Pre-clinical Pharmaceutical R&D

We are uniquely placed to offer biotech, pharmaceutical companies and CDMOs a range of (R&D) services in a co-creative manner in support of pre-clinical drug substance and drug product development programs, aligned with regulatory guidelines to facilitate development toward the clinical phase. Our independent, interdisciplinary team of experienced and highly qualified/world-class scientists and consultants has expertise ranging from analytical, inorganic, organic & physical chemistry covering a broad range of materials from small molecules, polymers and peptides through to antibodies and proteins.

We work in a dedicated and professional manner to meet your specific pharmaceutical R&D needs assisted by extensive state of the art research equipment. Intellectual property ownership lies solely with the client and is handled, confidentiality assured, in professional manner through, for example, regular update meetings, timely written reports and the efficient transfer of data packages to outsource partners.

Identification is one of the first universal tests for any drug substance specification sheet under ICH Q6A (LINK). Unambiguous structure elucidation of new drug substances through comprehensive analytical characterization form the basis of validated test methods – e.g. MS, 1D and 2D NMR and chiral chromatography in the event of chiral compounds – during early pre-clinical discovery/development and reference spectra used for the identification of safety and clinical batches during later pre-clinical and clinical phases. We offer the following orthogonal analytical techniques and more to enable a comprehensive structure elucidation typically working on a milligrams of compound:

• • FTIR & UV/VIS spectroscopy: functional groups and conjugated systems.
  • GC-MS, UHPLC MS/MS, MALDI-MS & HRMS : molecular weight compound and information about characteristic fragments.
  • NMR spectroscopy : atom connectivity.
  • Vibrational circular dichroism spectroscopy : solution-phase determination of absolute configuration.
  • Single crystal X-ray diffraction: solid-phase determination of atom connectivity and absolute/relative configuration.

The identification and quantification of organic, product and process-related impurities during early pre-clinical development can help to accelerate later-stage pre-clinical and early development, during which new batches of new drug substances require identification and qualification when present above predefined thresholds, before release for use in safety and clinical studies, for example in the case of organic impurities under ICH Q3A(R2) for drug substance and ICH Q3B(R2) for drug product. With this in mind, our team can align with your specific development project making use of a broad range of chromatographic, mass spectrometry, spectroscopic techniques.

The control of solvents used for or generated during the manufacture of batches of drug substance and drug product to within predetermined safety criteria is a requirement for use in the clinic according to ICH Q3C(R8) and is thus an important consideration during pre-clinical development, especially when it concerns solvents classified as Class I and II.

Elemental impurities originating from starting materials, reagents, especially metal-based catalysts and solvents as well as process equipment, especially metal-based containers, lines and reactors, could potentially accumulate in the final drug product and must therefore be controlled to within acceptable limit according to ICH Q3D(R1). For this purpose we offer SEM-EDX and ICP-AES techniques for qualitative and quantitative elemental analysis.

During pre-clinical and clinical development, the continuous development and up-scaling of chemical processes is known to unexpectedly throw up novel, anomalous impurities (e.g. black particles or fibres) that visually distinguish themselves from the bulk material. This occurrence can raise quality concerns that should be quickly addressed so that they can be controlled or better prevented. Frequently, the root-cause investigation into such impurities involves some form of analytical characterisation. Our team and the broad range of available analytical techniques are ideally suited to the solving of such complex quality issues.

It is essential that every new drug substance and product meet the regulatory requirements for stability described in ICH Q1A-Q1F prior to use in the clinic. As such, stability testing during the pre-clinical phase aligned with the regulatory guidelines can alleviate development bottlenecks by generating useful information on potential storage conditions and the environmental factors (e.g., temperature, light, humidity etc.) and the chemical and physical properties that influence the drug substance and drug product quality.

• • Our Stability Analysis Services include:
    • Solid-state stability analysis
    • Solution-state stability analysis
    • APIs-excipients compatibility analysis
  • The following techniques are used for stability studies:
    • Thermogravimetric Analysis (TGA)
    • Raman Spectroscopy
    • FT-IR Spectroscopy
    • Differential Scanning Calorimetry (DSC)
    • GC/LC MS
    • X-Ray Diffraction