Director / Senior Director, CMC Drug Substance

About the Role:

We are seeking a versatile Director / Senior Director to lead early-stage CMC Drug Substance development in a virtual environment. The ideal candidate will have extensive experience in route scouting, process development, polymorphism, salt selection, crystallization, and production and solid-state development to improve solubility, stability, and PK. Experience managing toxic and mutagenic impurities and preparing regulatory documentation is highly preferred.

Key Responsibilities

Route Scouting

• Propose alternative synthetic routes that optimize yield, purity, and scalability.
• Manage CDMOs to execute route scouting and scale-up to small demonstration batches.

Process Development

• Develop scalable, robust processes and purification strategies, including purging critical reagents and byproducts.
• Design processes capable of delivering large initial toxicology batches, especially when high NOAEL demands atypically large quantities.
• Support aggressive timelines where 13-week toxicology studies may run in parallel with Phase 1, requiring early establishment of a solid, scalable process.

Solid-State Development

• Lead solid-state development to enhance solubility, stability, and PK through salt or co-crystal formation.
• Hands-on experience in salt/co-crystal and polymorph screening, stability and solubility evaluation, and PK comparison.
• Develop crystallization processes, determine metastable zones, and establish control strategies for the desired form.

Production & Scale-Up

• Ensure timely delivery of materials with required quantity and purity under aggressive timelines.
• Lead development and execution of impurity-enriched 28-day toxicology batches, including scale-up and spiking of impurities.
• Support subsequent campaigns at increasing scale to meet Phase 1, Phase 2, and extended toxicology requirements.

Toxic Reagents & Mutagenic Impurities

• Develop and implement phase-appropriate strategies to identify, control, and purge toxic reagents, byproducts, and mutagenic impurities.

CMC Quality & Compliance

• Ensure adherence to cGMP standards and internal quality expectations.
• Review and approve manufacturing documentation, including batch records and deviation reports.
• Support audits, investigations, and continuous improvement initiatives.

Regulatory & Documentation Support

• Author and review CMC sections of regulatory filings (INDs, IMPDs, briefing packages, annual reports, amendments).
• Contribute to regulatory strategy and responses to health authority inquiries.
• Maintain comprehensive documentation to support product lifecycle management.

Cross-Functional & Strategic Contributions

• Collaborate with Drug Product, Analytical, Quality, Regulatory, Toxicology, and Clinical Supply teams.
• Provide scientific and operational input to project teams.
• Contribute to intellectual property strategy and cross-functional CMC initiatives.

Timeline & CDMO Leadership

• Develop and manage realistic timelines for R&D, manufacturing campaigns, and IND preparation aligned with clinical and toxicology milestones.
• Lead CDMOs proactively, providing clear guidance, actionable solutions, and rapid problem-solving.

Business Awareness & Late-Stage Development

• Understand the business value of CMC development and its impact on program strategy.
• Apply DoE and QbD principles for late-stage development (post-2029).

Qualifications

• M.S. (15+ years) or Ph.D. (10+ years) in Organic Chemistry or related field.
• Expertise in small molecule synthesis, process development, and analytical method development for intermediates, drug substances, and structural alert impurities.
• Proven experience in impurity management, solid-state development/characterization, and GMP manufacturing.
• Demonstrated success in technology transfer and CDMO management.
• Experience authoring regulatory documents (INDs, IMPDs, amendments, annual reports).
• Experience managing GMP clinical supply, labeling, storage, and shipment.
• Strong leadership, collaboration, and communication skills; ability to influence across disciplines.
• Excellent interpersonal, technical writing, presentation and oral communication skills.
• Strong business awareness and ability to prioritize in a fast-moving, lean organization.
• Willingness to travel domestically and internationally as needed.

Ideal Candidate

• Expected to operate with high ownership, accountability for delivery, timelines, and decision-making in a lean, fast-paced organization.