# Novel Process Analytic Technology for Continuous Bioprocessses

> **NIH FDA U01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $1,000,000

## Abstract

Abstract
This proposal aims to demonstrate how real-time measurement of protein product quality
attributes and rapid assessment of adventitious agent contamination can be used for
manufacturers’ risk-based decision making in continuous protein production. While Quality by
Design has been a successful approach for maintaining product quality, its adoption is a
byproduct of difficulties in measuring product quality in real time. We will experimentally
demonstrate two novel platforms for in-line protein quality assessment (1) a micro/nanofluidic
platform for assessing high- and low-molecular weight protein impurities, protein structure and
binding, and glycosylation and (2) swept source Raman (SS-Raman) – using a novel approach
of a tunable laser and low-cost, fixed-wavelength detector instead of a traditional, expensive
spectrometer or interferometer – to measure process parameters and product quality at all points
of the process. We have previously demonstrated the use of micro- and nano-fluidic assays to
measure protein quality attributes off-line, constructed an automated sampling system to feed
bioreactor supernatant to the micro/nanofluidic assays, and used Raman spectroscopy to identify
and quantify therapeutic proteins dissolved in buffer solutions at concentrations found in drug
product and at volumes equivalent to or less than one dose. This work will be the first
demonstration of these technologies for real-time protein quality assessment. Additionally, this
work will develop novel approaches for rapid adventitious agent detection and demonstrate their
use in CHO cell culture. We will demonstrate the use of Raman spectroscopy to obtain metabolic
fingerprints (intracellular metabolites) and footprints (extracellular metabolites) of protein
producing CHO cells when challenged by various pathogens and classify these fingerprints and
footprints as either normal or anomalous, indicating the presence of a potential infection. We will
also evaluate rapid Next Generation Sequencing and bioinformatic approaches for their suitability
to rapidly detect virus contaminations of continuous CHO cell culture. Finally, this proposal will
investigate the impact of integrating these novel technologies into a continuous monoclonal
antibody manufacturing process. At its completion this work will improve (a) product and process
knowledge by demonstrating the use of real-time protein attribute measurements (b) process
control by enabling direct measurement of critical quality attributes during manufacturing and
feedback or feedforward control strategies to be tested, and (c) safety through development of
rapid adventitious agent assays to more rapidly assure sterility of biopharmaceuticals which can
improve patient safety, assure supply of medicines, and reduce business risk.

## Key facts

- **NIH application ID:** 9987601
- **Project number:** 5U01FD006751-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** JONGYOON HAN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2020
- **Award amount:** $1,000,000
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987601

## Citation

> US National Institutes of Health, RePORTER application 9987601, Novel Process Analytic Technology for Continuous Bioprocessses (5U01FD006751-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9987601. Licensed CC0.

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