Molecular Analysis
The Molecular Analysis team delivers structural characterisation and identification of biological medicines and related materials using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry; including both qualitative and quantitative (SI-traceable) analysis of these materials. We undertake research to aid the development of standards and control testing of biological medicines. We also perform control testing of biological medicines and ad hoc testing of small molecule drug products, counterfeit pharmaceuticals, and cosmetic-pharmaceutical products.
For NMR analysis we utilise a 700 MHz Bruker Avance NEO NMR Spectrometer fitted with a QCI-F (quadruple resonance (HCNF/D)) cryoprobe and a SampleJet robot, and TopSpin and MestReNova software.
For mass spectrometry analysis we utilise a Thermo Scientific Orbitrap Eclipse Tribrid Mass Spectrometer fitted with a High-Field symmetric Waveform Ion Mobility System (FAIMS Pro), or Thermo Scientific TSQ Quantiva Triple-Stage Quadrupole Mass Spectrometers, each coupled to a Vanquish HPLC. We use a variety of software, including Peak Studio, Peak GlycanFinder, Biopharma Finder and Proteome Discoverer. We also possess a Thermo Scientific KingFisher Apex automated sample preparation system.
Contact nmr@mhra.gov.uk and tim.rudd@mhra.gov.uk for further information.
Recent publications:
GLP-1 agonist, semaglutide use in acute pulmonary embolism recovery: a four0week proof-of-concept study including proteomic profiling
NMR reveals functionally relevant thermally induced structural changes with the native ensemble of G-CSF
Formulation Science
The Formulation Science team produce pilot batches of freeze-dried candidate biological reference materials. We screen various excipients (buffers, salts, sugars, polyols, etc.) to select the best performing formulation for each biological, using the appropriate functional and biophysical tests, with modalities ranging from peptides to polysaccharides, proteins to viral vectors, bacteria to mammalian cells, and vaccines.
We use thermal analytical methods such as Differential Scanning Calorimetry (DSC) and Freeze-Drying Microscopy (FDM) to find the glass transition temperature of the frozen solution (Tg’) and the collapse temperature (Tc), respectively. Tg’ and Tc help us determine the freeze-dry cycle parameters, especially the temperature of the primary drying step, and so produce an elegant ‘cake’. Our quality control measures include weight checks of fill homogeneity, and measurement of oxygen and water vapour levels in the headspace of the sealed vials or ampoules after freeze-drying; these confirm long stability of our products.
Optimal formulation and freeze-dry cycle parameters for each biological reference material are then technology transferred to our Production team for the ‘definitive fill’ of eventual NIBSC catalogue products.
Recent publications:
Impact of Formulation Choives on the Freeze-Drying of an Interleukin-6 Reference Material.
Contact formulationscience@mhra.gov.uk for more information.
NGS & Bioinformatics
The NGS team leads or collaborates on projects covering multiple omics modalities: whole genome sequencing (WGS), whole exome sequencing (WES), RNA sequencing (RNAseq), amplicon and shotgun sequencing. These projects span a variety of biological samples, including viruses, bacteria, microbiomes, and human cell lines. We utilise the Illumina MiSeq and NextSeq2000 for short-read sequencing, alongside the Oxford Nanopore Technologies MinION for long-read sequencing. Recently, we’ve enhanced our capabilities in single-cell omics with the BD Rhapsody Single Cell Analysis System.
Our facility is committed to supporting innovative biological research by developing reference standards for a diverse range of organisms. We actively participate in WHO studies, evaluating virus panels using both short-read and long-read sequencing technologies. Additionally, our team contributes to the development of guidance documents.
Contact ngs.bioinformatics@mhra.gov.uk for more information.
Biostatistics
The Biostatistics team provide expert statistical input across the Research, Standardisation and Control Testing programmes.
We provide statistical consultancy and analysis as required by Research projects, including the development and maintenance of relevant statistical methodologies, models and tools. We also guide the design, analysis and interpretation of international multi-centre collaborative studies to establish biological reference materials, and contribute to assay validation, experimental design and analysis, data monitoring and review, by our Control Testing teams.
The team collaborates with various external organisations and working groups including the World Health Organisation (WHO) and the European Directorate for the Quality of Medicines & Healthcare (EDQM), contributing to regulatory scientific publications, reports and WHO/Pharmacopoeial documentation.
Contact statistics@mhra.gov.uk for more information.