Kevin L.

Head of Regulatory Affairs at Centus, a JV between AZ and FKB

Lead RA-CMC function for biosimilar development and regulatory submission. Activities includes regulatory strategy, health authority meeting preparation, Module 3 BLA preparation, and post submission defense. US RA lead for cross functional collaboration with development, quality, statistics and commercial teams.

Reviewing CMC section of novel biologics and biosimilar INDs/BLAs Developing best review practice for CMC activities Participating in PLI/PAI inspections

Drug product reviewer at Office of Life Cycle Product, Office of Pharmaceutical Quality, FDA

Led analytical support for a late stage mAb project in the CMC team. Responsibilities include:  Authoring IND/IMPDs and leading gap analysis for the draft BLA  Reviewing and authoring analytical and stability protocols and reports  Developing drug substance (DS and drug product (DP) specifications using QbD principles  Coordinating DS/DP stability study  Developing comparability study plan to support process changes (scale up, site change etc)  Coordinating analytical support for process/formulation development/characterization and deviation investigation  Leading analytical method qualification, transfer and validation activities between different companies/sites Led protein chromatography group (up to 5 FTEs) to support product developments and technology transfer. Responsibilities include:  Providing technical guidance and coordinated analytical testing support for cell culture, purification, and formulation development  Developing/qualifying/validating/transferring analytical methods among different companies and sites  Leading the characterization of a critical quality attribute (CQA) in a mAb  Leading the investigation of a major quality deviation in a clinical manufacturing campaign

The heterogeneity of carbohydrates attached to monoclonal antibody, arisen from the intrinsic property of the cells, makes producing pure homogenous antibody with superior effectiveness extremely challenging. My objective is to develop novel chemoenzymatic methods to produce pure homogenous monoclonal antibody (mAb) with superior effectiveness. What I have done includes: • Purified monoclonal antibody and engineered them with specific carbohydrates, isolated the resulted proteins and analyzed the purity by SDS-PAGE, HPLC and immunoblotting. Homogenous antibodies with >90% purity were prepared • Purified individual chitinase from Bacillus sp. through SEC and IEC to near homogeneousness, applied this enzyme for the synthesis of novel glycoprotein for the very first time, isolated the newly synthesized glycoprotein through RP-HPLC and confirmed the identity of the proteins by ESI/MOLDI-TOF MS.

• Identified the substrate recognition domain of an enzyme called Rubisco activase by protein engineering, purified the protein by FPLC and characterized its detailed kinetics and mechanism for the first time (Li, C et al. JBC 2005) • Identified the roles of critical arginines in the functioning of Rubisco activase through rational design and site directed mutagenesis (Li, C et. al. ABB 2006) • Engineered Rubisco activase with improved thermostability (10 C more stable than wild type) and generated heat resistant plant (5 C better performance under heat/drought condition)

Molecular biology