Aramus Single Use Bag Particle Testing and the Importance of SUT Testing

The cleanliness of enclosures or parts is critical to avoid the presence of particulate contamination which can be bad for quality or performance.

A good method to establish cleanliness is the utilization of liquid particle counters to measure the size and number of particles in water after exposure to the part of interest.

How the AccuSizer liquid particle counter can be used to determine the cleanliness of the Entegris Aramus single-use 2D bag assemblies is outlined below.

Introduction

Single-use technologies (SUT) or single-use systems (SUS) or are becoming increasingly typical and accepted in bioprocessing, they now incorporate downstream steps like filling operations, mixing, and storage.

As usage becomes more common in SUS/SUT components, so does the consideration of purity levels in these components, including the level of particulate contamination. No compendial or regulatory guidance has been written which specifically addresses particulate levels in SUS/SUT components.

Recently, the Bio-Process Systems Alliance (BPSA) issued a practical document on this topic, entitled “Recommendations for Testing, Evaluation, and Control of Particulates from Single-Use Process equipment”¹. The BPSA document discusses a variety of relevant topics, including:

• How to control particulates during the use of SUT?
• Why are particulates an issue with SUT?
• How to control particulates during the manufacture of SUT?
• How to address situations when particulates are found in or attributed to SUT?
• Clarify why particles in SUT may be a contamination risk to:
  • the active ingredient and/or formulated product
  • the biological cells which produce the product
  • the patient who is treated with the product.

The BPSA document states (under the topic of Liquid Measurement Methods) that the “Liquid measuring methods for free particles in SUT have evolved from those methods used for final formulation, e.g. USP <788>², because of the absence of a standard or another methodology for more appropriate assessment of the level of particles within the SUT.”

USP 788

Most USP 788 tests are carried out with an optical liquid particle counter, for example, the Entegris AccuSizer, Figure 1. The particle limits for large volume drugs (>100 mL) are lower than 25 particles/mL ≥ 10 μm and lower than 3 particles/mL ≥ 25 μm.

Parenteral drugs administered by injection to patients should be free of visible particles. USP test 788, Particulate Matter in Injections, states how to quantify sub-visible particles present in injectable drugs and sets particle concentration limits which are acceptable.

The presence of sub-visible particles in parenteral drugs can be discovered through the microscopic inspection of a filter, a light obscuration particle counter, or both.

Figure 1: The Entegris AccuSizer SIS system.

AccuSizer System

Available from Entegris the AccuSizer A7000 SIS system is the most advanced instrument available for USP <788> testing. It easily passes all system standardization tests described in USP <1788>  and meets or surpasses all requirements in USP <788> by producing size and count data at the necessary 10 & 25 μm³.

The LE400 sensor, operated by the AccuSizer software, automates both operation and reporting per USP 788, takes measurements from 0.5-400 μm, and calculates results in up to 1024 size channels.

To avoid the presence of particulate contamination that can be detrimental to performance or quality, cleanliness of parts or enclosures is critical. The employment of liquid particle counters to quantify size and count of particles in water after exposure to the part of interest is a good method to determine cleanliness.

This article explains how the use of the AccuSizer liquid particle counter to qualify the cleanliness of the Entegris Aramus single-use 2D bag assemblies.

Aramus Single-Use Bags

The configuration of Aramus™ bags is shown in Figure 3. The Aramus™ single-use 2D bags consist of a high-grade, gamma-stable fluoropolymer, delivering greater compatibility, higher purity, and increased safety for final products and critical process fluids.

With the new single-layer technology that contains no adhesives, curing agents, antioxidants, or plasticizers, the number of potential contaminants has been massively reduced. These assemblies offer the largest operating temperature range, making them more durable in frozen applications (to -85 °C [-121 °F] or lower) without negatively affecting the film.

Figure 3: Aramus bag configuration.

Particle Testing Procedure

The basic technique utilized to determine particulate contamination level on a part or within an enclosure is as follows:

1. Expose the part to clean water
2. Add energy to remove particles from the device
3. Measure the water using a liquid particle counter

The standard method for enclosure testing is “sloshing or swirling.” In the case of testing Aramus™ bags, the bags are filled with clean water, placed on a 3D rocker (Figure 4) and agitated for a set amount of time.

Figure 4: Aramus bag on a 3D rocker.

The process used is as follows:

1. Connect bag to test-system plumbing.
2. Flush process line with ultrapure water through a 0.45-μm filter, bypassing the single-use bag.
3. Pump ultrapure water through a 0.45-μm filter into the single-use bag.
4. Agitate the bag using the 3D rocker for 2 minutes
5. Pull two 50-mL samples from the effluent stream to be subjected to USP <788> testing.

Repeat with the next sample.

Results

The Aramus™ single-use bags pass the USP 788 specifications of less than 25 particles/mL ≥ 10 μm and less than 3 particles/mL ≥ 25 μm.

Multiple measurements are made on each sample to assure statistical accuracy, and the average result is recorded. The measurement noted in step 5 is made by the AccuSizer liquid particle counter.

Conclusions

Entegris has both the analysis technology and experience available from Entegris and the ability to manufacture components and materials and such as the Aramus™ single-use bags. This unique combination provides a complete micro-contamination solution and pure advantage to our customers.

References

1. Recommendations for Testing, Evaluation, and Control of Particulates from Single-Use Process equipment, available at: http://bpsalliance.org/technical-guides/  

2. USP 788, Particulate Matter in Injections, available at: https://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/revisionGeneralChapter788.pdf

3. USP 1788, Methods for the Determination of Particulate Matter in Injections and Ophthalmic Solutions

This information has been sourced, reviewed and adapted from materials provided Entegris

For more information on this source, please visit Entegris