Evidence map›Paper›PMID 32436993›Full record

ArticleBiotechnology and bioengineering2020

Impacts on product quality attributes of monoclonal antibodies produced in CHO cell bioreactor cultures during intentional mycoplasma contamination events.

Erica J Fratz-Berilla, Phillip Angart, Ryan J Graham, David N Powers, Adil Mohammad, Casey Kohnhorst, Talia Faison, Sai Rashmika Velugula-Yellela, Nicholas Trunfio, Cyrus Agarabi

Open access · hybridAbstract read
In one paragraph

Article in Biotechnology and bioengineering, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.4field-weighted citation impact, top 40% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 11 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Erica J Fratz-BerillaDivision of Biotechnology Review and Research II, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Biotechnology Products, Silver Spring, Maryland.ORCID 0000-0002-9259-0540
Phillip AngartDivision of Biotechnology Review and Research II, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Biotechnology Products, Silver Spring, Maryland.
Ryan J GrahamDivision of Product Quality Research, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Testing and Research, Silver Spring, Maryland.
David N PowersDivision of Biotechnology Review and Research II, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Biotechnology Products, Silver Spring, Maryland.ORCID 0000-0002-9607-1270
Adil MohammadDivision of Product Quality Research, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Testing and Research, Silver Spring, Maryland.ORCID 0000-0003-0310-1088
Casey KohnhorstNova Biomedical, Waltham, Massachusetts.
Talia FaisonDivision of Biotechnology Review and Research II, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Biotechnology Products, Silver Spring, Maryland.ORCID 0000-0001-7211-9121
Sai Rashmika Velugula-YellelaDivision of Biotechnology Review and Research II, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Biotechnology Products, Silver Spring, Maryland.
Nicholas TrunfioSartorius Stedim Data Analytics, Bohemia, New York.
Cyrus AgarabiDivision of Biotechnology Review and Research II, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Biotechnology Products, Silver Spring, Maryland.ORCID 0000-0002-3803-2943
United States Food and Drug Administration · USEP Analytics (United States) · USNovatio Engineering (United States) · US

Funding

CDER Critical Path Program CA #1-13CDER Manufacturing Science & Innovation Center of Excellence Program Berilla-2319Oak Ridge Institute for Science and Education
6 · The paper itself

Abstract

A mycoplasma contamination event in a biomanufacturing facility can result in costly cleanups and potential drug shortages. Mycoplasma may survive in mammalian cell cultures with only subtle changes to the culture and penetrate the standard 0.2-µm filters used in the clarification of harvested cell culture fluid. Previously, we reported a study regarding the ability of Mycoplasma arginini to persist in a single-use, perfusion rocking bioreactor system containing a Chinese hamster ovary (CHO) DG44 cell line expressing a model monoclonal immunoglobulin G 1 (IgG1) antibody. Our previous work showed that M. arginini affects CHO cell growth profile, viability, nutrient consumption, oxygen use, and waste production at varying timepoints after M. arginini introduction to the culture. Careful evaluation of certain identified process parameters over time may be used to indicate mycoplasma contamination in CHO cell cultures in a bioreactor before detection from a traditional method. In this report, we studied the changes in the IgG1 product quality produced by CHO cells considered to be induced by the M. arginini contamination events. We observed changes in critical quality attributes correlated with the duration of contamination, including increased acidic charge variants and high mannose species, which were further modeled using principal component analysis to explore the relationships among M. arginini contamination, CHO cell growth and metabolites, and IgG1 product quality attributes. Finally, partial least square models using NIR spectral data were used to establish predictions of high levels (≥10

Indexed as

Antibodies, MonoclonalBiological ProductsMycoplasmaAnimalsBioreactorsCell Culture TechniquesCHO CellsCricetinaeCricetulusDrug ContaminationStatistics as TopicAntibodies, MonoclonalBiological ProductsbiomanufacturingbioprocessingChinese hamster ovary (CHO) cell culturecritical quality attribute (CQA)monoclonal antibody (mAb)mycoplasmapartial least squares (PLS) regressionprincipal component analysis (PCA)

Identifiers

PMID32436993
PMCPMC7496122
OpenAlexW3026387107

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.