summary of research and development studies - triple s · summary of research and development...

© Skinvisible Pharmaceuticals, Inc. 2005

Summary of Research and Development Studies

A Skinvisible patented technology product This document is an overview of independent laboratory studies sponsored by Skinvisible Pharmaceuticals, Inc. We believe that these results demonstrate not only the superiority of the Protec-4™ Antimicrobial formulation, but also reveal the vast potential of the Invisicare® family of polymers as a topical delivery system for other active ingredients.

Written in Microsoft Word 2003, this document represents a condensed version of results, laboratory methods, protocols and final reports that were issued by the independent laboratories listed in chapter 9. These documents are covered by US copyrights in addition to the copyright by Skinvisible Pharmaceuticals, Inc.

Table of Contents © Skinvisible Pharmaceuticals, Inc. 2005

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Table of Contents

Chapter 1: Antimicrobial Efficacy and Performance Study 3 Chapter 2: Antiviral Performance Study 10 Chapter 3: Skin Sensitivity Study 12 Chapter 4: In Vivo Hand Wash Evaluation Study 14 Chapter 5: Persistence Study 19 Chapter 6: Impermeability Study 22 Chapter 7: FHSA Acute Oral Toxicity Study 25 Chapter 8: Invisicare® Polymer Delivery Technology 26 Chapter 9: Participating Independent Laboratories Profiles 29 Chapter 10: Protec-4™ Binding When Exposed to Alcohols 35

Chapter 1 - Antimicrobial Efficacy & Performance Study © Skinvisible Pharmaceuticals, Inc. 1999

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ANTIMICROBIAL EFFICACY AND PERFORMANCE STUDY Purpose of Study: The purpose of the study was to determine the effectiveness of the Protec-4™ Antimicrobial Skin formulation as a useful adjunct in the food handling and health care working environments to eradicate pathogenic organisms on contact with treated skin. For purposes of this discussion “treated skin” refers to skin treated With Protec-4™ Antimicrobial Skin formulation. Agar Patch Studies:

Testing Laboratory: BIOSCIENCE LABORATORIES, INC. (COMPANY) 300 North Willson, Suite 1 Bozeman, Montana 59771-0190 Daryl S. Paulson, Ph.D. - CEO and Associate Study Director Terri Eastman - Principal Study Director Michael Douthit - Associate Study Director All studies conducted by BioScience Laboratories, Inc., follow Good Laboratory Practices (GLPs) and utilize methods from AOAC, the FDA’s Tentative Final Monograph (TFM), and the Healthcare Continuum Model of the Cosmetics, Toiletries and Fragrances Association (CTFA) and the Soap and Detergent Association (SDA). In addition, BioScience Laboratories, Inc. maintains active membership and involvement in a number of scientific organizations including: the American Society for Testing and Materials, American Society for Microbiology, American Society for Quality, Society for Quality Assurance, American Practitioners in Infection Control, and American Association for the Advancement of Science.

In Vivo Protocol: Human In these studies, the antimicrobial efficacy and persistence of the Protec-4™ Antimicrobial formulation was examined utilizing the Agar Patch Technique. These agar button patches (approximately 1” in diameter) were inoculated with a known count of specific challenge microorganisms. The challenge organisms chosen for the test protocols were carefully selected as those organisms of most interest to the food supply system and health care personnel use as defined by the HealthCare Continuum Model (HCCM) proposed in 1995 by the CTFA and SDA as a comprehensive model to address public and professional use of topical antimicrobial products in these respective workplaces. The patches were then applied to the skin at 10 minutes, 2 hours and 4 hours following application of the Protech-4™ Antimicrobial formulation for one (1) minute and five (5) minutes to reflect more accurately the working environments of food handling and health care, and then allowed to further incubate for up to 48 hours. The agar patches were subsequently examined for bacterial growth and should any survival of microorganisms be noted, the colonies were counted and noted as Log10


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reductions or increases from the baseline state prior to application to the treated skin. All studies were carried out with cohort controls to ensure accuracy.

The following tables summarize the results following contact times at 10 minutes, two (2) hours and four (4) hours post application on treated skin.

Reduction Summary of Klebsiella pneumoniae ATCC #10031 log10 Values

Sample Sample Size

Baseline Log10

Post ProductLog10

Log10 Reduction

Percent Reduction

Immediate 10 2.41 0.00 2.41 99.99%

2 Hour 10 2.28 0.45 1.83 98.52%

4 Hour 10 2.35 1.45 0.90 87.41%

Reduction Summary of Staphylococcus aureus ATCC #6538 log10 Values

Sample Sample Size

Baseline Log10

Post ProductLog10

Log10 Reduction

Percent Reduction

Immediate 10 2.71 0.03 2.68 99.79%

2 Hour 10 2.63 0.39 2.24 99.42%

4 Hour 10 2.62 1.01 1.61 97.55%

Reduction Summary of Staphylococcus epidermidis ATCC #12228 log10 Values

Sample Sample Size

Baseline Log10

Post ProductLog10

Log10 Reduction

Percent Reduction

Immediate 10 2.46 0.00 2.46 99.65%

2 Hour 10 2.50 0.36 2.14 99.28%

4 Hour 10 2.19 1.36 0.83 85.21%


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Reduction Summary of Escherichia coli ATCC # 11229 log10 Values

Sample Sample Size

Baseline Log10

Post ProductLog10

Log10 Reduction

Percent Reduction

Immediate 10 2.41 0.14 2.27 99.46%

2 Hour 10 2.34 1.81 0.53 70.49%

4 Hour 10 2.39 1.97 0.42 61.98%

In-Vivo Agar Patch Study Summary

0

10

20

30

40

50

60

70

80

90

100

Klebsiellapneumoniae #10031

Staphylococcusaureus # 6538

Staphylococcusepidermidis #12228

Escherichia coli#11229

Microorganism Tested

Perc

ent R

educ

tion

Immediate

2 Hours

4 Hours

In Vitro Protocol: Pigskin The remainder of the test organisms were carried out using a pigskin substrate model. In this study, inoculated agar patch plates with specific test challenge microorganism species were applied to the fresh samples of treated pigskin and allowed to remain in contact for one (1) minute and five (5) minutes. The Log10 reduction of each microorganism from the control plates (inoculated agar patch plates exposed to untreated pigskin) was calculated.


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The following Table summarizes the results of kill for one (1) minute contact times for the In Vitro test organisms.

Microorganism Species

ATCC #

Incub. Time

Media Percent

Reduction at 1 min

Enterococcus faecalis MDR/VRE 51299 16 - 48 hours TSB/TSA 100 %

Listeria monocytogenes 7644 16 - 48 hours TSB/TSA 100 %

Salmonella typhi 6539 16 - 48 hours TSB/TSA 100 %

Staphylococcus aureus MRSA 33592 16 - 48 hours TSB/TSA 100 %

Staphylococcus pyogenes 19615 16 - 48 hours BHIB/BHIA 100 %

Clostridium perfringens 13124 16 - 48 hours RCM/RCA 100 %

Neisseria gonorrheae 49926 16 - 48 hours CHOC-XV 100 %

Shigella dysentariae Clinical Isolate

16 - 48 hours TSB/TSA 100 %

Vibrio vulnificus 27562 16 - 48 hours MAR 100 %

Bacillus cereus** 14579 16 - 48 hours TSB/TSA 100 %

**Bacillus cereus had a contact time of 5 & 30 minutes respectively. Simulated Infected Food Study:

In Vivo Protocol: Human In this study, subjects were subjected to hand contact with high-fat hamburger patties inoculated with Escherichia coli (ATCC #11229). The subjects were asked to knead hamburger patties inoculated with a known titer of the Escherichia coli and instructed to repeat this procedure for 5 cycles. A cycle was defined as a period of kneading, followed by a 2 minute wash and an air dry period. After cycle 1 and cycle 5, organism survival was measured utilizing glove juice sampling followed by culturing the glove juice for colony count. To further demonstrate the benefits of Protec-4™ Antimicrobial Skin formulation the following four subject subsets were used:

• Configuration 1: Protec-4™ Antimicrobial formulation applied to hands / wash with bland soap (no antimicrobial properties) • Configuration 2: Protec-4™ Antimicrobial formulation applied to hands / wash with antimicrobial soap • Configuration 3: wash with bland soap (no antimicrobial properties) • Configuration 4: wash with antimicrobial soap


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The following tables summarize the results of the above configurations:

Table I: Statistical summary of test configuration 1 (Protec-4™ Antimicrobial formulation and Bland Soap) log10 values

Sample SampleSize

Mean StandardDeviation

95.0% Confidence

Interval

log10 Reduction

from Baseline

Percent Reduction

from Baseline

Baseline 10 7.34 0.38 7.07 to 7.61 N/A N/A

wash 1 10 3.57 0.49 3.21 to 3.92 3.77 99.98%

wash 5 10 4.61 0.44 4.29 to 4.92 2.73 99.81%

Table II: Statistical summary of Test Configuration 2 (Protec-4™ Antimicrobial formulation and Antimicrobial Soap) log10 Values

Sample Sample Size

Mean Standard Deviation

95.0% Confidence

Interval

log10 Reduction

from Baseline

Percent Reduction

from Baseline

Baseline 10 7.19 0.54 6.81 to 7.58 N/A N/A

wash 1 10 3.76 0.56 3.35 to 4.16 3.43 99.96%

wash 5 10 3.94 0.41 3.65 to 4.23 3.25 99.94%

Table III: Statistical summary of Test Configuration 3 (Bland Soap) log10 Values

Sample Sample Size


95.0% Confidence

Interval

log10 Reduction

from Baseline

Percent Reduction

from Baseline

Baseline 10 6.76 0.39 6.48 to 7.05 N/A N/A

wash 1 10 4.27 0.57 3.86 to 4.68 2.49 99.68%

wash 5 10 4.62 0.49 4.27 to 4.97 2.14 99.28%


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Table IV: Statistical summary of Test Configuration 4 (Antimicrobial Soap) log10 Values

Sample Sample Size


95.0% Confidence

Interval

log10 Reduction

from Baseline

Percent Reduction

from Baseline

Baseline 10 6.67 0.68 6.18 to 7.16 N/A N/A

wash 1 10 4.44 0.53 4.06 to 4.82 2.23 99.41%

wash 5 10 4.46 0.77 3.91 to 5.01 2.21 99.38%

Summary Hand Wash Study

98

98.2

98.4

98.6

98.8

99

99.2

99.4

99.6

99.8

100

Invisicare + BlandSoap

Invisicare +Antimicrobial Soap

Bland Soap Antimicrobial Soap

Configuration

Perc

ent R

educ

tion

Wash 1

Wash 5

Results:

• Based on our studies of Protec-4™ Antimicrobial formulation and our prior experience in testing antimicrobial skin lotion products formulated under the FDA Tentative Final Monograph over-the-counter (OTC) Antimicrobial Topical Product Monograph, we believe the Protec-4™ Antimicrobial formulation to be a superior topical antimicrobial product in the following categories: It’s capabilities of demonstrating bacteriostatic and/or bactericidal effects

against a broad spectrum of test pathogens within one (1) minute of contact.

We note specifically these effects against organisms demonstrating

marked antimicrobial resistance to antibiotics such as Staphylococcus


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aureus MRSA, Enterococcus faecalis MDR/VRE, Vibrio vulnificus and Escherichia coli.

It’s capability of demonstrating skin persistence and ongoing antimicrobial

activity for the full test period of four (4) hours It’s capability under a simulated in-use food handling environment to

outperform antimicrobial hand wash scrubs alone in reducing Escherichia coli bacterial loads. We believe, as well, that on the basis of our other pathogen kill studies this product should perform equally effectively under comparable test conditions on a broad spectrum of other disease-causing pathogens in the food industry.

• In the hamburger study, in all cases where the Protec-4™Antimicrobial

formulation was utilized it performed exceptionally in antimicrobial effect on the test organism Escherichia coli (ATCC #11229) relative to the reference group where the lotion was not utilized.

• We note in fact that in the case where the Protec-4™ Antimicrobial

formulation was used with only the bland soap scrub (no antimicrobial properties), it performed significantly better than the antimicrobial scrub Without the aid of applied Protec-4™ Antimicrobial Skin Lotion.

• The uniqueness of the Protec-4™ Antimicrobial formulation appears to result

from the ability of the polymer constituents to reduce adhesion of bacteria and food molecules to the skin surface during hand washing. This factor alone will augment reduction of bacterial loads being transferred during the process of proper hand washing protocols.

• Our data indicate that use of Protec-4™ Antimicrobial formulation in the

health care environment in combination with proper hand washing techniques will augment the reduction of transient pathogens, important in nosocomial disease.

• Our data indicate, also, that use of Protec-4™ Antimicrobial formulation with

in the food handling environment in combination with proper hand washing techniques will more effectively reduce transient pathogens important in foodborne disease, with or without the ancillary use of gloves.

Note: This document is an excerpt taken from Chapter 6 of the “Report of The Scientific

Advisory Committee on The Skinvisible Line of Products”.

Chapter 2 - Antiviral Performance Study © Skinvisible Pharmaceuticals, Inc. 1999

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ANTIVIRAL PERFORMANCE STUDY: EX VIVO PIGSKIN SUBSTRATE Purpose of Study: Demostrate the viricidal efficacy of Protec-4™ Antimicrobial formulation on skin utilizing an ex vivo skin model. To accomplish this task the Protec-4™ Antimicrobial formulation was tested against the Human Immunodeficiency Virus (HIV) and Influenza A, representing the envelope viruses. Hepatitis A, Rhinovirus, and Rotavirus were also tested, representing the non-envelope viruses.

Testing Laboratory: VIROMED BIOSAFETY LABORATORIES / ATS Labs 6101 Blue Circle Drive Minneapolis, MN, 55343 Karen M. Ramm, B.A. Study Director Protocol: Utliziing a pigskin substrate as an ex vivo skin model, the Protect-4™ Antimicrobial formulation was applied to the pigskin. At post-application periods of ten (10) minutes, 2 (two) hours and 4 (four) hours, the viricidal capabilities of the Protec-4™ Antimicrobial formulation were assessed by allowing contact of live virus to the treated skin for one minute. The virus titer of the stock virus was determined by the median cell culture infective dose (TCID50). The virus-antimicrobial mixture was then assayed in numerous units of the host system. Results were recorded as the median value of log10-virus inactivation. Table 1: Viricidal Performance Results Summary

10 Min. Post Application

2 Hours Post Application

4 Hours Post Application

Virus Strain Log

Reduction Percent

Reduction Log

Reduction Percent

Reduction Log

Reduction Percent

Reduction HIV Type 1 HTLV-IIIB 3.00 99.90% 2.50 99.70% 2.50 99.70% Influenza A HK Type A2 4.25 99.994% 4.50 99.997% 4.00 99.99% Hepatitis A HM-175 0.25 43.80% 0.50 68.40% 0.25 43.80% Rhinovirus 151-1 Type 37 0.00 0.00% 0.20 36.90% 0.14 27.60% Rotavirus WA 0.14 27.60% 0.25 43.80% 0.00 0.00%

Chapter 2 - Antiviral Performance Study © Skinvisible Pharmaceuticals, Inc. 1999

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Graph 1: Viricidal Performance Summary

Viricidal Performance Study

0.00

10.00

20.00

30.00

40.00

50.00

60.00

70.00

80.00

90.00

100.00

HIV Type 1 Influenza A Hepatitis A Rhinovirus Rotavirus

Virus Tested

Perc

ent R

educ

tion

10 Minutes

2 Hours

4 Hours

Results: • Protec-4™ Antimicrobial lotion formulation demonstrated the ability to completely

inactivate HIV (Human Immunodeficiency Virus) and Influenza A upon contact for the test period over the four (4) hour post application period.

• Unable to demonstrate complete inactivation during the test period time for the non-envelope viruses tested including: Hepatitis A, Rhinovirus and Rotavirus, with percent inactivation ranging from 0.0% to 68.4%.

• A primary benefit of the Protec-4™ Antimicrobial formulation is its ability to resist

adherence of particulate matter. One of the most significant protective properties of the Protec-4™the ability to prevent adherence of viral particles, thereby reducing or preventing transmission of infectious particles.

Note: This document is an excerpt taken from chapter 7 of the “Report of the Scientific Advisory Committee on the Skinvisible Line of Products”.

Chapter 3 - Skin Sensitivity Study


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SKIN SENSITIVITY STUDY Purpose of the Study: Evaluate the Protec-4™ Antimicrobial formulation for its capacity to induce skin irritation or sensitization in users who require reapplication of the product over an extended period of time, and on an ongoing basis.

Testing Laboratory: CALIFORNIA SKIN RESEARCH INSTITUTE (CSRI) 15222-B Avenue of Science San Diego, CA 92128 Lawrence A. Rheins, Ph.D. - Investigator: Gin Chuang - Project Leader: In Vivo Protocol: Human A minimum of 30 human subjects were needed to complete the 21-Day Cumulative Irritation Test requiring twenty-one consecutive applications of each test article to the upper arms. Skin evaluations were made approximately twenty-four hours after the patch applications. Reactions were evaluated according to a numerical scale based upon the degree of erythema. At the conclusion of the patch applications, the subjects entered a Rest phase of 14 to 17 days. At the conclusion of the rest phase, the Protec-4™ Antimicrobial formulation was applied to naïve skin sites. Visual evaluations were conducted approximately 48 and 96 hours after patch application. Results: • There was no visible evidence of cumulative irritation (e.g. redness, swelling)

following 14 days of repeated exaggerated patch exposure of the Protec-4™ Antimicrobial formulation using industry standard predictive patch testing, an important result as the Protec-4™Skin formulation ideally will be used multiple times for long periods of exposure to the skin. Thirty-three (33) subjects completed the study.

• There was no visible evidence of sensitization (i.e. contact skin allergy) to the

Protec-4 ™ Antimicrobial formulation following industry standard the exaggerated predictive patch testing.

Test Articles: • Protec-4™ formulation: 0.1% triclosan topical antimicrobial formulation • Negative Control: 0.9% saline (NaCl in distilled water) • Positive Control: 0.1% SLS (sodium lauryl sulfate in distilled water)

Chapter 3 - Skin Sensitivity Study


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Table 1: Summary of findings from 21-Day Accumulative Skin Sensitivity Study

Test Article Total Group

Scores Class

(Base 10) Irritation Classification Protec-4™ 88.57 2 Probably Mild in Normal Use

Negative Control 31.14 1 No Experimental Irritation

Positive Control 511.14 4 Experimental Cumulative Irritant

Table 2: 21-Day Accumulative Skin Sensitivity Scoring Table

Scores Class Irritation Classification Description 0 - 49 1 Mild material

no experimental irritation Essentially no evidence of cumulative irritation under conditions of test

50 - 199 2 Probably mild in normal use

Evidence of a slight potential for very mild cumulative irritation under conditions of test

200 - 449 3 Possibly mild in normal use

Evidence of a moderate potential for mild cumulative irritation under conditions of the test.

450 - 580 4 Experimental cumulative irritant

Evidence of a strong potential for mild to moderate cumulative irritation under conditions of test.

581 - 630 5 Experimental primary irritant

Evidence of potential for primary irritation under conditions off test.

Note: This document is an excerpt taken from Chapter 7 of the Skinvisible Research

and Development CD.

Chapter 4 - InVivo Hand Wash Evaluation Study © Skinvisible Pharmaceuticals, Inc. 1999

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IN VIVO HAND WASH EVALUATION STUDY Purpose of Study: The study was performed to determine the effectiveness of Protec-4™ as a protective barrier in preserving skin health as compared to the effects of repetitive hand washing using a standard hospital antimicrobial soap.

Testing Laboratory: BIOSCIENCE LABORATORIES, INC. (COMPANY) 300 North Willson, Suite 1 Bozeman, MT 59771-0190 Daryl S. Paulson, Ph.D. - Project Director/Associate Study Director Christopher Beausoleil - Principal Study Director Carol Riccardi - Associate Study Director Protocol: Twenty (20) human test subjects were recruited and divided into two groups. One group was provided the Protec-4™ Antimicrobial formulation to use at the recommended four (4) hour intervals, the other group (control group) was not. The control group performed ten (10) hand washes each per day for five (5) days with a healthcare personnel hand wash product, but with no lotion applications. Each group was then required to wash their hands for (thirty) 30 seconds followed by a thirty (30) second rinse, ten times each day for a period of five (5) days. Each member of both groups was brought into the lab twice a day for visual inspection of the hands and measurements using the TC 350 Skin Centre which measures two important quantifiable parameters not readily apparent on visual inspection. These parameters are the trans-epidermal water loss (TEWL) and stratum corneum moisture content.

Results:

Subjects Not Using Protec-4™: • Forty percent (40%) of the participants from the group without

Protec-4™ didn’t complete the study due to the effects of the delipidation by detergents with onset of painful dermatitis.

• Subjects who did not use the Protec-4™ Antimicrobial formulation had a significant increase in irritation, as assessed visually; compared to those subjects who did.

• A significantly lower skin moisture content was noted after six (6) days among subjects who did not use the Protec-4™ Antimicrobial formulation.

Subjects Using Protec-4™: • Protec-4™ Antimicrobial formulation demonstrated an ability to prevent skin

irritation caused by extensive use of a common 4% chlorhexidine gluconate healthcare personnel hand wash product.


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• Trans-epidermal water loss (TEWL) and stratum corneal moisture retention measurements indicated an increase in natural skin barrier protection.

• Group using the Protec-4™ Antimicrobial formulation showed an improvement in epidermal moisture content over pre-study baselines.

• Adherence characteristics of the Protect-4™ Antimicrobial formulation, and its proven ability to form a protective barrier on the skin, suggests that it is a solution to the potentially devastating problems caused by frequent hand washing.

Visual Assessment: Initial visual assessments were made prior to the treatment phase to ensure that none of the subjects exceeded the maximum dryness and erythema scores. Baseline visual assessments evaluated skin dryness and erythema prior to the start of the treatment phase. One trained evaluator conducted all visual evaluations during the treatment phase. A grading scale (Table 1) was used to assess the hands for dryness and erythema. The sites on each hand assessed included: (1) back of hand, (2) back of fingers, (3) interdigital webs, and (4) the palm. The overall condition of each hand was then assigned a grade.

Table 1: Visual Evaluation Grading Scale

Grade Description 0 No Visible damage, "perfect" skin 1 Slight dryness, ashen appearance, usually involving dorsum only 2 Marked dryness, slight flaking involving dorsum only 3 Severe dryness dorsum, marked flaking, possibly fissures in webs 4 Severe flaking dorsum, surface fissures possibly with slight palmar

dryness 5 Open fissures, slight erythema (>10% of dorsal and interdigital surface),

with or without severe dryness, no bleeding 6 Bleeding cracks, deep open fissures, or generalized erythema (>25% of

area)

Statistical Summary: A statistical summary of the visual evaluation scores is presented in Table 2 below. The probability values (p values) from the Mann-Whitney two (2) sample test comparing Configuration 1 (With Invisicare®) and Configuration 2 (Without Invisicare®) at each evaluation are also listed. The changes from baseline scores for each configuration are graphically presented in Figure 1.


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Table 2: Mean Visual Evaluation Score, Mean Change from Baseline Scores

and p Values from Comparisons of the Test Configurations Session

Mean Configuration

1 With

Invisicare®

Mean Configuration

2 Without

Invisicare®

Change from Baseline

Configuration 1

With Invisicare®

Change from Baseline

Configuration 2

Without Invisicare®

P

Value

Baseline 0.95 0.40 N/A N/A N/A

Eval 1 1.75 1.65 0.80 1.25 0.1382

Eval 2 1.90 2.05 0.95 1.65 0.0202

Eval 3 1.20 1.45 0.25 1.05 0.0090

Eval 4 1.65 2.10 0.70 1.70 0.0012

Eval 5 1.80 2.67 0.85 2.22 0.0018

Eval 6 1.55 2.22 0.60 1.78 0.0101

Eval 7 2.20 2.67 1.25 2.22 0.0145

Eval 8 2.20 2.94 1.25 2.22 0.0145

Eval 9 1.50 2.50 0.55 2.06 0.0004

Eval 10 2.20 3.17 1.25 2.70 0.0002

Eval 11 2.35 3.39 1.40 2.94 0.0000

Eval 12 1.40 3.25 0.45 2.81 0.0000

Eval 13 2.30 3.75 1.35 3.31 0.0000

Eval 14 2.40 3.63 1.45 3.19 0.0000

Eval 15 1.05 3.19 0.10 2.75 0.0000


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Figure 1: Graph of the Mean Change from Baseline Scores for Visual

Evaluations for Both Test Configurations

Visual Epidermal Evaluation (Mean Change from Baseline)

0

0.5

1

1.5

2

2.5

3

3.5

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16Evaluation Interval

Vis

ual S

core

(Bas

elin

e A

djus

ted)

Change from Baseline Configuration 1 with Invisicare®

Change from Baseline Configuration 2 without Invisicare®

Baseline

Note: Mean scores (minus the Day 1, Baseline Sample Value) for the Tewameter and Corneometer are presented in the Table 4 and Table 5, respectively. A significant difference was noted between Configuration 1 Corneometer and Configuration 2 Corneometer readings on Day 6 (p<0.047). The mean baseline-adjusted Corneometer scores are graphically presented in Figure 2.

Table 4: Mean Baseline-Adjusted Tewameter Scores (transepidermal water

loss) for both Configurations

Configuration 1 With Invisicare®

Configuration 2 Without Invisicare®

DAY Sample Size


Sample Size


Day 2 Evaluation

10 -0.26 1.77 10 -2.66 3.76

Day 3 Evaluation

10 0.01 3.37 9 0.98 3.94

Day 4 Evaluation

10 3.98 4.81 8 0.96 4.46

Day 5 Evaluation

10 3.96 2.90 7 1.03 2.18

Day 6 Evaluation

10 4.95 3.68 6 6.33 3.26


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Figure 2: Graph of the Mean Baseline-Adjusted Corneometer Scores for Both Test Configurations

Epidermal Moisture Content

-14

-12

-10

-8

-6

-4

-2

0

2

1 2 3 4 5

Evaluation Day

Mea

n C

orne

omet

er S

core

Configuration 1 with Invisicare®Configuration 2 without Invisicare®

Baseline

Table 5: Mean Baseline-Adjusted Tewameter Scores (transepidermal water loss) for both Configurations

Configuration 1

With Invisicare® Configuration 2

Without Invisicare® DAY Sample

Size Mean Standard

Deviation Sample

Size Mean Standard

Deviation Day 2

Evaluation 10 -1.80 8.02 10 -5.50 8.32

Day 3 Evaluation

10 -1.60 9.26 9 -6.11 6.75

Day 4 Evaluation

10 0.02 5.20 8 -6.63 9.65

Day 5 Evaluation

10 -1.20 7.41 7 -843 9.43

Day 6 Evaluation

10 0.40 7.47 6 -12.20 11.40


Chapter 5 - Persistence Study


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PERSISTENCE STUDY

Purpose of the Study: Demonstrate ability of polymers to adhere to skin under conditions that simulate normal working conditions. Reveal polymers ability to persist on skin throughout multiple hand washes and exposure to detergents, chemicals and solvents.

In Vitro Study: Testing Laboratory: APPLIED CONSUMER SERVICES, INC. (ACS) 95th NW 77 Thea Ave., Bay 5, Hialeah Gardens, FL 33016 Burch Stewart, Ph.D President / Technical Director Protocol: Protec-4™ was applied to fritted glass membranes to simulate a normal application on skin. The membranes were subjected to an agitated 5% Ammonium Hydroxide wash with tests being conducted over six hours. Gravimetric analysis was used to determine the level of adherence to the glass membranes. An additional test with artificial perspiration yielded no change in persistence. Results: • 82% remained bonded to membrane after 3 hours. • 68% remained bonded to membrane after 6 hours. In Vivo Study: Testing Laboratory: CALIFORNIA SKIN RESEARCH INSTITUTE (CSRI) 15222-B Avenue of Science San Diego, CA 92128 Lawrence A Rheins, Ph.D President, California Research Institute Protocol: Utilizing 30 ethnically diverse human subjects, Protec-4™ was applied to the volar forearm, and then scrubbed with gauze saturated with 5% Ammonium Hydroxide at intervals of 10 minutes, 2 hours and 4 hours. The same gravimetric analysis as used in the in vitro studies, were performed on the skin wash solutions. Throughout the four-hour test period, punch biopsies were harvested from random subjects for examination under Electron Microscopy and Atomic Force Microscopy.



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Results: • Protec-4™ bound to skin greater than to fritted glass membrane. • Human perspiration studies replicated the results from In vitro study.



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Note: This document is an excerpt taken from Chapter 4 of the “Report of The Scientific

Advisory Committee on The Skinvisible™ Line of Products”.

Chapter 6 - Impermeability Study


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IMPERMEABILITY STUDY Purpose of the Study: Demonstrate ability of Protec-4™ to act as an effective barrier to noxious agents. In Vitro Study: Testing Laboratory: APPLIED CONSUMER SERVICES, INC. (ACS) 95th NW 77 Thea Ave., Bay 5, Hialeah Gardens, FL 33016 Burch Stewart, Ph.D President / Technical Director Protocol: Impermeability studies were conducted under in vitro laboratory conditions using a gravimetric method to determine levels of challenge liquid passing through diffusion chambers separated by a fritted glass membrane coated with Protec-4™. In the first study, twenty-eight (28) different toxic agents representative of a chemically diverse group of solvents, acids, bases, dyes, insecticides, herbicides and hydrocarbons were tested for their ability to permeate the Invisicare® polymer matrix. In a subsequent study following the same protocol, 26 chemotherapy drugs were also tested for their ability to permeate the Invisicare® polymer matrix. Results: • In all cases the Protec-4™ resisted permeation by all tested substances. • In all cases permeability exclusion exceeded 99% except for the following: 100% gasoline (96.7 % / 96.6%) Methylene Chloride (28.6% / 31.8 % )

Note: Additional clinical studies measuring Trans-epidermal Water Loss (TEWL) and Corneometer measurements show that Protec-4™ exhibits selective impermeability required to allow for normal respiration and prevent hazardous environmental challenge.



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Table 1: Summary of findings from Challenge Liquid Impermeability Test

Test No.

Chamber A Challenge Liquid

Receiving Chamber (H2O) 3 Hr / 6 Hr Conc.

Percent Retained in Original Chamber

1 16% Acetone 0.18 % / 0.47 % 99.9 % / 97.1 %

2 10 % Formaldehyde 0.04 % / 0.07 % 99.6 % / 99.3 %

3 5 % Ammonia 0.02 % / 0.04 % 99.6 % / 99.2 %

4 5 % nAc1O (Clorox) 0.09 % / 0.12 % 98.2 % / 97.6 %

5 3 % Hydrogen Peroxide 0.036 % /0.060% 98.8 % / 98.0 %

6 10 % Conc. HC1 (38) 0.005 % / 0.009 % 99.9% / 99.8 %

7 10 % Sodium Hydroxide 0.04 % / 0.07 % 99.6 % / 99.3 %

8 1 % Baygon 0.005 % / 0.007 % 99.5 % / 99.3 %

9 1 % Malathion <0.01% / <0.01% >99% / >99%

10 1 % Dursban/ Chlorpyrifos <0.01% / <0.01% >99% / >99%

11 1 % Diazinon <0.01% / <0.01% >99% / >99%

12 1 %Atrazine <0.01% / <0.01% >99% / >99%

13 100 % Perchloroethylene 0.670 % / 0.673 % 99.33 % / 99.33 %

14 100% Methylene Chloride 28.6% / 31.8 % by vol. 71.4 % / 68.2 %**

15 100 % Gasoline 3.3 % / 3.4% PPM 96.7 % / 96.6 %

16 100 % Diesel Fuel 2.1 /2.1 PPM 99.99 % / 99.99 %

17 100 % Paint Thinner <1 / 27 PPM 99.99 % / 99.99 %

18 100 % Paint Stripper 7.7 / 37.0 PPM 99.99 % / 99.99 %

19 6 % Latex With Protein <0.005 % (4hrs) > 99.92 %

20 1 % D & C Red 33 9.8 / 20.9 PPM 99.90 % / 99.71%

21 1 % D & C Green 28 <10 / <10 PPM >99.90 % / >99.90 %

22 1 % D & C Green 6 0.037 / 2.53 PPM 99.99 % / 99.97 %

23 1 % D & C Yellow 5 18.4 / 45.9 PPM 99.82 % / 99.64 %

24 1 % D & C Red 4 1.86 / 14.8 PPM 99.88 % / 99.85 %

25 1 % D & C Red 40 0.019 / 8.50 PPM 99.99 % / 99.91 %

26 1 % D & C Blue 1 2.98 / 10.48 PPM 99.97 % / 99.90 %

27 1 % D & C Red 3 14.8 / 22.68 PPM 99.85 % / 99.77 %

28 100 % Wax Stripper 84.7 / 226 PPM 99.99 % / 99.98 %



24

Table 2: Summary of findings from Chemotherapy Drug Impermeability Test

Test No.

Challenge Compound (%conc.)

% perm 2hr

% perm 4hr

% excluded

2Hr.

% excluded

4Hr. 1 Aredia, 9% < 1.5% < 1.5% > 98.50% > 98.50% 2 Platinol-AQ, 0.1% 0.93% 1.11% 99.07% 98.89% 3 Taxol, 0.6% 0.09% 0.15% 99.91% 99.85% 4 Kytril, 0.1% 0.07% 0.15% 99.93% 99.85% 5 Fluorouracil, 5.0% 2.52% 3.78% 97.48% 96.22% 6 Mesnex, 10% 0.08% 0.33% 99.92% 99.67% 7 Camptosar, 2% 0.27% 0.30% 99.73% 99.70% 8 Zofran, 0.2% 0.04% 0.04% 99.96% 99.96% 9 Gemzar, 3.8% 0.04% 0.05% 99.96% 99.95%

10 Ethyol, 5.0% 0.34% 0.43% 99.66% 99.57% 11 Anzemet, 2% 1.20% 1.40% 98.80% 98.60% 12 Paraplatin, 1% 0.07% 0.08% 99.93% 99.92% 13 Hycamtin, 0.1% 0.01% 0.01% 99.99% 99.99% 14 Intron A, IU x MM/0.5ml 0.50% 0.56% 99.50% 99.44% 15 Ardvoa,ucom PFS, 0.2% 0.00% 0.00% 100.00% 100.00% 16 Sargramostim L, 0.025% 0.01% 0.02% 99.99% 99.98% 17 Doxil, 0.2% < 0.01% < 0.01% > 99.99% > 99.99% 18 Herceptin, 2.1% 0.20% 0.20% 99.80% 99.80% 19 Navelbine, 1.0% < 0.001% < 0.01% >99.999% >99.99% 20 Epoetin Alfa, 2000 U/ml 6.20% 7.90% 93.80% 92.15% 21 Neupogen, 1.0% 0.03% 0.03% 99.98% 99.97% 22 Rituxan, 1.0% 0.74% 1.05% 99.26% 98.95% 23 Blenoxane, 150 U/ml 10.90% 13.10% 89.10% 86.90% 24 Taxotere, 1.09% 0.79% 0.99% 99.21% 99.01% 25 Vincasal, PFS, 0.1% 0.79% 0.99% 99.21% 99.01% 26 Vinblastine, 0.1% 0.01% 0.01% 99.99% 99.99%


Chapter 7 – FHSA Acute Oral Toxicity Study © Skinvisible Pharmaceuticals, Inc. 1999

25

FHSA ACUTE ORAL TOXICITY STUDY Purpose of Study: This procedure is designed to determine the acute oral toxicity Protec-4™ Antimicrobial formulation.

Testing Laboratory: NORTHVIEW PACIFIC LABORATORIES NORTHVIEW BIOSCIENCES 2800 Seventh Street Berkely, CA 94710

Timothy V. Doherty, D.V.M., Director, In Vivo Services Blesila Castro, Ph.D., Toxicology Manager, In Vivo Services In Vivo Protocol: A 15 gram quantity of the Protec-4™ Antimicrobial formulation was diluted to 30 mL with deionized water prior to administration. The animals were fasted 16 hours before dosing. Food was withheld three hours after dosing to facilitate gastrointestinal absorption of Protec-4™ Antimicrobial formulation. A single level screening test using ten test animals was performed at a dose of 5000 mg/kg and compared to two control animals dosed with vehicle. Five males and five females received the Protec-4™ Antimicrobial formulation. One male and one female were dosed with the deionized water as a control. If more than 50% of the animals survive for 14 days after dosing, no further testing was done. The dose was administered by means of an oral gavage needle attached to a hypodermic syringe.

Twelve Sprague-Drawley rats (six males and six females) per dose level were used to determine the oral toxicity of the Protec-4™ Antimicrobial formulation.

All of the animals were observed on the day of dosing and at least once each day for fourteen days or until death. The animals were observed for clinical signs of toxicity such as unkempt appearance, altered feeding habits, weight loss, and other signs of distress or physical depression, and for any signs of recovery from these signs. All of the animals were weighed on Day 0 (prior to test material administration), Day 7, Day 14, and at death.

Results:

• All of the animals remained healthy throughout the duration of the study. • All animals gained weight during the test period. • An oral dose of 5000 mg/kg of Protec-4™ Antimicrobial formulation produced

no mortalities or toxic signs when given to five male and five female Sprague-Dawley rats.

Note: This document is an excerpt taken from chapter 2 of the Skinvisible Pharmaceuticals research and development CD.

Chapter 8 - Invisicare® Polymer Delivery Technology © Skinvisible Pharmaceuticals, Inc. 1999

26

INVISICARE® POLYMER DELIVERY TECHNOLOGY Invisicare® polymers utilize a patented process for formation of a complex between hydrophilic and hydrophobic polymers. The result is a water soluble emulsion capable of delivering a wide variety of biologically active agents to the skin for extended periods of time. To prove the value and efficacy of the Invisicare® polymer delivery system, and to generate reasonable expectations of polymer based product performance, Skinvisible Pharmaceuticals developed the Protec-4™ Antimicrobial Skin Formulation, utilizing Triclosan as an active ingredient. Products using the Invisicare® polymer technology will have the following properties: • Persistence: Invisicare® polymers persist on the hands for 4-6 hours or until natural

skin turnover or abrasion removes it. • Protection: Invisicare® polymers produce a barrier on the skin, which is

impermeable to many noxious chemicals and environmental pollutants that can damage the skin.

• Carrier: Invisicare® polymers carry a wide variety of active ingredients to promote healthy skin. As a carrier, the Invisicare® polymers can deliver water insoluble or water soluble active agents equally well.

• Resists Wash-off: Invisicare® polymers do not wash off with soap and water. • Non-Occlusive: Invisicare® polymers do not occlude the skin, allowing for normal

skin respiration and excretory processes. • No Solvents: Invisicare® polymer product formulations do not contain, nor do they

require alcohol or other drying or defatting organic solvents to be effective. • Nontoxic & Nonirritating: Invisicare® polymers are nontoxic, having an oral toxicity

in excess of 5g/kg, and have been shown to be nonirritating to the skin. • Neutral pH: Invisicare® polymer delivery systems are most effective in a pH range of

6.5-7.75. Skinvisible’s Invisicare® polymers are available internationally to the pharmaceutical, personal care and cosmaceutical industries. Note: All of the data presented herein is available by request in unabridged form,

including complete protocols and the conclusions drawn by the contributing laboratories.


27

THE EARLY DAYS OF INVISICARE® In the beginning, Skinvisible had focused its product development attention towards utilizing its Invisicare® polymer technology to produce a protective hand lotion that not only provided impervious protection against noxious chemical agents in the work environment, but also was an active antimicrobial to known pathogens. Such a premier product could effectively reduce or prevent the spread of disease-producing bacteria, and prevent dermal contact with allergens to reduce or eliminate contact dermatitis. Skinvisible’s primary goal at this stage was to develop a product that incorporated not only these qualities, but also the crucial ability to demonstrate superior persistence on the skin, providing the most effective possible solution to these problems. To accomplish this task, Skinvisible established a core Scientific Advisory Committee which designed study protocols to produce objective evidence that would support product claims and validate the superior performance of the Invisicare® polymer delivery system. This committee included: James Roszell, Ph.D. (Nevada), chemist for Skinvisible; Professor Christiaan Barnard, M.D., Ph.D. (South Africa), renowned medical expert famed for completing the first human heart transplant; Claude Paul, L.D.S., D.M.D. (Switzerland); and Bruce Jezior (Florida), inventor/developer of the proprietary polymers. During its initial research, development, analysis and testing phase, the Committee was chaired, on virtually a full-time basis, by Mark Frobb, M.D. (British Columbia), noted for his medical and business expertise. Skinvisible recognized the markets increasing dissatisfaction with existing hand sanitizing products. In the medical/health care and food handling service industries, the use of latex and vinyl gloves to prevent hand contact with patients and food materials provided less than optimal protection. Wearing gloves increased perspiration, creating an environment conducive to the growth and proliferation of skin bacteria. Combined with the high incidence of glove defects (from 5 to 50%), exposure to greater numbers of microorganisms were more likely while wearing gloves than if no gloves were worn. Other protective lotions in the marketplace were wax, petrolatum or silicone based, combining off-the-shelf cream or ointment bases with various antimicrobial agents. Their major drawback still remains that they wash off with soap and water and must be reapplied after each handwashing. Considering increasing mandated handwashing protocols, this was a costly and potentially ineffective solution. Often little or no data is provided to back up advertising claims. In fact, few have been subjected to scientific scrutiny to establish their range and level of protection or their ability to persist on the skin.


28

After considerable research and analysis of available antimicrobial agents allowed under the FDA’s Tentative Final Monograph for Over The Counter (OTC) antimicrobial lotions, Skinvisible chose Triclosan 1% as the antimicrobial active agent to be incorporated into its Protec-4™ Antimicrobial formulation. Triclosan gives the lotion the broadest spectrum of pathogen toxicity for the target market, and has a long history of safe usage with a benign toxicological and skin sensitivity profile. Having identified market requirements and established its focus, Skinvisible intensified its efforts for product development and committed to undertake and implement extensive in vivo and in vitro laboratory tests utilizing independent, FDA-recognized laboratories with qualifications for carrying out investigative protocols using Good Lab Practice/Good Clinical Practice (“GLP/GCP”) standards. Profiles of the eight participating laboratories are detailed in the following chapter. RESEARCH RESULTS Laboratory tests were undertaken to demonstrate the Protec-4™ Antimicrobial formulation’s premier capabilities and effectiveness in the following areas:

• Persistence • Impermeability • Safety and Preservation of Dermatological Integrity • Antimicrobial Activity • Antiviral Activity • Product Stability • FHSA Acute Oral Toxicity

CONCLUSIONS Based on research conducted to date, it was determined that in all aspects of investigation of the Protec-4™ Antimicrobial formulation, whether applied to the barrier protective effects or the antimicrobial activity, no other product on the market today has been subjected to such intense study. A review of dermatological literature and other products presently available has failed to reveal any dermatological product that can stand up to the rigors under which the Protec-4™ Antimicrobial formulation has been tested.

Chapter 9 - Participating Independent Laboratories Profiles


29

PARTICIPATING INDEPENDENT LABORATORIES PROFILES APPLIED CONSUMER SERVICES, INC. 95Th NW Thea Ave., Bay 5, Hialeah Gardens, FL 33016 Founded in 1986, Applied Consumer Services, Inc., provides superior technical services to a wide variety of biological, chemical, physical, and engineering clients including: Shell Oil, Pfizer, Royal Caribbean Cruise Lines, Lufthansa, and Perfumania. Numerous pharmaceutical companies, food companies, law firms, and inventors also utilize their services. Applied Consumer Services is a listed laboratory with the FDA, and is DEA licensed. ACS maintains active memberships in the following national organizations: American Council of Independent Laboratories (ACIL), American Water Works Association, American Chemical Society (ACS), Association of Official Analytical Chemists (AOAC), American Society for Testing Materials (ASTM), Society of Sigma XI, Friends of Physics (University of Miami), Miami Mineralogical Society, Who’s Who Executive Club, and the Smithsonian Institute. Applied Consumer Services has EPA/HRS certification from All State Engineering, with Dr. Burch Stewart, Consultant, and is listed in several national directories including the Thomas Register for laboratory testing, consulting, textile chemistry, and food analysis. Their occupational licenses were completed through Hialeah Gardens, Dade County, and the State of Florida. The laboratories of Applied Consumer Services rank among the most versatile of all US labs. Testing can be conducted within the ACS facilities, on-site, or in conjunction with other labs. ACS has completed cooperative work with several facilities including: All State Engineering, Applied Research Laboratories, Kappa Laboratories, Panair Laboratories, QC Metallurgical Laboratories, National Health Laboratories, US Testing, and Worth Engineering. The investigative experience of ACS covers the following specialized areas: air quality surveys including sick building syndrome, analysis of contaminants in various systems, failure analysis of defective or dangerous material, chemical and nutritional analysis, determination of physical properties, performance testing, slip-fall investigations, and forensic investigations. ACS is also equipped for the development of inventions and formulations, formulation of trial batches, production of complete material safety data sheets, and the deformulation of many types of consumer products with instructions on how to prepare them.



30

CALIFORNIA SKIN RESEARCH INSTITUTE (CSRI) 15222-B Avenue of Science San Diego, CA 92128 Since its inception in May, 1996, the California Skin Research Institute has been conducting testing for clients who develop and market skin-related products. As a privately owned, clinical contract-research organization, CSRI clients include pharmaceutical companies, medical device companies, consumer product organizations, and the chemical industry. CSRI maintains key alliances with the Departments of Dermatology and Opthamology at the nationally recognized Scripps Clinic, enabling access to world-renowned clinical investigators in the area of skin disease. Other affiliations of strategic benefit to CSRI exist in the areas of pediatrics, microbiology, and animal toxicology. Additional expertise is tapped via nationwide clinical sites (DermNetSM). Located in San Diego, CA, CSRI has access to many ethnically-diverse research subjects, as well as an optimum climate for year-round dermatological testing. A large senior population provides additional opportunities for specialized research. Along with routine safety studies such as irritation and sensitization, photoallergy, and phototoxicity, the Company provides testing for a full spectrum of topical products addressing issues from anti-microbial hand washing to sun damage. In conjunction with leading scientists in the field of molecular biology, CSRI is developing innovative research programs in the areas of irritation and sensitization. Further, the Company’s proprietary DermPatchSM method combines the simplicity of “tape stripping” with the molecular power of the Ribonuclease Protection Assay (RPA). The senior management team of CSRI includes Lawrence A. Rheins, Ph.D., Founder and President; Robert A. Harper, Ph.D., Executive Vice President, Clinical Operations; Vera B. Morhenn, M.D., Vice President, Scientific Affairs; and Nancy A. Mathewson, Esq., Vice President, Quality Assurance and Regulatory Affairs.



31

ADVANCED SURFACE MICROSCOPY, INC. 6009 Knyghton Rd. Indianapolis, IN 46220 Advanced Surface Microscopy, Inc. (ASM) was founded in 1990 by Don Chernoff, Ph.D. Dr. Chernoff’s contributions to the advancement of microscopy and related technology, have resulted in more than 30 publications and patents. Throughout his career, Dr. Chernoff has presented strategic research and development of laser spectroscopy and optics, electron microscopy, and practical applications of microscopy to material characterizations and improvements. He has held a variety of research and engineering positions and is an active member of numerous professional societies including: the American Chemical Society, the American Physical Society, the American Vacuum Society, and the Microscopy Society of America. Dr. Chernoff is an active participant in setting of a number of industry-accepted standards such as the ASTM E42.14 Surface Analysis Cmte, sub-committee on Scanning Probe Microscopy. His work in this area has additionally led to the co-authoring of a guide to recognizing artifacts in Scanning Probe Microscopy (SPM) images. Advanced Surface Microscopy, Inc. is an independent analytical testing and contract research laboratory specializing in Scanning Probe Microscopy (SPM) and Atomic Force Microscopy (AFM). Their services are used in a variety of industries including biomedicine, chemicals, electronics, data storage, and metal work. State of the art equipment utilized by ASM includes: Digital Instruments NanaScope IIIA/Dimension 3000 large sample Atomic Force Microscopy, with phase electronics and diamond-tipped nanoindentation options; Leitz Orthoplan compound optical microscope, for observation in reflected and transmitted light; and a Wild M3B stereomicroscope.



32

BIOSCIENCE LABORATORIES, INC. (COMPANY) Laboratory Facilities: 300 North Willson Suite 1 Corporate Offices: 316 North 20th Mailing Address: P.O. Box 190 Bozeman, MT 59771-0190 Since its formation in 1991, BioScience Laboratories, Inc., has been instrumental in product research and development for the US HealthCare industry due to their expertise in Federal and State Regulatory requirements, as well as their proficient services available at three state-of-the-art laboratories. All studies conducted by BioScience Laboratories, Inc., follow Good Laboratory Practices (GLPs) and utilize methods from AOAC, the FDA’s Tentative Final Monograph (TFM), and the Healthcare Continuum Model of the Cosmetics, Toiletries and Fragrances Association (CTFA) and the Soap and Detergent Association (SDA). In addition, BioScience Laboratories, Inc., maintains active membership and involvement in a number of scientific organizations including: the American Society for Testing and Materials, American Society for Microbiology, American Society for Quality, Society for Quality Assurance, American Practitioners in Infection Control, and American Association for the Advancement of Science. Volunteer human subjects are used at the BioScience Clinical Trials Laboratory and the BioScience Irritation Laboratory. At the Clinical Trials lab, medically-oriented, food service/processing and consumer topical products are studied. The latter facility employs the TC350 Skin Monitoring Center, a cutting-edge research mechanism that obtains objective data on changes in skin water content and Trans-epidermal water loss. The third BioScience lab is the In Vitro Product Evaluation Laboratory. Here in vitro microbiological evaluations are performed on topical products, drugs, and hard-surface disinfectants. As active members of numerous strategic organizations, the personnel of BioScience Laboratories, Inc. remain at the forefront of scientific advancements and involvement in testing method development. Under the leadership of President and CEO Daryl S. Paulson, Ph.D., BioScience performs a broad spectrum of testing services for the evaluation of HealthCare, over-the-counter, and pharmaceutical products.



33

VIROMED BIOSAFETY LABORATORIES / ATS LABS Product Efficacy Testing Services Division 6101 Blue Circle Drive Minneapolis, MN 55343 Since 1982, ViroMed Biosafety Laboratories, Inc. has been recognized as one of the premier private clinical laboratories in the USA. Their Product Efficacy Testing Services division specializes in testing services for the disinfectant/chemical industry, specifically for EPA and FDA claims. The Company’s accreditation includes: USDA, FDA, American Association for Accreditation of Laboratory Animal Care (AAALAC), American Association of Blood Banks (AABB), Clinical Laboratory Improvement Act (CLIA), College of American Pathologists (CAP), International Organization of Standardization (ISO 9002), Nuclear Regulatory Commission (NRC), and Office for Protection for Research Risks (OPRR). ViroMed is registered in the following states: California, Florida, Illinois, Maryland, Minnesota, New York, and West Virginia. ViroMed works in close partnership with clients in the medical device, biotechnology, and pharmaceutical industries to develop and perform specialized testing for specific data. A highly trained, internal quality assurance unit monitors all testing for accuracy, precision, reliability and timeliness. A continuous quality improvement process is in place to review discrepancies and to implement required improvements. Close contact with regulatory agencies, combined with years of experience in testing services, enables ViroMed to advise clients on validation studies and product submissions. All ViroMed laboratories meet GLP and GMP regulations. Their Minneapolis headquarters are located in a 48,000 sq. ft., custom-designed structure, constructed in 1994. Further facilities include Axios, located in Atlanta, Georgia, and Quality Biotech, located in Camden, New Jersey. Working areas consist of both BSL-2 and BSL-3 laboratories, with off-site facilities available for human subject testing. Toxicology studies are performed at secure, sophisticated laboratories following strict regulatory and animal care requirements.



34

NORTHVIEW BIOSCIENCES Northview Atlantic Northview Laboratories Northview Pacific 136 Southport Road 1880 Holste Road 2800 Seventh Street Spartanburg, SC 29306 Northbrook, IL 60062 Berkely, CA 94710 Northview Biosciences is an independent laboratory offering comprehensive testing capabilities in analytical chemistry, microbiology, sterility assurance, biocompatibility, toxicology/ pharmacology and immunology. The laboratory facilities are conveniently located in Northbrook, Illinois, Berkeley, California, and Spartanburg, South Carolina. All Northview facilities are registered with the FDA and ISO 9002 certified. Their animal science program is accredited by the AAALAC (The Association for the Assessment and Accreditation of Laboratory Animal Care). Northview Biosciences has a reputation of quality assurance and excellent regulatory compliance. They conduct all tests in accordance with applicable Good Manufacturing Practice (GMP) and, when requested, Good Laboratory Practice (GLP) regulations. To insure the quality of data for all clients and the FDA, quality assurance managers routinely perform internal audits in all divisions of the laboratory. Their Operations Manual, consisting of an extensive body of Standard Operating Procedures, is a key component of their quality systems. Northview has a thorough, documented training system to insure that all technical staff can capably perform designated procedures and remain current with SOP revisions. Clients ranging from small specialty companies to Fortune 500 corporations have utilized their services for over 25 years. The Laboratory has gained a national reputation for quality in service and excellence in science.

Chapter 10 - Protec-4™ Binding When Exposed to Alcohols


35

INVISICARE® BINDING WHEN EXPOSED TO ALCOHOLS Purpose of the Studies: Demonstrate the ability of Invisicare® to adhere to hydrophilic nylon membrane substrates when exposed to Ethanol and Isopropyl Alcohol. Hydrophilic Membrane Studies: Testing Laboratory: SKINVISIBLE PHARMACEUTICALS, INC. 6320 S. Sandhill Rd., Suite 10 Las Vegas, NV 89120 James Roszell Ph. D. Director of Research and Development Protec-4 with Invisicare® exposed to Ethanol and Isopropyl Alcohol: In Vitro: Protec-4 antimicrobial lotion was applied to a hydrophilic nylon membrane and allowed to dry at room temperature for a period of 30 minutes to simulate a normal application on skin. The membranes were immersed for 2 hours in 10 different solutions of between 50-90% Ethanol and water, simulating a normal application of a typical alcohol hand sanitizer. Upon drying, gravimetric analysis was used to determine the level of adherence to the membranes. An additional test using 70% Isopropyl Alcohol was also performed under the same conditions. Results: • Over 95% of Protec-4 remained bonded to membrane after transient exposures of

60, 70, 80 and 90% Ethanol. • Over 98% of Protec-4 remained bonded to membrane after transient exposure of

70% Isopropyl Alcohol.

Chapter 10 - Protec-4™ Binding When Exposed to Alcohols


36

Graph 1: Percentage of Protec-4 Remaining Bound to Membrane After Transient Exposure to Ethanol.

Effects of Ethanol on Binding of Safe4Hours

70

75

80

85

90

95

100

0 50 60 70 80 90

% Ethanol Used

% S

afe4

Hou

rs R

emai

ning

% Safe4hoursRemaining

Invisicare® M-1 versus Ethanol:

In Vitro Protocol: Hydrophilic Membrane Binding Method Invisicare® M-1 and three Penederm Poloylprepolymers were applied to hydrophilic nylon membranes and allowed to dry at room temperature for a period of 30 minutes. The membranes were then immersed in a 95% Ethanol solution for a period of 2 hours. Upon removal from the solution, the membranes were allowed to dry for 30 minutes. Gravimetric analysis was then used to determine the level of adherence to the membranes for the polymers tested. Results: • 53% of Invisicare® remained bound to membrane after 2 hour exposure to Ethanol. • 3% or less of Penederm polymers remained bound to membranes after 2 hour

exposure to Ethanol.

summary of research and development studies - triple s · summary of research and development...

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