Cereform ®

Technical informations

Breast implants pre-filled with silicone gel

2012 edition

0459

Introduction

Raw materials used by ceReplas...............................................................

Technical characteristics of ceRefoRm ® implants.....................................

controls performed on ceRefoRm ® implants.............................................

certification and ec marking of ceRefoRm ® implants...............................

evaluation of clinical datas............................................................................

prospective clinical follow-up for ceRefoRm ® implants.............................

monitoring post implantation ceRefoRm ® implants on the market.............

ceReplas guarantee...................................................................................

civil liability of ceReplas.............................................................................

appendix 1 ......................................................................................................mechanical tests and biocompatibility trials performedon ceRefoRm ® implants

appendix 2 ...................................................................................................fda certificates for the raw materials for ceRefoRm ® implants

appendix 3 ...................................................................................................certificates for ceReplas and ceRefoRm ® implants

appendix 4 ...................................................................................................civil liability insurance certificate

Useful links

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/// introduction

for several years breast implants pre-filled with silicone gel have been very widely used. The rules governing the manufacturing process and usage of breast implants and more generally those which apply to all medical devices, have been strengthened to ensure safe and effective devices are offered to the patient. The strict regulations have lead to improved manufacturing process and the quality of the medical devices.

In the interest of transparency ceReplas would like to provide you with more information on the technical characteristics of its ceRefoRm ® range of breast implants pre-filled with silicone gel.

our ability to offer high quality implants at a competitive price is a direct result of the choices ceReplas made in its manufacturing process. These revolutionary manufacturing choices have, of course, required significant investment by ceReplas but the results are a superior product at affordable price to clients. The state of the art design and manufacturing facility employs the latest technology available and in some instance very unique and exclusive to ceRefoRm ® breast implants. The robotics used in creating implant envelopes is just one of such examples, ceReplas has also devised a very unique envelope surface texturing process where texture is achieved by a negative replica of the mould surface, ceReplas uses autogenous welding of the patch and performs numerous controls on each implant. This enables us to obtain repeatability, reliability, and faultless, 100% pure silicone implant of excellent quality without any contaminants.

We have complete control of our manufacturing process and raw materials and therefore of the finished product. ceRefoRm ® confirms the product standard and quality with a battery of about thirty standardised tests for biocompatibility and mechanical performance as well as by physical, chemical and biological tests.

3

/// rAW MAtEriALS uSEd BY cErEPLAS

ceReplas specifies that ceRefoRm ® implants are ce certified and have undergone more than 20 biocompatibility tests and 12 mechanical tests to attest to this (see appen-dix 1). The silicon raw materials used by ceReplas are pure, approved, biocompatible and can be used for long-term implantation.

Rigorous controls are conducted by our supplier (Nusil Technology ; the leading company in the field of implantable medical silicones) on each new batch of material in order to comply strictly with our specifications. In addition, the materials we use have all been the subject of an approval by the american Health administration ; the fda (food and drug administration) (see appendix 2).

/// tEcHnicAL cHArActEriSticS oF cErEForM ® iMPLAntS

The silicone envelope of ceRefoRm ® implants has a medical grade silicone layer known as the “ Barrier layer ”. This silicone “ Barrier ” has been developed and optimised with the specific aim of maximum limitation of the passage of silicone gel particles through the envelope. This barrier layer is contained between two layers of “ envelope ” silicone. This provides the ceRefoRm ® envelope with a trilaminar structure.

more than 120 hours of work, i.e. 5 days working continuously, are required to produce an implant before sterilization

The automated manufacturing process: automation of the raw material filtration stages, measurement of viscosity, loading of raw materials, filling, dip coating of the envelope and barrier layers (14 to 16 dippings depending on the implant profile), cross-linking stages, etc. provides great repeatability and prevents human error.

e

eB

Trilaminar structure envelope

G

e eB

e : « envelope » layerB : « Barrier» layerG : Cohesive gel

« Barrier»layer incorporated

into the patch

B G

Patch

4

This process also makes it possible to obtained managed thicknesses with no discon-tinuity or fragility (particularly around the equator).

The patch for ceRefoRm ® implants also contains a “ silicone barrier ” layer in order to limit the phenomenon of the silicone perspiration at any point in the implants. for better patch resistance, the patch is over-molded to the envelope, making it possible to obtain autogenous welding which is more effective mechanically than simple bonding.

ceRefoRm ® implants are made of a medical grade cohesive cross-linked gel reducing any risk of excessive inflammation if the envelope should rupture. The cohesiveness of the gel also ensures that the gel does not spread into the breast tissue if the envelope breaks.The implant is filled through a "filling channel” along the patch thus making it possible to avoid weakening the patch by perforating it.

The mechanical performance of the implant and the compatibility between the gel and the envelope are also constantly monitored by the performance of stability studies and regular quality controls. This enables us to state that the gel we use does not weaken our envelope.

Texturing of ceRefoRm ® breast implants is performed directly on the mould and not by the addition of a texturing agent (such as salt). This avoids any weakening of the envelope by the texturing agent.

The breast implants are sterilised with ethylene oxide and are single use.

/// controLS PErForMEd on cErEForM ® iMPLAntS

So that production and product conformity are properly managed, our implants are controlled individually :

• 12 point thickness control ;• control of the autogenous welding of the patch ;• visual inspections of the implant at several stages during the manufacturing process ;• control of the sealing of blister packs ;• control of the sterilisation parameters ;• visual inspection after sterilisation. These unit controls are completed by destructive controls on implants sampled regularly and randomly from the production line (see appendix 1) :

• Integrity of the envelope :- lengthening on rupture- Remanence to traction- Resistance to tearing

• Patch bonding resistance;• Static rupture (compression);

5

• Fatigue test;• Impact test; • Cohesiveness and gel penetration;• Fatigue test;• Characterisation of the silicone ;• Measurement of the gel perspiration through the envelope ;• Endotoxins and bioloads.

The implants are manufactured in a clean room, Type Iso 7 (or “ class 10,000 ”) in which the atmospheric parameters (temperature ; pressure and hygrometry) are controlled.

In addition, 25 weekly microbiological controls are carried out to check the cleanliness of our working environment, which is validated every year by an independent organisation.

/// cErtiFicAtion And cE MArKinG oF cErEForM ® iMPLAntS

CEREPLAS is ISO 13485 certified and complies with the requirements of European Directives 93/42/CEE and 2007/47/CE relating to medical devices. These standards enable CEREPLAS to obtain CE marking (See Appendix 3).

To prove the conformity of its products with the regulations in force, ceReplas is subjected at least once a year to quality audits. These audits are carried out by the Organisme Notifié (LNE/G-Med [French notified body], accreditation number 0459) appointed by the ministry of Health and renowned for its rigorous regulatory procedures.The purpose of these audits is to control our activities concerning medical devices. In particular this involves our traceability system and our strict control of quality of our raw materials.

during 2011, ceReplas was audited 3 times by the lNe/G-med and was inspected by afssaps (french Health products safety agency). In particular, the aim of this inspection was to check that the declarations made by breast implant manufacturers about the raw materials and processes were in line with what occurs in practice.

To date CEREPLAS has not been implicated in any non-conformity affecting the integrity of its products or the raw materials it uses. our raw materials are traced from their manufacture to transformation. our traceability system also enables us to retrace accurately the manufacturing history of a given implant at any time.

/// EVALuAtion oF cLinicAL dAtA

The evaluation of clinical data has involved an analysis by ceReplas of the scientific literature concerning existing breast implants on the market. This has contributed to setting the thresholds for the occurrence of complications generally encountered in breast implants pre-filled with silicone gel.

6

This evaluation was performed in two stages. The initial report summarised the data for 100% silicone breast implants, including all generations up to 2006 ; its amendment focuses on third generation breast implants (publications dating from 2006 onwards). an update of the bibliographical data will be made during the 2nd half of 2012.

as a reminder, the third generation implants evolved after the moratorium on breast implants, which until then were filled with silicone oils or more liquid gels and which presented a very high perspiration “ gel bleed ” rate through the envelope. The manufac-turers, therefore, have designed more effective implants, said to be “ third generation ” or “ shape memory ”, with a very cohesive silicone gel and an envelope that greatly limits perspiration (incorporation of a layer known as a “ Barrier ” layer). ceRefoRm ®

implants come into this category.

The statistics gathered in the amendment are thus more relevant, but it must be stressed that the follow-up for third generation implants is not yet sufficient to obtain long-term data from this.

Adverse effects

Implanttype

Operationindication

Date of occurencee Extrem values

Capsule contracture

All

All

2 years 0.8 to 7.5%3 years 1.9 to 18.9%5 years 20.6%6 years 14.8 to 20.5%

Primary augmentation

2 to 6 years

0.8 to 14.8%revision augmentation 2.2 to 20.5%Primary reconstruction 5.9 to 18.9%revision reconstruction 6.1 to 16.3%

rupture All All3 years 0.0 to 7.7%6 years 2.3 to 9.3%11 years 8.0%

Infection All All 2 to 11 years 0.0 to 7.4%Pain All All 2 to 6 years 1.1 to 9.6%

Hematoma / Seroma All All 2 to 5 years 1.0 to 9.3%

Wound healing problem All All 2 to 6 years 1.5 to 6.4%

Incorrect position / Displacement All All 2 to 6 years 1.4 to 8.5%

Asymmetry AllAll 3 to 6 years 0.8 to 22.9%

Augmentation3 to 6 years

0.8 to 3.7%revision 6.7 to 22.9%

folds / Undulations All All 3 to 11 years 0.5 to 10.2%

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► Performance of third generation implantsThe complication rates obtained in the amendment were mostly lower than those in the initial report. This rate reduction is explained by better quality implants and by better managed surgical technique. The complications for which a rate increase is observed are complications that are better detected and better supervised today.

► Critical analysis of this dataThe number of studies used to gather the data for the amendment remains low. This is explained by the fact that the research studies are studies published from 2006 onwards in order to select articles dealing with 3rd generation breast implants, equivalent to those from ceReplas. as breast implants have been closely studied due to their history, the new publications consider very specific cases and are not therefore useful for our amendment.

The maximum prevalence in the initial bibliographical study and the amendment are summarised in the table below :

Adverse effects

Type d’implant

Operation indication

Date of

occurence

Maximum prevalence (bibliographical study) All generations of implants

included

Maximum preva-lence (amendment)

3rd generation implant

Capsularcontracture

All All

2 years 9% 7.5%3 years - 18.9%5 years - 20.6%6 years - 20.5%10 years 67.1% -

rupture All All

3 years - 7.7%6 years - 9.3%8 years 10% -10 years 40% -11 years - 8%

Infection All All - 7.7% 7.4%Pain All All - 53% 9.6%

Hematoma / Seroma All All - 11.8% 9.3%

Incorrect position / Displacement All All - 3.9% 8.5%

Asymmetry AllAugmentation

-11.8% 6.7%

reconstruction 61% 11%folds or Undulations All All - 8% 10.2%

Healing problem All All - 2.8% 8.4%

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a new analysis of the bibliographical data will be performed during the 2nd half of 2012 in order to obtain even more accurate data.

This bibliographical analysis serves as a reference and is, of course, completed by a specific clinical follow-up involving 210 patients with ceRefoRm ® implants, which began in January 2009, and by increased market surveillance. These subjects are dealt with in the following chapters.

/// ProSPEctiVE cLinicAL FoLLoW-uP For cErEForM ® iMPLAntS

The preclinical trials performed on ceRefoRm ® breast implants pre-filled with silicone gel have made it possible to obtain ce marking. However, we know that a certain number of complications can be associated with breast implants. for this reason, in order to improve the knowledge about events linked to breast implants occurring in the long term and to assess the safety of ceRefoRm ® implants, ceReplas has decided to extend patient follow-up (initially planned as 2 years in accordance with the meddeV 2-5/7 Rev1 (July 1998) guideline: Guidelines for conformity assessment of breast implants according to directive 93/42/cee relating to medical devices) to 10 years for all patients included in the follow-up.

In this context, and in compliance with the request from the agence française de sécurité sanitaire des produits de santé [french Health products safety agency (afssaps)], this clinical follow-up will make it possible to observe the evolution of ceRefoRm ® breast implants over the long term. This follow-up has also been set up in accordance with the standard, Nf eN Iso 141555 : Clinical investigation of medical devices on human subjects - Right clinical practises and began in January 2009.

> Follow-up objectives

Main objectiveThe main objective is to evaluate the performance and safety of the ceRefoRm ® breast implant for breast augmentation and breast reconstruction by estimating, at regular intervals and finally at 10 years after implantation, the frequency of occurrence of the three following local complications :

• sudden or progressive rupture of the implant / deflation ;• retractile capsular contracture ;• rotation rate (for anatomical implants) ;• the systemic complication rate.

Secondary objectivesThe secondary objectives are to evaluate the frequency of occurrence of other adverse events that could be caused by ceRefoRm ® breast implants.

They are:• revision surgery ;

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• problems with nipple sensitivity ; • problems with breast sensitivity ; • displacement of the implant ;• poor wound healing (hypertrophic or cheloid scar) ; • haematoma ;• modification of breast consistency, a lump in the breast ;• modification of breast volume or breast shape, ptosis ;• pain in the breast ;• change in the appearance of the breast, skin folds ;• a discharge or a seroma ;• a local (around the implantation area) or general infection ;• asymmetry ;• inflammation ;• an autoimmune disease ;• breastfeeding difficulties ;• local complications ;• any other complication linked to the implant, to be specified by the investigator.

The secondary objectives will involve evaluating and assessing patient satisfaction and well-being as well as the satisfaction of the investigator with the aesthetics of the result obtained.

> Study populationIn order to define the desired population in the context of this follow-up, inclusion and non-inclusion criteria have been defined so that, the study population represents, the best way possible all women that may contemplate having breast implants.

Main inclusion criteria• the patient is female ;• the patient is over the age of 18 and under the age of 60 ;• the patient will receive at least one CEREFORM ® breast implant during a breast reconstruction following a mastectomy or during cosmetic breast surgery.

Main non-inclusion criteria• the patient refuses to sign the informed consent form ;• the patient presents with evolving (unstabilised) breast cancer.

> Method of observation and investigation selected

Evaluation by the investigatorThe evaluation of the safety and performance of ceRefoRm ® implants by the inves-tigator is based on the evaluation of the main variables, which are the rate of retractile capsular contracture and the rupture rate.

Retractile capsular contracturecapsular contractures are evaluated using the Baker classification as reference.

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Rupture / Deflation of the implantIf a rupture is suspected, the surgeon may need to use medical imaging to confirm / overturn the diagnosis.

Evaluation by the patientThe patient participates fully in the evaluation of the efficacy of ceRefoRm ® implants. To do this, the self-assessment questionnaire will be given to the patient before the insertion of the implant, during the inclusion consultation (cinc) and also during the consultation 4 months after implantation (c4m) in order to evaluate her satisfaction and the changes in her quality of life.

> Origin and nature of the personal information collected No complete personal information is required for this follow-up. only the two first letters of the surname and first name will be used. all this information is necessary for the traceability of data. all this information will be collected by the investigator after the patient has agreed to participate in this follow-up.

> Duration and method of follow-upIt is an observational, non-interventional, non-comparative, multi-centre study after placing the device on the market, observing a group of patients with ceRefoRm ® implants in the context of a breast augmentation or reconstruction. The total duration of this observational study is 10 years, with an inclusion duration of 4 years.

This study will be performed by means of several follow-up consultations: 1 inclusion consultation the week before the operation, 3 consultations during the first year after implantation, and 1 annual control consultation during the following 9 years.

The patients will be included in 20 centres. Inclusion frequency is 1 patient per centre per month during the inclusion period (4 years). The number of patients to be included is 30 with a maximum of 50 patients per centre.

> Data analysis method

Analysis factorsan ITT analysis will be used. The other analysis factors are: an analysis per implant, per patient, per type of indication, per type of reconstruction, a global analysis of the popu-lation by evaluation criterion, a global analysis and by clinical evaluation criterion group.

Analysis criteriaa global analysis for each group of different complication rates based on the Kaplan meier method will be performed. a presentation of the rate of complications with their confidence interval at 95% will be carried out.

> Justification of the number of patientsTo evaluate the main objective, we define the four main evaluation criteria (studied variables) :

• the capsular contracture rate ;• the post-operative rupture rate ;• the rate of implant rotation (anatomical implants) ;• the rate of systemic diseases.

The size of the sample is determined by the formula :

With : n = sample size, e = margin of error, then you set e=5%, t = the margin coefficient deducted from the confidence level. If a result presented in the form of a confidence interval at 95% is required, then t = 1.96The term p(1-p) varies between the values 0 and 0.25. If an upper bound of the sample size is required, the maximum value of p(1-p) is taken, i.e. 0.25, corresponding to p = 0.5 (e.g. the appearance of a rupture occurs in one in two cases at the end of 10 years – the most unfavourable case. If a finer approach which minimises the error on the evaluation of size is required, the average value is taken, i.e. 0.175 which corresponds to p = 0.226. p(1-p) = 0.226*(1-0.226) = 0.1749 is set.

from it you deduct n = 1.96² x 0,1749 / 0,05² = 268,8 ~ 269 patients

after a decision by the ccTIRs*, the number of patients has been reduced to 210.

> Intermediate results of the follow-upTo date, 137 patients have been included, of whom 124 patients have undergone operations. The inclusion period will end in october 2013. out of these 124 operated patients, 116 came for their consultation at 1 month, 77 at 4 months and 32 at 1 year. The complications encountered with ceRefoRm® breast implants were minimal.The most significant complications were :

• At 1 month : - a stage 3 contracture in 1 patient (0.9%)- an infection in 2 patients (1.8%), including one due to incorrect placement of the Redon drain- a seroma in 2 patients (1.8%)

• At 4 months : - a stage 3 contracture in 1 patient (1.4%). This contracture was combined with a seroma and seemed to be due to an intolerance to the analgesics- a rotation in 1 patient (1.6%)- a fold in 1 patient (1.6%)

• At 1 year : no complications were reported

No cases of rupture have been shown.

patient satisfaction at 4 months is excellent because 100.0% of patients answering the questionnaire were satisfied with the results.

* (french advisory committee on Information processing in material Research in the field of Health)

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n = t². p.(1-p)e²

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/// MonitorinG AFtEr PLAcinG cErEForM ® iMPLAntS on tHE MArKEt

> Prospective clinical follow-up for CEREFORM ® implantssee previous paragraph

> Market monitoringThis is possible through feedback from clients from increased market monitoring both through the sales force in the field and government agencies.

client feedback sources are:

• client claims made to telephone exchange operators ;• analysis of clinical complications observed with our implants ;• analysis of product returns ;• materials vigilance declarations relating to our products and competitor products ;• reports from marketing managers ;• information gathered directly from the engineers and the Quality Department.

> Clinical complications observedon 31/12/11, 261 clinical complications have been observed in a total of 151 187 implants supplied, i.e. 0.17%. These complications are summarised in the table below:

In the majority of cases, gel fractures are detected at implantation. The implants are exchanged immediately and this does not cause any consequences for the patient.

Number of observed complications (31/12/11)

80

70

60

50

40

30

20

10

0

fracture o

f the g

elfolds

rotation / tu

rning over / d

isplac

ement

loss of en

velope in

tegrity

Baker III

& IV capsular

contracture

infection

abrasion

seroma

74

3751

3919 23

153

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When the integrity of the envelope is in question, we ask for the implant to be returned to us for investigation, in order to determine whether it can be proven that the implant is at fault.Ruptures of the envelope that we have observed and analyzed are all linked to the implant coming into contact with hard objects.

No ruptures linked to implant wear have been demonstrated.

Investigation procedure carried out on each returned implant

1- Traceability of raw materials using the production monitoring software

during this stage, we routinely check the material batch numbers and the quality controls performed on the implant under consideration. even though this step is performed when the batches are released on return from sterilisation, it is performed again to ensure that the implant has been manufactured in compliance with our manufacturing processes.

2- microscopic observations if the implant has ruptured

The shape, size and depth of the lesion on the envelope routinely shows us if the implant envelope has been weakened by coming into contact with a sharp or hard object as it was implanted.

3- Registration of the claim with the Quality System

> Materials vigilance declarationsIn 2011, eight materials vigilance declarations concerning our breast implants were made by surgeons to afssaps.

1- The complication concerns a gel fracture detected at implantation (January 2011).

2- The complication concerns a rupture of the implant envelope after being implanted for less than a year. after investigation on our part, it proved that the rupture was linked to the use of surgical instruments during the operation.

3- an erroneous declaration concerning a pIp brand breast implant (february 2011).

4 & 5- The complication concern gel fracture detected at implantation (april 2011).

6- The complication concerns a suspicion of self-mutilation with injection of liquid and gas into the interior of the prosthesis (september 2011).

7- The complication concerns a suspicion of rupture, not confirmed on explantation (November 2011).

8- The complication concerns a cohesiveness problem not checked yet by our services (december 2011).

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In 2011, ceReplas made 3 materials vigilance notifications :

1- one complication concerns an implant rotation which led to explantation (November 2011);

2- one complication concerns a problem of folds leading to explantation (december 2011);

3- one complication concerns a rupture of the implant envelope after being implanted for 7 months. after investigation on our part, it proved that the rupture was linked to the use of surgical instruments during the operation (december 2011).

> Evolutions / Modifications to the rangeThe analysis of client feedback also enables us to adapt our products to the expectations of surgeons, within the regulatory framework.

any modification to the ceRefoRm ® range and the procedure is only made after analysis, management and control of possible new risks which could appear.

It is within this approach that the various evolutions and modifications to the range (addition of a reference ; addition of identification marks on anatomical implants ; improvement of the differentiation between ceRefoRm ® implants, the pre-filled sizers and the samples) were made. lNe/Gmed are notified of significant modifications so that they may be evaluated within the framework of ce marking before being implemented.

/// tHE GuArAntEE oFFErEd BY cErEPLAS

Within the scope of the guarantee for its ceRefoRm ® breast implants, ceReplas offers to replace breast implants for which rupture is linked to a loss of envelope integrity which was confirmed by ceReplas. The implant alone must be at fault. Implants in which the envelope has been damaged by an instrument during the operation are not covered by the guarantee.

as soon as it is confirmed by ceReplas that the implant alone is at fault, ceReplas offers free replacement of damaged implants by any other implant in the ceRefoRm ® range.

/// tHE ciViL LiABiLitY oF cErEPLAS

civil liability insurance is compulsory. all ceReplas products are insured within the framework of civil liability. The insurance certificate is attached at appendix 4.

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Driven by a stated, constant desire to develop and perfect the quality of the products and services it offers you, CEREPLAS is implementing the necessary means to meet your requirements in the best possible way.

We remain at your disposal to answer any possible remarks or questions at

the following address:

questions@cereplas.com

To illustrate our commitment to excellence we can arrange for you to visit our manufacturing facility on request.

Sébastien FERRET / Scientific Manager

David LELEU / Director of CEREPLAS

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— Appendix 1 —

17

— t

EcH

nic

AL c

HAr

ActE

riS

ticS

oF

cEr

EFo

rM

® iM

PLAn

tS —

S

TAN

DA

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VA

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RE

QU

IRE

D B

Y T

HE

STA

ND

AR

DC

ER

EF

OR

M ® R

ES

ULT

S

EN

VE

LOP

ME

NT

leng

then

ing

Nf

eN Is

o 1

4607

> 4

50%

869%

Rup

ture

forc

eN

f eN

Iso

146

07≥

17,3

N (a

vera

ge v

alue

cal

cula

ted

from

im

plan

ts o

f com

petit

ors)

21.5

N

Rem

anen

ce to

trac

tion

Nf

eN Is

o 1

4607

< 1

0%4.

22%

Res

ista

nce

to te

arin

gN

f eN

Iso

146

0724

.4 k

N/m

(ave

rage

val

ue c

alcu

late

d fro

m

impl

ants

of c

ompe

titor

s)37

.3 k

N/m

patc

h bo

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g re

sist

ance

Nf

eN I

so 1

4607

Res

ista

nce

of th

e bo

ndin

g fo

llow

ing

300%

stre

tchi

ng fo

r 10

seco

nds

Hol

d o

K -

Impl

ant i

ntac

t

GE

L C

OH

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ION

ove

rflow

of t

he p

endu

lous

sec

tion

afte

r 30

min

utes

Nf

eN Is

o 1

4607

≤ 30

mm

0 m

m

RE

SIS

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CE

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TIG

UE

com

pres

sion

cyc

le ;

40 m

m ;

3.3

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Nf

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4607

The

impl

ant m

ust r

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n in

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CT

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a 4

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the

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ant

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o 1

4607

The

impl

ant m

ust r

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n in

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d o

K -

Impl

ant i

ntac

t

DIF

FU

SIO

N T

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loss

of s

ilico

ne th

roug

h pe

rspi

ratio

nN

f eN

Iso

146

07N

o sp

ecifi

c re

quire

men

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ompl

iant

with

our

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cific

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ns

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ates

Nf

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o 1

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No

spec

ific

requ

irem

ent

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plia

nt w

ith o

ur s

peci

ficat

ions

AB

RA

SIO

N T

ES

T

mea

sure

men

t of l

oss

of m

ass

afte

r 500

0 ab

rasi

on c

ycle

s (a

bras

ive:

woo

l)N

f eN

129

47-2

No

spec

ific

requ

irem

ent

com

plia

nt w

ith o

ur s

peci

ficat

ions

18

— BiocoMPAtiBiLitY tEStS PErForMEd on cErEForM ® iMPLAntS —

Types of test Standards applicable

pyrogenicity test european pharmacopoeia (Version 5)

cytotoxicity test Nf eN Iso 10993-5

Haemocompatibility test: haemolysis test on human blood Nf eN Iso 10993-4

Haemocompatibility test: complement activation test

on human plasmaNf eN Iso 10993-4

micronucleus test Nf eN Iso 10993-3

Test for induction of chromosomal aberrations Nf eN Iso 10993-3

mutagencity test (ames test) Nf eN Iso 10993-3

acute systemic toxicity test Nf eN Iso 10993-11

Irritation test Nf eN Iso 10993-10

Irritation test by intradermal injection Nf eN Iso 10993-10

chronic toxicity and local tolerance test (implantation)

Nf eN Iso 10993-6Nf eN Iso 10993-11

Toxicity test on reproduction: prenatal evaluation Nf eN Iso 10993-3

Toxicity test on reproduction: evaluation on the first generation Nf eN Iso 10993-3

19

— Appendix 2 —

20

21

22

23

24

— Appendix 3 —

25

26

27

28

29

30

31

32

33

34

35

36

37

38

— Appendix 4 —

39

40

l100

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-aN

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