Senior Scientist, Large Molecule Analytical & Formulation Dev (Characterization)

Denali Therapeutics•South San Francisco, CA

30d•$147,000 - $191,000

About The Position

Denali Therapeutics is a biotechnology company focused on developing breakthrough therapies for neurodegenerative diseases. We are seeking a talented and motivated Senior Scientist with a strong background in characterizing protein therapeutics using mass spectrometry-based tools to provide technical oversight and execution of protein characterization activities in our large molecule CMC analytical development group. This role involves leading internal large molecule CMC-focused mass spectrometry and extended characterization activities, developing phase-appropriate product extended characterization strategies, and hands-on execution of LC-MS based characterization to support various development activities. The position also requires authoring and reviewing technical documents, maintaining lab records, providing analytical support for development activities, and contributing to the overall analytical control strategy for commercialization of complex biotherapeutics.

Requirements

PhD in Analytical Chemistry, Chemical Engineering, Biophysics or related scientific discipline and 3+ years of direct CMC-focused analytical development experience in protein therapeutics within the biotech/biopharma industry (MS with 8+ or BS with 10+ years' experience).
In depth knowledge and extensive hands-on experience developing and applying mass spectrometry-based methods (Intact/reduced MS, subunit analysis, peptide mapping, N-/O-glycosylation profiling, disulfide linkage determination, LC-MS/MS analysis) for protein sequence confirmation, identification and characterization of product variants, and comparability in the context of protein therapeutics.
Well versed in characterizing protein therapeutic product variants and forced degradation samples.
Previous experience authoring relevant IND/BLA sections (e.g. Analytical comparability, Elucidation of Structure, Justification of Specifications, etc.)
Previous experience in developing a wide array of analytical protein characterization and biophysical methods (e.g. HPLC-based methods, cIEF, capillary electrophoresis, LC/MS – based multi-attribute methods (MAM), peptide mapping, spectrophotometry, light scattering, etc.)
Demonstrated track record of successfully transferring and qualifying analytical methods for protein therapeutic development programs, developing control strategies, and successful health authority submissions
Strong grasp of statistical approaches for design-of-experiments (DoE) analytical method development, robustness testing, and data analysis.
Excellent communication, collaboration, organizational, and scientific problem-solving skills.

Responsibilities

Lead internal large molecule CMC-focused mass spectrometry and extended characterization activities including primary sequence determination, PTM analysis, and higher order structure characterization for large molecule CMC portfolio.
Develop phase-appropriate product extended characterization strategies for large molecule CMC portfolio including elucidation of structure for early vs. late phase programs as well as characterization strategy for product variants and forced degraded samples.
Hands-on, technical execution of LC-MS based characterization activities to support comparability evaluations, inform CQA assessments, determine structure-function-activity relationships, and further product understanding.
Author and review technical development documents and relevant sections of health authority filings.
Maintain timely and accurate lab records consistent with good documentation practices.
Ensure rapid and timely analytical support for cell-line, bioprocess, and formulation development activities.
Support late phase analytical development and product characterization activities for one or more large molecule programs in CMC development.
Contribute to the development & implementation of overall analytical control strategy to enable commercialization of complex biotherapeutics.
Oversee product characterization strategy and execution including elucidation of structure as well as characterization of forced degraded panel and minor variants.
Perform critical quality attributes (CQAs) assessments to support phase-appropriate control system strategy.
Provide oversight of analytical method transfer, qualification, and validation activities at external/internal QC laboratories.
Provide oversight of analytical activities supporting late-phase process characterization and process validation studies at external/internal QC laboratories.