DC Discussion Group

Host Cell Proteins (HCPs) – Risk-based Control Strategies for Established and Novel Therapeutic Biological Products | April 30, 2024 | 15:00 - 17:00 EDT

This DCDG session will discuss best practices to control HCPs for established recombinant protein products and challenges associated with HCP measurements for emerging cell and gene therapy products. In particular, we will discuss how to apply a risk-based approach and leverage prior knowledge to assure product quality and to meet regulatory expectations.

Join us in person at the IBBR campus where you can network with DC-area CASSS members. The April Discussion Group will be fully in-person. Registration will close April 29, 2024.

Location:
Institute for Bioscience and Biotechnology Research
9600 Gudelsky Dr.
Rockville, MD, USA 20850

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Host Cell Proteins (HCPs) – Risk-based Control Strategies for Established and Novel Therapeutic Biological Products 

Host cell proteins (HCPs) are process-related impurities deriving from host organisms used for the expression of biological products like recombinant proteins or viral vectors. HCPs, if not adequately controlled, can present potential risks to patient safety and compromise product quality, including stability, and have been the focus of regulatory agencies and industry for years. 

The most common approach to test HCPs is to use an ELISA method that allows assessment of the level of HCPs at different stages of product manufacture, their clearance by manufacturing process, and content in the final drug product. However, the outcome of ELISA testing depends on test sensitivity and detection (coverage) of a variety of proteins constituting the HCPs for a given product. Furthermore, ELISA assays do not provide individual HCP identities and thus lead to underestimation of the risk HCPs pose to product quality. Therefore, LC-MS/MS and other more suitable analytical methods have been incorporated to qualitatively assess HCPs including higher risk impurities that may co-purify with the intended molecule and so called “bad character ” that may affect quality and safety of the product especially during the long-term storage.

Panelists:
Andrew Chang, Novo Nordisk Inc.
Alexey Khrenov, CDER, FDA 
Ling Wa, Arcellx, Inc.

Andrew Chang, Novo Nordisk Inc.

Chang is Vice President of Quality and Regulatory Compliance, Quality Intelligence and Inspection at Novo Nordisk, Inc. Previously Chang served more than 11 years in US FDA most recently as an Associate Director for Policy and Regulation, Acting Deputy Director, Lab Chief and Senior Regulatory Scientist in the Division of Hematology, Center for Biologics Evaluation and Research (CBER).

Chang received his BSc in Pharmaceutical Chemistry from China Pharmaceutical University and his Ph.D. in Biochemistry from State University of New York Health Science Center at Brooklyn. He completed a post-doctoral fellowship at the National Institutes of Health in 1995.

Chang served as the FDA co-chair for the 2005 and 2006 WCBP symposiums and helped initiate the CMC Strategy Forums in Europe and, most recently, China. In addition, Andrew was an expert and topic leader to ICH Q12 Expert Work Group and implementation work group, helping develop the guideline on Pharmaceutical Products Lifecycle Management. He also served as the FDA deputy topic leader for developing ICH Q5E guideline and the FDA observer for European and US Pharmacopeia’s Expert Groups on Blood and Blood Derived Products.

Alexey Khrenov, CDER, FDA 

Dr. Alexey Khrenov is Branch Chief of the Hemostasis Branch 1 (HB1) in the Division of Hemostatis (DH), in the Plasma Protein Therapeutics CMC (OPPT), in the Office of Therapeutic Products (OTP), CBER/FDA. Khrenov received his PhD in biochemistry from the Institute of Biochemical Physics of Russian Academy of Sciences in Moscow, Russia and did post-doctoral research in the laboratory of Dr. Saenko at the American Red Cross Holland Laboratory focusing on the biochemistry of coagulation factor VIII. Prior to joining the FDA, Khrenov worked in the United States Pharmacopeia and National Institutes of Health.

Ling Wa, Arcellx, Inc.

Dr. Chunling Wa is the Director of Analytical Development at Protein Sciences Department at Arcellx, leading analytical activities for protein products generated in-house and at CDMO. She and her team also develop methods and strategies to characterize process-related impurities in lentiviral vector and CAR-T cell process and products. Prior to joining Arcellx, Wa spent 5 years at AstraZeneca and Boehringer Ingelheim leading analytical activities for several muti-specific antibody and antibody-drug conjugate projects. Wa holds a PhD in analytical and bioanalytical chemistry from University of Nebraska-Lincoln with a focus on mass spectrometry and chromatography technologies.