Engineer III, mRNA Process Development-Downstream

CRISPR Therapeutics•South Boston, MA

35d•Onsite

About The Position

We are seeking an Engineer III to own downstream process development for mRNA drug substance and to carry those processes into GMP production at external CDMOs. This person will design, develop, and scale the purification process from bench through pilot scale in-house, then facilitate the technical transfer, engineering runs, and GMP campaign support at partner sites. The role is engineering-forward and externally facing.

Requirements

BS in Chemical Engineering, Biochemical Engineering, Bioengineering, or related field with 4-6+ years of relevant industry experience; MS with 2-5+ years
Hands-on downstream process development experience with biologics or nucleic acids, including chromatography and TFF at bench and pilot scale
Demonstrated scale-up experience and a working command of mass balance, sizing, and engineering fundamentals applied to bioprocess unit operations
Direct experience transferring a process to an external manufacturing partner, including authoring transfer documentation and supporting execution on site
Experience with DoE and statistical analysis (JMP, Design-Expert, or equivalent)
Strong written and verbal communication, and the ability to influence technical outcomes at a partner site without direct authority

Nice To Haves

Direct mRNA, plasmid DNA, or oligonucleotide downstream experience, including oligo-dT affinity capture and dsRNA clearance
Multiple completed GMP campaigns at CDMOs in a person-in-plant or technical lead capacity
Experience with process characterization supporting late-phase development or BLA filing
Familiarity with single-use technology selection, extractables and leachables considerations, and partner-site automation or recipe configuration
Understanding of LNP formulation and drug product manufacturing as it constrains drug substance specifications

Responsibilities

Develop and optimize downstream unit operations for mRNA drug substance: DNase treatment and reaction quench, clarification and depth filtration, chromatographic capture and polishing (oligo-dT affinity, ion exchange, reverse phase, hydrophobic interaction, core bead or multimodal), precipitation-based purification, TFF/UFDF, and sterile filtration
Screen and select resins, membranes, filters, and single-use components; define binding capacity, loading, buffer, and elution conditions, and generate the data supporting each selection
Develop impurity clearance strategies with defined logs or fold reduction for dsRNA, residual template DNA, protein and enzyme, residual nucleotides and small molecules, endotoxin, and truncated or aggregated RNA species
Address mRNA-specific downstream challenges including viscosity at high concentration, shear sensitivity, aggregation and HMW species formation, membrane fouling, and product loss across the train
Assisting in building scale-up and scale-down models; define scaling parameters, sizing bases, and hold and hydraulic constraints for each unit operation
Perform mass balance, yield accounting, and process fit analysis against each CDMO's actual equipment trains, single-use platforms, and facility constraints — and identify early where the process must be adapted or the site is not a fit
Contribute to CDMO technical assessment and selection: capability gap analysis, equipment and automation compatibility, analytical readiness, and capacity
Design the process to be transferable, favoring platform-standard equipment, commercially available consumables with second sources, and operating ranges that hold at a site you do not control
Own downstream technology transfer to CDMOs end to end: transfer packages, process descriptions, scale-appropriate parameter tables, risk assessments, gap analyses, and resolution of site-specific questions
Review and approve partner-generated documents — batch records, protocols, sampling plans, engineering run plans — and hold the line on parameters that matter while accommodating site practice where it does not
Assist with technical readiness for engineering, toxicology, and GMP campaigns; run pre-campaign risk reviews and define the decision criteria and escalation path before the batch starts
Serve as person-in-plant at partner sites: real-time data review, in-process decision support, and troubleshooting during execution
Drive post-campaign activities: batch data review, yield and impurity reconciliation against the model, deviation investigations, CAPA input, and process improvements for the next campaign
Support commercial and quality colleagues on technical content for statements of work, change controls, quality agreements, and tech transfer timelines
Partner with upstream and IVT process development to co-optimize the process rather than each half in isolation, particularly where reaction conditions drive downstream burden
Work with Analytical Development on method suitability, sample plans, method transfer to the CDMO, and interpretation of purity and integrity data
Interface with Formulation/LNP on drug substance attributes that affect drug product performance, and with Supply Chain on raw material and consumable lead times, second sourcing, and partner procurement timelines
Present development and campaign data at program and platform forums