Microwave-Assisted Freeze-Drying of Monoclonal Antibodies: Product Quality Aspects and Storage Stability.

Julian Hendryk Gitter,Gerhard Winter,Ingo Presser,Raimund Geidobler

doi:10.3390/pharmaceutics11120674

Julian Hendryk Gitter, Gerhard Winter + Show 2 more

Open Access

https://doi.org/10.3390/pharmaceutics11120674

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Abstract

In order to overcome the downside of long conventional freeze-drying (CFD) process times for monoclonal antibody formulations, microwave-assisted freeze-drying (MFD) was introduced. Recently, the general applicability and potential shortening of drying times were shown. However, little is known about the storage stability of MFD products compared to CFD references. Additionally, batch homogeneity issues were seen within MFD in the past. In this study, we examined four different formulations of two different monoclonal antibodies using three different glass-forming excipients: sucrose, trehalose, and arginine phosphate. These formulations were freeze-dried with two different drying protocols (CFD and MFD), stored for 24 weeks, and analyzed for solid-state and protein-related quality attributes. Moreover, a new microwave generator setup was investigated for its potential to improve batch homogeneity. In all investigated formulations, comparable stability profiles were found, although the classical magnetron generator led to inferior batch homogeneity with respect to residual moisture distribution. In contrast, the new MFD setup indicated the potential to approximate batch homogeneity to the level of CFD. However, for future applications, there is an unabated need for new machine designs to comply with pharmaceutical manufacturing requirements.

Highlights

Conventional freeze-drying (CFD), referred to as lyophilization, is a gentle drying method to improve the long-term stability of pharmaceuticals, of protein drugs [1]
The first usage in pharmaceutical freeze-drying was presented by Evans et al [24] at the CPPR Freeze Drying of Pharmaceuticals & Biologics Conference in 2014, showing the general applicability to monoclonal antibodies and vaccine formulations
Two major questions that have been raised have not been answered yet: (1) How do different microwave-assisted freeze-dried antibody formulations perform in accelerated stability studies with respect to solid-state and protein stability compared to a conventionally freeze-dried reference? (2) Is the inferior batch homogeneity found for microwave-assisted freeze-drying (MFD) samples a general issue associated with microwave drying, or are there ways to improve it?

Summary

Introduction

Conventional freeze-drying (CFD), referred to as lyophilization, is a gentle drying method to improve the long-term stability of pharmaceuticals, of protein drugs [1]. One alternative drying method utilizing microwaves is known from the food industry: microwave-assisted freeze-drying (MFD) [13] It is used for high-value goods like dry fruit [14]. The heating mechanism in pharmaceutics occurs due to dipolar and ionic mechanisms When such a polar compound is placed in an oscillating field, dipoles or ions try to realign in the direction of the electric field. The first usage in pharmaceutical freeze-drying was presented by Evans et al [24] at the CPPR Freeze Drying of Pharmaceuticals & Biologics Conference in 2014, showing the general applicability to monoclonal antibodies and vaccine formulations On this basis, a handful of international patents were filed claiming engineering- [25] or formulation-/process-focused [26,27] intellectual property. Two major questions that have been raised have not been answered yet: (1) How do different microwave-assisted freeze-dried antibody formulations perform in accelerated stability studies with respect to solid-state and protein stability compared to a conventionally freeze-dried reference? (2) Is the inferior batch homogeneity found for MFD samples a general issue associated with microwave drying, or are there ways to improve it?

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