AZ Global Technical Operations

AZ Global Technical Operations

• Technical and Organizational Leadership/Influence without Authority: Accountable team lead for process/late stage formulation development and technology transfer to CMOs for cGMP DP aseptic fill/finish process of all early and late-stage molecules in MacroGenics’ portfolio- Critical team responsibilities include:1) Providing oversight to DP CMO partners,2) Development of internal platform process and formulation capabilities, and3) Scouting and developing innovative technologies and academic/consortium collaborations.• Human Capital Development: - Managing and developing three direct reports in team: Scientist I, Scientist II and Sr. Development Associate• Scientific Leadership and Partnering with Peers: - Headed and planned with co-Chair, Prof. Christopher J. Roberts (Univ. of Delaware) , successful 1st Gordon Research Conference (GRC) on Development of Bio-Therapeutics and Vaccines, held in Galveston, TX, Jan. 6-11, 2019; wrote successful peer-reviewed proposal with Prof. Roberts to Gordon Research Conference (GRC) organization to secure funding of app. $ 25, 000 for this conference from the Board of Trustees of the GRC organization

• Key accomplishment: developed and recommended platform lead/custom-designed back-up liquid formulations for phase I trials of N6-LS, an anti-HIV mAb co-developed with GSK• CMC Development activities included biophysical characterization of antibody molecule, buffer screening (using JMP), excipient screening, freeze/thaw stability, short and long-term stability studies• Tech. transfer: leading tech transfer to internal CMO for cGMP DP aseptic fill/finish process • Biophysics core expertise: Hands-on experimental experience and theoretical knowledge of biophysical assays: absorbance and fluorescence spectroscopy, capillary electrophoresis, dynamic and static light scattering, zeta potential, differential scanning calorimetry, osmometry, rheometry, near & far-UV circular dichroism spectroscopy, size exclusion chromatography, light obscuration (HIAC) & flow microscopy (MFI)• Assay development: Developing analytical HIAC method based on USP <787> for tech. transfer to QC lab in internal CMO; initiated collaboration with Dr. Dean Ripple at NIST • Specifications setting: Made recommendations to Regulatory Affairs and Analytical Development for setting specs. for Ph. I DP• Development and regulatory writing: technical protocols, reviewed tech. transfer documents and master batch records, and technical reports documenting formulation, stability and method development studies/qualification reports• Key responsibilities: cross-functional coordination, project timeline development and management, scientific data analysis and interpretations with recommendations to VPP senior leadership

- Leading cross-functional team at sending unit for tech. transfer of manufacturing process of a phase III oncology orphan indication drug to a leading CMO in European Union for process validation and commercial manufacturing- Designed commercial manufacturing process for lyo drug product comprising a cyttoxic molecule and wriote protocols for engineering runs to prepare for process validation

Project responsibilities and key accomplishments- Learning aseptic processing and sterile fill/finish of parenterals in vials, syringes and other cartridge-based container closure systems- Responsible for process design and scale up for commercial manufacturing of a current Phase III oncology drug, process validation (to be completed 4th quarter 2015) and technology transfer to CMO with isolator facilities for fill/finish in a sterile cleanroom environment; assisting cross-functional team in CMO search- Supporting cGMP production of an approved commercial product at a CMO with cross-functional team of colleagues in Operations, Quality, Regulatory etc.; attending commercial fills in person to oversee thaw of drug substance, compounding, pooling, filling and lyophilization- Developing analytical and CFD models of viscosity and fluid rheology (bulk and interfacial shear stress) effects on fill-finish process equipment towards building robust scaled-down models of time-pressure pumps and on unit operations such as mixing in bags; experimentally validating outputs from these models to support process design and technology transfer- Reading PDA Technical Report 60 Process Validation: a Lifecycle Approach and ICH Q8 FDA Guidelines for Industry – Process Validation: General Principles and PracticesManagement - Continued to manage and develop two employees: a post-doctoral research fellow, Dr. Prasad Sarangapani, and a M.S. Chemical Engineer Associate Scientist I, Ms. Nayoung Kim- Recruited Ms. Sushrutha Gujjula (M.S. student, Mechanical Engineering, University of Cincinnati) for six month internship to perform CFD modeling of time pressure pump filling operations and also of mixing in final formulation of drug substance in LevTech and magnetic mixer bagsProfessional Training- Aseptic Processing Fundamentals, Parenteral Drug Association (PDA), Bethesda, MD- ANSYS Fluent 15 Computational Fluid Dynamics (CFD) Training Course, ANSYS, Evanston, IL

Scientist II, November 2009 - Oct. 2013 Job responsibilities and key accomplishments:- Studying the molecular rheology of highly concentrated monoclonal antibody formulations towards development of various delivery devices towards developing drug delivery devices for pipeline biologic drugs and vaccines under development as part of a cross-functional team of MedImmune and AstraZeneca scientists and engineers- Contributed to team effort to design delivery device for H1N1 flu vaccine (2009)- CMC representation responsibilities from Drug Delivery & Devices Group for post-CD to pre-IND projects- Received training in Quality Management Systems;learned international standards for risk management in medical devices (ISO 14971)- Fully skilled in cGxP, cGLP and cGMP operations

Research projects:- Rheology and morphology (by SAXS) of segmented Polyurea block copolymer; uniaxial extensional rheology of Polyurea at high strain rates (between 100 and 1000 inverse s) using a custom-designed and built high speed tensile tester- In-situ rheo-dielectric experiments to probe chain conformation during non-linear viscoelastic response of well- entangled and concentrated solutions of cis-1,4-Polyisoprene- Investigation of miscibility, thermal behavior and synergistic mechanical properties in blends of Ethylene-Propylene copolymer with Ethylene-Propylene terpolymer containing Ethylidene Norbornene (cross-linked elastomeric component with multi-modal distribution of network chain lengths)

Summary of post-doctoral research:- Measured the interfacial tension of surfactant-laden oil/water and water/oil emulsions by microfluidic interfacial tensiometry; designed microfluidic devices that produce contraction flows for this purpose and fabricated them by soft lithography - Measured flow-induced birefringence in wormlike micellar surfactant solutions flowing through microfluidic channels designed as cross-slots and built to produce planar elongational flow - Investigated micro-rheology of polymeric emulsions under confinement by means of steady shear rheology and video microscopy under shear- Studied the rheology and flow-induced structure of multi-walled carbon nanotube suspensions- Investigated purely elastic flow instabilities in model elastic fluids in Poiseuille flows in microfluidic channels

Summary of dissertation research: - Experimentally investigated the anomalous dynamics of polymer chains in miscible polymer blends by applying rheology, dielectric spectroscopy and differential scanning calorimetry- Developed a strong background in linear viscoelasticity, polymer rheology and polymer dynamics- Modeled the complex shear modulus of the miscible blends using tube models of polymer dynamics