Considerations for risk and control of mycoplasma in bioprocessing

Angart, Phillip; Kohnhorst, Casey; Chiang, Meng-Jung; Arden, Nilou

doi:10.1016/j.coche.2018.09.012

Cited by 7 publications

(4 citation statements)

References 29 publications

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“…PCR analysis for the detection of various mycoplasma species is a convenient method for monitoring contamination both in upstream processes and in the final preparations. Highly sensitive and specific kits for real-time consensus PCR are commercially available [82]. Gene therapy product regulators recommend limiting the amount of free residual DNA to less than 10 ng per dose, and the DNA size to below approximately 200 base pairs [83].…”

Section: Dna Impuritiesmentioning

confidence: 99%

PCR-Based Analytical Methods for Quantification and Quality Control of Recombinant Adeno-Associated Viral Vector Preparations

Shmidt

Егорова

2021

Pharmaceuticals

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Recombinant adeno-associated viral vectors (rAAV) represent a gene therapy tool of ever-increasing importance. Their utilization as a delivery vehicle for gene replacement, silencing and editing, among other purposes, demonstrate considerable versatility. Emerging vector utilization in various experimental, preclinical and clinical applications establishes the necessity of producing and characterizing a wide variety of rAAV preparations. Critically important characteristics concerning quality control are rAAV titer quantification and the detection of impurities. Differences in rAAV constructs necessitate the development of highly standardized quantification assays to make direct comparisons of different preparations in terms of assembly or purification efficiency, as well as experimental or therapeutic dosages. The development of universal methods for impurities quantification is rather complicated, since variable production platforms are utilized for rAAV assembly. However, general agreements also should be achieved to address this issue. The majority of methods for rAAV quantification and quality control are based on PCR techniques. Despite the progress made, increasing evidence concerning high variability in titration assays indicates poor standardization of the methods undertaken to date. This review summarizes successes in the field of rAAV quality control and emphasizes ongoing challenges in PCR applications for rAAV characterization. General considerations regarding possible solutions are also provided.

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Section: Dna Impuritiesmentioning

confidence: 99%

PCR-Based Analytical Methods for Quantification and Quality Control of Recombinant Adeno-Associated Viral Vector Preparations

Shmidt

Егорова

2021

Pharmaceuticals

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“…Off-line analysis typically includes MS to identify structures and, in the case of proteins, molecular weights or detection of aggregates. Other analyses target detection of the presence of contaminants, including bacteria and mycoplasma [ 39 , 40 ]. Near-line methods may also include tests for pyrogens (derived from bacteria).…”

Section: Downstream Processingmentioning

confidence: 99%

Process Analytical Technologies and Data Analytics for the Manufacture of Monoclonal Antibodies

Maruthamuthu

Rudge

Ardekani

et al. 2020

Trends in Biotechnology

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Process analytical technology (PAT) for the manufacture of monoclonal antibodies (mAbs) is defined by an integrated set of advanced and automated methods that analyze the compositions and biophysical properties of cell culture fluids, cell-free product streams, and biotherapeutic molecules that are ultimately formulated into concentrated products. In-line or near-line probes and systems are remarkably well developed, although challenges remain in the determination of the absence of viral loads, detecting microbial or mycoplasma contamination, and applying data-driven deep learning to process monitoring and soft sensors. In this review, we address the current status of PAT for both batch and continuous processing steps and discuss its potential impact on facilitating the continuous manufacture of biotherapeutics.

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“…8 There are several technologies used for this purpose, such as gamma irradiation, ultraviolet light (UV), high-temperature short-time (HTST) sterilization, and filtration. 9 Sterile filtration is typically used for aseptic transfer to the bioreactor while preventing the denaturation of the media components and ingredients, without specific irradiation and steam system utilities and facilities. Currently, 0.2 micron-rated sterilizing grade filtration is used to prevent bacterial contamination and 0.1 micron-rated sterilizing grade filtration is used to protect high-risk raw materials from mycoplasma.…”

Section: Introductionmentioning

confidence: 99%

“…There are several technologies used for this purpose, such as gamma irradiation, ultraviolet light (UV), high‐temperature short‐time (HTST) sterilization, and filtration 9 . Sterile filtration is typically used for aseptic transfer to the bioreactor while preventing the denaturation of the media components and ingredients, without specific irradiation and steam system utilities and facilities.…”

Section: Introductionmentioning

confidence: 99%

Effect of particle size distribution on filtration performance of cell culture medium

Chan

Tomioka

Mok

et al. 2021

Biotechnology Progress

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Cell culture media used in CHO-based biologic processes are typically sterile filtered to prevent microbial contamination prior to inoculation. In this study, the impact of common sterile filter throughput on a different, commercially available cell culture media was evaluated from the intermediate-adsorption fouling model of the filtration model. The key particle size range for optimum filter performance was discussed and identified by measuring the submicron order particle size distribution. It may be possible to predict the performance of filter capacity with size-exclusive separation by understanding the media particle counts and size distribution.

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Considerations for risk and control of mycoplasma in bioprocessing

Cited by 7 publications

References 29 publications

PCR-Based Analytical Methods for Quantification and Quality Control of Recombinant Adeno-Associated Viral Vector Preparations

PCR-Based Analytical Methods for Quantification and Quality Control of Recombinant Adeno-Associated Viral Vector Preparations

Process Analytical Technologies and Data Analytics for the Manufacture of Monoclonal Antibodies

Effect of particle size distribution on filtration performance of cell culture medium

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