# Advancing continuous biomanufacturing of monoclonal antibodies using an experimentally validated modeling platform

> **NIH FDA U01** · UNIVERSITY OF DELAWARE · 2022 · $529,598

## Abstract

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.

## Key facts

- **NIH application ID:** 10709083
- **Project number:** 3U01FD007695-01S1
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** Marianthi Ierapetritou
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2022
- **Award amount:** $529,598
- **Award type:** 3
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10709083

## Citation

> US National Institutes of Health, RePORTER application 10709083, Advancing continuous biomanufacturing of monoclonal antibodies using an experimentally validated modeling platform (3U01FD007695-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10709083. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*