G-TwYST GMP Two Year Safety Testing. WP 3 Feeding trials. Dagmar Zeljenková, Jana Tulinská Slovak Medical University Bratislava.

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1 G-TwYST GMP Two Year Safety Testing WP 3 Feeding trials Dagmar Zeljenková, Jana Tulinská Slovak Medical University Bratislava Slovak Republic 1st G-TwYST Stakeholder Meeting, Vienna 2014Stakeholder Forum Dialogue II 1

2 Slovak Medical University in Bratislava 1. Faculty of Medicine 2. Faculty of Public Health Department of Toxicology Animal rooms 3. Faculty of Nursing and Professional Health Studies 4. Faculty of Health in Banska Bystrica 2

3 Experimental Animal Rooms - Slovak Medical University in Bratislava Current status at SMU Experimental animal rooms were built in The complex consists of 4 parts: 1. Specific Pathogen Free Unit 2. Conventional Unit and Surgery 3. Virology Animal Room / GMO animals/ 4. Aquatic Laboratory In 1995, this workplace obtained Statement of Good Laboratory Praxis Compliance certified by the Slovak National Accreditation Service. Since 1995, workplace observed an authorization for using laboratory animals in experiments certified by the State Veterinary and Food Administration of the Slovak Republic. 3

4 Studies are carried out in the SPF unit following: The revision of EU Directive EC 2010/63 on the Protection of Animals used for Experimental and other Scientific Purposes which determines the minimum Requirements for the Regulation of Animal Experimentation by Member States of the EU. European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes, [Strasbourg, ] The implementation of the principle of the 3R s (Replacement, Reduction, and Refinement) requires that all personnel involved in laboratory animal care and use have the proper education, training and experience when performing animal studies. 4

5 Accreditation In compliance with the Direction of Government of the Slovak Republic No. 377 from November 14, 2012, the experiments which use the animals can be only carried out in experimental facility, which is certified to perform animal experiments by the State Veterinary and Food Administration of the Slovak Republic Accreditation records: Photocopy of the acquisition register References of the Veterinary organisation Operating instructions of experimental facilities 5

6 Accreditation records: Approved projects of experiments Written delegation of responsibility for experimental animal keeping Ethical Committee and Advisory Board Animal source records Regional Veterinary Administration Inspection: once a year Project of experiment - for each individual experiment Once a year report on the number of used animals and the character of animal experiments 6

7 Experimental Rooms Organizational set-up Conventional breeding: laboratory mice, rats, guinea pigs, rabbits, poultry, pigs (Sus scrofa) Barrier breeding (SPF): laboratory mice and rats Ichthyologic laboratory : Danio rerio 7

8 Maximal single-use built-up area: mouse 500 individuals rat 1600 individuals guinea pig 130 individuals rabbit 18 individuals poultry 30 individuals turkey 10 individuals pig (Sus scrofa) 15 individuals 8

9 SPF UNIT 9

10 SPF UNIT 10

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12 Department of Toxicology - Cryobanking 12

13 Toxicity Studies Acute toxicity studies Short-term toxicity studies (repeated dose) Sub-chronic toxicity studies Long-term toxicity studies Chronic toxicity studies Carcinogenicity studies Chronic toxicity/carcinogenicity studies Reproductive toxicity studies Developmental (teratology) studies Genotoxicity (mutagenicity) studies Aquatic toxicity 13

14 Documentation in Experimental Animal Rooms - Principles of Good Laboratory Practice - Operating procedures carried out in experimental animal rooms - Study plans - Methodical Standard Operating Procedures - All records (e.g. records on animal health status, records on food consumption, records on body weight) (accepted by the Slovak National Accreditation Service). 14

15 PROFESSIONAL AND SUPERVISORY STAFF Dagmar Zeljenková, MVD., PhD - Head of Toxicology dpt. Jana Tulinská, MUDr., PhD Imunotoxicology Elena Szabová, RNDr., PhD - Genetics, senior scientist Eva Rollerová, RNDr., PhD Toxicology, Teratolology, scientist Anton Kebis, Dipl. Ing., PhD Toxicology, senior scientist Jevgenij Kovrižnych, Ecotoxicology - scientist Katarína Ambrušová, VMD. - Veterinary and gross pathology Aurélia Líšková, RNDr., PhD Immunotoxicology, Haematology Miroslava Kuricova, Mgr., PhD - Genetics, senior scientist Viera Spustová, Prof., MD., DSc - Clinical chemistry, professor Zora Krivošíková, RNDr., PhD - Clinical chemistry, senior scientist Andrej Černák, Prof., MD., DSc - Ophthalmology, professor Radka Aláčová, MVD. - Veterinary and gross pathology Soňa Wimmerová, RNDr. Statistics Eva Němcová, Mgr. Quality assurance manager Ethics Committee-Ľudmila Novotná, MSc. - Cancer Research Institute, Slovak Academy of Sciences, Vlárska 7, Bratislava 15

16 Laboratory of Clinical and Experimental Biochemistry SMU The Laboratory of Clinical and Experimental Biochemistry of the Slovak Medical University holds an accreditation certificate (M-013) from the Slovak National Accreditation Service and is subject to the national quality control programme for clinical biochemistry and is controlled by the quality assurance unit (QAU) of the Slovak Medical University. The Vitros 250 Chemistry System (Ortho-Clinical Diagnostics, No , USA) performs discrete clinical tests on serum, urine and cerebral spinal fluid specimens. Methodologies include colorimetric, potentiometric and rate tests using multi-layered Vitros Slides 16

17 Laboratory of Clinical and Experimental Biochemistry SMU Laboratory of Clinical and Experimental Biochemistry SMU: Tests in accordance with the Norm STN EN ISO/IEC Methods of clinical chemistry ( ŠPP/LEKB/M001) are proceeded according to the following international Norm IFCC (International Federation of Clinical Chemistry and Laboratory Medicine) a CLSI, or NCCLS (National Committee on Clinical Laboratory Standards). Laboratory takes part in the external quality control twice a year Following control cycle INSTAND e.v., Düsseldorf, Germany. In % success Calibration with certificated reference materials from producer of apparatus Accreditation No. : 061/M

18 Haematological Laboratory (part of Immunotoxicological Laboratory) Blood samples from tail vein will be taken for haematological examination. EDTA will be used as anticoagulant. Blood samples will be stored under room temperature (17-25 C) maximum up to 4 hours until measurement. Haematology analysis will be performed in accordance with SOP: ŠPP/IMU/M002 using Haematological analyzer Sysmex K-4500, SYSMEX TOA Medical Electronics Co. LTD, Japan, No. VČ F

19 Animal Room - Surgery Gross necropsy - A complete necropsy wil be performed on all animals at study termination - The weight of organs will be recorded - Organs will be examined macroscopically for any deviations from normal. - Tissue sampling and trimming of organs - Formalin-fixed and trimmed tissues will be shipped to the Department of Pathology in Hannover (In accordance with ŠPP / TOX / 005) 19

20 Thank you for your attention 20