U01FD007695

Advancing Continuous Biomanufacturing of Monoclonal Antibodies Using an Experimentally Validated Modeling Platform - Project Summary

Due to increased demand for biologics, there is an ongoing need to scientifically and commercially advance manufacturing in both upstream cell culture and downstream purification steps. Our goal is to provide an experimental infrastructure complemented by a computational framework to investigate the continuous manufacturing of monoclonal antibodies (mAbs).

The modeling approach will be based and validated using specific experimental evidence to enhance our process understanding and improve model performance and utilization during the design phase.

The proposed innovations stem from the following objectives that will be delivered as the outcome of this project, namely,

1) To develop a multiscale model for perfusion bioreactor capturing the effects of operating parameters and cell line characteristics on critical quality attributes (CQAs) validated by experimental results;

2) To develop methods for optimizing continuous chromatographic operations, including primary capture and polishing steps, under a range of process conditions for optimal clearance of process- and product-related impurities; and

3) To develop predictive models that will enable determination of optimal operating conditions with direct coupling of upstream and downstream units accounting for product quality attributes.

To enable process control, which is the ultimate target of advanced manufacturing, we will explore the design space and identify the relationships between critical process parameters (CPPs), critical material attributes (CMAs), and targeted CQAs. We will develop predictive models for all the important unit operations, validated by experiments, that can be used to determine the design space along with statistical analysis of experimental data to identify all critical parameters/attributes.

The validated models will then be used as a virtual tool to perform risk assessment for in-plant downstream operations such as scale-up/start-up/shutdown and compare process operating scenarios.

In terms of combining the developed strategies, we envision the integration with a continuous upstream facility to achieve a fully automated continuous biomanufacturing line exploring and optimizing the process interactions. This proof-of-concept line will be used to clearly quantify risk and performance-based metrics.

University Of Delaware

TO ASSIST INSTITUTIONS AND ORGANIZATIONS, TO ESTABLISH, EXPAND, AND IMPROVE RESEARCH, DEMONSTRATION, EDUCATION AND INFORMATION DISSEMINATION ACTIVITIES, ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS), BIOLOGICS, BLOOD AND BLOOD PRODUCTS, THERAPEUTICS, VACCINES AND ALLERGENIC PROJECTS, DRUG HAZARDS, HUMAN AND VETERINARY DRUGS, CLINICAL TRIALS ON DRUGS AND DEVICES FOR ORPHAN PRODUCTS DEVELOPMENT, NUTRITION, SANITATION AND MICROBIOLOGICAL HAZARDS, MEDICAL DEVICES AND DIAGNOSTIC PRODUCTS, RADIATION EMITTING DEVICES AND MATERIALS, FOOD SAFETY AND FOOD ADDITIVES. THESE PROGRAMS ARE SUPPORTED DIRECTLY OR INDIRECTLY BY THE FOLLOWING CENTERS AND OFFICES: CENTER FOR BIOLOGICS EVALUATION AND RESEARCH (CBER), CENTER FOR DRUG EVALUATION AND RESEARCH (CDER), CENTER FOR DEVICES AND RADIOLOGICAL HEALTH (CDRH), CENTER FOR VETERINARY MEDICINE (CVM), CENTER FOR FOOD SAFETY AND APPLIED NUTRITION (CFSAN), NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH (NCTR), THE OFFICE OF ORPHAN PRODUCTS DEVELOPMENT (OPD), THE CENTER FOR TOBACCO PRODUCTS (CTP), AND OFFICE OF REGULATORY AFFAIRS (ORA), AND THE OFFICE OF THE COMMISSIONER (OC). SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAMS: TO STIMULATE TECHNOLOGICAL INNOVATION, TO ENCOURAGE THE ROLE OF SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION BY MINORITY AND DISADVANTAGED PERSONS IN TECHNOLOGICAL INNOVATION. FUNDING SUPPORT FOR SCIENTIFIC CONFERENCES THAT ARE RELEVANT TO THE FDA SCIENTIFIC MISSION AND PUBLIC HEALTH ARE ALSO AVAILABLE.

93.103 - Food and Drug Administration Research

FDA Office of Acquisition and Grant Services (OAGS) [HHS - FDA]

Center for Drug Evaluation and Research (CDER) [HHS - FDA]

Newark, Delaware 197131325 United States

Single Zip Code

Enhancing Regulatory Science for Advancing Pharmaceutical Quality and Manufacturing (U01) Clinical Trials Optional (PAR-20-083)

COVID-19 $529,598 (15%) percent of this Cooperative Agreement was funded by COVID-19 emergency acts including the Consolidated Appropriations Act of 2021.
Amendment Since initial award the total obligations have increased 293% from $929,598 to $3,650,216.