Biocompatible materials in bioreactor gas flow controllers
Wetted materials considerations for bioprocessing
Bioprocessing has very specific and often stringent requirements to ensure that biocompatible materials are used for all wetted materials. This is to ensure that the bioreactor environment is not contaminated and can be fully cleaned between each batch, ensuring the integrity of the final biologic drug product.
Key considerations include designing for cleanability, with no crevices and minimal sharp corners in which contaminants such as bacteria would be able to avoid sterilization and proliferate. Similarly, metal components should be smooth to optimize the effectiveness of cleaning procedures.
Elastomers, however, present a different challenge: materials which were adsorbed onto the elastomers during polymerization may outgas and release contaminants into the bioprocess. Outgassed components are of concern as they are thought to be inhibitory towards microbial growth and have been shown to have toxic effects in whole animal studies.
Outgassing most frequently occurs under vacuum conditions, but it can be a concern in any situation where a pressure drop is present – such as any gas flow line, including the gas lines feeding bioreactors. A number of studies have demonstrated outgassing from elastomeric components under a variety of conditions.
ASME BPE design standards to prevent contamination
The ASME bioprocessing standards call out specific materials to be used in the construction of bioprocessing equipment. These recommendations apply primarily to equipment which comes into direct contact with biologic material. As such, mass flow controllers are generally not subject to these material specifications: they lie outside of the sterile boundary, flow only clean, dry gases (introducing no opportunity other than unintentional backflows for bacteria), and do not come into contact with the intermediary or final biological product.
However, it is still considered best practice to follow the BPE-2016 design standards where able. For mass flow controllers, this requires specific materials for both the elastomers and the metal flow bodies and process connections.
Mass flow controllers use elastomers for their sealing properties, which result in low leak rates and high precision mass flow measurement. Materials outgassed from elastomers would likely pass through sterilizing filters and are thus a potential source of process contamination – even though the flow controllers themselves are outside of the sterile boundary. The BP-2016 standards are therefore often applied to materials in the flow meters which have the potential for outgassing.
The rigid materials in mass flow devices must be similarly monitored. The flow bodies and process connections of flow instrumentation may be made of any one of a number of materials, ranging from inexpensive ABS plastics to exotic stainless steels. Using 316L stainless steel for elements in the flow path such as the flow body and laminar flow elements minimize any concerns that the mass flow controllers could harbor bacteria and introduce contaminants into the bioprocess.
Using high quality components ensures that fragile bioreactions will not be contaminated by the equipment itself, particularly when the appropriate cleaning and sterilization protocols are also closely adhered to.
USP Class VI elastomers
The BPE-2016 standards recommend using corrosion resistant, high-durability elastomers such as EPDM (Ethylene Propylene Diene), FKM (Fluoroelastomer) or FFKM (perfluoroelastomer). The standards further recommend using USP Class VI elastomers in any components likely to be in contact with the final biological or drug product.
If any liquids (such as growth media or water) are present in the environment, only USP Class VI elastomers with good permeation resistance should be used. Outgassing is only able to occur after materials have first been permeated – so resistance to permeation is the critical factor in preventing subsequent outgassing. Marco Rubber & Plastics publishes a comparison of permeation rates of common elastomers indexed with commonly used gasses.
Elastomers can also be FDA certified. Those which are USP Class VI and FDA certified have minimal reactivity and are certified to be safe for hygienic use. Alicat uses Viton brand FKM (Fluoroelastomer ASTM D1418) where necessary in applications requiring flow devices which meet the BPE-2016 standards. Viton is often the preferred biocompatible material for hygienic applications such as bioprocessing, for its outstanding sealing characteristics, permeation resistance, high performance, and available certifications.