ABX-CRO advanced pharmaceutical services GmbH

Phase 0 studies, also called micro-dosing studies, are a new regulatory category, guided by the EMEA (CPMP/SWP/2599/02, 2003) and FDA (Exploratory IND draft, 2005) allowing to perform human studies with a considerably reduced tox package, compared to a conventional first in human study, provided that not more than 100 µg substance are administered.

For CNS drug candidates, microdosing is of special interest to investigate BBB penetration, receptor binding, or dose-to-target-organ relationships. Also, first evidence on metabolism can be obtained. Microdosing represents a considerable cost and time advantage and helps to minimise attrition rates in CNS compound development.

ABX-CRO offers different PET study types

Pharmacokinetic PET studies

PET studies using radioanalogues of NCEs labelled with 11carbon allow to quantitatively assess pharmacokinetics and metabolism. In combination with behavioural, clinical or paraclinical data, pharmacokinetic PET studies allow the establishment of dose-efficacy relationships and dose finding.

Pharmacodynamic PET studies

PET studies using cold NCEs in combination with established radiotracers allow to assess pharmacodynamic properties. Using metabolic tracers such as e.g. [18F]FDG, drug effects on metabolism can be studied. Using [11C]-labelled standard ligands to a target molecule, receptor binding properties of the NCE can be assessed in vivo by displacement studies.

PET tracer development studies

For PET radiopharmaceuticals to be developed as diagnostic products in their own right, ABX-CRO performs integrated development programmes from preclinical through to registration.

Services include:

• Strategy consultancy
  
• Custom labelling (11C, 18F, 68Ga)
  
• GMP-radiosynthesis
  
• Radiopharmacology & dosimetry
  
• Human dosimetry
  
• Advanced data analysis
  
• Kinetic modelling
  
• Receptor occupancy
  
• Full service projects

As a dedicated Molecular and Functional Imaging Core Lab, we provide you with comprehensive turn-key solutions covering all aspects of pre-clincal and clinical Imaging:

• Design of Imaging Studies or Sub-studies
  
• Site set-up, including
  
  • Camera QA and certification for study purposes
    
  • Quantitative cross-calibration of PET, SPECT & MRI scanners
    
• Multicentre PET, SPECT & MRI studies, including
  
  • Quantitative normalisation of multi-institutional data
    
  • Handling of data in proprietary formats
    
• Set-up of world-class image analysis panels for
  
  • Visual,
    
  • Semiquantitative (SUV) or
    
  • Quantitative analysis, e.g.
    
  • Kinetic modelling,
    
  • Receptor occupancy studies

Absolute quantification of activity concentrations (Bq/ml) can establish direct comparability of parametric images between systems, points in time, or different subjects.

Using camera-specific calibration factors, along with standardized attenuation and scatter correction, the QSPECT suiteTM, enables absolute quantification of SPECT data obtained on any conventional SPECT or SPECT/CT system. The quantitative comparison of image data between sites (multi-centre setting), intra-individually (follow-up), or against reference data is facilitated.

QSPECT was developed by Prof. Hidehiro Iida at the NCVC, Osaka, Japan.

*The QSPECT suite*TM

The QSPECT suiteTM consists of a core module for quantitative reconstruction, specialized modules for summary report, and a regions-of-interest analysis tool. One or two sets of single- or dynamic-frame images can be reconstructed, in which the two images may be co-registered, enabling two independent scans being combined in a single analysis.

The quantitative accuracy and inter-equipment reproducibility have been demonstrated in previous studies. Several phantoms including a 3-dimensional brain phantom with a realistic head contour and precise grey matter and skull-equivalent structures are available. Experience in more than 186 clinical institutions on more than 60000 clinical scans is a strong support for real quantitative studies using existing SPECT cameras installed at clinical environment.

• Multicentre PET, SPECT & MRI studies, including
  
  • Quantitative normalisation of multi-institutional data
    
  • Handling of data in proprietary formats

Our data management team brings their extensive industry experience to any project. Combining their expertise with our robust CDMS and IT infrastructure, it allows our clients the peace of mind that their data will be captured and validated in strict accordance with industry standards and FDA regulations.
ABX-CRO utilises a validated, 21 CFR part 11 compliant off-the-shelf EDC/ CDMS solution that is capable of handling small single site Phase 1 trials, as well as multinational Phase 3 and 4 trials with ease.

Our services include:

• eCRF, paper CRF or Hybrid solution
  
• CRF Design / guidelines
  
• Double Data entry (paper)
  
• Medical Coding
  
• Electronic loading of external data (i.e. laboratory or central ECG)
  
• CDISC compliant databases

Human radiation safety and efficacy dosimetry in diagnostic and therapeutic imaging using PET and SPECT radionuclides

Toxicology studies from mice to NHP

ABX-CRO´s biostatistics department is headed by Dr. Norman Bitterlich, a pragmatic mathematician, understanding the needs of clinical research and familiar with standard and advanced biostatistical methods (e.g. fuzzy methods).

Sound case number estimations, based on even scarce early phase or literature data, help to minimize our sponsors risk, always having in mind the best trade-off between cost reduction, and trial success.

CFR part 11 compliant high-security hard & software, state-of-the–art customizable EDC solutions, along with specific understanding for the peculiarities of image data, make our biostatistics department an attractive partner for isolated biostatistics projects, or full service projects alike.

By the way - Dr. Norman Bitterlich is a direct decendent of Germany´s famous calculus master Adam Ries (1492 – 1559), who introduced the Arabic numbering system to central Europe.

International multicentre phase II and III trials are challenging for the sponsor, due to differences in language, health care systems, regulatory environments, medical practice, and cultural background.

From our experience with smaller phase II and larger phase III trials, we have come to learn the importance of respecting the local specificities of each country, while placing extreme importance on assuring high standards and comparable data quality for each participating site.
For the successful placement of multinational trials, ABX-CRO provides you with all relevant information, not only on epidemiology and suitable investigators, but also on the regulatory environment, health care system, local therapeutic guidelines, or potential competitive projects.

With our own or collaborative offices in Australia, Brazil, France, Italy, Japan, South Africa, Switzerland, and the US, and a network of home based pharmaceutical research experts, we provide global clinical coverage, at highest quality, affordable not only for big pharma.

International multicentre phase II and III trials are challenging for the sponsor, due to differences in language, health care systems, regulatory environments, medical practice, and cultural background.

From our experience with smaller phase II and larger phase III trials, we have come to learn the importance of respecting the local specificities of each country, while placing extreme importance on assuring high standards and comparable data quality for each participating site.
For the successful placement of multinational trials, ABX-CRO provides you with all relevant information, not only on epidemiology and suitable investigators, but also on the regulatory environment, health care system, local therapeutic guidelines, or potential competitive projects.

With our own or collaborative offices in Australia, Brazil, France, Italy, Japan, South Africa, Switzerland, and the US, and a network of home based pharmaceutical research experts, we provide global clinical coverage, at highest quality, affordable not only for big pharma.

Imaging studies with PET or MRI are of particular interest for drug developments in oncology and the neurosciences. Whether you require small animal imaging in tumor-bearing rodents, or CNS imaging in small or large non-human primates (marmosets, cynomoglus apes), ABX-CRO with its top class service partners provides you with a turn-key solution, ranging from radiopharmaceutical services (e.g custom labelling of drug candidates), through advanced experimental or surgical interventions, performed by specially trained veterinarians, up to quantitative data analysis, using standard or special solutions, optimised around the study purposes. If human metabolism is to be modelled, mini-pig imaging may be an attractive alternative to primate imaging.

According to sponsor and project requirements, we offer PET projects in collaboration with leading institutions in Europe, North America and Japan.

Phase 0 studies, also called micro-dosing studies, are a new regulatory category, guided by the EMEA (CPMP/SWP/2599/02, 2003) and FDA (Exploratory IND draft, 2005) allowing to perform human studies with a considerably reduced tox package, compared to a conventional first in human study, provided that not more than 100 µg substance are administered.

For CNS drug candidates, microdosing is of special interest to investigate BBB penetration, receptor binding, or dose-to-target-organ relationships. Also, first evidence on metabolism can be obtained. Microdosing represents a considerable cost and time advantage and helps to minimise attrition rates in CNS compound development.

ABX-CRO offers different PET study types

Pharmacokinetic PET studies

PET studies using radioanalogues of NCEs labelled with 11carbon allow to quantitatively assess pharmacokinetics and metabolism. In combination with behavioural, clinical or paraclinical data, pharmacokinetic PET studies allow the establishment of dose-efficacy relationships and dose finding.

Pharmacodynamic PET studies

PET studies using cold NCEs in combination with established radiotracers allow to assess pharmacodynamic properties. Using metabolic tracers such as e.g. [18F]FDG, drug effects on metabolism can be studied. Using [11C]-labelled standard ligands to a target molecule, receptor binding properties of the NCE can be assessed in vivo by displacement studies.

PET tracer development studies

For PET radiopharmaceuticals to be developed as diagnostic products in their own right, ABX-CRO performs integrated development programmes from preclinical through to registration.

Services include:

• Strategy consultancy
  
• Custom labelling (11C, 18F, 68Ga)
  
• GMP-radiosynthesis
  
• Radiopharmacology & dosimetry
  
• Human dosimetry
  
• Advanced data analysis
  
  • Kinetic modelling
    
  • Receptor occupancy
    
• Full service projects
  

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