Director, Drug Product SME
Madrigal Pharmaceuticals
Summary
The Director, Drug Product SME is an experienced scientific leader, with responsibility for advancing the CMC development of Madrigal's siRNA/oligonucleotide and small molecule portfolio. This role focuses on drug product formulation and process development, ensuring preclinical and clinical studies are supported with phase appropriate quality investigational medicinal product, delivered on time and guided by scientific rigor, risk assessment and data-driven decision-making.
Job description
As a key member of CMC development project teams within Technical Operations, this leader will also serve as a program-level CMC lead across preclinical development, clinical development, scale-up, registration, and commercialization. The Director is expected to lead at least one cross-functional CMC team supporting the development of a clinical-stage asset.
Key Responsibilities
Drug Product Development and Technical Strategy
- Lead or support generation of comprehensive pre-formulation data packages and asset profiles to inform developability assessment, development strategy, and program planning.
- Lead or support phase-appropriate development, optimization, and delivery of siRNA/oligonucleotide and small-molecule formulations, associated processes, and material supply from preclinical through early clinical development.
- For small-molecule candidates, lead or support formulation and process strategies to address bioavailability risks and enable fixed-dose combination development with Rezdiffra® (resmetirom), where applicable.
- Lead or support registration, final scale-up, process validation, and commercial presentation development in accordance with cGMP, ICH, FDA, and internal target product profile requirements.
External Partner and CDMO Oversight
- Serve as the primary drug product contact for CDMOs and oversee key deliverables, including protocols, batch records, reports, investigations, and technical documentation.
- Troubleshoot drug product issues, develop root-cause hypotheses, and coordinate resolution with cross-functional internal and external partners.
- Support drug product technology transfer readiness, including process descriptions, control strategies, sampling plans, comparability considerations, and transfer documentation.
- Support leadership and Global Procurement in defining and maintaining a CDMO/CRO network that meets current and future CMC business, regulatory, and quality needs.
Quality, Regulatory, and CMC Documentation
- Implement Quality-by-Design and Quality Risk Management principles throughout the development lifecycle, ensuring clear decision logs, assumptions, data traceability, and alignment with Quality, Regulatory, and Supply Chain standards.
- Ensure adherence to sound decision-making processes established through strong scientific rigor and robust data, leveraging cross-functional expertise.
- Use statistical design-of-experiment practices and AI-enabled tools, to increase efficiency and effectiveness in generating CMC knowledge and phase-appropriate control strategies.
- Author, compile, and review drug product technical reports, regulatory source data, CMC regulatory documents, and quality documentation as required.
- Provide direction and oversight for authoring and reviewing Module 3 eCTD content for INDs, NDAs, meeting briefing books, and other regulatory submissions.
- Review quality agreements, participate in audit programs, maintain inspection readiness, and represent the company as a CMC subject matter expert in regulatory inspections and audits as required.
Cross-Functional Leadership and Operational Excellence
- Partner across Technical Operations, MSAT, Quality, Research, Regulatory Affairs, Drug Safety, Clinical, Supply Chain, and other stakeholders to ensure alignment across all stages of development.
- Promote early development collaboration with MSAT to support future product robustness, supply resilience, and cost efficiency.
- Support creation, submission, and tracking of fiscally responsible project budgets aligned with phase-appropriate and risk-tolerant project goals.
- Champion a Right First-Time culture focused on data integrity, scientific rigor, continuous improvement, and operational excellence across CMC and Technical Operations.
Requirements
- PhD degree in Pharmaceutics, Chemistry or Material Sciences, or BS/MS degree and commensurate Pharmaceutical Science development and leadership experience.
- Minimum of 15 years of experience in Pharmaceutical Science and CMC leadership within the biopharmaceutical industry, with a strong background in CMC and Drug Product development.
- Proven experience in siRNA/oligonucleotide drug product formulation/process development is a must.
- Experience in small molecule drug product formulation/process development is desirable.
- Proven experience in working with CDMO/CRO's in a fully outsourced paradigm, providing technical leadership and oversight to development & clinical supply manufacture, and driving technical solutions in an external environment.
- On-boarding and accelerating the mobilizing of new assets post-acquisition is desirable.
- Demonstrated success in transitioning programs from clinical development to commercial manufacturing, including process validation and regulatory approval, in a cross-functional matrixed organization.
- Working knowledge of statistical design of experimental approaches, execution and analysis, development of CMC risk assessments & control strategies.
- Strong knowledge of cGMP and ICH guidelines, global regulatory requirements and regulatory document authoring.
- Regulatory agency interactions is desirable.
- Strategic and operational leader with a balance of scientific depth and business acumen.
- Strong Leadership skills with an ability to both influence and empower.
- Strong technical expertise in Pharmaceutical Science, pharmaceutical development, processes and technologies.
- Excellent problem-solving and risk management skills to address complex issues.
- Strong written and verbal communication and interpersonal skills with the ability to collaborate across functions, with external partners, and present to executive stakeholders.
- Detail-oriented with a focus on maintaining high standards of quality and compliance.
- Proactive and strategic thinker with an empowering approach to solving technical challenges.
- Aptitude for identifying inefficiencies and driving process improvements within CMC, Supply Chain, and QA.
- Meticulous in review of documentation to ensure regulatory and quality robustness.
- Ability to mentor others in quality and best practices.
- Initiative in shaping compliance culture across the organization.
Benefits
- Bonus
- Equity
- Medical Insurance
- Dental Insurance
- Vision Insurance
- Life Insurance
- Disability Insurance
- 401(k)
- Flexible Paid Time Off
- Mental Health Benefits
- Employee Assistance Program
Company overview
Madrigal Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on developing novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), a serious form of fatty liver disease. The company's lead product, Rezdiffra (resmetirom), is a once-daily, oral thyroid hormone receptor (THR)-β selective agonist that targets key underlying causes of MASH in the liver. Rezdiffra received FDA approval in 2024 as the first treatment for MASH with moderate to advanced liver fibrosis, representing a significant breakthrough in hepatology. Headquartered in Conshohocken, Pennsylvania, Madrigal is publicly traded on NASDAQ under the symbol MDGL. The company continues to advance its clinical development programs, including ongoing Phase 3 trials evaluating Rezdiffra for the treatment of compensated MASH cirrhosis. Madrigal's innovative approach addresses a critical unmet medical need in liver disease therapeutics.