Shyam Subramanian

Lead technical development, manufacturing and quality functions for Obsidian Manage TIL program including external collaboration with world leading cancer center

Lead for newly formed Technologies center of excellence supporting core technologies and key reagent support for research Program leader for first independently owned oncology targeted cell therapy program Lead all technical development and manufacturing related activities for Obsidian portfolio

Lead development and manufacturing for cell therapy candidates in Casebia portfolio

Responsible for upstream process development for all biologics in portfolio, management of laboratories, and personnel.

Project lead for late stage development and next generation platform development , with responsibility for development, technology transfer, and process validation. Manager with direct reports and matrix reports (>10) with broad range of education/ experience across different sites. Cell culture technical forum leader with responsibility to ensure scientific rigor in process development, adoption of best practices, and deliberate adherence/evolution of platform. Cross-functional technical forum leader with responsibility to guide decisions at project stage-gate reviews.

Viral Vaccine Process Development: Introduced micro-carrier technology to be implemented in single-use bioreactors for viral vaccine projects (Phase II pipeline and Lifecycle management for approved product). Phase I/II Clinical Supply: Supervised process development on conditionally replication-competent virus vaccine candidate manufacture utilizing a novel cell substrate for toxicology and clinical development requiring novel disposable reactor for scale-up and innovative process conditions to reduce residuals in an aseptic process.

Expression Technology Development: Expanded use of novel insect substrate developed at Merck and updated recombinant baculovirus derivation technology. Developed end-to-end microscale, high-throughput workflow for production-purification-analytics to enable efficient screening for nine recombinant vaccine antigens (with multiple variants). Preclinical Vaccine Development: Directed process development (upstream and/or downstream) for four different vaccine candidates (live-attenuated virus, 4-valent recombinant protein, recombinant enveloped VLP, intracellular bacterial OM derived protein ) using different cell substrates to assess manufacturing feasibility to support phase I/II clinical development and identify gaps for launch. Lead cross-functional (process, analytical and formulation) team for two of the vaccine candidates, coordinating efforts beyond process development. Technically transferred and supervised mammalian cell banking at CMO. Expression Screening: Established expression systems group and managed expression systems evaluation of diverse recombinant protein and VLP vaccine candidates (bacteria, yeast, insect, mammalian cells) and cell line development using both internal resources and a network of external partners. Introduced insect cell technology platform for human vaccines at Merck and licensed insect cell substrate and demonstrated industry leading levels of production for multiple recombinant proteins that outcompetes product in late stage clinical trials from competitor. Lead expression screening for the manufacture of virus-like particle (VLP) vaccine candidate against infectious disease (in collaboration with NIH) and developed a novel insect cell substrate that produces VLPs at levels exceeding published levels in mammalian cells.

Antibody Process Development: Lead collaborative project with external partner (IBET, Portugal) to evaluate novel process development approach for glycoengineered Pichia pastoris expressing monoclonal antibodies, utilizing multi-phase fermentation & advanced control strategies and demonstrated feasibility. Laboratory Management: Managed bioreactor laboratory with multiple 15L, 30L, 200L SIP/CIPable bioreactors that supported process development department and implemented automated sampling and several inline process monitoring tools. Marketed Viral Vaccine Technical Operations: Lead team of six scientists and collaborated with Merck Manufacturing Division to trouble-shoot and fix problems in Varicella-Zoster vaccine manufacture, enabling early restart. Demonstrated Varicella-Zoster vaccine manufacturing process was robust with respect to complex raw material (serum) quality variation as part of a corrective and preventive action (CAPA). Identified several leads that resulted in higher productivity in the Varicella-Zoster vaccine manufacturing process, which are currently being evaluated for implementation. Implemented 96-well plate based high-throughput MRC-5 cell growth and Varicella-Zoster virus production screens to enable media development and process improvements. Technically transferred and supervised process to manufacture critical glycoprotein reagent at CMO.

Viral-Vectored Vaccine Process Development: Implemented aseptic recovery operations under cGMP for manufacture of Adenovirus stock seed (encoding HIV antigens) for Phase I/II clinical supply. Developed clarification/concentration recovery unit operations for Adenovirus (encoding HIV antigens) from infected mammalian cells. Optimized and scaled up calcium phosphate mediated transfection for recombinant Adenovirus production using adherent mammalian cells using Nunc Cell factories (upto 10-tray scale). Implemented a HPLC based Adenovirus quantitation assay that supported process development.

Viral-Vector Process Development: Enabled process scaleability through adaptation of an attachment dependent retroviral FVIII vector producer cell line (HT-1080 based) to suspension growth without loss in productivity. Developed serum-free media for growth of retroviral vector producer cell line and evaluated effects on FVIII vector productivity. Improved retroviral FVIII vector production for gene therapy through identification of optimum operating conditions w.r.t temperature, refeeds etc. Recombinant Protein Process Development: Evaluated impact of glycosylation for a Hepatitis C vaccine candidate in mammalian cells. Developed a serum-free cell culture process (from clone selection through 100 L perfusion culture) for the manufacture of MCP/DAF (CD55/CD59) fusion protein for inhibiting complement activation (in collaboration with Cephalon). Created a serum-free adapted CHO/DG44 cell bank for serum-free transfection and selection procedures.