Scalability Studies for Alioth Alidep® Depth Filters

Introduction

With the continuous development of biopharmaceutical indus-try, large-scale drug production has become increasingly prevalent. In the production process, depth filtration, as the first step in the downstream processes, is critical for the perfor-mance and efficiency of subsequent purification and separa-tion process steps.

However, the linear scale-up of depth filters from process development scale to production scale presents a significant challenge, as multiple factors need to be considered during clarification scale-up, such as pressure control, turbidity control, safety factor, etc. Therefore, scalability studies are crucial for evaluating the performance of depth filters.

Scalability studies are defined as the research conducted to determine the appropriate filter size for actual production by comparing the performance of filters of different sizes, such as flux, capacity, and filtrate quality. Alioth adopts a method of gradually increasing the filtration area to simulate the process performance of depth filters in actual drug production, aiming to provide a theoretical basis for the selection of depth filter products in drug scale-up drug production.

The results of following experiment are provided as a general example and do not represent product claims or specifications. Therefore, the test results for actual drugs should be confirmed by the representative feed liquid and process conditions used by the end-user.

Materials and methods

In this experiment, yeast suspension was used to evaluate the linear scale-up performance of the Alioth depth filters with different sizes from process development scale to production scale.

Table 1. Info of Alioth depth filters and sterilizing-grade filters used for scalability studies

According to the maximum pressure methodology, a scalability study was carried out under constant flow conditions (150 LMH) with the Alidep® HA02 series filters. At the same time, a CEC52 series sterilizing-grade filter was connected downstream of the HA02 series filters to verify the impact of the depth filter filtrate on the sterilizing filter (detailed information is shown in Table 1, 2).

Table 2. Filters for scalability studies

Firstly，the filter was rinsed with at least 100 L/m² of purified water before filtration. During the experiment, the yeast suspension was filtered at a flow rate of 150 LMH, and the turbidity of the filtrate was measured periodically.

The results showed that the turbidity of the yeast suspension samples increased from 3680 NTU to 3820 NTU indicating no significant change in sample characteristics (Table 3).

Table 3. Feed liquid information for scalability studies

Results

Depth filter scalability tests are typically conducted at a single process flux to conserve cell culture feed stream volumes and to minimize the test duration. In this serial study, the tests are conducted at 150 LMH process flux.

Table 4 summarizes the filter throughput and turbidity results of Alioth Alidep® HA02 Depth Filters using yeast suspensions at different endpoint pressures. The data shows that Alioth Alidep® Depth Filters in different scales have good consistency in throughput and turbidity control.

Table 4. Filter scalability test results for Alioth Alidep® depth filters - HA02 using selected yeast suspension

Scalability results of Alioth Alidep® depth filters - HA02 (study 1)

Fig.1 ΔP and throughput results of Alioth Alidep® process-scale depth filters (0.0023m²) and production-scale depth filters (0.11m²,1.1m² and 9.9m²)

Figure 1 shows that Alioth Alidep® process-scale depth filters (0.0023m²) and production-scale depth filters (0.11m²,1.1m² and 9.9m²) have similar trend in pressure drop and throughput change at constant flowrate of 150LMH.

Scalability results of Alioth Alidep® depth filters - HA02 (study 2) 

Fig.2 Throughput & instant turbidity results of Alioth Alidep® process-scale depth filters (0.0023m²) and production-scale depth filters (0.11m²,1.1m² and 9.9m²)

Figure 2 presents the similar instant turbidity and throughput results between Alioth Alidep® process-scale depth filters (0.0023m²) and production-scale depth filters (0.11m2,1.1m2 and 9.9m2) at different endpoint pressure under same flowrate. 

Fig.3 Setup of filters and equipment  

Fig.4 Comparison of feed solution before and after filtration with Alidep® depth filters

Summary

This article presents the good scalability of Alidep® HA02 series from different aspects, indicating that the Alioth Alidep® depth filters are able to provide a great scalability performance and accurate depth filter sizing estimates for customers' clarification process whichallow customers to accurately estimate the quantity of depth filter required, and ensure a high-level quality assurance system to reduce concerns.