Position SummaryThe BioProcess Engineer II, Upstream role is responsible for process development, engineering, and technical support of upstream viral vector manufacturing for the Company's gene therapy programs. This position serves as a technical expert for cell culture and bioreactor unit operations, from cell bank thaw and seed train expansion through transfection/infection, vector production, and harvest. The individual will design and execute process development experiments, lead scale-up and scale-down activities, and use a data-driven approach to troubleshoot manufacturing issues, identify root causes, and implement improvements, working cross-functionally to deliver a robust and scalable clinical production process.
Essential Functions- Serve as the process owner/subject matter expert for upstream viral vector unit operations, including cell bank thaw, seed train expansion, cell culture in adherent and suspension formats, transient transfection or infection, vector production, and harvest.
- Design and execute experiments (including DOE) to develop, optimize, and characterize upstream processes for viral vectors with the goal of improving cell growth, productivity, vector titer and quality.
- Lead scale-up of upstream processes from bench scale to pilot and cGMP manufacturing scale (e.g. shake flasks, benchtop, and single-use stirred-tank bioreactors up to 200L), applying engineering scale-up principles such as P/V, tip speed, kLa, mixing time and gas sparging strategy.
- Develop, qualify, and maintain representative scale-down models to support process troubleshooting, process characterization, and robustness studies.
- Operate and support bioreactor systems including set-up, inoculation, monitoring, and control of critical process parameters (pH, DO, temperature, agitation, feed, gassing).Participate in the collection, trending, and interpretation of data from bench scale experiments and large-scale manufacturing, and aid in organization of data for statistical process control.
- Provide technical support during tech transfer and scale-up to internal cGMP manufacturing as well as external CDMO partners.
- Trouble shoot, perform root cause analysis, and recommend corrective and preventive actions for the resolution of deviations, investigations, and process issues.
- Contribute to manufacturing operations, including collaboration with facilities, quality, and manufacturing groups for implementation of the production process in cGMP clinical manufacturing facilities. This can include equipment FAT/SAT, commissioning and qualification, defining user requirements, and support of validation from a process perspective.
- Provide equipment engineering support for upstream processes with a focus on single-use technologies, including support in the creation of custom single-use consumables from design through testing to cGMP operations.
- Draft and review documents including batch records, Standard Operating Procedures (SOPs), qualification protocols, development and tech transfer reports, and investigation reports.
- Meticulously maintain experimental records with detailed observations and maintain laboratory equipment.
- Train Manufacturing personnel and less experienced team members in equipment and process operations.
- Perform ad-hoc and cross-functional laboratory work and/or projects assigned to support business needs and provide developmental opportunities.
Education & Experience- Bachelor's degree in Chemical Engineering, Bioengineering, Biotechnology, or related fields with 5+ years of experience in biopharmaceutical process development and/or cGMP manufacturing operations, including direct hands-on experience in downstream processing required; or
- Master's degree in Chemical Engineering, Bioengineering, Biotechnology, or related fields with 3+ years of experience in biopharmaceutical process development and/or cGMP manufacturing operations, including direct hands-on experience in downstream processing; MS preferred.
- Hands-on experience with viral vector purification for gene therapy applications required.
- Industrial/cGMP experience in upstream cell culture and bioreactor operation required.
- Demonstrated experience with process scale-up and scale-down model development required.
- Cross training across the entire process of viral vector manufacturing (upstream, harvest, downstream purification, and formulation/fill) is a plus.
Knowledge, Skills, & Abilities- Working knowledge of gene therapy principles, including biology and critical quality attributes of viral vector products (vector genome titer, infectious titer, potency, and product- and process-related impurities).
- Strong expertise in mammalian cell culture for viral vector production, including media and feed optimization.
- Knowledge of cell banking operations and seed train expansion
- Extensive hands-on experience with upstream equipment such as incubators, biosafety cabinets, cell counters and metabolite analyzers, and single-use stirred-tank bioreactors.
- Strong understanding of bioreactor engineering and scale-up/scale-down principles (mass transfer, mixing, shear, power input, gassing strategy) and qualification of scale-down models.
- Familiarity with upstream harvest operations (e.g. cell lysis, nuclease treatment) and in-process analytics for viral vectors.
- Good aseptic technique and strong knowledge of cGMP aseptic manufacturing.
- Must have strong authorship and be able to critically review technical GMP documents, interpret results and generate technical conclusions.
- Understanding of relevant regulations and regulatory guidance associated with cGMP and gene therapy products, such as 21 CFR 210-211, FDA CBER guidance for human gene therapy products (CMC), ICH Q5A/Q8/Q9/Q11 and USP.
- Ability to build strong relationships with Quality and Manufacturing to ensure a compliant manufacturing environment and work collaboratively with other team members to support the transfer of processes from Process Development to Manufacturing.
- Good computer skills, including MS Office; familiarity with JMP or similar statistical software.
- Ability to adapt to rapidly changing work environment and shift in priorities; excellent skills in prioritizing, time management, and multitasking across multiple functional areas.
- Ability to work independently with minimal supervision as well as being part of a team.
- Good interpersonal and strong written/verbal communication skills.
- Strong aptitude for problem solving and technical writing; possess a high level of honesty and integrity, highly motivated and detail oriented.
Working Environment / Physical Environment- This role works on site in Louisville, CO.
- Regular work schedule is Monday - Friday, within standard business hours. Flexibility in working schedule, i.e., off hours, weekend work and extended runs, may be required to support manufacturing campaigns.
- This role works in lab, manufacturing, warehouse, and classified cleanroom environments with specific gowning, including exposure to various temperature ranges (ambient, refrigerator and freezer).
- Must be able to gown and gain entry to lab, manufacturing, and cleanroom environments.
- Work involves handling of Biosafety Level 2 (BSL-2) materials, including viral vectors, and requires adherence to biosafety and PPE requirements.
- Travel approximately 10%, including occasional travel to support technical transfer of processes to internal or external (CDMO) manufacturing sites.
- Must possess mobility to work in a standard office setting and to use standard office equipment, including a computer.
- Ability to lift and carry materials weighing up to 50 pounds on occasion.
This position is eligible for a discretionary bonus and equity award. The annual base pay range for this position is below. The specific rate will depend on the successful candidate's qualifications, prior experience as well as geographic location.
$99,100 (entry-level qualifications) to $109,000 (highly experienced) annually
The application window is anticipated to close on 60 days from when it is posted or sooner if the position is filled or closed.
