Eurofins Ats - 710506

Report N°: 710506A01v2.doc Version: .......................... n° 2 Page: ................................... 1

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Eurofins ATS -Pôle d'activité d'Aix-en-Provence - Actimart - 1140, Rue Ampère - 13851 Aix-en-Provence Cedex 3 - France TEL +33 (0)4.42.39.78.08 - FAX +33 (0)4.42.39.77.81

N° SIRET : 33761796300083 – Code APE : 7120B

STUDY REPORT

07/09/2015

ASSESSMENT OF THE ORAL TOLERANCE AND OF THE QUALITIES OF A PRODUCT, APPLIED ONCE AT THE LABORATORY, IN NORMAL CONDITIONS OF

USE, BY 20 ADULT VOLUNTEERS: Use Test

This report replaces and cancels the report N°710506A01 dated 2nd of September, 2015 which has to be destroyed. The laboratory should not be hold as responsible in case of the previous report is used. The

present report modifies the study sponsor and deletes the quotation number according to sponsor request. Study sponsor: LABORATORIO BONIQUET Study manager: Marion HARO Tested product: Product 1 Product 2 Name INSTANT SMILE

Product code 59991732 - PRETREATMENT

59991733 - WHITENING GEL

ATS reference 525668 525667

Brand -

Product type Pretreatment gel Whitening gel Study n°: 145TUTE20V15

The copy of this report is only authorized by unabridged edition. It is made of 33 pages.

These results concern only the samples tested in the laboratory which are defined here after. The samples will be kept in our premises during 2 months from the date mentioned below.

The sample and the information regarding sample have been provided by the client. All information related to the sample are under liability of the client and have not been checked by the Eurofins ATS company.

EUROFINS BioPharma Product Testing Spain S.L.U. C/ Josep Argemí 13 Esplugues de Llobregat 08028 BARCELONA ESPAGNE

710506A01 Version n°2

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AUTHENTICITY OF THE STUDY REPORT

The study concerned by this report was carried out under my responsibility, according to the experimental protocol, the quality plan of EUROFINS ATS laboratory, and in accordance with the good clinical practices. All observations and data taken during this study are reported in this report. Study Manager, Marion HARO I certify the rereading of this report and I agree with its content, Quality Assurance Reader, Sandrine GOBARD


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STUDY SUMMARY

ASSESSMENT OF THE ORAL TOLERANCE AND OF THE QUALITIES OF A

PRODUCT, APPLIED ONCE AT THE LABORATORY, IN NORMAL CONDITIONS OF USE, BY 20 ADULT VOLUNTEERS: Use Test

♦ Tested products: Product 1 Product 2 Name INSTANT SMILE

Product code 59991732 - PRETREATMENT


♦ Study sponsor: LABORATORIO BONIQUET ♦ Objective: The aim of the study is to assess the oral tolerance and the

qualities of the INSTANT SMILE product, applied once at the laboratory used in normal conditions of use, by 20 adult volunteers.

♦ Investigator: Frederic BIANCHI, M.D Dentist ♦ Place of the study: EUROFINS ATS, ACTIMART 4 allée des Informaticiens 1140 rue André Ampère 13851 AIX EN PROVENCE cedex 3 FRANCE ♦ Study dates: Session 1: 05/08/2015 Session 2: 06/08/2015

♦ Method: Directions for use:

Area of application: Teeth Quantity of product: As much as necessary Frequency and duration: Once at the laboratory Conditions of application:

1. Brush the teeth with regular toothpaste. The toothpaste used is “Signal Integral 8”. 2. Charge the fluorescent bite under a direct light source (ideally sun light) for at least

5 minutes. 3. Press slightly the pre-treatment tube to soak the sponge and apply it over the

external face of the teeth.


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4. Apply a thin stripe of the gel Instant Smile inside the fluorescent bite. Cover the whole internal face of the bite.

5. Fold the bite and put it inside your mouth by covering the teeth. Bite it directly and close the lips for a better fluorescent effect.

6. Leave it for 15 minutes. Assessment methods:

Oral tolerance: clinical observations are made by the Dentist to assess the oral intolerance reactions (assessment of the functional and clinical signs) at the beginning and at the end of the study. Bleaching efficacy: The Dentist assessed the teeth whiteness thanks to the R-20 Bleaching® shade guide at the beginning (T0) and after the use (Timm). Acceptability: assessment of the qualities and performances of the product is made by the volunteers, using a suitable questionnaire. Panel:

22 healthy female and male adult volunteers with yellowed teeth aged from 19 to 70 years old. The assessment of the oral tolerance was made on 22 volunteers. The bleaching efficacy was assessed in 22 volunteers. The product acceptability was evaluated by the 22 volunteers. ♦ Results:

- Assessment of the bleaching efficacy by clinical scoring After a single use, the teeth whiteness increased for 22 volunteers (100% of the panel). The average bleaching efficacy is equivalent to a benefit of 5.4 shades (2.7 grades) in the 22 volunteers. These results allow highlighting a bleaching efficacy of the product after a single use. - Assessment of the oral tolerance Assessment of the oral tolerance by the Dentist (clinical signs): No clinical manifestation was noticed, by the Dentist, after a single use, on the 22 volunteers. Discomfort manifestations (functional signs): No discomfort manifestation was reported to the dentist by any of the 22 volunteers.


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However, 2 volunteers (9%) reported the following discomfort manifestations on their acceptability questionnaire:

- Moderate tingling inside the mouth, during the whole time of use, by the volunteer n°15.

- Slight tingling on the lips, during a few minutes, by the volunteer n°21.

- Assessment of the acceptability The INSTANT SMILE product was globally very well appreciated by the 22 volunteers who took part in the study, with a satisfaction rate of 82% and 18% are not satisfied. Moreover, 64% of the volunteers who were involved in the study would like to buy this product. The qualities of the product were assessed by the volunteers through an acceptability questionnaire. The positive answers obtained are presented in the following table.

USE TEST PARAMETERS Added % of “totally agree” and “agree”

1. The whitening kit is easy to use 91% 2. The whitening kit is pleasant to use 55% 3. During the use, the whitening kit gives a pleasant freshness feeling 91% 4. After use, your teeth are whiter 77% 5. The whitening kit provides a fresh breath 100% 6. The whitening kit is gentle to the gums 95% 7. Your gums feel protected 100% 8. The product is gentle to the teeth enamel 91% 9. The product improves visibly the whiteness of your teeth 73% 10. At the end of the study, you would like to keep using the product 68%


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♦ Conclusion: To conclude, the INSTANT SMILE product, referenced 59991732 - PRETREATMENT and referenced 59991733 - WHITENING GEL, used in normal conditions of use, a single use at the laboratory, by 22 healthy female and male adult volunteers, with yellowed teeth, is considered as well tolerated regarding the oral tolerance. The INSTANT SMILE product, led to a bleaching teeth improvement in 100% of the volunteers with a mean benefit of 5.4 shades (i.e. 2.7 grades). The performances and the qualities of the product were globally very well appreciated by the 22 volunteers who participated in the study, with a satisfaction rate of 82% and a purchase intention of 64%.


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TABLE OF CONTENT

AUTHENTICITY OF THE STUDY REPORT .................................................................. 2 STUDY SUMMARY ........................................................................................................ 3 TABLE OF CONTENT ................................................................................................... 7

1 OBJECTIVE............................................................................................................. 8

2 METHODOLOGY .................................................................................................... 8

3 ETHIC AND REGULATORY CONSIDERATIONS CONCERNING PROTECTION OF PERSONS .................................................................................................................. 9

3.1 Legislative and regulatory references ................................................................... 9 3.2 Ethic considerations .............................................................................................. 9 3.3 Confidentiality ..................................................................................................... 10 3.4 Archiving ............................................................................................................. 10

4 QUALITY CONTROL AND INSURANCE ............................................................. 11

5 STUDIED PANEL .................................................................................................. 11 5.1 Number of volunteers .......................................................................................... 11 5.2 Recruitment, selection and final admittance of volunteers for a study ................ 11 5.3 Inclusion criteria .................................................................................................. 12 5.4 Non-inclusion criteria .......................................................................................... 12 5.5 Banning and restrictions ..................................................................................... 12 5.6 Volunteers withdrawal ......................................................................................... 13

6 TESTED PRODUCTS ............................................................................................ 13

7 CLINICAL STUDY ................................................................................................. 14 7.1 Applying .............................................................................................................. 14 7.2 Study protocol ..................................................................................................... 14 7.3 Clinical assessments .......................................................................................... 15 7.4 Data analysis and results interpretation .............................................................. 16

8 RESULTS .............................................................................................................. 18 8.1 Description of the panel ...................................................................................... 18 8.2 Study exits .......................................................................................................... 18 8.3 Results analysis .................................................................................................. 19 APPENDIX I ................................................................................................................. 21 Individual results of the clinical scoring by the Dentist ................................... 22 APPENDIX II ................................................................................................................ 23 Assessment of the oral tolerance after a single application in the laboratory (functional and clinical signs) ................................................................................... 24 APPENDIX III ............................................................................................................... 26 Global satisfaction and purchase intention graphs .......................................... 27 Acceptability table ............................................................................................... 28 Acceptability histogram ...................................................................................... 29 APPENDIX IV ............................................................................................................... 30

Answers to open questions ................................................................................ 30 APPENDIX V ................................................................................................................ 31 List of the personnel who participated in the study ......................................... 31 APPENDIX VI ............................................................................................................... 32 Results authenticity ............................................................................................. 33


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1 OBJECTIVE The aim of the study is to assess the oral tolerance and the qualities of the INSTANT SMILE product, used in normal conditions of use, applied once at the laboratory, by 20 healthy volunteers, presenting with yellowed teeth, aged from 18 to 70 years old.

2 METHODOLOGY

Clinical observations are made by the Dentist at the beginning of the study to confirm the inclusion criteria and to examine the area that will be put in contact with the tested product.

The product is applied by the volunteers at the laboratory, according to the normal

conditions of use. The oral tolerance (clinical signs) is assessed by the Investigator, by clinical

examination after the single application at the laboratory. The subjective tolerance (functional signs) is assessed by the volunteers from

predefined criteria (teeth or gums sensitive to cold/hot, mouth ulcer, cracks, bleeding, itching, bad breath) in presence of the Dentist, after the single application at the laboratory.

The qualities of the product are assessed by the volunteers using a suitable

questionnaire, developed with the study sponsor, before the beginning of the study.


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3 ETHIC AND REGULATORY CONSIDERATIONS CONCERNING PROTECTION OF PERSONS

3.1 Legislative and regulatory references The French law relative to the Public Health n° 2004-806 of August 9, 2004 (articles 88 to 97) applied by the French Decree n° 2006-477 of April 26, 2006 for the research integrates the dispositions regarding the biomedical researches and replaces the French law of December 20, 1988 relative to the protection of persons who take part in biomedical researches called Law “Huriet-Serusclat". All tests carried out within EUROFINS ATS, even if they are not submitted to this law, are carried out according to this law. The studies are carried out according to the most recent recommendations of the World Medical Association (Helsinki Declaration 1964, in its current version), and to the AFSSAPS recommendations relative to the biomedical researches on cosmetic products entering in the application field of the French law relative to the Public Health n° 2004-806 of August 9, 2004 (Version of September 7, 2006). However, no information is sent to the national folder of people who takes part in biomedical research and the opinion of the “Committee of Persons Protection” is not asked. The studies follow the “Guidelines for the Assessment of Skin Tolerance of Potentially Irritant Cosmetic Ingredients”, COLIPA, Edition of 1997.

3.2 Ethic considerations The ethic requirements, necessary to studies on Human, are respected: The volunteers are selected according to inclusion and non-inclusion criteria. All volunteers are informed of the aim and the type of the study, of the possible risks

they are taken by participating in this study and give their free and informed consent before the beginning of the study.

Before volunteers are exposed to the tested product, minimum information regarding the safety of the product is asked to the sponsor.

All care is taken in order to avoid excessive oral or skin reactions or undesired effects on the volunteers’ health during the study.

Safety procedures are taken in case of bad reactions. The volunteers are paid in compensation for the time spent and the risks due to the

study.


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3.3 Confidentiality The complete data regarding the health of the volunteers, collected during their final admittance in the volunteers database of EUROFINS ATS and necessary when recruiting and selecting them for the studies, are strictly confidential and submitted to the medical secret according to the article 378 of the “Penal Code” and to the article 4 of the “Medical Ethics Code” (R-4127-1 to R-4127-112 of the “Public Health Code” of December 14, 2006). The anonymity of the volunteers is respected within all studies carried out in our laboratories. However, each volunteer can be easily identified by the Investigator, the doctors and all the persons in charge of the study, thanks to its personal volunteer’s code. According to the article R. 5121-13 of the “Public Health Code”, the product type studied, the trials, the volunteers, and the results are strictly confidential and the secret is respected by the Doctors and all the persons working with them. EUROFINS ATS ensures not to divulge all the data and results collected during a study. Treatment of personal data is declared to CNIL.

3.4 Archiving All data related to the study will be stored in the archives of EUROFINS ATS (Pôle d’activités d’Aix les Milles - ACTIMART – 4 allée des Informaticiens, 1140 rue André Ampère – 13851 AIX EN PROVENCE) and at a service provider’s, Société Générale d’Archives (ZI Les Estroublans - 49 boulevard de l’Europe – 13127 VITROLLES), for 10 years. At the end of this period, the study sponsor will have to specify whether the data related to the study should be thrown away or restored to him. Eurofins ATS can also consider extending the storage period of these documents, at the study sponsor’s expenses.

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4 QUALITY CONTROL AND INSURANCE In order to meet client expectations and legal and regulatory requirements, EUROFINS ATS established all necessary resources for the management of its structural organizations and methods. With a constant client satisfaction policy, EUROFINS ATS chooses to follow the ISO 9001 requirements in order to establish the company organisation. In this direction, this study was carried out in accordance with the procedures defined in the quality system. In order to insure results reliability, quality auto-controls are made all through the process. Thus, during this study, all the documents, materials, environment and raw data were checked in order to avoid deviations from the protocol. In the same way, under quality policy, the clinical tests laboratory is audited every year in order to assess that the procedures and instructions are well applied and to check their conformity with our internal requirements and process efficiency.

5 STUDIED PANEL

5.1 Number of volunteers The product was tested by 22 volunteers. The test was carried out in open.

5.2 Recruitment, selection and final admittance of volunteers for a study All volunteers recruited in this study come from the volunteers’ data base of EUROFINS ATS, and answer the inclusion and non inclusion criteria presented in the paragraphs below. Their final admittance was determined by the study manager from the answers given in a pre-study questionnaire and after a preliminary interview. During this interview, the following information is explained to the volunteers: title, objective, protocol, planning of the study, payment methods, as well as the possible effects expected and the study constraints. The admittance of the volunteers is validated by the signature of the Information Note and a free and informed consent, by the investigator and the volunteers.



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5.3 Inclusion criteria The volunteers corresponding to the following criteria are included: Age : 18-70 years old, Gender: female and male, Teeth: yellowed, Social welfare: the volunteers must be affiliated at National insurance (French law :

“Public Health Code” article L1121-11), No oral lesion on the studied area, Volunteers having a proof of home address, Volunteers able to understand French and the study requirements.

5.4 Non-inclusion criteria Volunteers not answering the previous inclusion criteria, Volunteers which used a whitening kit at home, Volunteers within an exclusion period between two tests, Minors or majors protected by the law and people admitted in a sanitary or social

institution for other purpose than research (French law : “Public Health Code” article L1121-7),

Persons deprive of liberty by legal or administrative decision, patients in emergency situation (French law : “Public Health Code” article L1121-6),

Pregnant or breastfeed women (French law : “Public Health Code” article L1121-5) Volunteers presenting an evolutive oral pathology or a known contact allergy to one of

the ingredients of the tested product, Volunteers who refused to give their free and informed consent, Volunteers under antihistaminic, corticoids, desensitizing treatment and/or under any

treatment which could interfere with the oral metabolism.

5.5 Banning and restrictions For the whole length of the study, it is asked to volunteers: Not to modify their alimentary and health habits, Not to use another product from the same category than the one tested, Not to take aspirin, anti-histamines, corticoids or anti-inflammatories that could

interfere with the test results.



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5.6 Volunteers withdrawal Volunteers may be excluded from the study for the following reasons: They no longer follow the requirements and constraints of the study, explained during

the signing of the consent, They suffer from an illness developed during the study which may interfere with the

objectives of the study, They no longer wish to participate in the study.

6 TESTED PRODUCTS Product 1 Product 2 Product name INSTANT SMILE

Reference 59991732 - PRETREATMENT


ATS reference 525668 525667 Presentation (galenic, colour) Blue liquid Transparent gel

Packaging Plastic tube Plastic tube Number of samples received 25

Use by date >30 months

Storage conditions room temperature, away from light and heat A sample of the tested product is kept in EUROFINS ATS laboratory, during 2 months after the end of the study. After this date and except contrary order from the study sponsor, the product will be destroyed.



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7 CLINICAL STUDY

7.1 Applying The applications are made by the volunteer, at the laboratory, according to the following recommendations (developed with the study sponsor). Area of application: Teeth Quantity of product: As much as necessary Frequency and duration: Once at the laboratory Conditions of application:

1. Brush the teeth with regular toothpaste. The toothpaste used is “Signal Integral 8”. 2. Charge the fluorescent bite under a direct light source (ideally sun light) for at least

5 minutes. 3. Press slightly the pre-treatment tube to soak the sponge and apply it over the

external face of the teeth. 4. Apply a thin stripe of the gel Instant Smile inside the fluorescent bite. Cover the

whole internal face of the bite. 5. Fold the bite and put it inside your mouth by covering the teeth. Bite it directly and

close the lips for a better fluorescent effect. 6. Leave it for 15 minutes.

7.2 Study protocol 2 weeks before D0: Selection of the volunteers from the data base, an appointment is taken. D0: Welcoming of the volunteers, signature of the information and consent form, by the

volunteers and the Study Manager. The volunteers also complete medical auto questionnaire confirmed by the Investigator.

Clinical exam at the beginning of the study: the Dentist examines individually the volunteers and assesses the mouth areas put in contact with the tested product.

Teeth colour is scored by the Dentist using the R-20 Bleaching® Shade guide. Using of the whitening kit according to the normal conditions of use. D0Timm: Clinical observations of end of study: the Dentist examines individually the volunteers

and assesses the mouth areas put in touch with the product. Teeth colour is scored by the Dentist using the R-20 Bleaching® Shade guide.



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Volunteers’ interview: the volunteers describe the discomfort manifestations (functional signs) they may have felt during the study from predefined criteria and in presence of the Dentist.

Recovery of the acceptability questionnaire.

7.3 Clinical assessments Assessment of the oral tolerance by the Dentist: The oral tolerance is assessed by the Investigator, starting from macroscopic examination (clinical signs: inflammation, oedema, mouth ulcer, bleeding, crack) of the mouth areas in contact with the product. The subjective tolerance (functional signs) is assessed by the volunteers from predefined criteria (sensitive to cold/hot teeth or gingiva, mouth ulcer, bleeding, itching, cracks, bad breath) during the consultation with the Dentist at the end of the study. Clinical and functional signs are graded with the following scale:

. 0 => No

. 1 => Slight

. 2 => Moderate

. 3 => Intense Evaluation of the product acceptability by the volunteers: The qualities and the performances of the product are assessed by the volunteers, through a suitable questionnaire developed with the study sponsor, after the use of the product in normal conditions, once in the laboratory. Assessment of the whitening efficacy by the Dentist:

The teeth colour is scored by the Dentist, using the R-20 Bleaching® Shade guide. This guide allows ranking the teeth whitening level for each volunteer on D0 and D0Timm.



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Figure 1: R-20 Bleaching® Shade guide

7.4 Data analysis and results interpretation The results obtained are collected, analysed and interpreted by the study manager according to the normal conditions of use and of the effects investigated by the study manager. Assessment of the oral tolerance by the Dentist: Depending on the percentage of volunteers that showed clinical signs or reported functional signs, the product global tolerance is determined according to the scale found in table 1. For each conclusion line, only one criterion has to be reached to lead to the corresponding conclusion. If the conclusion given by the percentage of volunteers that showed clinical signs is different from the conclusion given by the percentage of volunteers that reported functional signs, the global tolerance will be determined by the worst result. For example, if 10% of the volunteers showed clinical signs of slight or moderated intensity (good tolerance) and 50% of the volunteers reported functional signs of slight or moderate intensity (moderate tolerance), the conclusion on the product global tolerance will be of moderate tolerance.



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Table 1: Tolerance evaluation regarding the percentage of volunteers that showed

intolerance reactions

% of volunteers that showed

clinical signs of intensity: % of volunteers that reported functional signs of intensity:

Global tolerance Slight or moderate Intense Slight or moderate Intense

Very well 0% 0% 0% 0%

Well ]0%-10%] 0% ]0%-30%] 0%

Moderate ]10%-20%] ]0%-10%] ]30%-50%] ]0%-30%]

Bad >20% >10% >50% >30% Evaluation of the product acceptability (qualities and performances) by the

volunteers: The global volunteers’ satisfaction regarding the product they tested is determined according to the positive answers obtained for the following question: «Globally are you satisfied with the product you tested». The scale presented in table 2 is used to determine the global satisfaction according to the calculated satisfaction rate.

Table 2: Scale to determine product global satisfaction

Added % of “totally agree” and “agree” Global satisfaction

[80%-100%] Product very well appreciated

[60%-80%[ Product well appreciated

[40%-60%[ Product moderately appreciated

[20%-40%[ Product little appreciated

[0%-20%[ Product badly appreciated Assessment of the whitening efficacy by the Dentist: For each volunteer, the variation of shade is calculated.



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8 RESULTS

8.1 Description of the panel This study was carried out on 05/08/2015 and on 06/08/2015 and includes 22 healthy female and male adult volunteers, whom characteristics are presented in table 3:

Table 3: Volunteers characteristics and events occurred during the study

VOL VOL CODE Gender Age (years) Yellowed teeth Events occurred during the study

1 GEODA F 70 Yes - 2 MALEL F 58 Yes - 3 MOCLA F 48 Yes - 4 BLAMI F 19 Yes - 5 BLAMA3 F 48 Yes - 6 PASFA1 M 43 Yes - 7 EL TA M 62 Yes - 8 FANMI F 65 Yes - 9 ZANCA F 25 Yes -

10 GIAMI1 F 65 Yes - 11 VIDJO F 64 Yes - 12 CARLA11 F 47 Yes - 13 RIBST F 35 Yes - 14 SERVA1 F 45 Yes - 15 MAGNA F 53 Yes - 16 ALTAN F 53 Yes - 17 DELCL F 65 Yes - 18 BOUME1 F 37 Yes - 19 BOUZO F 42 Yes - 20 BOUAI1 M 51 Yes - 21 CANJU F 19 Yes - 22 LESCO F 41 Yes -

Average 48 None of the volunteers selected took a treatment contraindicated with the study.

8.2 Study exits The 22 volunteers who participated in this study gave their opinion regarding the tested product through the acceptability questionnaire. The oral tolerance assessment was made on 22 volunteers. The bleaching efficacy was assessed on 22 volunteers. The product acceptability was evaluated by the 22 volunteers.



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8.3 Results analysis - Assessment of the bleaching efficacy by clinical scoring After a single use, the teeth whiteness increased for 22 volunteers (100% of the panel). The average bleaching efficacy is equivalent to a benefit of 5.4 shades (2.7 grades) in the 22 volunteers. These results allow highlighting a bleaching efficacy of the product after a single use. Appendix I presents the individual results of the clinical scoring by the Dentist. - Assessment of the oral tolerance Assessment of the oral tolerance by the Dentist (clinical signs): No clinical manifestation was noticed, by the Dentist, after a single use, on the 22 volunteers. Discomfort manifestations (functional signs): No discomfort manifestation was reported to the dentist by any of the 22 volunteers. However, 2 volunteers (9%) reported the following discomfort manifestations on their acceptability questionnaire:

- Moderate tingling inside the mouth, during the whole time of use, by the volunteer n°15.

- Slight tingling on the lips, during a few minutes, by the volunteer n°21. Appendix II presents the results of the oral tolerance assessment by the Dentist. - Assessment of the acceptability The INSTANT SMILE product was globally very well appreciated by the 22 volunteers who took part in the study, with a satisfaction rate of 82%. Moreover, 64% of the volunteers who were involved in the study would like to buy this product.



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The qualities of the products were assessed by the volunteers through an acceptability questionnaire. The positive answers are presented in table 4:

Table 4: Acceptability

USE TEST PARAMETERS Added % of “totally agree” and “agree”

1. The whitening kit is easy to use 91% 2. The whitening kit is pleasant to use 55% 3. During the use, the whitening kit gives a pleasant freshness feeling 91% 4. After use, your teeth are whiter 77% 5. The whitening kit provides a fresh breath 100% 6. The whitening kit is gentle to the gums 95% 7. Your gums feel protected 100% 8. The product is gentle to the teeth enamel 91% 9. The product improves visibly the whiteness of your teeth 73% 10. At the end of the study, you would like to keep using the product 68%

Appendix III presents the graphs of global satisfaction, the purchase intention and the acceptability graph and table. ♦ Conclusion: To conclude, the INSTANT SMILE product, referenced 59991732 - PRETREATMENT and referenced 59991733 - WHITENING GEL, used in normal conditions of use, a single use at the laboratory, by 22 healthy female and male adult volunteers, with yellowed teeth, is considered as well tolerated regarding the oral tolerance. The INSTANT SMILE product, led to a bleaching teeth improvement in 100% of the volunteers with a mean benefit of 5.4 shades (i.e. 2.7 grades). The performances and the qualities of the product were globally very well appreciated by the 22 volunteers who participated in the study, with a satisfaction rate of 82% and a purchase intention of 64%.



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APPENDIX I

Individual results of the clinical scoring by the Dentist


APPENDIX I Assessment of the whitening efficacy by the Dentist

Product: INSTANT SMILE Starting date : 05/08/2015

Reference:59991732 - PRETREATMENT / 59991733 - WHITENING GEL

End date : 06/08/2015

ATS sample n°: 525668 / 525667Study code: 145TUTE20V15

INCLUSION NUMBER

VOLUNTEER CODE

Whiteness onT0 Whiteness on Ti Ti-T0

1 GEODA 28 22 -6

2 MALEL 28 24 -4

3 MOCLA 22 16 -6

4 BLAMI 14 12 -2

5 BLAMA3 32 26 -6

6 PASFA1 26 16 -10

7 EL TA 26 18 -8

8 FANMI 30 26 -4

9 ZANCA 16 12 -4

10 GIAMI1 30 24 -6

11 VIDJO 28 16 -12

12 CARLA11 16 12 -4

13 RIBST 22 16 -6

14 SERVA1 24 22 -2

15 MAGNA 24 22 -2

16 ALTAN 26 24 -2

17 DELCL 32 26 -6

18 BOUME1 26 16 -10

19 BOUZO 26 22 -4

20 BOUAI1 32 28 -4

21 CANJU 14 10 -4

22 LESCO 26 22 -4

-5,40

WHITENING EFFICACY

Average



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APPENDIX II

Assessment of the oral tolerance after a single application in the laboratory (functional and clinical signs)


APPENDIX II ASSESSMENT OF THE ORAL TOLERANCE: evaluation of the clinical signs by the Dentist

Product INSTANT SMILE Starting date : 05/08/2015 Number of volunteers : 22

Reference 59991732 - PRETREATMENT / 59991733 - WHITENING GEL End date : 06/08/2015

Study code : 145TUTE20V15 ATS sample n° 525668 / 525667

Product imputabilityD0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti D0T0 D0Ti

1 GEODA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

2 MALEL 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

3 MOCLA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

4 BLAMI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

5 BLAMA3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

6 PASFA1 1 1 0 0 0 0 0 0 0 2 2 0 0 0 0 0 0 0

7 EL TA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

8 FANMI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

9 ZANCA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

10 GIAMI1 1 1 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0

11 VIDJO 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

12 CARLA11 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

13 RIBST 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

14 SERVA1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

15 MAGNA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

16 ALTAN 1 0 -1 0 0 0 0 0 0 1 0 -1 0 0 0 0 0 0

17 DELCL 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

18 BOUME1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

19 BOUZO 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

20 BOUAI1 1 0 -1 0 0 0 0 0 0 1 0 -1 0 0 0 0 0 0

21 CANJU 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

22 LESCO 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

No reaction 18 20 20 22 22 22 22 22 22 18 20 20 22 22 22 22 22 22

Number of slight reactions 4 2 0 0 0 0 0 0 0 3 1 0 0 0 0 0 0 0

Number of moderate reactions 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0

Number of intense reactions 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

* scale from 0 to 3 : 0 = no, 1 = slight, 2 = moderated, 3 = intense

LocationINCLUSION NUMBER

VOLUNTEER CODE

CLINICAL SIGNSinflammation œdema mouth ulcer bleeding crack other comments

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APPENDIX II ASSESSMENT OF THE ORAL TOLERANCE: functional signs reported to the Dentist by the volunteers

Product INSTANT SMILE Starting date : Number of volunteers : 22

Reference 59991732 - PRETREATMENT / 59991733 - WHITENING GEL End date : Study code 145TUTE20V15 ATS sample n° 525668 / 525667

D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0Ti - D0 D0T0 D0Ti D0T0 D0Ti D0T0 D0Ti D0T0 D0Ti

1 GEODA 0 0 0 0 0 0 1 0 -1 0 0 0 2 0 -2 2 0 -2 1 0 -1 0 0 0 0 0 0

2 MALEL 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

3 MOCLA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

4 BLAMI 0 0 0 1 0 -1 0 0 0 0 0 0 0 0 0 0 0 0 1 0 -1 0 0 0 0 0 0

5 BLAMA3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

6 PASFA1 1 0 -1 1 0 -1 1 0 -1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

7 EL TA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

8 EL TA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

9 FANMI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

10 GIAMI1 0 0 0 1 0 -1 0 0 0 0 0 0 0 0 0 0 0 0 1 0 -1 0 0 0 0 0 0

11 VIDJO 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

12 CARLA11 0 0 0 0 0 0 1 0 -1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

13 RIBST 0 0 0 0 0 0 1 0 -1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

14 SERVA1 0 0 0 0 0 0 0 0 0 0 0 0 1 0 -1 1 0 -1 1 0 -1 0 0 0 0 0 0

15 MAGNA 0 0 0 0 0 0 1 0 -1 0 0 0 1 0 -1 0 0 0 0 0 0 0 0 0 0 0 0

16 ALTAN 0 0 0 0 0 0 2 0 -2 0 0 0 1 0 -1 0 0 0 0 0 0 0 0 0 0 0 0

17 DELCL 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

18 BOUME1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

19 BOUZO 0 0 0 1 0 -1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

20 BOUAI1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

21 CANJU 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

22 LESCO 0 0 0 0 0 0 0 0 0 0 0 0 1 0 -1 0 0 0 0 0 0 0 0 0 0 0 0

No reaction 21 22 21 18 22 18 16 22 16 22 22 22 17 22 17 20 22 20 18 22 18 22 22 22 22 22 22Number of slight reactions 1 0 0 1 0 0 1 0 0 1 0 0 1 0 0 1 0 0 1 0 0 1 0 0 1 0 0Number of moderate reactions 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0Number of intense reactions 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

* scale from 0 to 3 : 0 = no, 1 = slight, 2 = moderated, 3 = intense

INCLUSION NUMBER

VOLUNTEER CODE

VISIBLE FUNCTIONAL SIGNS FELT FUNCTIONAL SIGNSDuration

05/08/2015

06/08/2015

mouth ulcer bleeding bad breath other sensitive teeth to cold sensitive teeth to hot sensitive gingiva itching other Location Frequency comments

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N° SIRET : 33761796300083 – Code APE : 7120B

APPENDIX III

Global satisfaction and purchase intention graphs

Acceptability table

Acceptability histogram


APPENDIX III Satisfaction rate and purchase intention

Study code : 145TUTE20V15 Starting date : 05/08/2015End date : 06/08/2015

Product : INSTANT SMILE

Reference : 59991732 - PRETREATMENT / 59991733 - WHITENING GEL

Registration : 525668 / 525667SATISFACTION RATE

PURCHASE INTENTION

NO

36%

YES

64%

Satisfied

82%

Unsatisfied

18%

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APPENDIX III Acceptability table

Study code : 145TUTE20V15 Starting date : 05/08/2015End date : 06/08/2015

Product : INSTANT SMILEReference : 59991732 - PRETREATMENT / 59991733 - WHITENING GEL

Registration : 525668 / 525667

USE TEST PARAMETERS Totally agree Agree Disagree Totally disagree

1. The whitening kit is easy to use 55% 36% 9% 0%

2. The whitening kit is pleasant to use 45% 9% 27% 18%

3. During the use, the whitening kit gives a pleasant freshness feeling 55% 36% 9% 0%

4. After use, your teeth are whiter 36% 41% 23% 0%

5. The whitening kit provides a fresh breath 77% 23% 0% 0%

6. The whitening kit is gentle to the gums 59% 36% 5% 0%

7. Your gums feel protected 41% 59% 0% 0%

8. The product is gentle to the teeth enamel 41% 50% 9% 0%

9.The product improves visibly the whiteness of your teeth 27% 45% 27% 0%

10. At the end of the study, you would like to keep using the product 41% 27% 23% 9%

710506A01v2.xlsx


APPENDIX III Acceptability histogram

Study code : 145TUTE20V15 Product : INSTANT SMILE Starting date : 05/08/2015

Reference : 59991732 - PRETREATMENT / 59991733 - WHITENING GEL End date : 06/08/2015Registration : 525668 / 525667

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

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N° SIRET : 33761796300083 – Code APE : 7120B

APPENDIX IV

Answers to open questions

Reasons why volunteers would buy the product (64%)

Reasons why volunteers would not buy the product (36%)

For much clearer appearance of the teeth and clean appearance It does not whiten teeth

Pleasant sensation of freshness complex use product Unpleasant to use

Easy to apply and pleasant taste Always present tasks / whiter teeth on the top but not down

Ease of Use I do not know. I did not see any difference, but normal for one use

Whiteness visible effect Unpleasant to use. Little visible results

Because it works Inefficiencies at certain spots on the lower teeth

My teeth look a little whiter Unpleasant (exposure time) I have whiter teeth It does not whiten teeth It provides a feeling of freshness and slightly whitened my teeth.

Feeling fresh and whitens teeth Teeth Whitening

Remarks and suggestions reported by volunteers regarding the investigational product

Some mandatory application Difficult to close the mouth which causes an unpleasant sensation use. Problem if not properly applied, the teeth do not have the same color Very nice Difficulty keeping your mouth closed without swallowing Swallowing light towards the end of the exposure time. Unconvinced. Bleaching is not uniform, he laundered some of my teeth



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N° SIRET : 33761796300083 – Code APE : 7120B

APPENDIX V

List of the personnel who participated in the study Main investigator: Name: Frederic BIANCHI, M.D Dentist Address: ACTIMART 4 allée des Informaticiens 1140 rue André Ampère 13851 AIX EN PROVENCE cedex 3 Phone: 04 42 39 30 92 Study Manager: Name: Marion HARO Address: ACTIMART 4 allée des Informaticiens 1140 rue André Ampère 13851 AIX EN PROVENCE cedex 3 Phone: 04 42 37 16 21 Laboratory technician, production assistant: Name: Camille RAVON Address: ACTIMART 4 allée des Informaticiens 1140 rue André Ampère 13851 AIX EN PROVENCE cedex 3 Phone: 04 42 39 30 92



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N° SIRET : 33761796300083 – Code APE : 7120B

APPENDIX VI

Results authenticity


710506A01

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