BioPharm June eBook: Single-Use Systems

Issue link:

Contents of this Issue


Page 33 of 46

Single-Use Systems Supply Chain June 2018 BioPharm International eBook 33 structure aspects such as molecu- lar weight distribution, thermal properties, polymer chain stabil- it y, chemical composition, and crystallinity all effect film extru- sion a nd we ld i ng pa ra mete r s. Control of the process is impacted by the design of the processing equipment (e.g., resin transport, extrusion screw design, die design, and winding control). CRITICAL PROCESS PARAMETERS BioPharm: What are the critical pro- cess parameters in the manufac- ture of single-use bags? Bell: The most critical parame- ters involve the film cutting, seal- ing, and port bonding. These steps, as well as the equipment used for them, are qualified and validated to ensure a consistent and repeat- able process. Time, temperature, and pressure are closely moni- tored and controlled. In addition, sta nda rd operat ing procedu res and operator training are used to ensure quality and consistency for the final assembly (e.g., attachment of tubing and other single-use com- ponents and packaging steps). BioPharm: Can you describe the tests that are carried out to ensure consistent performance of single- use bags? Bell: At the film level, there are several tests performed to ensure consistent performance—such as tensile strength, seam strength, g a s t r a n s m i s s io n , f i l m t h ic k- ness, c y totox ic it y, heav y met- als, as well as others. At the bag or assembly level, the following test i ng is p e r for me d on eve r y item, or using a statistical sam- pling approach across a process lot: first article testing on equip- ment, visible inspection for loose and/or embedded particles, leak/ integrity testing, and testing for bacterial endotoxins and subvis- ible particles. EXTRACTABLES AND LEACHABLES BioPharm: Can you describe the extractables and leachables testing procedures for bag characteriza- tion? Bell: Per for ming ext rac tables studies on the individual compo- nents that make up a bag assem- bly is key. It prevents the need to do repeat testing for the entire bag assembly if there is a minor design change (e.g., change of one com- ponent within the bag assembly). A representative sample of each component (e.g., film, filter, tub- ing) is used to perform extractables testing. Exctractables testing is per- formed using pre-defined model solvents, which represent exagger- ated conditions (e.g., high or low pH, extended duration, high tem- perature). The extracted samples are tested using several different ana- lytical methods and the results are generated as mg/cm 2 , which can then be scaled up to the surface areas of the component used in the assembly. As an example, 5L bags of film would be used for the extrac- tion, which could then be scaled up to the surface area of a 200L storage bag. Extractables represent worst- case conditions. The results are used to calculate total extractables, assess patient risk, and determine if leach- ables testing is required. In some cases, leachables test- ing is required. This testing is per- formed using the actual process stream and conditions, and rep- resents any chemicals that come out of the plastic materials into the drug product. For this reason, leachables testing is typically only performed for critical downstream applications. REFERENCE 1. E. Isberg et al., BioProcess Int. 15 (5) 18–23 (2017). BP "Resin and film specifications are established by defining the critical quality attributes of the endproduct, such as a single-use bag chamber. The attributes are then used to define the specifications of the raw materials that make up that bag chamber (e.g., film)." —Sara Bell "Several different tests are performed to ensure the film used to manufacture single-use bags does not pose any adverse impact to the product or solution in the bag, and that it maintains product and process sterility and stability over time." —Sara Bell

Articles in this issue

Links on this page

Archives of this issue

view archives of BioPharm - BioPharm June eBook: Single-Use Systems