Job Description

We are currently looking for highly motivated scientists to join the Pharmaceutical Development Sciences department at UCB’s UK Research and Development Hub in Slough. You will be working on a project with, Polysorbates 80 and 20 (PS80 and PS20) are common surfactants used in biological formulations to promote protein stability, minimise particle formation and prevent interfacial adsorption. However, polysorbates are prone to chemical and enzymatic degradation that can lead to the formation of aldehydes, ketones and fatty acids (lauric, myristic and palmitic acid) which can have a detrimental effect on protein stability. Over long-term storage, these fatty acids can accumulate and precipitate leading to the formation of subvisible particles. Sub visible particles are a critical quality attribute (CQA) for biopharmaceutical formulations and their presence can compromise the safety and efficacy of the drug product. The US Pharmacopeia (USP) <787> requires parenteral formulations to have ≤6000 particles of 10 µm and ≤600 particles of 25 µm per container. Current analytical techniques for sub visible particle analysis are time-consuming, require large sample volumes and fail to distinguish proteinaceous particles from polysorbate particles. Therefore, there is a critical need for the development of fast and selective methods for the identification and quantification of polysorbate-related particles³.

You will be tasked with conducting laboratory-based operations utilizing state-of-the-art technology for particle characterization and analysis. You will receive training in the relevant techniques and will have your own mentor to provide help and advice during your time at UCB. You will help to enable the laboratory to function effectively whilst adhering to correct procedures and health and safety guidelines. This represents a great opportunity to work in industry-leading laboratories at the cutting edge of drug development.

Job Responsibilities

You will be tasked with conducting laboratory-based operations utilizing state-of-the-art technology for particle characterization and analysis. You will receive training in the relevant techniques and will have your own mentor to provide help and advice during your time at UCB. You will help to enable the laboratory to function effectively whilst adhering to correct procedures and health and safety guidelines. This represents a great opportunity to work in industry-leading laboratories at the cutting edge of drug development.

Some of the specific tasks you would carry out are:

• Analyse data and interpret results
• Critically analyse information and drive good quality, data driven
• Prepare solutions, samples, materials
• Perform analytical tests, e.g. Subvisible particle analysis, protein concentration measurements, pH
• Literature review, laboratory training

Project Description

The aim of this project is to develop a high-throughput method to identify and quantify free fatty acid (FFA) particles formed through the degradation of polysorbate 80/20 using Backgrounded Membrane Imaging (BMI) and Fluorescence Membrane Microscopy (FMM) in the Aura+ system (Halo Labs). Different mAb formulations (stressed and non-stressed) will be prepared with various protein and polysorbate concentrations and the total particle count will be determined by BMI. The use of fluorescent labels that selectively bind to different types of particles will enable the identification of proteinaceous vs FFA particles. Samples will be labelled through membrane phase staining with Thioflavin T which specifically binds to protein aggregates and with BODIPY Fl C₁₆ which binds to FFAs and the labelled particles will be counted with FMM. Particle counts obtained through BMI and FMM will then be used to confirm the presence of FFA particles and quantify their relative concentration.

Project Timeline

The estimated duration for this project is 6 months, The general activities are:

• Literature review
• Lab Training
• DoE and study set up
• Sample preparation
• Proof-of-concept studies (try available protocols)
• Confirmation studies (orthogonal testing)
• Thioflavin T staining protocol optimisation
• PS80 staining protocol optimisation
• PS20 staining protocol optimisation
• Data Analysis
• Report Writing