Scale-up and process transfer considerations in lentiviral vector manufacturing

Increasing clinical demand for lentiviral vector–based therapies is driving the need for scalable and reproducible manufacturing workflows. This article presents an evaluation of lentiviral production across shake flask, 2 L, and 50 L formats, achieving infectious titers approaching 1 × 10⁸ TU/mL with comparable metabolic performance between formats. A 3 L implementation study further examines transferability of upstream parameters and identified operational variables influencing reproducibility at intermediate scale.

Scalable lentiviral vector manufacturing requires reproducible upstream and downstream workflows. This article evaluates production from bench to 50 L, examines downstream yield losses, and assesses process transferability at 3 L CDMO scale.

What you will learn

01

How LV production scales from shake flask to 50 L single-use bioreactors

02

Where infectivity is lost across the downstream purification train

03

What governs reproducibility during CDMO process transfer at 3 L

The LV manufacturing pathway

1

Upstream culture & transfection

2

Harvest & clarification

3

AEX chromatography

4

TFF concentration

5

Sterile filtration & fill

Key findings

Titers of ~1×10⁸ TU/mL were preserved from shake flask through to 50 L, with comparable metabolic profiles across all formats

Cumulative downstream losses reduced overall infectivity recovery to approximately 10%, with sterile filtration identified as a key bottleneck

Seeding density and transfection control were the critical determinants of reproducible titer at intermediate CDMO scale

Key interests

Cell Therapy

Gene Delivery

Gene Therapy

Manufacturing Scale-up

CDMO

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