Reporting to:Senior Manager, MSAT

Location:London

Job Summary

Orchard Therapeutics, recently acquired by Kyowa Kirin with the goal of accelerating the delivery of new gene therapies to patients around the globe, is looking for a dynamic and experienced Senior Scientist in the Drug Substance (DS)/Drug Product (DP) Manufacturing Sciences & Analytical Techonologies (MSAT) team.

The successful candidate will be responsible for supporting thelate-phaseDS/DP MSAT team and late-phase process development, validation (as required) and the maintenance of all DS/DP manufacturing processes to ensure the implementation of effective control strategies and assessment of CQAs in support of product lifecycle management.

The post holder is a key member of the MSAT team and will implement phase appropriate management of all product manufacturing processes in line with program plans, company objectives and health authority expectations. The individual will work collaboratively with both internal and external stakeholders to ensure timely and robust process controls as well as represent DS DP MSAT with Orchard cross functional teams and with CDMO cross function teams. The individual will have relevant experience in Cell Gene Therapy products particularly in viral vector and cell therapies.

The post-holder will have a comprehensive understanding of GMP, statistical methods and quality control of data, with excellent attention to detail, communication, presentation, and organizational skills, effective troubleshooting ability, and the ability to work independently and as part of a team. A good understanding of microbiological control strategies or chemistry including but not limited to leachable & extractables, nitrosamines assessments and material compatibility studies would be advantageous.

Key Responsibilities

· Serve as SME for commercial GMP manufacture and testing of Drug Substance (DS) and Drug product (DP) product at CDMOs including but not limited to: review and approval of master & executed batch records, test records, manufacturing investigations and associated documentation for DP manufacture & release.

· Provide expert compilation, review, editing and approval of relevant documentation including but not limited to: master production records, standard operating procedures, development/validation protocols and reports & quality documentation.

· Support technical transfer of commercial DS/DP process manufacture within GMP & to future CDMOs in line with company and program goals and ensure PPQ and validation status of products are maintained in line with applicable ICH, EMA, FDA or other health authority guidance.

· Support drug product characterization analysis and establishment of cellular gene therapy product CQA and markers that predict clinical efficacy and safety.

· Engage in collaborations with internal and external stakeholders and industry trade organizations to identify trends and expectations and incorporate them into Orchard’s DS DP control strategies.

· Collect, assemble, analyze and summarize production data post PPQ using appropriate statistical methods for Continued Process Verification (CPV). Ensure timely monitoring and reporting of DS/DP manufacturing data, spec revisions and participate in OOS and OOTs investigations according to internal SOPs. Lead post PPQ modification of control strategy and maintaining up to date revisions as appropriate

· Maintain a high Quality standard by complying with all SOPs related to GxP, trainings, data integrity, participation in quality investigations and ensuring timely resolution of all manufacturing quality events.

· Maintain the validated status of post-PPQ and commercial phase products in accordance with current industry standards, CMC regulatory standards and best practices in the evolving field of cell and gene therapy.

· Maintain the lifecycle of commercial products including but not limited to post approval regulatory commitments and supporting requirements for market expansion .

· Lead & participate in multi-disciplinary teams to conduct science-based, data driven, phase appropriate, risk-based and QbD based process development and validation strategy to support clinical programs from pivotal phase to commercial registration and manage process life cycle for commercial products as required.

· Assess the impact of process changes of commercial products and support change implementation in line with internal SOPs and current HA regulations

· Author/ review of technical documents and relevant sections related to Health Authority submissions.

· Author/review of technical documentation related to health authority submissions and other technical deliverables as necessary.

· Travel as required to provide on-site oversight during key DS/DP manufacturing activities at CDMO & provide support to CDMOs

Requirements

Required knowledge

· Experience in Cell and Gene Therapy in one or more of the following areas: lentiviral vectors, plasmids & cell banks, haematopoietic stem cell biology and characterization. Candidates with relevant experience of vaccines/biologics characterization will be considered.

· Strong Experience with risk-based approaches, such as Failure Modes and Effects Analysis

· Proven track record of using Quality management systems, change management, deviations and quality events.

· Experience in working with third party laboratories executing assay technology transfers and testing

· Experience in defining and planning comparability studies.

· Experience of helping with the compilation of high-quality regulatory submissions.

· Experience of regulatory authority inspections, including FDA and/or EMA inspections.

· Working knowledge and interpretation of FDA/EU, GMP and ICH regulations and guidelines.

· Knowledge of QbD principles and application

· Understanding of the Product Life Cycle, with reference to industry standards and guidelines

· Experience with manufacturing or process development within the pharmaceutical or biopharma industry, preferably in vector, cell and gene therapy.

· Experience within a Process Validation role/ commercial product asset management.

· Experience and understanding of technology transfer

· Experience within other aspects of Process Validation.

· Understanding of GMP manufacture, process development and process characterization

Skills & Abilities

· Sound scientific and technical proficiency with an awareness of developments in novel technologies within the industry.

· Ability to make reasoned decisions regarding complex technical issues and communicate them effectively, as appropriate.

· Strong verbal, presentation, and written communication skills.

· Ability to think critically & operate in a fast-paced, multi-disciplinary industrial environment.

Education and Experience

· At minimum, a BSc. in a relevant scientific discipline, such as Chemistry, Biochemistry, Molecular Biology, Cell Biology, Chemical Engineering, or another relevant field,

· Degree or equivalent higher education qualifications in a relevant science or engineering discipline.

· Extensive experience in the biopharmaceutical industry executing process validation activities or process development