Principal Scientist, CMC Analytical Development - Commercial Products

Denali Therapeutics•South San Francisco, CA

2d•$159,000 - $207,000

About The Position

Denali Therapeutics is a biotechnology company focused on developing breakthrough therapies for neurodegenerative diseases. The company has recently launched its first product, AVLAYAH, and is seeking a Principal Scientist to join the Large Molecule Analytical Development Team as a Commercial Analytical Lifecycle Lead. This role will provide technical analytical expertise for commercial manufacturing and QC activities, lead analytical method transfers for in-country testing, and support international registration with global health authorities. The individual will collaborate with peer leads on analytical transfer and registration for a second-source manufacturing site, with the scope expected to expand as more programs advance. Key Responsibilities include providing technical analytical review and approval for commercial manufacturing documents, assessing change controls, serving as an analytical SME for manufacturing deviations and QC investigations, monitoring CMO performance, and ensuring compliance with industry guidelines. The role also involves owning and overseeing analytical method transfers for international testing, developing transfer protocols and reports, and coordinating with regulatory teams. Additionally, the Principal Scientist will provide analytical/CMC technical expertise for health authority responses and collaborate cross-functionally with various departments and CMO counterparts to ensure uninterrupted commercial supply.

Requirements

BS/MS/PhD in Chemistry, Chemical Engineering, Analytical Chemistry, Biochemistry, or related scientific discipline (PhD with 10+ years or MS/BS with 14+ years of relevant industry experience)
Demonstrated track record as a recognized analytical/technical subject matter expert, able to operate with a high degree of independence and exercise sound scientific judgment on complex, ambiguous problems with limited managerial oversight
Significant hands-on experience with biologics analytical methods (e.g., potency/enzymatic activity assays, ELISA, HPLC/UPLC, capillary electrophoresis, mass spectrometry, glycan analysis) relevant to protein/enzyme-Fc fusion products
Direct experience supporting commercial (post-approval) biologics manufacturing, including batch record review, change control, and QC deviation/investigation support (e.g., OOS/OOT root cause analysis and CAPA frameworks)
Experience with analytical method transfer, method validation/qualification (ICH Q2), and technical transfer documentation
Working knowledge of global regulatory requirements and experience supporting health authority interactions or submissions (FDA, EMA, and other international agencies)
Experience working with and providing oversight of external CMOs/contract testing laboratories
Strong written and verbal communication skills, with ability to author clear, defensible technical and regulatory documentation
Ability to travel domestically and internationally as needed

Nice To Haves

Experience with enzyme replacement therapies, Fc-fusion proteins, or rare disease biologics
Experience with products launched under accelerated approval or other expedited regulatory pathways
Familiarity with ex-US and ex-EMA health authority expectations regarding analytical and QC testing requirements
Experience supporting pre-approval inspections (PAI) or health authority audits
Prior experience managing multiple external manufacturing/testing sites simultaneously

Responsibilities

Provide technical analytical review and approval of CMO manufacturing documents for routine commercial production
Perform technical assessment and approval of change controls impacting analytical methods, specifications, reference standards, and QC testing processes in close collaboration with Late Stage Analytical Development, Bioassay Development, and Drug Product Development Leads.
Serve as analytical subject matter expert (SME) for manufacturing deviations and QC laboratory investigations (OOS/OOT, atypical results), including root cause assessment and CAPA evaluation
Monitor ongoing method and process performance trends at the CMO to proactively identify risks to commercial supply or product quality
Provide technical review and approval of APQR in collaboration with Quality.
Ensure continuous compliance of methods and control strategies with current industry guidelines (ICH, Pharmacopeia, FDA/EMA guidance) and best practices (BioPhorum or other consortia white papers).
Own and oversee analytical method transfer activities to support in-country/regional testing requirements as new marketing applications are submitted and approved internationally
Develop and execute method transfer risk assessments and protocols, acceptance criteria, and transfer reports in collaboration with receiving testing laboratories
Coordinate with Regulatory Affairs, CMC, and QA to align method transfer timelines with global submission and launch schedules
Ensure consistency methods/specifications across testing sites and support harmonization where appropriate
Provide analytical/CMC technical expertise in response to health authority questions from regulatory agencies as part of international expansion.
Draft and review technical responses to information requests related to analytical methods, specifications, validation, and control strategy
Partner closely with the peer analytical leads responsible for method/process transfer and scale-up at the second-source CMO to ensure consistent analytical strategy across manufacturing sites and international QC labs.
Collaborate with CMC, Quality, Regulatory Affairs, Supply Chain, and CMO counterparts to support uninterrupted commercial supply
Represent Analytical Sciences on cross-functional teams for commercial lifecycle management activities