Sr Scientist I - Analytical Development, Biologics CMC

Exelixis•Alameda, CA

9d•Hybrid

About The Position

The Senior Scientist, Analytical Development, Biologics CMC will support CMC analytical development for biologic therapeutics, with a primary focus on protein characterization using high-resolution mass spectrometry and analytical assay development for antibody-drug conjugates (ADCs). The incumbent will apply deep technical expertise in mass spectrometry, liquid chromatography and electrophoresis to perform assay development and product characterization, and to advance pre-IND and clinical-stage biologics programs. The individual is expected to work hands-on in the laboratory to develop, optimize, qualify, and transfer analytical methods supporting internal CMC development activities and external CDMO/CTL execution. This role will support extended characterization of ADCs, monoclonal antibodies, bispecifics, and other biologic modalities, including intact and subunit mass analysis, peptide mapping, post-translational modification assessment, sequence confirmation, conjugation site analysis, linker-payload related variant identification, DAR-related characterization, and chromatographic peak identification. Strong ownership is critical to ensure the speed, cost-effectiveness, and technical quality of our CMC activities. The individual will work independently and in cross-functional teams, and work effectively with third-party CDMOs and partners.

Requirements

Ph.D. in chemistry, biochemistry, analytical chemistry, pharmaceutical sciences, chemical engineering, protein chemistry, or a related field with relevant industry experience; or, Master’s degree in chemistry, biochemistry, analytical chemistry, pharmaceutical sciences, chemical engineering, protein chemistry, or a related field with 5+ years relevant industry experience; or, Bachelor’s degree in chemistry, biochemistry, analytical chemistry, pharmaceutical sciences, chemical engineering, protein chemistry, or a related field with 7+ years relevant industry experience; or, Equivalent combination of education and experience.
Demonstrated hands-on experience in protein characterization and structural elucidation using high-resolution mass spectrometry, such as Orbitrap and Q-TOF, is highly desired.
Strong technical experience with LC-MS/MS workflows for intact protein analysis, reduced/subunit analysis, peptide mapping, PTM analysis, disulfide mapping, glycan/glycopeptide analysis, sequence confirmation, and chromatographic peak identification is highly desired.
Experience in analytical assay development for ADCs is strongly preferred, including SEC, HIC, RP-HPLC, icIEF, CE-SDS, DAR-related analysis, and residual-free drug analysis.
Experience in higher order structure analysis, such as SEC-MALS, DSC, FTIR, and CD is a plus.
In-depth knowledge of biologics analytical development, protein chemistry, mass spectrometry, chromatography, electrophoresis, and CMC product characterization.
Strong understanding of critical quality attributes for biologics and ADCs, including size variants, charge variants, purity, glycosylation, PTMs, sequence variants, fragmentation, aggregation, conjugation-related attributes, DAR-related species, and linker-payload related variants.
Ability to design scientifically sound studies, interpret complex analytical data, and translate findings into actionable CMC development decisions.
Strong technical writing skills for protocols, reports, SOPs, regulatory sections, and investigation summaries.
Ability to work effectively with cross-functional internal teams and external CDMOs/CTLs.
Excellent communication, presentation, collaboration, and problem-solving skills.
Ability to prioritize multiple programs and deliver high-quality work in a fast-paced environment.
Strong ownership, scientific curiosity, attention to detail, and commitment to technical excellence.

Responsibilities

Serve as a subject matter expert for high-resolution mass spectrometry-based protein characterization of biologics, including ADCs, monoclonal antibodies, bispecific antibodies, and related novel biotherapeutic proteins.
Develop, optimize, and execute LC-MS methods for intact mass, reduced and non-reduced mass analysis, subunit analysis, peptide mapping, PTM identification, sequence confirmation, disulfide mapping, glycosylation assessment, and product variant characterization.
Lead or support assay development for biologics, including methods such as SEC, HIC, RP-HPLC, icIEF, CE-SDS, and residual-free drug analysis
Support ADC-specific characterization, including conjugation site analysis, drug-antibody ratio distribution, linker-payload related variants, conjugatable impurities, payload-related degradation products, and process- or storage-related modifications.
Perform method development and analytical testing to support upstream, downstream, bioconjugation, and formulation process development.
Transfer analytical methods from internal development to CDMOs/CTLs and provide technical oversight for method qualification, validation, and routine testing.
Review and author analytical procedures, SOPs, protocols, technical reports, method qualification/validation documents, and product characterization reports.
Review GMP release and stability testing results, and support OOS/OOT, deviation, change control, and investigation activities related to analytical methods and product quality.
Support CQA assessment and control strategy development by integrating analytical results from mass spectrometry, chromatography, electrophoresis, biophysical characterization, and functional assays.
Support IND/IMPD and other regulatory submission activities, including authoring and reviewing analytical development, characterization, method validation, and control strategy sections.
Collaborate closely with Process Development, DS and DP Manufacturing, Quality Assurance, Regulatory Affairs, Project Management, Discovery, external CDMOs, CTLs, and other partners.
Contribute to building and maintaining internal laboratory capabilities for advanced biologics characterization, including instrument operation, maintenance, troubleshooting, and implementation of new technologies.
Work independently and collaboratively in a fast-paced, matrixed environment while delivering high-quality technical results and documentation.