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Dynamic Light Scattering: A Tool to Accelerate Oncolytic Vaccine Development

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The Vaccinia virus (MVA) was originally utilized as a viral vaccine against the Smallpox disease. However, recent advancements and increased interest from the pharmaceutical industry have revealed that MVA has potential as a robust vector for vaccines against infectious diseases and cancer treatments. One critical aspect in the development of engineered MVA viruses is particle size. In this case study, we highlight the significance of particle size measurement utilizing dynamic light scattering (DLS) in the development of vaccines based on the MVA virus.

The Problem

To optimize process scalability, enhance impurity removal, and increase product yield, significant modifications were made to the downstream process train. However, the development of a process for the manufacture of large viruses such as MVA can pose a challenge as there is a tendency towards aggregation of the virus. As a consequence, the in-process virus yield may fail to meet the established Critical Quality Attributes (CQAs), leading to concerns regarding the quality and stability of the MVA virus in the downstream process.

The Breakthrough

Routine monitoring of the MVA particle size by DLS was introduced after each of the unit operations from Step 1 to Step 6 to ensure consistency of the virus across the downstream process train.

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Downstream process train

A fit-for-purpose experimental approach including system suitability and data quality checks was developed. The first overnight hold, Step 3, particularly affected the quality of the product. It was responsible for causing a 40 % increase in particle size and also causing an increase the polydispersity of the product (PdI ~ 0.6 characteristic of highly polydisperse sample) and this increase was maintained in the subsequent unit operation.

The Impact

The particle size increase identified by DLS after the first overnight hold post clarification highlighted the presence of residual host cell protein potentially bound to MVA. An additional step (protein digestion enzyme) was introduced in the DSP process train to ensure complete removal of host cell proteins from the product. This was crucial to accelerate decision making, leading to a faster route to manufacturing by meeting CQA requirements on particle size and PdI.

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Aquisition, Data, Results


Dynamic Light Scattering (DLS) is a technique with wide application for in solution particle size and size distribution measurements. With a sample of only 50µL, any particle ranging from 0.1 nm to 10 µm can be detected. This can elucidate the presence of aggregates occurring during the development of the purification process.

The acquisition of data is user friendly, however the interpretation and data quality acceptance require expert level knowledge and experience. At APC, we have a team of analytical scientists dedicated to Drug Substance and Drug Product characterisation using DLS (Malvern Zetasizer Ultra Red), Nanoparticle Tracking Analysis (Nanosight NS300), sub-visible Particle counter (HIAC 9703+), SEC with UV/FLD/MALS detection (1260 Infinity II Bio-SEC Multi-Detector System). We have built expertise in particle sizing, determination of aggregation status, charges, and particle count (Titre), all of which we can measure as a function of pH and temperature (below ambient to 100 °C). Over the past 10 years, we have supported our clients dealing with a wide variety of challenging products from Enzymes, mAbs, ADCs, viruses (Adenovirus, AAV, Vaccinia), and nanoparticles for advanced drug delivery (LNPs) assisting them on their CMC journey. 

Learn more about our Vaccine Development Capabilities