The human digestive system provides a layer of protection from undesirable microbes and foreign bodies through acidic digestive processes. This protection allows a certain tolerance vis-à-vis delivery of oral delivery methods.
However, parenteral drugs are not subject to that same level of tolerance as they are injected directly into tissue or bloodstream. For these dosage forms, there is a particular need to guard against other risks, such as contamination and blood vessel occlusion.
Single-use systems (SUS), which are by nature more sterile, have therefore found a home naturally and with more celerity in parenteral drug manufacture. In fact, the global single-use bioprocessing market is projected to experience double digit growth between 2022 and 2030, reaching $15.1 billion by the end of that specified period (1).
Regulations concerning particulates
As adoption of SUS in parenterals is becoming firmly established, attention turns to both process optimization of therapeutic segmentation, alongside regulation evolution. “Visible particulate contamination in SUS is typically performed using procedures adapted from USP [United States Pharmacopeia] <790> (2), Visible Particulates in Injections,” says Mark Bumiller, technology manager, Entegris. “The USP <729> protocol calls for sampling General Inspection Level II, single sample plan, AQL [acceptable quality limit] of 0.65% (3). SUS products typically approach 100% of guidance goals for visual particulate contamination before final packaging. USP <790> suggests testing against black and white background with illumination between 2000 and 3750 lux (2). Many SUS products are tested using normal fluorescent cleanroom lighting on a light table and against a black background.”
Bumiller goes on to state that the extraction method to collect loose particles from the SUS surfaces for testing components and assemblies comes from the ASTM E3230-20 validating extraction process (4). “The approach was inspired by an automotive industry standard used for parts which require critical cleanliness,” he explains. “The guidance on the method for counting the particles is not provided.”
Polymer materials predominate
A wide-range of high-performance polymer materials are used for SUS as a result of their ability to withstand the varying and challenging bioprocessing conditions. For example, polyethylene and polypropylene can withstand a range of conditions; polyethersulfone is used when heat resistance is required; polytetrafluorethylene (also known as Teflon) are useful as inner layers of SUS when using more aggressive materials; cellulose acetate is a hard material that is popular for filtration cartridges; and polyamide (nylon) is a suitable material for outer layers in composite components (5).
As a result of the unique properties of each polymer and the challenging characteristics of the compounds being processing in bioreactors, it is common for SUS to consist of more than just one plastic material. It is common for bioreactors to comprise several layers that all work to contain and protect the expensive and sensitive materials being processed (5).
SUS and advanced therapies
Initially, SUS were employed for larger batch volumes in the production of vaccines, biosimilars, and monoclonal antibodies. Nowadays, in line with the industry’s increased focus on developing novel therapies to treat conditions such as cancer and autoimmune diseases, more highly potent drugs are being processed (6).
