Process Engineer – Upstream/Downstream Process

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Process Engineer – Upstream/Downstream Process

Role
Provide technical expertise in Upstream/Downstream processing to offer support to the commercial manufacturing of therapeutic proteins in a mammalian cell culture facility.
The successful candidate will be responsible for ensuring that manufacturing processes are validated and maintained within their validated states. Take leadership for on-going optimization of the Upstream/Downstream process and, in additional, act as a manufacturing Subject Matter Expert (SME) to support the continued manufacture and supply of quality biologic products.
Ensure the delivery of process excellence and reliability in all areas of the manufacturing process. Provide input to ensure the facility design meets end user requirements.
Provide previous technical experience and process knowledge to support ongoing optimisation of the upstream/downstream process. The Process Scientist/Engineer will be a key contact in technical troubleshooting of upstream/downstream unit operations and leading/supporting major process investigations as request.
May be required to support both upstream and downstream areas as needed and according to areas of expertise.

Duties/Responsibilities:
• Provide expertise in the design, commissioning, and qualification of the new manufacturing facility, ensuring that all necessary plans are executed and delivered in a timely matter.
• Provide technical knowledge in establishing the routine manufacturing operations and commercial process by serving as a commercial manufacturing process SME.
• Use Six sigma tools to lead root cause problem solving.
• Identify and lead process improvement projects and cost reduction projects and work cross functionally to prioritize projects/support demands from the Business Unit.
• Work closely with the extended manufacturing team, ensuring any actions and plans are understood and accounted for in alignment with plant operations plans.
• Participate in cross-functional project teams as applicable; Implement process CAPA’s and performance improvements, conduct investigation trending.
• Ensure investigations are closed on time, recurring deviations are tracked, and that true root cause and effective CAPA are identified and implemented.
• Author APQR and process impact assessments to support investigation closure as applicable.
• Author or review, and approve process validation strategies, protocols and reports.
• Coaching fellow process engineer/scientist and manufacturing personnel to increase technical knowledge of critical process steps and develop plans to build competencies and expertise.

Upstream
• Provide SME support for cell harvest technologies e.g., centrifugation, depth filtration and perfusion technologies.
• Provide expertise for all aspects of mammalian cell culture process; vial thaw through to harvest.
• Assess and monitor culture performance through Viable cell density, metabolite and nutrient monitoring relating to cell culture performance and product quality.
• SME for bioreactor control strategies, e.g.; DO, pH, feed, base CO2 etc.

Downstream
• Proven expertise for associated purification equipment and technologies.
• Expertise in the modes of operating downstream processes such as Chromatography, Virus Filtration and Inactivation, Depth Filtration, UFDF and Bulk Drug Substance Filling
• Lead the analytical monitoring on processes such as protein concentration, impurity monitoring and clearance (HCP, DNA etc) and the impact to product quality.
• Proven expertise in technical troubleshooting and column packing techniques.

Technical Skills/Knowledge:
Upstream
 Operation of upstream processes: cell culture, perfusion and harvest technologies
 Skilled at interfacing with project teams and inter-departmental / inter-site stakeholders to ensure the manufacturing facility will operate as per the user requirements.
 Upstream analytical monitoring: Viable cell density, nutrient and metabolite monitoring and how these are related to cell culture performance and product quality.
 Knowledge of Bioreactor design and concepts.
 Deep understanding of bioreactor control strategies e.g. DO, pH, feed, base CO2, etc.
 Have an awareness of cell culture characterization and validation studies e.g. LIVCA, KLa Studies and their purpose

Downstream
 Operation of downstream processes.
 Downstream analytical monitoring; protein concentration, impurity monitoring and clearance (HCP, DNA etc) and the impact to product quality.
 Column packing techniques and troubleshooting.
 Proficient with design and development of automation control recipes (Delta V and applicable PLCs).
 Deep understanding of chromatography theories and principles
 Skilled at interfacing with project teams and inter-departmental / inter-site stakeholders to ensure the manufacturing facility will operate as per the user requirements.
 Strong understanding of downstream segregation principles and contamination prevention, e.g. viral, microbial and cross product control

Requirements
• Third level qualification in a Science or Engineering related subject is essential.
• Substantial knowledge and experience in Upstream and/or Downstream processing in a large-scale biopharmaceutical facility with proven expertise.
• Proven ability of delivering tech transfer activities for new products is an advantage for the candidate.
• Experience in a GMP/Commercial manufacturing in a mammalian Cell culture and/or associated Downstream processing.
• Previous experience in the generation of sampling plans.
• Interpretation of process trends e.g. bioreactor profiles, chromatograms, etc.
• Experience in the design and execution of process validation studies e.g. PPQ- mixing, hold, membrane and resin lifetime studies etc.
• Experience in a client facing role is an advantage.