The adoption of disposable, or single-use technology (SUT), in biopharmaceutical manufacturing is growing rapidly. SUT offer improved flexibility, reduced risk of contamination and lower costs. Bags made from laminated polymers are widely used as disposable containers for the freezing and storage of bulk drug substance (BDS), but where the properties of the BDS require it to be stored at -70°C, fluoropolymer (PFA or FEP) bottles are the only choice due to their much wider working temperature range. And while single-use bags were purposely designed for biopharma manufacturing, the only fluoropolymer bottles available were originally designed for use in the chemical industry. Savillex’s PurillexTM PFA and FEP bottles are the first fluoropolymer bottles designed specifically for the biopharma industry.
Closure Design and Seal Quality
The GL45 closure, which is standard on all Purillex bottles from 100 mL to 2 L, is a biopharma industry standard. The use of stretch blow molding enables more accurate molding of the bottle threads. A full 2.5 turns of thread engagement, greater than any other fluoropolymer bottle, ensures long term seal integrity. The threads, neck and lip are injection molded at the preform stage, which eliminates the need for secondary machining of the lip, which in turn eliminates the risk of burrs and “flash” on the lip that can generate particles.
Single Resin Grade
Due to the stretch blow molding process used, Purillex bottles are uniquely manufactured from a single grade of PFA (or FEP) resin. Because the bottle preform and closure are both injection molded, this means the same injection molding grade resin can be used for both components, which greatly simplifies testing and qualification.
The presence of particulates in SUT containers is a critical issue since most drugs stored in SUT containers are injectables and also, subsequent filtration may not be feasible. Purillex bottles are blow molded in an ISO 7 clean room, and operators wear clean room coats, hairnets and overshoes, so the risk of extraneous particulate airborne contamination including viable contaminants, such as hairs during the blow molding step is significantly reduced. The prevention of extraneous particulate contamination is critically important: although fluoropolymer bottles for SUT use are typically washed by the end user prior to use, static electricity makes surface contaminants very difficult to remove. Equally of concern are particulates embedded in the bottle walls. With traditional extrusion blow molding, carbon forms on the extrusion die, which detaches and can become embedded in the bottle wall. The stretch blow molding process used to manufacture Purillex bottles greatly reduces the formation of carbon particulates since the bottle preforms are injection molded prior to the blow molding step – no extrusion process is used. Every Purillex bottle undergoes a visual inspection for embedded particulates and flaws prior to release.
In comparison testing, Purillex bottles have been found to retain seal integrity at higher internal pressures that all other competitive bottles tested. This is due to the greater thread engagement and improved thread molding and lip surface quality through stretch blow molding. The practical benefit for biopharma use is greater protection of bottle contents over longer periods, under changing conditions and during transportation.
Certification and Validation Support
Purillex bottles have been certified by third party labs to meet and exceed the requirements of the following USP tests: USP <87>, <88>, <661> and <788>. Purillex bottles are manufactured only from virgin resin and are BSE/TSE free. Each lot is shipped with a certificate of conformance and is also tested externally using FTIR to verify the fluoropolymer used. Bottles are shipped bagged and can also be provided sterilized and ready to use (RTU). Contact us for more information on RTU bottle supply. We have compiled extensive validation binders for both PFA and FEP bottles to assist in qualification.
To support end user validation for extractables beyond the requirements in USP <661>, Purillex bottles were subjected to extensive third party testing for organic and inorganic extractables. Both 7-day and 28-day extraction tests using five different solvents were carried out. More information is available on the Extractables Testing page. Complete reports, giving results for both PFA and FEP bottles, along with methodology and instrumentation used, are included in the validation binders.
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