Ensuring process integrity – which means being able to effectively test for leaks – is a critical factor in biopharmaceutical manufacturing processes, especially given the high value placed on drug products and the potency of the products being produced.
It’s a factor in some cases that has led to a delay in the adoption of single-use technology and a continued reliance on stainless steel systems when a similar testing regime has been demanded. This issue is one of five critical challenges in single-use bioprocessing.
With stainless steel systems, integrity is tested by pressurizing the system and holding it at a known pressure for many hours looking for a drop in pressure to test for leaks. This high-pressure method of testing can’t be applied to single-use assemblies, as they are manufactured from flexible polymeric materials.
Instead, manufacturers employ visual inspection and low-pressure decay testing to ensure the integrity of single-use assemblies. This has caused a certain level of concern, with some end users worried about the level of assurance these methods offer.
However, despite our knowledge of stainless steel systems and how to test them, it could, in fact, be viewed as having a higher risk of leaks compared to single-use assemblies.
Stainless steel components and pipework must be repeatedly cleaned and sterilized, placing significant thermal stress on the system’s integrity, not to mention operational flexibility. In addition, stainless steel systems contain multiple line connections and during steam sterilization are subject to an extreme level of temperature fluctuation.
Application of quality by design to single-use assembly manufacturing
Quality by design (QbD) is a strategy employed to ensure integrity in building single-use systems, not just with the final product. By applying this methodology to the integrity and quality throughout the entire manufacturing process, quality assurance is built in from the start of the manufacturing process.
The single-use assembly manufacturing process starts by identifying areas of risk throughout the process and then continues by developing best practices and procedures to minimize risks. In Parker's own single-use assembly manufacturing operations, several methods have been employed to build quality and integrity into the process.
- Carefully selecting raw material and component suppliers and ensuring that they meet current biopharmaceutical regulations (such as USP <88> — Biological Reactivity, USP <661> — Containers — Plastics) as well as gamma stability and rigorous in-house testing of physical properties
- Minimizing risk of assembly damage by manufacturing in a purpose-built ISO Class 7 cleanroom, where furniture and equipment has rounded edges when possible to avoid punctures, and any sharp edges are shielded
- Ensuring connections are robust by clamping to a defined torque setting so they do not leak under the validated operating conditions
- Performing a final visual inspection and low-pressure decay test of assemblies before packaging
- Shipping assemblies via a validated method, ASTM4169 to ensure they arrive at the customer site undamaged
Read the full white paper: Single-Use Technology: The Next 5 Challenges to Conquer
This post was contributed by Graeme Proctor, product manager - single-use technologies, Parker Bioscience Division, United Kingdom.