyde Releasers Profile
Target Organisms: Bacteria Mode of Action: Denatures Proteins Applications: Rinse-offs, Most Leave-ons Limited Approval in Japan Imidazolidinyl Urea, Diazolidinyl Urea, DMDM Hydantoin,
Quaternium-15 Recent Controversy: Gas vs. Liquid Formaldehyde measurement Formulating Tips
Highly Water Soluble High Temperatures, Reducing Agents pH range: 3 - 10 0.1 – 0.5% as Product
slide 20
Alcohols Profile
Target Organisms: Bacteria Mode of Action: Denatures Proteins Applications: Rinse-offs, Leave-ons Wide Global Acceptance Phenoxyethanol, Benzyl Alcohol, Ethyl Alcohol, Usually Combined
with Fungicides Formulating Tips
Highly Water Soluble May Impact Viscosity May Add Odor pH range: 3 - 10 0.5 - 1% as Active
slide 21
Isothiazolinone Profile
Target Organisms: Bacteria and Fungi Mode of Action: Disulfide Linkage With Cell Wall Proteins Applications: Rinse-offs, Some Leave-ons Wide Global Acceptance (BIT has Limited Approvals) Chloromethlyisothiazolinone, methylisothiazolinone,
benzisothiazolinone – CMI/ MI Most Common Blend Formulating Tips
Sensitizations Issues Add at <50°C Primary Amines, Sulfites pH range: 2 - 8 Up to 15 ppm Active R/O
slide 22
Acids Profile
Target Organisms: Fungi Mode of Action: Denatures Proteins Applications: Rinse-offs, Leave-ons Wide Global Acceptance Sorbic, Benzoic, Salicylic, Dehydroacetic, Boric, Citric (and salts) Typically used in combination with a bactericide Formulating Tips
Low Water Solubility (acid forms) Add at <50°C Primary Amines, Sulfites pH range: <6 Up to 0.5% as Free Acid
slide 23
IPBC Profile
Target Organisms: Fungi Mode of Action: Nucleophilic Reaction with Thiols, Amines in Cell Applications: Rinse-offs, Leave-ons Wide Global Acceptance Available in Surfactant, Water or Solid Carriers – not sold as 100% Typically used in combination with a bactericide Recent Controversy: EU Dosage Levels and Applications Formulating Tips
Low Water Solubility Reducing Agents pH range: Up to 9 0.05 – 0.1% as Active
slide 24
Other Conventional Preservatives Bactericides
Benzalkonium Chloride Benzethonium Chloride Chlorophenesin Methyldibromo Glutaronitrile Sodium Hydroxymethylglycinate Thimersal Triclosan Triclocarbon
Fungicides Glutaral Zinc Pyrithione Zinc Oxide
slide 25
Top Global Choices
Goal: Broad Spectrum, Global As Possible Blends Acids – Benzoic, Citric, Dehydroacetic, Salicylic, Sorbic Alcohols – Phenoxyethanol, Benzyl, Ethyl Formaldehyde Donors – Imidazolidinyl Urea, DMDMH, DI Isothiazolinones – MI, CMI Parabens – Methyl, Propyl, Butyl, Ethyl Many Blends are Patented or Proprietary
Phenoxyethanol + IPBC Formaldehyde Donors + IPBC Phenoxyethanol + Parabens Acids + Alcohols + Quats
slide 26
Examples of Blended Preservative Systems
Pert Shampoo (P&G) CMI + MI
Herbal Essences Shampoo (Clairol / P&G) DMDMH + IPBC
Nivea Visage Cream (Beiersdorf) Phenoxyethanol + Diazolidinyl Urea
Plenitude Facial Lotion (L’Oreal) Imidazolidinyl Urea + Parabens
Head-to-Toe Baby Cleansing Cloths (J&J) Phenoxyethanol + Parabens + Citric Acid
Alternative Preservative Approaches
slide 28
Alternative Approaches Alternative Ingredients
Naturals Glycols Glycerins Antioxidants Surfactants Potentiators
Alternative Non-Ingredient Approaches Water Activity pH Adjustment Raw Material Specifications Plant GMP Package Design
A cosmetic Ingredient is NOT a Preservative if: It’s NOT on Europe’s Positive List It’s NOT on Japan’s Positive List It has an INCI Name Claiming Another Function It Helps Create a More Hostile Formulation Environment
slide 29
Create a Self-Preserving Environment
Use Ingredients and Essential Oils that have Antimicrobial Properties but are NOT classified as Preservatives
Create an Environment that is Unfavorable to Microbial Growth either through
substituting alternative chemistries lowering water activity changing pH increasing alcohol, surfactant, other ingredient levels
Ensuring that the product is manufactured under GMP conditions Use a Package that minimizes introduction of microbes into mass Minimize incoming ingredient bioload
Alternative Ingredients with Antimicrobial Activity
slide 31
Natural Ingredients
Many on the market Used in Combinations or with Traditional Preservatives
Addresses Growing Natural Trend, but Difficult to Execute
Typically Have Multi-Functionality and INCI Listed
Often have Odor, Color and Allergen Issues
Tend to be Organism-Specific, not Broad Spectrum
slide 32
Natural Ingredients (2)
Grapefruit Seed Extract Bactericide Activity may be due to Other Ingredients introduced during
processing
Gluconolactone Bactericide Moisturizer
Tea Tree Oil Bactericide Humectant
slide 33
Natural Ingredients (3)
Usnic Acid Mostly Gram positive Bactericide May impart blue color to products
Neem Seed Oil Bactericide May impart color and odor to products
Other Oils and Extracts Cinnamon, eucalyptus, lavender, lemon, rosemary, thyme,
honeysuckle…..
Challenge Test, Ensure Compatibility
slide 34
Glycols
Possess Humectancy and Potentiation
Propylene, Butylene Glycol (6.0%) Improves solubility and product stability Reduces oil/water partitioning Assists in preservation, lowers water activity
Hexylene, Pentylene Glycol (2.0%) Preservation Efficacy
Caprylyl Glycol (1.0%) Preservation Efficacy
slide 35
Caprylyl Glycol
Some Broad Spectrum Activity
Often used in Combination with Phenoxyethanol, Other Preservatives
Wide Global Approval
Compatible with Most Formulation Types
Some reports of Irritation when used in combination with other glycols
slide 36
Ethylhexylglycerin
Similar to Other Glycerins Activity against most Gram Positive Species Lowers Water Activity
Often used in Combination with Phenoxyethanol
Wide Global Approvals
Compatible with Most Formulation Types
Some reports of Irritation when used in combination with other ingredients
Good Humectant Properties
slide 37
Antioxidants
BHA, BHT, Propyl Gallate, t-Butyl Hydroquinone, Tocopherol All Provide Varying Benefits, Mainly as Formulation Stabilizers
Sodium Sulfites Technically are Preservatives Strong Reducing Agents Stabilizer for Other Ingredients
Sodium Erythorbate Isomer of Vitamin C Strong Reducing Agent GRAS, wide use in food industry
slide 38
Other Ingredients with Antimicrobial Activity
Lauricidian Surfactant Effective Against Gram Positive Bacteria Sometimes combined with Lactic Acid and EDTA
Biosurfactants Activity against Pseudomonas
Fragrances and Fragrance Mixtures
Enzymes, Phospholipids, Mono-Esters
slide 39
Potentiators: Multifunctional EDTA
Chelating Functionality Improves Preservative Performance
Has Activity against Pseudomonas
Helps Prevent Resistance to Antimicrobials
Helps Stabilize Color and Fragrance, Control Fading
Other Chelators/ Potentiators Include: HEDTA, DTPA, Etidronic Acid
Other Preservative Alternative Approaches
slide 41
Water Activity
Definition: A measure of water’s energy status in a system, aw. “Bound” water is not available for microorganism growth.
Microorganisms need “free” water within a product to survive and proliferate
Water activity and not water content is a better measure of the free water
Pure water has aw of 1.0, typical shampoo 0.96
Goal: lower water activity = less preservative!
slide 42
Water Activity Requirements
0.95 - 1.0 Gram Negatives
0.90 - 0.95 Staphylococci
0.87 - 0.90 Common Yeast
0.80 - 0.87 Common Mold
0.65 - 0.75 Xerophilic Mold
0.60 - 0.65 Osmophilic Yeast
Therefore…lower aw, create a more hostile microbe
environment
slide 43
Water Phase pH
Knowing the optimum pH for each of your preservatives is important in using preservatives effectively
Extreme pH’s can have an inhibitory affect on bacteria, yeast and mold
By using a combination of pH and Water Activity control, you are creating an environment which is hostile to microbial growth
slide 44
Water Phase pH Impact on Preservatives
Methyl Paraben Optimum pH 3.5 - 6.5 Generally poor activity >7.0
Organic Acids Optimum pH <6.0 Generally poor activity >7.0
Phenoxyethanol, Formaldehyde Releasers Not affected by pH
slide 45
Raw Material Specifications
Ensure that incoming raw materials are as clean as possible to minimize bioburden
Recommended <100 cfu per gram
Ensure that the water system is checked frequently and is free of bacteria
Consider it a critical “raw material” with specifications Beware of biofilm buildup in your holding tank, pipes and
valves Use hot water when possible
slide 46
Good Manufacturing Practice (GMP)
Ensure that the manufacturing tanks and filling lines are properly cleaned and sanitized
All transfer lines and storage tanks are properly cleaned and sanitized
That stored product is tested before filling and that partial drums are not returned to the warehouse
slide 47
Product Package Design
Package design can play a big role in minimizing contamination once in the hands of the consumer
It can act as a physical barrier to the external environment
Examples include: One way valves Pressurized components Airless tubes, sealed tops Unit dose packaging
slide 48
Conclusions
The Cosmetic Preservative Market Will Continue to Fragment
Regulations and Perception Will Continue to Drive Conventional Preservative Choices, Particularly as More Studies are Published
There is No Conventional or Alternative Preservative “Holy Grail”. The Market Will Mix and Match Preservatives to Meet Product Needs.
“Alternative Approaches” Should Focus on Creating as Hostile and Self-Preserving an Environment as Possible
There are Many Alternative Ingredients Available in the Market, as Reviewed. Most Have Unique, But Limited, Applicability.
There are Many Non-Ingredient Approaches Possible, Such as Water Activity Reduction, Which Can be Used Widely to Improve the Self-Preserving Environment
slide 49
Acknowledgements
My Thanks to the Following Colleagues and Groups forTheir Input and Support in Creating this Presentation
Lonza Teammates: Carl Cappabianca, Crystal Arlea
David Steinberg: Steinberg & Associates
Steve Schnittger: Estee Lauder
SCC Ontario Chapter
The CTFA Microbiology Committee