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 |
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| 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) |
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| Development, implementation and validation of analytical method (subcontracted) |
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| Sample analysis and results evaluation and statistics (subcontracted) |
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| 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) |
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| Development, implementation and validation of analytical method (subcontracted) |
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| Sample analysis and results evaluation and statistics (subcontracted) |
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| 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) |
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| Development, implementation and validation of analytical method (subcontracted) |
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| Sample analysis and results evaluation and statistics (subcontracted) |
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| Wipe test | Dogs, cats Wiping, samples collection |
EMA/CVMP/SWP/ 721059/2014 |
| Implementation and validation of analytical method (subcontracted) |
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| Development, implementation and validation of analytical method (subcontracted) |
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| Sample analysis and results evaluation and statistics (subcontracted) |
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| 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 |
