About Third Harmonic Bio
Third Harmonic Bio is a biopharmaceutical company with a singular purpose: To create a breakthrough treatment for people living with severe allergy and inflammation – debilitating conditions that can take a significant toll on overall health and well-being.
We are developing a highly selective oral wild-type KIT inhibitor for millions of people living with chronic urticaria, severe asthma, and other mast cell-mediated diseases. Despite the availability of multiple approved medicines, there is an urgent need for new treatment options. We are grounded in our purpose of developing medicines to meaningfully improve the lives of the patients we serve.
We are seeking smart, fun, and talented individuals seeking a fast-paced environment where they can meaningfully contribute to building a successful company.
Our Values
Our values provide the foundation for our culture and our operating principles – and underly how we hold ourselves accountable and how we interact with each other, with our partners, and with the global medical and patient community.
Be Human
Relationships are important. Bring your full self to work and create space for others to do the same. Balance candor with empathy.
Own the Big Picture
Context is critical. Ground every decision and action in the entirety of what we are trying to achieve.
Go THRD
We hold ourselves to a higher standard. Work with urgency, purpose, and passion.
The Role
Reporting to the Senior Director of CMC Development - Drug Substance, the Director, Process Chemistry and Manufacturing will use his/her experience in small molecule and GMP Manufacturing to support a new development program. This role will help deliver THRD’s development strategy and regulatory filing, as well as partner with the CMC team members and cross-functional teams to ensure delivery of material and support non-clinical and clinical drug development. The Director will be responsible for process chemistry R&D, technology transfer, non-GMP and GMP manufacturing, and preparation of regulatory filing. This is an exciting opportunity to join a growing biotech company.
Responsibilities
- Prepare SOWs (scope of work) and RFPs (request for proposal) for R&D and manufacturing activities including route scouting, process optimization, technology transfer, GMP and non-GMP campaigns, polymorphism studies, development and control strategy of crystallization process, purge of mutagenic impurities, and synthesis of metabolites and radiolabeled drug substance.
- Propose new synthetic routes, manage route scouting at CRO/CDMO, and provide technical support to deliver new synthesis or radiolabeled product in a timely fashion.
- Propose R&D direction in optimization, develop scalable process and implement the optimized condition into manufacturing
- Manage polymorph and salt screening, identify thermodynamic polymorph, develop crystallization condition, and support the nomination of the final form for CMC development.
- Optimize the solvent conditions for crystallization, identify metastable zone and seeding conditions and establish a control strategy to control the polymorph before isolation of the drug substance.
- Manage activities in CDMOs, review updates, interpret raw data, and support problem-solving and troubleshooting. Review and organize process development and manufacturing reports.
- Deliver impurity-enriched non-GMP batches for tox studies, GMP batches for clinical development, and radiolabeled drug substance under GMP to support human mass balance study.
- Review master batch records and executive batch records and work with the quality manager to release drug substance under GMP.
- Organize historical data and impurity profile and learn the formation and purge of impurities in the process to support decision-making.
- Justify the retest date of major batches according to stability data and ICH guidelines in collaboration with analytical chemistry and QA.
- Draft and review IND and IMPD quality CMC modules.
- Propose experiments and control strategies to address mutagenic impurities and perform the nitrosamine risk assessment.
- Contribute to timeline and budget of projects to support CMC activities. Summarize progress and future R&D direction and present at project development team meetings.
- Provide process information to support formulation development.
- Work with CMC teams and consultants in drug substance, analytical chemistry, regulatory, and quality assurance to achieve the CMC team goals.
- Travel to support and oversee GMP campaign of key steps or critical purification when needed, approximately 10~15% of the time.
Minimum Qualifications
- PhD in organic chemistry with 7-10 years (MS with 10+ years) in small molecule process chemistry, development and non-GMP/GMP manufacture.
- Hands-on experience in route scouting, process chemistry research, development, scale-up, crystallization and manufacturing through projects.
- Ability to develop scalable processes from bench scale to late-stage manufacturing.
- Experience in virtual CMC environment. Ability to lead external R&D/manufacturing projects and ensure delivery of product successfully.
- Ability to provide development strategy and propose required resources and timeline to execute development projects.
- Has strong problem-solving skills in chemistry and manufacturing to support external projects.
- Experience in polymorphism, form conversion, and control strategy in crystallization to produce desired form robustly.
- Ability to design and propose studies to secure GMP manufacturing.
- Expert knowledge in analytical methods and techniques and data interpretation.
- Ability to draft IND CMC modules M2 and M3 to support regulatory filing.
- Experience in control strategy option 1~4 in mutagenic impurities and nitrosamine risk assessment according to ICH M7, related references and guidelines.
- Experience in working in a multi-functional project team environment.
The base salary range for this role is $197,000 - $226,000
All qualified applicants will receive consideration for employment without regard to race, sex color, religion, sexual orientation, gender identity, national origin, protected veteran status, or on the basis of disability.
