MediTox s.r.o.


EXPERIMENTAL SERVICES

Custom tailored program for non-clinical development, testing and support of CTA/MA to meet the needs of the clients and partners from pharma/biotech/medical device/food industry (EMA, ICH/VICH, FDA, ISO 10993/USP 88, EFSA)

Standard safety testing program to meet the needs of the clients and partners from chemical/agrochemical industry (ECHA, OECD TG - Section 4, US EPA)

In vitro test system: bacteria, mammalian cells

In vivo test system: rodents (mouse, rat, hamster, guinea pig), non-rodents (rabbit, ferret, cat, dog, non-human primates, pig/mini pig)

Facilities available:
Experimental housing: conventional and barrier housing, BSL II facility for small laboratory animals
Laboratory premises: fully equipped experimental surgery room, X-ray imaging, Laboratory of toxicology, Laboratory of clinical pathology, Laboratory of pathology and histopathology

Administration routes: besides of common administration routes (oral and parenteral, topical), intra-cardial, intra-articular, intra-ocular, intra-nasal and implantation (sub-cutis, muscle and bone) are available

Alternative methods of testing according to OECD, and/or ECVAM/ICVAM are strictly preferred whenever it is rational and justified.

Other services: consultancy in non-clinical toxicology, toxicopathology, quality assurance (revision of study documentation, consultany and implementing GLP)

Species: Non-rodent: Dogs, cats, rabbits, ferrets, pigs/mini pigs, non-human primates
Rodent: Mice, rats, hamsters, guinea pigs
Bacteria/mammalian cell cultures
Way of administration: Oral, buccal, sub-lingual, intra-venous, intra-muscular, intra-peritoneal, intra-cardial, intra-dermal, intra-cranial, intra-nasal, intra-tracheal, intra-articular, intra-vitreal, rectal, vaginal, dermal, sub-cutaneous, ocular, implantation (into the muscle, sub-cutis, bone)

HUMAN MEDICINE AREA

General toxicology - Exploratory
Test/Study Specification Method
Maximum tolerated dose (MTD) Rodents, non-rodents
Clinical and clinical-laboratory observation, gross pathology
EMA/CHMP/SWP/81714/
2010, CHMP/SWP/302413/08
Dose range finding study
(DRF, 7 – 90 days)
Rodents, non-rodents
Repeated administration, 7d/wk exposure, clinical and clinical-laboratory examination, gross pathology, optional histopathology
CPMP/SWP/1042/99 Rev. 1 Corr.
Pilot, proof-of concept studies Rodents, non-rodents
Depends on the study range
-
General toxicology - Regulatory
Test/Study Specification Method
Acute (Single dose) toxicity Rodents
Limit test/Full study
OECD 420, 423, 425, 402, EMA/CHMP/SWP/81714/2010
Extended single dose toxicity study Rodents
Clinical and clinical-laboratory observation, gross and histopathology
CPMP/ICH/286/95,
ICH M3(R2)
Sub-acute toxicity studies (7 – 28 days) Rodents, non-rodents
Repeated administration, 7d/wk exposure, clinical and clinical-laboratory examination, gross pathology, full set of histopathology
Optionally: TK sampling, recovery
CPMP/SWP/1042/99 Rev. 1 Corr,
OECD 407, 410
Sub-chronic toxicity studies (90 days) rodents, non-rodents Rodents, non-rodents
Repeated administration, 7d/wk exposure, clinical and clinical-laboratory examination, gross pathology, full set of histopathology
Optionally: TK sampling, recovery
CPMP/SWP/1042/99 Rev. 1 Corr,
rodents OECD 408, 409, 411
Chronic toxicity study (6 months) Rodents, non-rodentsrodents
Repeated administration, 7d/wk exposure, clinical and clinical-laboratory examination, gross pathology, full set of histopathologyrodents
Optionally: TK sampling, recovery
CPMP/SWP/1042/99 Rev. 1 Corr, CPMP/ICH/300/95
OECD 452
Chronic toxicity study (9 – 12 months), Non-rodents
Repeated administration, 7d/wk exposure, clinical and clinical-laboratory examination, gross pathology, full set of histopathology
Optionally: TK sampling, recovery
CPMP/SWP/1042/99 Rev. 1 Corr, CPMP/ICH/300/95
OECD 452
Genetic Toxicology (subcontracted)
Test/Study Specification Method
Gene mutation in bacteria Ames test (plate incorporation method) OECD 471, ICH S2(R1)
Mammalian chromosome aberration in vitro Human lymphocytes, two experiments OECD 473, ICH S2(R1)
Erythrocyte micronucleus in vivo, rodents
Note: males only, subcontracted
Murine micronucleus, three dose levels OECD 474, ICH S2(R1)
Erythrocyte micronucleus in vitro Human erythrocytes, three dose levels OECD 479, ICH S2(R1)
Mouse lymphoma assay (MLA) Mice, two experiments OECD 476, ICH S2(R1)
Comet assay Mammalian cells OECD 489
Cytotoxicity in vitro Murine fibroblasts ISO 10993-5
Local Effects (Irritation, Sensitization, Local Tolerance)
Test/Study Specification Method
Skin irritation in vivo Rabbit
Observations at 24h, 48h, 72h, (-7d & 14d)
OECD 404
Skin irritation in vitro RHE OECD 431
Eye irritation in vivo Rabbit
Observations at 24h, 48h, 72h, (7d, 14d & 21d)
OECD 405
Eye irritation in vitro ICE OECD 438
Skin sensitization: LLNA Mouse
Reduced LLNA/Individual nodes
OECD 429
Skin sensitization in vivo Magnusson, Buehler method OECD 406
Non-clinical local tolerance testing of medicinal products, rodents, non-rodents Guinea pig
Dermal, ophthalmic, vaginal, rectal, etc.
CPMP/SWP/2145/00, ISO 10993
Local tolerance after implantation Rodents, non-rodents
Implantation into sub-cutis, muscle, bone, intra-cardial, etc. including histomorphometry
ISO 10993-6
Safety Pharmacology
Test/Study Specification Method
Safety Pharmacology:
CNS Note: Safety pharmacology end-points can
be included into repeated dose toxicity study
Rodents
Modified Irwin test, rodents
Single or repeated dose
ICH S7
Safety Pharmacology:
CVS Note: Safety pharmacology end-points can
be included into repeated dose toxicity study
Rat, rabbit, Dog, NHP
Single or repeated dose
ICH S7
Pharmacokinetics/Toxicokinetics/Bioavailability (bioanalytical subcontracted)
Test/Study Specification Method
TK/PK/BA/studies Rodents, non-rodents
Administration, blood sampling, samples preparation
CPMP/ICH/384/95, 3BS11A, OECD 417,
Implementation and validation of analytical method
(subcontracted)
Development, implementation and validation of analytical method
(subcontracted)
Sample analysis and results evaluation and statistics
(subcontracted)
Non-Clinical Safety
Test/Study Specification Method
Nonclinical evaluation of the potential for delayed ventricular repolarization Rat, rabbit, dog, NHP
SD/RD administration, ECG, body temperature, blood pressure recording
CPMP/ICH/423/02, CPMP/ICH/539/00,
ICH S7A, ICH S7B
Non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals Rodent, non-rodents
SD/RD administration, clinical, clinical-laboratory examination, gross pathology, histopathology
CPMP/ICH/286/95, ICH M3(R2)
Immunotoxicity/Immunogenicity studies Rodents, non-rodents
SD/RD administration, complex evaluation of clinical, clinical-laboratory, gross pathology, histopathology data in terms of immunostimulation, immunosuppression or immunomodulation
CHMP/ICH/167235/04
Preclinical safety evaluation of biotechnology-derived products Rodents, non-rodents
SD/RD administration, clinical, clinical-laboratory examination, gross pathology, histopathology
CPMP/ICH/302/95, EMA/CHMP/ICH/731268/1998, ICH S6(R1)
Preclinical pharmacological and toxicological testing of vaccines Rodents, non-rodents
SD/RD administration, clinical, clinical-laboratory examination, gross pathology, histopathology
CPMP/SWP/465/95, CVMP/IWP/52/97
Nonclinical evaluation for anticancer pharmaceuticals Rodents, non-rodents
Repeated dose administration, clinical, clinical-laboratory examination, gross pathology, histopathology
CHMP/ICH/646107/2008, ICH S9
Medical Device Biocompatibility
Test/Study Specification Method
Tests for genotoxicity, carcinogenicity and reproductive toxicity Mutagenicity in bacteria, chromosomal aberration test, micronucleus test, etc. ISO 10993-3,
OECD 471, 473, 475, 474, 476, 487, 489
Tests for in vitro cytotoxicity MTT ISO 10993-5
Tests for local effects after implantation Rodents, non-rodents
Implantation to sub-cutis, muscle and bone
ISO 10993-6
Tests for irritation and skin sensitization Eye, skin, mucosa ISO10993-10,
OECD 404, 405, 406, 429, 431, 438
Tests for systemic toxicity Rodents, non-rodents
Acute, sub-acute, sub-chronic, chronic
ISO 0993-11
Efficacy
Test/Study Specification Method
Antiviral efficacy/Immunogencity studies Mouse, rabbit, ferret
Efficacy of anti-influenza therapy (vaccines, small molecules)
EMA/CHMP/VWP/457259/2014,
EMA/CHMP/VWP/141697/2009
Antiglaucoma efficacy Dog
Efficacy of antiglaucoma therapy
Biodistribution (bioanalytical subcontracted)
Test/Study Specification Method
Biodistribution studies after single/repeated administration, non-labeled compounds, biological part (analytical part is subcontracted) Rodents, non-rodents
Biodistribution in blood, urine, feces and tissues, LCMS, HPLC, qPCR
OECD 417, CPMP/ICH/385/95, 3BS11A
Models Available
Chronic glaucoma model in dogs
Influenza model in ferrets
Osteoarthritis model in rabbits, dogs
Acute contact dermatitis model in pigs

VETERINARY MEDICINE and ANIMAL FEED AREA

Veterinary Drug Safety
Test/Study Specification Method
Target animal safety studies Dog, cat, rabbit
D administration, 7d/wk exposure, clinical and clinical-laboratory examination, gross pathology, full set of histopathology, if requested
VICH
Bioequivalence studies Dog, cat rabbit
Administration, blood sampling, samples preparation
VICH
Implementation and validation of analytical method
(subcontracted)
Development, implementation and validation of analytical method
(subcontracted)
Sample analysis and results evaluation and statistics
(subcontracted)
Immersion/Washout study Dogs
Immersion, water & blood sampling, samples preparation
EMA guidelines VICH (1998A), VICH (1998B) and EMA guideline (2012).
Implementation and validation of analytical method
(subcontracted)
Development, implementation and validation of analytical method
(subcontracted)
Sample analysis and results evaluation and statistics
(subcontracted)
Wipe test Dogs, cats
Wiping, samples collection
EMA/CVMP/SWP/
721059/2014
Implementation and validation of analytical method
(subcontracted)
Development, implementation and validation of analytical method
(subcontracted)
Sample analysis and results evaluation and statistics
(subcontracted)
Feed Testing
Test/Study Specification Method
Palatability study Rodents, non-rodents
Palatability testing in laboratory animals
EFSA
Feed safety studies RD administration, 7d/wk exposure, clinical and clinical-laboratory examination, gross pathology, full set of histopathology, if requested VICH, EFSA