Services

Toxicology

Timeline/Pipeline Bioresearch offers toxicology studies to help clients quickly and cost-effectively identify which compounds are unlikely to succeed in further pre-clinical development. Timeline/Pipeline Bioresearch specialises in the conduct of comparative studies in which several compounds are administered to small numbers of rats or mice and limited toxicological assessments are carried out. These studies give an idea of relative toxicity and effect, and facilitate selection of one or two candidates for further investigation.

Standard Protocols:  

  • Formulation
  • Non-specific toxicity
  • Dose Range Finding
  • Determination of maximum tolerated dose (MTD)
  • 7 or 14 days repeated dose toxicity
  • Local irritation/tolerance
  • Implant tolerance

Analysis: 

  • Haematology
  • Clinical chemistry
  • Histopathology

DMPK

Timeline/Pipeline Bioresearch offers a full range of drug metabolism and pharmacokinetic (DMPK) studies to support drug candidate selection.

Study types:

  • Pharmacokinetics
  • Bioavailability
  • Biliary excretion
  • Mass balance
  • Tissue distribution
  • Bioequivalence
  • Blood-Brain barrier permeability
  • Specialized models

Dosing:

  • Single
  • Repeated
  • Cassette
  • Continuous infusion, i.v.
  • Continuous infusion, s.c. Alzet Osmotic pumps

Route of Administration

  • Peroral
  • Intravenous
  • Intravenous infusion
  • Intraperitoneal
  • Intramuscular
  • Subcutaneous
  • Inhalation (nebulization)
  • Intranasal
  • Intratracheal
  • Topical
  • Intradermal
  • Intracardial
  • Intracolonic
  • Intracranial (stereotactic)

Catheterizations

  • Carotid artery
  • Femoral vein
  • Jugular vein
  • Portal vein
  • Bile duct

Samples

  • Blood
  • Urine
  • Faeces
  • Bile
  • Tissues

We perform DMPK studies in the following laboratory animals;

Species Supplier
Mouse Taconic, Harlan, CRL, Jackson
Rat Taconic, Harlan, CRL
Rabbit Harlan, Lidköbing Kaninfarm
Guinea Pig Harlan
Mini-Pig Göttingen/Ellegaard

Isotopes

Timeline/Pipeline Bioresearch offers standard pharmacokinetic studies with the following radioactive isotopes: 3H, 14C, 32P, 35S and 125I

PK screening programs

Timeline/Pipeline Bioresearch understands the need within drug discovery for rapid PK screening. We therefore offer PK screening programmes which allow our clients to evaluate the drugability of their NCE’s almost as quick as they are being synthesized.

Bioanalysis

At Timeline/Pipeline Bioresearch we focus on executing in-life phase services which is our core competence. Many of our sponsors prefer to perform bioanalysis at their own in house laboratories. For clients that do not have these capabilities at hand, we offer professional bioanalytical services at selected CRO’s that focus on this discipline.

Mathematical PK/PD modeling and simulation

Pipeline now offer in collaboration with CANDOR Simulation full mathematical pharmacokinetics/pharmacodynamics modeling service or support as an integrated part of the clients’ experimental animal studies.

Depending on the clients’ needs – and available a priori knowledge about the PK/PD and mechanism of action of the compound – we typically recommend applying mathematical modeling for the following issues:

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Optimal design of experimental in vivo studies

  • Population simulation-based analysis, preferably based on data from a minimal pilot study, enables optimum selection of e.g.
    • sampling times
    • number of animals (power calculations by bootstrap technique)
    • dosage regimens for in vivo PD (drug effect) studies

Processing of experimental time series data

  • Check for nonlinear or time-dependent pharmacokinetics
  • Standard PK noncompartmental analysis (finding T½, Vcc, cL, kel‘, AUC, etc.)
  • Compartmental PK and PK/PD analysis; semiphysiological/mechanism-based modeling
    • estimation of population model parameter distributions
    • quantification of uncertainty and population variance, e.g. confidence limits, and other statistics, such as probability of target attainment, by Monte Carlo simulation

Prediction of PK/PD for arbitrary (hypothetical) dosing scenarios

  • Simulation with fitted compartment model (future animal studies)
  • Translational simulation studies (prediction of human PK/PD) based on available combined data

Benefits of simulation and model-based analysis

  • Method is efficient and robust; works well on both rich and sparse data
  • Design of future studies: secure minimum number of measurements and maximal information through optimised dose size and sampling schedule
  • Once developed, semiphysiological population models can be used to explore various hypothetical animal experiments and untested clinical scenarios through simulation
  • Best way to secure a high scientific, and economic, benefit-cost of experimental studies

Efficacy

Timeline/Pipeline Bioresearch is working with a great variety of different disease models. Some of these are well-known as they are frequently used for research procedures of more general nature. Others on the other hand, are specifically designed and customized for special projects. We have substantial experience in establishing and validating customized models, or even developing new models to meet specific requirements in close collaboration with the client. Lately we have developed standards for validating such models that closely follows the steps in GMP validation.

Standard Protocols (Disease Models):

  • Anti-Haemostasis
  • Appetite Regulation, Schedule Fed Rats
  • Cancer, Breast, DMBA Induced
  • Cancer, Metastasis, B16F10 Lung Model
  • Cancer, Skin, UVB-induced
  • Cancer, Xenograft, Standard Efficacy Study
  • Cirrhosis
  • Colitis, Acute (DSS)
  • Diabetes Type I, STZ Induced
  • Haemostasis
  • Liver fibrosis, CCL4
  • Liver fibrosis, BDL
  • Multiple Sclerosis, Acute (EAE)
  • Multiple Sclerosis, Chronic Relapsing (CREAE)
  • Nausea, PICA Behaviour
  • Obesity, Dietary Induced (DIO)
  • Obesity, Diabetes Type II, Genetically Obese (GO)
  • Obesity, Diabetes Type II, High Palatability Dietary Induced (HP DIO)
  • Oedema, Carrageenin Induced Paw
  • Oedema, Mouse Ear Swelling (MEST)
  • Rheumatoid Arthritis, Collagen Induced (CIA)
  • Wound Healing

Test and Analyses:

  • Bleeding time, template
  • Bleeding time, transaction
  • Blood pressure
  • Body temperature
  • Haematology
  • Heart rate
  • Histopathology
  • Locomotor activity
  • Oral glucose tolerance (OGTT)
  • Volume displacement plethysmography

Cancer models

Timeline/Pipeline Bioresearch offers not only subcutaneous xenograft models but also disseminated and orthotopic models allowing our clients to have a tumor model comparable to human tumor with production of metastasis.

Below are some of our cancer models and cell lines presented. Timeline/Pipeline Bioresearch is highly experienced in setting up cancer models with client specific cell lines and needs with a high focus on quality, timelines and cost efficiency. Please contact us to hear more about a client specific set-up.

Subcutaneous xenograft models:

Tumor model Human cell line
Prostate C4-2; LNCap; PC-3; DU-145
Leukemia HL-60; L-1210;
B cell lymphoma DOHH-2; RAMOS
Hepatic cancer HepG2
Skin A431
Colorectal CT26; HT-29
Ovarian SKOV-3; OVCAR-3
Glioblastoma U-87 MG

Disseminated models:

Tumor model Human cell line
Leukemia 697
B cell lymphoma MEC-2; DOHH-2

Orthotopic models:

Tumor model Human cell line
Prostate LNCap
Breast MDA-MB-231; MDA-MB-453

Syngeneic models:

Tumor model Mice cell line
Colorectal CT26
Lung LLC1
Artificial lung metastases B16F10

Bioassays

Timeline/Pipeline Bioresearch provides bioassay programmes that are designed to meet individual client needs for special purpose testing. Technical services and project management are performed in close dialogue with the client. A flexible approach and direct person-to person communication means that we are able to act as a direct extension of the clients’ own QC departments.

The current batch release tasks of Timeline/Pipeline Bioresearch include potency testing of hormones and therapeutic antibodies according to EP/BP/USP pharmacopoeias. Timeline/Pipeline Bioresearch is certified to do batch release testing in GMP compliance. This implies that Timeline/Pipeline Bioresearch is fit to work with QC departments of production units in the pharmaceutical industry. Please contact us to learn more about the bioassay programmes.

Assays:

  • Complement-dependent cytotoxicity (CDC) assay
  • Phosphorylation-inhibition assay (PIA)
  • FSH stimulation activity
  • LH stimulating activity
  • Anti-Estrogenic activity
  • Estrogenic (Uterothropic) activity