Impact of Annealing and Controlled Ice Nucleation on Properties of A Lyophilized 50 mg/ml MAB Formulation

Wang, Jijun; Searles, James A.; Torres, E.; Tchessalov, Serguei; Young, Anthony L.

doi:10.1016/j.xphs.2022.05.016

Cited by 5 publications

(2 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moisture content was the lowest for shelf-ramped freezing and the highest for CIN. Annealing results were between those of shelf-ramped freezing and CIN for all the parameters cited above (Wang et al 2022).…”

Section: )mentioning

confidence: 78%

Recent advances and persistent challenges in the design of freeze-drying process for monoclonal antibodies

Hsein

Auffray

Noël

et al. 2022

Pharmaceutical Development and Technology

View full text Add to dashboard Cite

Monoclonal antibodies constitute nowadays an important therapeutic class and the number of approved molecules for clinical uses continues to increase, achieving considerable part of the therapeutic market. Yet, the stability in solution of these biopharmaceuticals is often low.That's why freeze-drying has been and remains the method of choice to obtain monoclonal antibodies in the solid state and to improve their stability. The design of freeze-drying process and its optimization are still topical subjects of interest and the pharmaceutical industry is regularly challenged by the requirements of quality, safety and efficiency set by the regulatory authorities. These requirements imply a deep understanding of each step of the freeze-drying process, developing techniques to control the critical parameters and to monitor the quality of the intermediate and the final product. In addition to quality issues, the optimization of the freeze-drying process in order to reduce the cycle length is of great interest since freeze-drying is known to be an energy-expensive and time-consuming process. In this review, we will present the recent literature dealing with the freeze-drying of monoclonal antibodies and focus on the process parameters and strategies used to improve the stability of these molecules and to optimize the FD process.

show abstract

Section: )mentioning

confidence: 78%

Recent advances and persistent challenges in the design of freeze-drying process for monoclonal antibodies

Hsein

Auffray

Noël

et al. 2022

Pharmaceutical Development and Technology

View full text Add to dashboard Cite

show abstract

“…The freeze-drying process is often composed of freezing, primary drying, secondary drying, and, if necessary, annealing. The annealing step keeps samples at a specified temperature higher than the glass transition temperature of the maximally freeze concentrated solution ( T g ’) during the freezing step for a specified period, which will influence the size and distribution of the ice crystals. − Webb et al also concluded that more native-like secondary protein structure was obtained in the dried solid through addition of an annealing step, which also inhibited the formation of air/liquid interfaces and recombinant human interferon-gamma aggregation during reconstitution . Fonte et al found that annealing was a tool to optimize the freeze-drying process and improve the stability of PLGA nanoparticle-loaded protein .…”

Section: Introductionmentioning

confidence: 99%

Effect of Annealing on Visible-Bubble Formation and Stability Profiles of Freeze-Dried High Concentration Omalizumab Formulations

Gao,

Ge,

Liu

et al. 2024

Mol. Pharmaceutics

View full text Add to dashboard Cite

In the clinical application of freeze-dried highly concentrated omalizumab formulations, extensive visible bubbles (VBs) can be generated and remain for a long period of time in the reconstitution process, which greatly reduces the clinical use efficiency. It is necessary to understand the forming and breaking mechanism of VBs in the reconstitution process, which is a key factor for efficient and safe administration of biopharmaceutical injection. The effects of different thermal treatments on the volume of VBs and stability of omalizumab, mAb-1, and mAb-2 were investigated. The internal microvoids of the cake were characterized by scanning electron microscopy and mercury intrusion porosimetry. Electron paramagnetic resonance was applied to obtain the molecular mobility of the protein during annealing. A large number of VBs were generated in the reconstitution process of unannealed omalizumab and remained for a long period of time. When annealing steps were added, the volume of VBs was dramatically reduced. When annealed at an aggressive temperature (i.e., −6 °C), although the volume of VBs decreased, the aggregation and acidic species increased significantly. Thus, our observations highlight the importance of setting an additional annealing step with a suitable temperature, which contributes to reducing the VBs while maintaining the stability of the high concentration freeze-dried protein formulation.

show abstract

Process control and design of drying technologies for biopharmaceuticals – A review

Brytan,

Amorim,

Padrela

2025

Powder Technology

View full text Add to dashboard Cite

Impact of Annealing and Controlled Ice Nucleation on Properties of A Lyophilized 50 mg/ml MAB Formulation

Cited by 5 publications

References 23 publications

Recent advances and persistent challenges in the design of freeze-drying process for monoclonal antibodies

Recent advances and persistent challenges in the design of freeze-drying process for monoclonal antibodies

Effect of Annealing on Visible-Bubble Formation and Stability Profiles of Freeze-Dried High Concentration Omalizumab Formulations

Process control and design of drying technologies for biopharmaceuticals – A review

Contact Info

Product

Resources

About