Strong medicine works miracles.

Rephartox is a Contract Research Organization unlike any other. Located in Lelystad, The Netherlands, Rephartox focuses on biotechnology companies, pharmaceutical companies and (functional) food industries. We do not offer standard solutions, but specialise in tailor-made research projects, consultancy and development programs.

Rephartox is a modest CRO with experts in their field. Rephartox’ focus is to closely work together with the Sponsor to produce results faster and without excess, reducing costs and limiting development time.

Although Rephartox worked on a variety of therapeutic areas over the past years, Rephartox has built a high level of experience on age-related diseases like (prostate) cancer, osteoporosis and cardiovascular diseases.

Services
The state-of-the-art laboratories and animal facilities, but also the dense network with other (in-house located) companies, enable Rephartox to offer a variety of services. These services include animal models, biomarker services, analytical support, formulation services.

Analytical services: Analytical support is essential in drug research and development. Rephartox offers analytical services in the field of bio-analysis and pharmaceutical analysis, including method development and method validation. Methods are performed and validated according to the appropriate guidelines, depending on your goals. Our laboratory is equipped with e.g. liquid chromatography systems (HPLC and FPLC), an atomic absorption spectrometer (AAS), a versatile microplate-reader capable of absorption, fluorescence (time resolved, polarised) and luminescence, as well as electrophoresis equipment.

Animal models:  The use of animals in preclinical studies starts with ethics. Rephartox attaches great value to responsible use of laboratory animals for pre-clinical drug testing. Laboratory animals play a vital role in the drug development process and should be governed with the highest standards of animal care. In order to oversee these standards, we use internal committees for the assessment of our animal protocols. This working method enables us to perform contract research within a competitive time frame while animal welfare is not compromised. This manifests in the use of platforms which comply with the three R’s (reduction refinement and replacement of animals). See for more information under ‘Platforms’.

Rephartox is able to develop, implement and validate animal models. The in-house knowledge of experimental and microsurgical techniques enables Rephartox to offer a wide range of models. Examples of animal models for different therapeutic areas that Rephartox offers are:

Biomarker services: Faster decision making with increased confidence will reduce development costs. Biomarkers can increase the amount of information on efficacy and/or safety of compounds, enabling decision making (pre-clinical lead selection and clinical go/no-go decisions) earlier during drug development. At Rephartox, biomarkers are used during the entire track of drug development from just after drug discovery through late clinical phase studies.
Rephartox is able to provide information on which biomarkers to use during a study, perform biomarker assay validation and bioanalysis.

Formulation:  A successful formulation of a drug is the key to successful delivery of a medicine. At Rephartox we have state of the art facilities to support you in different aspects of (re-)formulation development and subsequent kinetic studies and stability testing. Rephartox can be your strategic partner for the development of new liquid or lyophilised formulations, pre-clinical in vivo efficacy testing of new sustained release formulations to long term stability testing for finished products and active pharmaceutical ingredients (APIs).

Rephartox has developed several long acting proteins, which are currently on the market.

Drug development: Rephartox is using Fast Track Drug Development and Proof of Principle studies for full development of drugs from drug lead optimisation up to and including registration. The time to market of your drug is as short as possible, resulting in reduced development costs and an increased rate of success. Rephartox proved that especially small biotech companies and spin-offs from universities can profit from these services. Usually these companies are not fully aware of the pitfalls in drug development. Rephartox can prevent them from making the mistakes that are easily made in drug development and guide them to registration.

Platforms
Rephartox has different platforms in-house, which are routinely used, like biotelemetry and automated blood sampling.

Biotelemetry enables the collection of physiological data in a freely moving animal. The absence of restraint and connecting tubing during measurement produces reliable results for prolonged periods of time in the animal’s normal housing. Blood pressure, heart rate, ECG and temperature can be continuously collected in mice, rats and guinea pigs. Continuous data acquisition can last for up to three months. Depending on the parameters measured, the telemetric device – transmitter – is implanted subcutaneously or intra-peritoneal in the animal. Biotelemetry can be used to study a wide variety of parameters among which circadian rhythms, thermoregulation and inflammation, cardiovascular effects, gastrointestinal effects, respiration and animal welfare. The technique can be applied for the efficacy and PD of drugs as well as safety pharmacology. In safety pharmacology, biotelemetry can assist in core studies for cardiovascular safety, CNS safety as well as respiratory safety. We have successfully used the technique for the evaluation of QT interval prolongation. Rephartox uses DSI equipment for biotelemetry in mice, rats and guinea pigs.

Automated blood sampling is currently the best platform for pharmacokinetic and pharmacodynamic profiling. Besides the lack of stress for the animal, blood sampling is more precise and more consistent, leading to superior results. 

Recently, in close cooperation with DiLab, Rephartox has shown that with the DiLab AccuSampler® µ, a complete pharmacokinetic profile can be obtained from a single mouse

Rephartox has combined the advantages of permanent catheterizations with a novel automated micro blood sampling technique using the DiLab AccuSampler® µ. Blood is sampled with a “push pull” pump system reducing the dead volume of blood to the volume of the indwelling catheter. With this method volumes as low as 5 µl of whole blood is sampled in the connecting tubing and transported by two pumps to the sample vial.

The micro sampling technique using the AccuSampler® µ enabled Rephartox to perform a 5 sample serial blood sampling protocol. As an example, Rephartox used this method for the pharmacokinetic analysis of interferon and PEGIntron in freely moving and undisturbed mice (see Figures 1A and 1B).
 

Figure 1: Pharmacokinetic profile of interferon and PEG-interferon in mice. A) Interferon and PEGIntron plasma concentration after intravenous interferon (?) and PEGIntron (?) and intra arterial interferon (¦) administration and withdrawal of interferon. B) Interferon and PEGIntron plasma concentration after subcutaneous PEGIntron and interferon administration and intra venous interferon (?), PEGIntron (?) and intra arterial interferon (¦) blood withdrawal.

Quality
Quality is important to Rephartox. The quality system of Rephartox is designed according to international guidelines (e.g. GMP). Our staff is dedicated to maintaining and continuously improving our Rephartox Total Quality System. Our quality system is designed to be in line with the latest guidelines (including validation and bioanalysis guidelines but also AAALAC). This quality system does not prevent flexibility towards Sponsors with regard to data management or assay set-up procedures.

Data integrity is guaranteed by implementation of the NuGenesis scientific data management system (SDMS) at our facilities, which monitors the laboratory network for new or changed data files and automatically creates back-ups.

Please meet us
Rephartox understands that close contacts are important in drug development. Although drug development is a global business, a CRO and Sponsor should work closely together in order to obtain the best and fastest results. Due to Rephartox’ experience and our focus on timelines and quality, Rephartox is able to reduce risks, reduce time and reduce costs in drug development.

Rephartox is always open for discussions, so we would be delighted to meet you, by E-mail, phone or at our premises in Lelystad, The Netherlands.

Working together...