Director, Drug Substance

About the Company

Protego discovers and develops first in class small molecule therapeutics that reprogram protein folding to treat monogenic protein misfolding diseases, including myopathy, cardiomyopathy, stroke, renal, retinal, and other degenerative diseases and channelopathies. Our approach builds on the pharmacological chaperone strategy pioneered by our cofounders, Dr. Jeffery W. Kelly and Dr. Richard Labaudinière, in tafamidis for transthyretin amyloidosis.

About the job

Protego Biopharma is seeking a Director, Drug Substance Development and Manufacturing to provide scientific, technical, and operational leadership for active pharmaceutical ingredient development and manufacturing as our lead AL amyloidosis program advances from proof of concept into a global, registrational Phase 3 program. Reporting to the Head of CMC, this person will serve as the drug substance subject matter expert and accountable technical lead for external process development and manufacturing partners. The role will own small molecule API strategy across synthetic route development, process optimization, scale up, technology transfer, GMP manufacturing, process characterization and validation, solid state control, regulatory filings, supply resilience, and commercial readiness. The Director will partner closely with Analytical Development, Drug Product, Quality Assurance, Regulatory Affairs, Supply Chain, Clinical Supply, and Project Management to deliver reliable clinical supply while establishing a robust, scalable, and commercially suitable drug substance process and control strategy.

Primary Responsibilities

• Own the drug substance technical strategy and execution for small molecule API from late stage clinical development through registration, launch readiness, and lifecycle management.
• Lead synthetic route evaluation, process development, and process optimization for drug substance, intermediates, and regulatory starting materials with emphasis on scalability, robustness, safety, manufacturability, cost, and reliable supply.
• Define and maintain the regulatory starting material strategy and controls for raw materials, intermediates, reagents, and critical suppliers, including specifications, qualification requirements, and appropriate source redundancy.
• Lead process characterization and establish a science based control strategy using quality by design principles, risk assessment, and design of experiments as appropriate. Define critical process parameters, critical material attributes, critical quality attributes, proven acceptable ranges, and operating controls.
• Establish and defend an end to end impurity control strategy, including process impurities, degradation products, mutagenic impurities, nitrosamine risk, residual solvents, elemental impurities, and impurity fate and purge assessments.
• Lead drug substance solid state and physical property strategy, including salt and polymorph selection and control, crystallization, isolation, drying, particle size, residual solvent control, and attributes that can affect drug product manufacture, performance, and stability.
• Select, qualify, and provide technical governance for API CDMOs and other external partners. Lead technology transfer, scale up, engineering and registration campaigns, GMP manufacturing, technical troubleshooting, and resolution of deviations, investigations, change controls, OOS or OOT events, and CAPA relevant to drug substance.
• Lead late stage process validation strategy and execution, including process performance qualification readiness, validation protocols and reports, continued process verification planning, and technical preparation for preapproval inspections and commercial manufacturing.
• Partner with Analytical Development, Quality, and Supply Chain to establish phase appropriate specifications, reference standards, release and stability strategies, material comparability plans, and a resilient supply network capable of supporting global clinical and future commercial demand.
• Author and critically review drug substance sections of regulatory submissions and responses, including IND, IMPD, CTA, NDA, and MAA content, with primary ownership of CTD Module 3 drug substance sections. Support health authority interactions, CMC questions, and inspection readiness, and communicate technical risks, options, budgets, timelines, and recommendations clearly to CMC leadership and cross functional teams.

Required Qualifications

• Ph.D. in Organic Chemistry, Process Chemistry, Chemical Engineering, or a related discipline with 10 or more years of relevant pharmaceutical or biotechnology industry experience; M.S. with 12 or more years or B.S. with 15 or more years of directly relevant experience will also be considered.
• Deep expertise in small molecule drug substance process chemistry and development, including route selection, process optimization, scale up, technology transfer, GMP manufacturing support, and technical troubleshooting.
• Demonstrated experience advancing API through late stage clinical development, including Phase 3 manufacturing readiness, process characterization, registration campaigns, validation strategy, process performance qualification, and commercial readiness.
• Strong track record managing API CDMOs and external manufacturing partners in an outsourced biotechnology or pharmaceutical operating model, including review and approval of protocols, reports, batch records, investigations, and technical change controls.
• Strong working knowledge of cGMP and global regulatory expectations for small molecule drug substance, including relevant principles in ICH Q7, Q11, Q3A, Q3C, Q3D, M7, Q6A, and Q12, with experience authoring and reviewing high quality CTD Module 3 drug substance content and health authority responses.
• Demonstrated ability to integrate process chemistry, analytical, solid state, manufacturing, quality, and supply data; make practical risk based decisions under aggressive timelines; and influence cross functional teams and external partners without direct authority.
• Preferred Qualifications
• Experience with a successful NDA or MAA filing, preapproval inspection, product launch, or commercial API technology transfer and validation for a small molecule product.
• Experience developing and defending regulatory starting material designations, impurity fate and purge strategies, mutagenic impurity controls, nitrosamine risk assessments, and robust specifications for late stage drug substance.
• Experience with crystallization and solid state control, process safety and scale up, second source qualification, cost of goods optimization, or building drug substance systems and external manufacturing networks in a growing biotechnology company is desirable.

Compensation: $215,000 to $260,000 a year

In addition to a competitive base salary of $215,000 to $260,000, we offer stock options and a target bonus, plus a comprehensive benefits package for employees and their families, including medical, dental, vision, and supplemental disability insurance. Relocation assistance may be available. The salary range is a guideline; total compensation will vary based on qualifications, skill level, competencies, and internal equity.

Job Type: Full time

Benefits

Annual bonus program; incentive stock option plan; 401(k) plan with employer contribution; comprehensive medical, dental, and vision insurance; HSA, FSA, and supplemental insurance plans; Paid Time Off; Company Paid Holidays.

Schedule and Work Location

Monday to Friday. United States work authorization required. Hybrid work is preferred, with regular presence in the San Diego office. Ability to travel up to 25 percent for CDMO visits, manufacturing support, technical meetings, or other business needs.

Equal Opportunity Employer

Protego Biopharma is an equal opportunity employer committed to a work environment free of harassment, discrimination, and retaliation. AI tools may assist parts of the recruiting process, but final hiring decisions are made by humans. Contact us for more information on how your data is processed.