Best Practices and Guidelines (2022) for Scale-Up and Tech Transfer in Freeze-Drying Based on Case Studies. Part 1: Challenges during Scale Up and Transfer

Tchessalov, Serguei; Shalaev, Evgenyi; Bhatnagar, Bakul; Nail, Steven L.; Alexeenko, Alina; Jameel, Feroz; Srinivasan, Jayasree; Dekner, Michael; Sahni, Ekneet; Schneid, Stefan; Kazarin, Petr; McGarvey, Orla; Meervenne, Bert Van; Kshirsagar, Vaibhav; Pande, Paritosh; Philipp, Jens; Sacha, Greg; Ke, Wu; Azzarella, Joseph; Shivkumar, Gayathri; Bhatt, Shreyas

doi:10.1208/s12249-022-02463-x

Cited by 11 publications

(3 citation statements)

References 30 publications

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“…It has been suggested, for example, that the crystallization of a bulking agent during cooling can be beneficial in minimizing vial breakage. A case study that describes vial breakage as the result of annealing, and prevention of the vial breakage using step-wise cooling, is provided [32]. Also, the impact of timing of crystallization of the bulking agent (e.g., if it takes place during cooling or at the beginning of primary drying) during freeze-drying on protein stability was reported in [33]; in that case, crystallization of solute during cooling was beneficial for stability.…”

Section: Partially Crystalline Formulationsmentioning

confidence: 99%

Practical Advice on Scientific Design of Freeze-Drying Process: 2023 Update

Tchessalov,

Maglio,

Kazarin

et al. 2023

Pharm Res

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Objective The purpose of this paper is to re-visit the design of three steps in the freeze-drying process, namely freezing, primary drying, and secondary drying steps. Specifically, up-to-date recommendations for selecting freeze-drying conditions are provided based on the physical–chemical properties of formulations and engineering considerations. Methods and Results This paper discusses the fundamental factors to consider when selecting freezing, primary drying, and secondary drying conditions, and offers mathematical models for predicting the duration of each segment and product temperature during primary drying. Three simple heat/mass transfer primary drying (PD) models were tested, and their ability to predict product temperature and sublimation time showed good agreement. The PD models were validated based on the experimental data and utilized to tabulate the primary drying conditions for common pharmaceutical formulations, including amorphous and partially crystalline products. Examples of calculated drying cycles, including all steps, for typical amorphous and crystalline formulations are provided. Conclusions The authors revisited advice from a seminal paper by Tang and Pikal (Pharm Res. 21(2):191-200, 2004) on selecting freeze-drying process conditions and found that the majority of recommendations are still applicable today. There have been a number of advancements, including methods to promote ice nucleation and computer modeling for all steps of freeze-drying process. The authors created a database for primary drying and provided examples of complete freeze-drying cycles design. The paper may supplement the knowledge of scientists and formulators and serve as a user-friendly tool for quickly estimating the design space.

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Section: Partially Crystalline Formulationsmentioning

confidence: 99%

Practical Advice on Scientific Design of Freeze-Drying Process: 2023 Update

Tchessalov,

Maglio,

Kazarin

et al. 2023

Pharm Res

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“…While many tools and approaches were developed to assist in lyophilization cycle optimization at laboratory scale [1], establishing commercial processes at any scale is a complicated process due to numerous challenges that could arise with the change in scale. The challenges during lyophilization process scale-up and transfer were outlined and discussed in the first part of this paper [2]. It was demonstrated that due to differences in refrigeration capacity, shelf mass, and heat transfer coefficients between commercial and laboratory dryers, the same process parameters in laboratory scale may not be applied to commercial dryers.…”

Section: Introductionmentioning

confidence: 99%

Best Practices and Guidelines (2022) for Scale-up and Technology Transfer in Freeze Drying Based on Case Studies. Part 2: Past Practices, Current Best Practices, and Recommendations

et al. 2023

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Scale-up and transfer of lyophilization processes remain very challenging tasks considering the technical challenges and the high cost of the process itself. The challenges in scale-up and transfer were discussed in the first part of this paper and include vial breakage during freezing at commercial scale, cake resistance differences between scales, impact of differences in refrigeration capacities, and geometry on the performance of dryers. The second part of this work discusses successful and unsuccessful practices in scale-up and transfer based on the experience of the authors. Regulatory aspects of scale-up and transfer of lyophilization processes were also outlined including a topic on the equivalency of dryers. Based on an analysis of challenges and a summary of best practices, recommendations on scale-up and transfer of lyophilization processes are given including projections on future directions in this area of the freeze drying field. Recommendations on the choice of residual vacuum in the vials were also provided for a wide range of vial capacities. Graphical Abstract

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“…Various examples of mechanistic models of the primary drying phase describing this complex interplay of parameters have been developed ( Tang and Pikal, 2004 ; Fissore and Pisano, 2015 ; Mortier et al, 2016 ). For an in-depth recommendation on freeze-drying model practices the reader is referred to the literature ( Nail et al, 2017 ; Tchessalov et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%