Principal Scientist, Formulation & Drug Product Development

Key Accountabilities / Core Responsibilities

• Independently drive formulation and drug product development activities for one or more of Denali's large molecule biotherapeutics including: developing an understanding of key mechanisms of degradation for each potential therapeutic; designing and executing appropriate formulation development studies to identify clinical and commercial formulation & dosage form, establish shelf life of DS & DP, assess in-use compatibility, and support comparability assessments; developing stress comparability strategies to support process changes and scale-up; overseeing drug product process development activities as well as DP process characterization and process validation activities to support clinical and commercial manufacturing.
• Hands-on biophysical and biochemical characterization of protein therapeutics in the laboratory using chromatography-, capillary-, spectroscopy-based analytical methods with a focus on evaluating product stability, compatibility, and comparability.
• Translate understanding of critical quality attributes (CQA) and key mechanisms of degradation into robust, stable formulations and dosage forms that ensure product quality and efficacy.
• Perform rigorous risk assessments of the impact of drug product manufacturing and storage conditions on product quality.
• Author technical documents including formulation development reports, ICH-compliant stability protocols, and relevant sections of regulatory filings to support external QC partners and regulatory submissions.
• Oversee formulation and drug product manufacturing activities at external contract manufacturing organizations (CMO) including review of stability protocols, DP process development studies, tech transfer activities, review of drug product analytical control system specifications and DP-specific analytical method transfer and qualification protocols/reports.
• Lead troubleshooting activities and serve as subject matter expert (SME) for Quality investigations at CMOs.
• Participate and be actively engaged in cross-functional technical decision-making including collaborating with Discovery Biotherapeutics, Bioprocess Development, Analytical Development and Quality.
• Contribute to establishing internal state-of-the-art formulation capabilities to support accelerated CMC development.

Qualifications/Skills

• Typically a PhD in Chemical Engineering, Pharmaceutical Sciences, Biophysics, Analytical Chemistry, or related scientific discipline and 10+ years of relevant industry experience in formulation and drug product development for protein therapeutics or BS/MS with commensurately greater directly relevant experience.
• In-depth knowledge and extensive hands-on experience in developing a wide array of analytical protein characterization and biophysical methods (e.g. HPLC-based methods, cIEF, capillary electrophoresis, LC/MS, peptide mapping, spectrophotometry, SPR, light scattering, etc.).
• Prior experience with high concentration liquid formulation development; prefilled syringe (PFS)/combination device process development; and/or process characterization/validation considered a strong plus.
• Demonstrated track record of successfully developing biotherapeutic protein formulations as well as transferring and qualifying DP-related analytical methods at CMOs for protein therapeutic development programs including familiarity with applicable GMP requirements.
• Strong grasp of statistical approaches for data interpretation and analytical method development.
• Demonstrated ability to work effectively and collaboratively with other scientists on cross-functional projects teams as well as CMOs.
• Excellent critical thinking, scientific problem-solving, and organizational skills.
• Excellent oral and written communication skills.
• Motivated, detail-oriented, naturally curious individual with a creative approach to scientific problem solving and a positive outlook.