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.