eprintid: 1361931
rev_number: 37
eprint_status: archive
userid: 608
dir: disk0/01/36/19/31
datestamp: 2012-09-14 20:11:23
lastmod: 2022-01-02 23:59:56
status_changed: 2012-09-14 20:11:23
type: article
metadata_visibility: show
item_issues_count: 0
creators_name: Noyes, A
creators_name: Godavarti, R
creators_name: Titchener-Hooker, N
creators_name: Coffman, J
creators_name: Mukhopadhyay, T
title: Quantitative high throughput analytics to support polysaccharide production process development.
ispublished: pub
divisions: UCL
divisions: B04
divisions: C05
keywords: Capsular polysaccharides, Carbohydrates, Endotoxin assays, High throughput process development, Phenol sulphuric acid assay, Sugar quantification
note: © 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/3.0/).
abstract: The rapid development of purification processes for polysaccharide vaccines is constrained by a lack of analytical tools current technologies for the measurement of polysaccharide recovery and process-related impurity clearance are complex, time-consuming, and generally not amenable to high throughput process development (HTPD). HTPD is envisioned to be central to the improvement of existing polysaccharide manufacturing processes through the identification of critical process parameters that potentially impact the quality attributes of the vaccine and to the development of de novo processes for clinical candidates, across the spectrum of downstream processing. The availability of a fast and automated analytics platform will expand the scope, robustness, and evolution of Design of Experiment (DOE) studies. This paper details recent advances in improving the speed, throughput, and success of in-process analytics at the micro-scale. Two methods, based on modifications of existing procedures, are described for the rapid measurement of polysaccharide titre in microplates without the need for heating steps. A simplification of a commercial endotoxin assay is also described that features a single measurement at room temperature. These assays, along with existing assays for protein and nucleic acids are qualified for deployment in the high throughput screening of polysaccharide feedstreams. Assay accuracy, precision, robustness, interference, and ease of use are assessed and described. In combination, these assays are capable of measuring the product concentration and impurity profile of a microplate of 96 samples in less than one day. This body of work relies on the evaluation of a combination of commercially available and clinically relevant polysaccharides to ensure maximum versatility and reactivity of the final assay suite. Together, these advancements reduce overall process time by up to 30-fold and significantly reduce sample volume over current practices. The assays help build an analytical foundation to support the advent of HTPD technology for polysaccharide vaccines. It is envisaged that this will lead to an expanded use of Quality by Design (QbD) studies in vaccine process development.
date: 2014-05-19
official_url: http://dx.doi.org/10.1016/j.vaccine.2014.02.034
vfaculties: VENG
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_source: PubMed
elements_id: 439172
doi: 10.1016/j.vaccine.2014.02.034
pii: S0264-410X(14)00207-2
lyricists_name: Mukhopadhyay, Tarit
lyricists_name: Titchener-Hooker, Nigel
lyricists_id: TKMUK80
lyricists_id: NJTIT16
full_text_status: public
publication: Vaccine
volume: 32
number: 24
pagerange: 2819 - 2828
event_location: Netherlands
citation:        Noyes, A;    Godavarti, R;    Titchener-Hooker, N;    Coffman, J;    Mukhopadhyay, T;      (2014)    Quantitative high throughput analytics to support polysaccharide production process development.                   Vaccine , 32  (24)   2819 - 2828.    10.1016/j.vaccine.2014.02.034 <https://doi.org/10.1016/j.vaccine.2014.02.034>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1361931/1/1-s2.0-S0264410X14002072-main.pdf