Protection of therapeutic antibodies from visible light induced degradation: Use safe light in manufacturing and storage

Cheng, Du; Barnett, Gregory V.; Borwankar, Ameya; Lewandowski, Angela; Singh, Namrata; Ghose, Sanchayita; Borys, Michael

doi:10.1016/j.ejpb.2018.02.007

Cited by 29 publications

(19 citation statements)

References 26 publications

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“…Protein monomers may become more susceptible to aggregation after prolonged light exposure. The ultraviolet or visible light treatment of antibodies causes heavy aggregation, 169,170 perhaps due to oxidation at trypsin and methionine residues that facilitate aggregation. 171,172 Sonication affects protein aggregation and causes partial unfolding due to an increase in temperature, pressure, and void formation.…”

Section: Processesmentioning

confidence: 99%

Review of the current state of protein aggregation inhibition from a materials chemistry perspective: special focus on polymeric materials

et al. 2021

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Section: Processesmentioning

confidence: 99%

Review of the current state of protein aggregation inhibition from a materials chemistry perspective: special focus on polymeric materials

et al. 2021

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“…Higher aggregation rates (Arakawa & Timasheff, 1985;Shire, 2009;Shire et al, 2004) Include excipients to provide stabilizing effects (Chang et al, 1996;Kerwin, 2008;Mahler et al, 2005;Randolph & Jones, 2002) Higher aggregation rates under room temperature, room light conditions (Du et al, 2018) Use yellow lights with low/no UV output, use timebased light exposure controls during manufacturing (Du et al, 2018) Increased PS80 degradation risk due to greater concentration of lipases Use metal chelator in formulation (Yarbrough et al, 2019) Target problematic lipases for removal (Chiu et al, 2017) Appearance attributes of highconcentration drug substance Changes in appearance due to excipient degradation (Stroop et al, 2011), oxidation degradation (Amici et al, 1989), photo-induced degradation (Du et al, 2019) Use chelators, antioxidants, or radical scavengers (Lam et al, 1997; Minimize light exposure during manufacturing and storage (Du et al, 2019) Freezing of high-concentration drug substance Self-association kinetics exacerbated by cryoconcentration (Hauptmann et al, 2018;Rathore & Rajan, 2008) Minimize cryoconcentration effects with shorter freezing times (Cao et al, 2003) Mix immediately after thawing to minimize the development of protein cryoconcentration (Mehta et al, 2019) Abbreviations: DF, diafiltration; PS80, polysorbate 80; TMP, transmembrane pressure; UF, ultrafiltration.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…Figure 4 shows high molecular weight content for formulated drug substance as a function of hold time at room temperature versus RTRL conditions. Mitigation strategies include the use of yellow lights, lights with low/no UV output (i.e., light‐emitting diodes), and time‐based light exposure controls during manufacturing (Du et al, 2018).…”

Section: Stabilitymentioning

confidence: 99%

Strategies for high‐concentration drug substance manufacturing to facilitate subcutaneous administration: A review

Holstein

Hung

Feroz

et al. 2020

Biotech & Bioengineering

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To achieve the high protein concentrations required for subcutaneous administration of biologic therapeutics, numerous manufacturing process challenges are often encountered. From an operational perspective, high protein concentrations result in highly viscous solutions, which can cause pressure increases during ultrafiltration. This can also lead to low flux during ultrafiltration and sterile filtration, resulting in long processing times. In addition, there is a greater risk of product loss from the holdup volumes during filtration operations. From a formulation perspective, higher protein concentrations present the risk of higher aggregation rates as the closer proximity of the constituent species results in stronger attractive intermolecular interactions and higher frequency of self-association events. There are also challenges in achieving pH and excipient concentration targets in the ultrafiltration/ diafiltration (UF/DF) step due to volume exclusion and Donnan equilibrium effects, which are exacerbated at higher protein concentrations. This paper highlights strategies to address these challenges, including the use of viscosity-lowering excipients, appropriate selection of UF/DF cassettes with modified membranes and/or improved flow channel design, and increased understanding of pH and excipient behavior during UF/DF. Additional considerations for high-concentration drug substance manufacturing, such as appearance attributes, stability, and freezing and handling are also discussed. These strategies can be employed to overcome the manufacturing process challenges and streamline process development efforts for high-concentration drug substance manufacturing.

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“…The stability of proteins is also related to the amount of aromatic amino acid residues that can absorb UV light in the environment. It was determined that the tryptophan residue of the IgG exposed to UV turned into glycine or glycine hydroperoxide 29,30 . Therefore, the use of UV light exposed antibodies is not recommended.…”

Section: Configuration Of Antibodies and Disruptive Effectsmentioning

confidence: 99%

Presentation of Neutralizing Antibodies in Single- or Pooled-Convalescent Immune Plasma from Donors to Prevent the Current SARS-CoV-2 Pandemic

Özçeli̇k

Ercan

Güven

et al. 2020

IJCV

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As there is no specific treatment yet, the fight against the COVID-19 pandemic is being carried out with great difficulty today. The use of immune plasma is seen as a promising option since there is expectation that it will reduce mortality, as in influenza pandemics experienced in 1918 and 2009. However, the safety and effectiveness of this treatment option against SARS-CoV-2 viruses are not known for certain. In addition, the optimal obtaining methods and protection time of neutralizing antibodies to be used to provide passive immunization are not fully known. Therefore, it would be very useful to investigate the most effective neutralizing antibody collection methods without disrupting the overall structure and effectiveness of the antibodies subject to the use of the convalescent immune plasma. For this purpose, we found it appropriate to prepare a broad review on the structure and properties of antibodies, as well as the principles and storage conditions of antibodies to be used in passive immunization.

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Protection of therapeutic antibodies from visible light induced degradation: Use safe light in manufacturing and storage

Cited by 29 publications

References 26 publications

Review of the current state of protein aggregation inhibition from a materials chemistry perspective: special focus on polymeric materials

Review of the current state of protein aggregation inhibition from a materials chemistry perspective: special focus on polymeric materials

Strategies for high‐concentration drug substance manufacturing to facilitate subcutaneous administration: A review

Presentation of Neutralizing Antibodies in Single- or Pooled-Convalescent Immune Plasma from Donors to Prevent the Current SARS-CoV-2 Pandemic

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