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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
Alternative Preservative Approaches

Ingredients with Antimicrobial Activity

Other Preservative Alternative Approaches
Conclusions
slide 2
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 3
Without Preservatives

Risky Business

Product Spoilage, Recalls

Health, Infection Issues

Formulating Without a “Safety Net”
slide 4
With Preservatives

Preserved Formulations

Low Cost “Insurance”

Tradeoff between Preservation and Formulating Issues

Need Preservative Potency, Compatibility and Stability
slide 5
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 6
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 7
“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 8
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 9
Is the Perfect “Alternative” Preservative
Possible?

Water Soluble

Colorless and Odorless

Cost-Effective

Widely Compatible

Globally Approved

Available for Use Today…..
slide 10
Why Is It So Difficult?

Regulatory Barriers


Formulation Barriers



Few Ingredients Acceptable in All Regions
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?
slide 11
Preservatives Today: Where Are We?
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 13
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 14
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 15
Global Regulatory Overview (2)

Other Countries

Brazil, Australia, Korea, China

Many Driven by US or Europe

Gets Complicated……Seek Regulatory Assistance
slide 16
Conventional Preservatives Profiles
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 18
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 19
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 20
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 21
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 22
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 23
Other Conventional Preservatives


Bactericides
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Benzalkonium Chloride

Benzethonium Chloride

Chlorophenesin

Methyldibromo Glutaronitrile

Sodium Hydroxymethylglycinate

Thimersal

Triclosan

Triclocarbon
Fungicides

Glutaral

Zinc Pyrithione

Zinc Oxide
slide 24
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 25
Examples of Blended Preservative Systems

Pert Shampoo (P&G)


Herbal Essences Shampoo (Clairol / P&G)


Phenoxyethanol + Diazolidinyl Urea
Plenitude Facial Lotion (L’Oreal)


DMDMH + IPBC
Nivea Visage Cream (Beiersdorf)


CMI + MI
Imidazolidinyl Urea + Parabens
Head-to-Toe Baby Cleansing Cloths (J&J)

Phenoxyethanol + Parabens + Citric Acid
slide 26
Alternative Preservative Approaches
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 28
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
slide 29
Alternative Ingredients with Antimicrobial Activity
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 31
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 32
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 33
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 34
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 35
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 36
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 37
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 38
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
slide 39
Other Preservative Alternative Approaches
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 41
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 42
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 43
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 44
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 45
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 46
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 47
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 48
Acknowledgements
My Thanks to the Following Colleagues and Groups for
Their 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
slide 49