Akkreditiert durch ZentralsteIl d"" LAnd r

fOr Gesundhellsschulz bei Arzneimitteln

und Mediz.!nproduklen

ZLG-P·974.98.05

Project #

Sponsor

Study title

Test items

Reference item

Authors

Test facility

Study dates:

Arrival of test items

Begin of testing

End of testing

Final report date

mdt medical device testing GmbH

Grenzenstrasse 13 0-88416 Ochsenhausen Germany Phone +49· (0) - 73 52 - 91 14-0 Fax +49 - (0) - 7352 - 91 14-70

FINAL REPORT

09y138

BioCer Entwicklungs-GmbH Ludwig-Thoma Straße 36c 95447 Bayreuth Germany

Comparative material characterization of HaemoCer® and PerClotTM in accordance with ISO 10993-18

Sodium carboxymethyl starch: HaemoCer® and PerClotTM

Not applicable

Andreas Röhrig (Study Director) Jan Peeters (Director Testing Services)

mdt medical device testing GmbH physico-chemical laboratory Bahnhofstrasse 11 884160chsenhausen Germany in cooperation with

• FEM Forschungsinstitut Edelmetalle & Metallchemie

• PSS GmbH

• SGS Institut Fresenius GmbH

28-August-2009

14-September-2009

14-0ctober-2009

22-0ctober-2009

According to DIN EN ISO/IEC 17025, mdt medical device testing GmbH does not assume Iiability for potential misleading presentations of study methods and results of this report, if the report is reproduced in extracts.

Final report Date: 22-0ctober-2009 Page 1 of 36 of project # 09y138 Version # 1

C.

~

Copy of GLP Certificate

Baden~ürtteD1berg UMWELTMINISTERIUM

Gute Laborpraxis I Good Laboratory Practice

GLP-Bescheinigung I Statement of GLP Compliance (gemäß laCCOfding 10 § 19b ChemikalIengesetz)

Eine GLP-Inspektion zur Überwachung der EinhaltJJng der Assessment of conformity wlth GLP according 10 Chemi­

GLP-GrundsälZe gemäß ChemikaliengeselZ bzw. Richtlinie kaliengeselZ and Dlrectlve 8B1320/EEC at: 88/320/EG wurde durchgeführt In:

l:8J PrüfelnrichtungITest facility D Prüfstandortrrest site

mdt medical device testing GmbH

Grenzenstraße 13

88416 Ochsenhausen (Unverwechselbar. Bezeichnung und AdresselUnequlvocal name and address)

Prüfungen nach Kategorien/Areas 01 Expertise (gemäßlaccordlng ChemVwW-GLP Nr.5.3/0ECD guidance)

9 Biologische, chemische, physikalische, physikalisch­mechanische und vergleichende Prüfung von Medizinproduk­len

Mikrobiologische-hygienische Prüfungen von Medizinproduk­ten einschließlich Desinfektionsmittel, Reinigungs- und S1erili­sationsyerfahren

Datum der InspekUonlDate of Inspeclion (Tag. Mona!. Jahr/day. monlh. year)

5.8.2008

DielDer genannte Prüfeinrichtung/Prüfstandort befindet The above mentioned test facility/test site is included In the sich im nationalen GLP-Überwaehungsverfahren und wird national GLP Compllance Programme and Is Inspected on regelmäßig euf Einhallung der GLP-GrundsälZe überwecht a regular basis.

Aul der Grundlage des Inspektionsberiehtes wird hiermit Based on the inspecUon report it can be confirmed, that this bestätigt, dass In dieser Prüfelnrichtung/diesem Prüfstand­ test facllity/test site Is able to conduct the aforementioned ort die oben genannten Prüfungen unter Elnhallung der studies in compliance with the Principles of GLP. GLP-GrundsälZe durchgeführt werden können.

Unterschrift, DalumlSignature, Date

~~o..l...."--

Adebahr Stuttgart, 17.12.2008

(Name und Funktion der verantwortlichen Person/Name and lunebon 01 respenslble

Umweltministerium Baden-Württemberg Kemerplatz 9, 70182 Stuttgart

(Name und Adresse der GLP-Uberwachungsbeh5rdeINeme end address 01 GLP MonIIoring Authorlty)

Keroerplatz 9 . 70182 Stutlgart (WS: SI••tsgaJeno) . H8uptstätter Str. 67 . 70178 Stuttgart (WS: ÖS,ecreichiscber Platz)

Behinderteogerechle Parkplätze vorhanden

Telefon 0711 126-0· Telefax 0711 126-2881 . postslelle@um.bwl.de

WW'W.um.boden-wue.ra:emberg.de· www.service-bw.de

Final report Date: 22-0ctober-2009 Page 2 of 36 of project # 09y138 Version # 1

Statement of Compliance

mdt Project # 09y138

Title Comparative material characterization of HaemoCer® and PerClofTM in accordance with ISO 10993-18

Study Director Andreas Röhrig

The following parts of this study were performed in cooperation with accredited testing facilities and were, therefore, not be conducted in compliance with the GLP regulations:

• 'ICP Investigation of inorganics' (refer Chapter 3.3.): Forschungsinstitut Edelmetalle & Metallchemie (FEM), Schwäbisch Gmünd

• 'GPC Measurements (Molecular Weight Distribution)' (refer Chapter 3.4.): PSS Polymer Standards Service GmbH, Mainz.

• 'Scanning Electron Microscopic (SEM) Investigation' (refer Chapter 3.5.): SGS Institut Fresenius GmbH, Dresden

All other parts of this study, performed in the testing facilities of mdt medical device testing GmbH, were conducted in compliance with

• Good Laboratory Practice Regulations as laid down in the Chemical Act "Chemikalien­gesetz" of the Federal Republic of Germany, Annex 1 dated July 2, 2008 (BGBI. IS. 1146).

• OECD Principles of Good Laboratory Practice (as revised in 1997); OECD Environmental Health and Safety Publications; Series on Principles of Good Laboratory Practice and Compliance Monitoring - Number 1. Environment Directorate, Organisation for Economic Co-operation and Development, Paris 1999.

There were no relevant deviations trom the study protocol dated 10-September-2009 and no circumstances that may have affected the quality or integrity of the study.

Minor deviations, if applicable, are listed in Chapter 6, "Deviation from the study protocol".

Study Director:

Ochsenhausen, 2b : /0 "'OOS .

Andreas Röhrig Study Director mdt medical device testing GmbH

Final report Date: 22-0ctober-2009 Page 3 of 36 of project # 09y138 Version # 1

4.3. Investigation of Insoluble Inorganics

ICP-Screening

The ICP screening of the pulping extracts showed the presence of the following elements:

Sampie Detected Elements

09y138-01 HaemoCer® extract _......__._----_..­

Ca, Fe, K, Mg, P, Sand Sr ...._._----_.._-~ •....._.. ,.. __..._ ...

~.._­09y138-02 PerClot™ extract Ca, Fe, K, Mg, P, Sand Sr

Table 1: Results of the ICP screening

ICP-Quantification

After the screening the solutions of the starch sampies were subjected to the quantification of the identified inorganic ions. The individual results are given in the following Table 2.

Sampie HaemoCer® showed higher amounts of calcium (Ca) and phosphor (P), whereas the sampie PerClotTM showed higher values for iran (Fe) and magnesium (Mg). The content of strontium (Sr) was just above the limit of quantification for the HaemoCer®. A high amount of sulfur (S) was detected for sampie PerClotTM compared with sampie HaemoCer®.

Sampie # Amount [ppm] Ca Fe K Mg P S Sr

Limit of Quantification 1 2 5 1 5 5 1

09y138-01 HaemoCerQl) extract ._.

200 <2 16 18 670 17 ..._ ...­ ........_._-_...

2

09y138-02 PerClot™ extract 69 7 250 42 420 3900 <1

Table 2: Results related to the test material weight

Final report Date: 22-0ctober-2009 Page 20 of 36 of praject # 09y138 Version # 1