# Continuous Viral Vector Manufacturing based on Mechanistic Modeling and Novel Process Analytics

> **NIH FDA R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $600,000

## Abstract

The biopharmaceutical industry has shown significant interest in developing continuous
manufacturing processes for therapeutic protein production. This is partly due to advantages
compared to fed-batch production methods, which include higher productivity, increased product
quality, reduction in bioreactor sizes, and potentially better utilization of production infrastructure.
Continuous manufacturing approaches have clear advantages for processes that may be difficult
to scale up without inducing changes to the therapeutic product. Despite this progress, continuous
manufacturing approaches have yet to be applied to viral vector manufacturing. The growing cell
and gene therapy industry has three key needs that may be addressed by continuous manufacturing
of viral vectors. First, the anticipated worldwide demand for viral vectors cannot feasibly be met
using current batch production infrastructure, necessitating the use of new and alternative
manufacturing approaches. Second, continuous manufacturing could potentially allow rapid
production of quantities of vectors which would enable more rapid initiation of clinical trials, thus
increasing speed to market for novel gene therapy products. Third, as biologic products become
larger and more complex (with cell therapies being more complex than viral therapies being more
complex than proteins), scaling up from clinical scale to commercial scale manufacturing
processes becomes challenging. Manufacturing changes due to scale up (e.g. increasing from 500L
to 2000L and the accompanying changes in agitation rate) can lead to unanticipated changes in the
product quality and final clinical performance. Therefore, developing a large-scale process that
produces a comparable product as well as proving that comparability is both time consuming and
resource intensive. To help address these challenges, MIT is proposing the development and
demonstration of a continuous upstream viral vector manufacturing platform. This will be
accomplished through three distinct aims: first, we will develop a first principles mathematical
model for continuous viral vector cell culture unit operation process design; second, we will
demonstrate the application of novel analytics for the in-line measurement of plasmid transfection
and vector production parameters; and third, we will leverage these learnings to demonstrate the
continuous cell culture production of viral vectors. At the end of the project we will have exhibited
a generic approach for continuous viral vector manufacturing that can be applied to other viral
vectors of interest for the production of either gene or gene-modified cell therapies.

## Key facts

- **NIH application ID:** 10001352
- **Project number:** 5R01FD006584-03
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Richard Dean Braatz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2020
- **Award amount:** $600,000
- **Award type:** 5
- **Project period:** 2018-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001352

## Citation

> US National Institutes of Health, RePORTER application 10001352, Continuous Viral Vector Manufacturing based on Mechanistic Modeling and Novel Process Analytics (5R01FD006584-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001352. Licensed CC0.

---

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