Advances in Freeze Drying of Biologics and Future Challenges and Opportunities

Bhatnagar, Bakul; Tchessalov, Serguei

doi:10.1002/9783527802104.ch6

Cited by 7 publications

(4 citation statements)

References 126 publications

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“…A small caveat to keep in mind with the inclusion of an annealing step, is, although primary drying time is optimized, the smaller specific surface area left behind after sublimation, results in a requirement for a longer secondary drying step which was observed by some of co-authors [1].…”

Section: Cake Resistance Differences Between Products Made In Laborat...mentioning

confidence: 99%

“…Developing efficient and robust lyophilization processes at commercial scale remains a nontrivial task even in the twenty-first century. 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].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Cake Resistance Differences Between Products Made In Laborat...mentioning

confidence: 99%

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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“…The solubility of proteins is directly related to adsorption at the air-liquid interface and aggregation. Techniques that expose proteins to a high liquid interfacial area (e.g., SD, SFD), often require the use of additional excipients, such as cyclodextrins (Ramezani et al, 2017), surfactants (Bhatnagar B. and Tchessalov., 2020), ethanol (Johnson, 1997), or the utilization of acidic conditions (Liu et al, 1991). These excipients may also be necessary to modulate the dissolution of the protein.…”

Section: Solubility and Dissolutionmentioning

confidence: 99%

The Development of Thin-Film Freezing and Its Application to Improve Delivery of Biologics as Dry Powder Aerosols

Hufnagel

Sahakijpijarn

Moon

et al. 2022

KONA

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While the formulation of pharmaceuticals as liquids is common practice, powders are associated with enhanced stability, avoidance of the cold chain, lower dosing requirements, and more convenient administration. These are particularly critical for proteins, as they are expensive and complicated to manufacture. Powders also have improved aerosol properties for pulmonary delivery. Conventional techniques for formulating powders include spray-drying, shelf freeze-drying, spray freeze-drying, and spray freezing into liquid, but they produce powders with poor aerosol performance and/or activity due to suboptimal powder properties. Thin-film freezing (TFF) is a new cryogenic technique that can engineer highly porous, brittle, powder matrices with excellent aerosol performance properties and stability. Herein, we describe TFF in comparison to other cryogenic techniques. Physical properties of TFF powders such as morphology, moisture sorption, stability, solubility, and dissolution, as well as aerosol properties are discussed. In addition, factors that significantly affect the physical and aerosol properties of dry powders prepared by TFF, such as solids content, drug loading, solvent system, excipient, and dry powder delivery device, are analyzed. Finally, we provide evidence supporting the applicability of using TFF to prepare dry powder formulations of protein-based pharmaceuticals, enabling their cold chain-free storage as well as efficient pulmonary delivery.

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“…Technologies utilizing biochemical systems routinely require cold-chain infrastructure in the form of refrigeration or freezing for long-term storage, transportation, and point-of-care applications. − Biologics are estimated to be one of the fastest-growing sectors impacting the cold chain, growing 15–29% per year. , The dependence of the bioeconomy on the cold-chain creates challenges for infrastructure, supply chain logistics, and limits access to key regions of the world, restricting on-demand and point-of-care deployment. − The uncontrolled environments in which the end user may deploy the biologics further complicate cold-chain logistics and limit their effectiveness. − For existing biologics, routine breakdowns in cold-chain infrastructure have been documented to reduce the efficacy of vaccines, and cost the government, pharmaceutical industry, and consumers billions of dollars annually. − Multiple lyophilization strategies have been demonstrated to stabilize purified biochemical components, biologics, and simple mixtures for extended periods of time at room temperature. − …”

Section: Introductionmentioning

confidence: 99%

Development of Solid-State Storage for Cell-Free Expression Systems

et al. 2023

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The fragility of biological systems during storage, transport, and utilization necessitates reliable cold-chain infrastructure and limits the potential of biotechnological applications. In order to unlock the broad applications of existing and emerging biological technologies, we report the development of a novel solid-state storage platform for complex biologics. The resulting solid-state biologics (SSB) platform meets four key requirements: facile rehydration of solid materials, activation of biochemical activity, ability to support complex downstream applications and functionalities, and compatibility for deployment in a variety of reaction formats and environments. As a model system of biochemical complexity, we utilized crudeEscherichia colicell extracts that retain active cellular metabolism and support robust levels of in vitro transcription and translation. We demonstrate broad versatility and utility of SSB through proof-of-concepts for on-demand in vitro biomanufacturing of proteins at a milliliter scale, the activation of downstream CRISPR activity, as well as deployment on paper-based devices. SSBs unlock a breadth of applications in biomanufacturing, discovery, diagnostics, and education in resource-limited environments on Earth and in space.

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Advances in Freeze Drying of Biologics and Future Challenges and Opportunities

Cited by 7 publications

References 126 publications

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

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

The Development of Thin-Film Freezing and Its Application to Improve Delivery of Biologics as Dry Powder Aerosols

Development of Solid-State Storage for Cell-Free Expression Systems

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