Dir./Sr. Director, Downstream Biologics Manufacturing

Avalo Therapeutics•Chesterbrook, PA

2d•Hybrid

About The Position

At Avalo (ahh-vah'-low), we are 100% focused on developing treatments for immune-mediated inflammatory diseases with large unmet needs that affect millions worldwide. Our strategy is to develop medicines that target the IL-1β pathway, which is a central driver of the inflammatory process. We share a commitment to teamwork, passion for science, and dedication to patients suffering from acute and chronic inflammatory disorders. Our collective expertise in discovery, development, and regulatory approvals is evidenced in our strong individual track records of advancing multiple therapeutic programs to successful commercialization. Position Summary: The Dir./Sr. Director, Downstream Biologics Manufacturing will provide technical and strategic leadership for outsourced downstream drug substance manufacturing, with primary responsibility for supporting late-stage clinical development and advancing biologics manufacturing processes toward commercial readiness. This individual will serve as the Company's downstream manufacturing subject matter expert and primary technical representative with Contract Development and Manufacturing Organizations (CDMOs/CMOs), ensuring reliable clinical supply while driving manufacturing execution, process characterization, technology transfer, process validation/PPQ, regulatory readiness, and preparation for commercial manufacturing. The Dir./Sr. Director will partner closely with internal and consultant CMC resources, Quality, Regulatory Affairs, Analytical Development, Supply Chain, Program Management, and external manufacturing partners to ensure robust, compliant, scalable, and reliable production of biologic drug substance. The role requires strong technical judgment, ownership, and the ability to influence and drive results in a highly outsourced operating model.

Requirements

Ph.D., M.S., or B.S. in Chemical Engineering, Biochemical Engineering, Biotechnology, Biology, Biochemistry, or a related scientific/engineering discipline.
Typically 10+ years of progressive biopharmaceutical industry experience in biologics process development, technical operations, and/or GMP manufacturing; equivalent combinations of education and experience will be considered.
Demonstrated experience supporting late-stage biologics development, including Phase 3 manufacturing and progression toward process validation and commercial readiness.
Demonstrated experience leading or providing significant technical oversight of outsourced downstream biologics manufacturing at CDMOs.
Experience with monoclonal antibodies, recombinant proteins, or other biologic products.
Demonstrated experience with technology transfer, scale-up, process characterization, and process validation/PPQ.
Strong experience with downstream purification operations, including chromatography, filtration, viral clearance/inactivation, and UF/DF.
Experience leading manufacturing investigations, technical troubleshooting, process risk assessments, and change management in a GMP environment.
Working knowledge of ICH, FDA, EMA, cGMP, and biologics manufacturing regulatory requirements.
Downstream biologics process development, scale-up, and commercial-scale manufacturing.
Harvest clarification and primary recovery operations.
Chromatography operations, including affinity, ion exchange, and other purification modalities.
Viral inactivation, viral filtration, and viral clearance strategy.
Ultrafiltration/diafiltration, concentration, filtration, and bulk drug substance operations.
Resin, membrane, filter, buffer, and raw material strategy.
Process characterization, CPP/CQA assessment, control strategy development, and process validation.
Technology transfer and manufacturing scale-up methodologies.
Manufacturing data review, statistical process monitoring, process trending, and application of quality risk management principles (ICH Q9).
Process-related impurity clearance, including host cell proteins, residual DNA, aggregates, and other relevant impurities.
Comparability and change assessment for late-stage biologics manufacturing processes.
Strong technical leadership and sound scientific judgment.
Strategic thinking with the ability to anticipate and mitigate manufacturing and supply risks.
Demonstrated CDMO relationship management and ability to influence external partners without direct authority.
Strong ownership, accountability, and action orientation in a lean, highly outsourced biotech environment.
Excellent problem-solving, root-cause analysis, and decision-making skills.
Strong cross-functional collaboration and project leadership.
Ability to communicate complex technical issues, risks, options, and recommendations clearly to technical and executive audiences.
Strong regulatory, quality, and inspection-readiness mindset.

Nice To Haves

Direct experience supporting a BLA and/or MAA for a biologic product, including preparation or review of downstream CMC content and responses to health authority questions.
Experience supporting successful PPQ campaigns, pre-approval inspection readiness, and/or transition to commercial manufacturing.
Experience developing or supporting viral clearance strategies and validation studies.
Experience overseeing manufacturing activities across multiple global CDMO sites.
Experience with single-use downstream manufacturing technologies and commercial-scale purification systems.
Experience with digital manufacturing systems, MES, electronic batch records, and manufacturing data analytics platforms.

Responsibilities

Provide technical leadership for downstream drug substance manufacturing supporting all phases of clinical development with a primary focus on Phase 3 and progression toward commercial manufacturing.
Drive downstream manufacturing readiness for clinical supply, process validation/PPQ, regulatory submissions, and commercial launch.
Lead downstream process characterization and validation strategy, including assessment of critical process parameters (CPPs), their relationship to critical quality attributes (CQAs), process robustness, impurity clearance, and development of an appropriate commercial control strategy.
Provide technical oversight during engineering, demonstration, PPQ, validation, and other late-stage manufacturing batches.
Assess manufacturing and process changes for potential product quality, yields, comparability, validation, and regulatory impact in partnership with Analytical, Quality, and Regulatory CMC.
Serve as the technical lead and Company subject matter expert for downstream manufacturing activities performed at external CDMOs.
Lead the technical evaluation, selection, qualification, governance, and ongoing performance management of downstream CDMO partners.
Provide technical oversight of downstream purification processes, including harvest clarification, chromatography, viral inactivation and clearance, filtration, ultrafiltration/diafiltration (UF/DF), concentration, and bulk drug substance operations.
Review manufacturing readiness, campaign plans, batch records, production schedules, process performance, and manufacturing data to ensure successful execution.
Establish strong technical relationships with CDMO process development, manufacturing, quality, engineering, and project management teams; appropriately challenge and escalate technical or execution risks.
Provide technical input to scopes of work, manufacturing agreements, change orders, and contract discussions related to process requirements and CDMO capabilities.
Review and assess batch records, process trends, deviations, investigations, and manufacturing performance data.
Lead technical troubleshooting during manufacturing campaigns and drive or support root-cause investigations for process deviations, non-conformances, and unexpected manufacturing performance.
Evaluate downstream process performance, including step yields, chromatography performance, impurity clearance, viral clearance, filtration performance, product recovery, product quality, and process consistency.
Identify and oversee implement appropriate process improvements while maintaining alignment with late-stage development, comparability, validation, and regulatory requirements.
Working with CDMO’s evaluate resin, membrane, filter, buffer, raw material, and equipment considerations that may impact process robustness, scalability, supply continuity, or commercial readiness.
Lead downstream technology transfers between development laboratories, pilot facilities, and clinical/commercial manufacturing sites.
Own or lead development and review of downstream technology transfer packages, process descriptions, manufacturing instructions, risk assessments, and comparability documentation.
Ensure effective transfer of process knowledge, process controls, scale-up rationale, purification strategy, and manufacturing requirements to external partners.
Partner with Process Development, Analytical Development, and other CMC functions to ensure scale-down models and process knowledge appropriately support late-stage manufacturing and process characterization.
Ensure downstream manufacturing activities comply with current Good Manufacturing Practices (cGMP), applicable ICH/FDA/EMA requirements, and internal quality standards.
Provide technical review and approval, as appropriate, of change controls, deviations, CAPAs, risk assessments, batch records, process characterization reports, validation documentation, and related manufacturing records.
Serve as the downstream manufacturing subject matter expert for regulatory submissions and health authority interactions, including preparation and review of relevant IND/IMPD/BLA/MAA CMC content and responses to health authority questions.
Support regulatory inspections, CDMO audits, and pre-approval inspection readiness related to downstream manufacturing.
Partner with Analytical, Quality, and Regulatory CMC on process-related impurity clearance, viral safety, comparability, process validation, and control strategy.
Proactively identify manufacturing, capacity, process, raw material, resin/filter, equipment, scheduling, and supply continuity risks that could impact Phase 3 clinical supply or commercial readiness; develop and drive mitigation and contingency strategies.
Partner with Supply Chain and Program Management on production planning, inventory requirements, manufacturing schedules, and supply continuity.
Collaborate closely with Quality Assurance, Quality Control, Analytical Development, Regulatory Affairs, Process Development, Supply Chain, and CMC leadership to resolve issues and drive program objectives.
Provide clear technical assessments, risk evaluations, recommendations, and decision options to CMC and senior management.
Track key manufacturing deliverables, timelines, risks, and CDMO performance and ensure timely escalation and resolution of issues.