BioPharm June eBook: Single-Use Systems

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28 BioPharm International eBook June 2018 Single-Use Systems Quality The small batch sizes along with large dosages could result in need- ing low detection levels in evaluat- ing the patient safety assessment. THE ROLE OF EXTRACTABLES AND LEACHABLES BioPharm: How do extractables and leachables affect equipment qualifi- cation in single-use systems? Pora (Pall Biotech): W hile t his is a critical area to define, it is impossible to do so without data. Depending on your system, E&L data will be a part of the general validation processes. Risk assess- ment will dictate how much data are needed. Bulpin (MilliporeSigma): The E&L assessment and qualification of a single-use system is largely inde- pendent from equipment qualifi- cation, assuming the processing conditions (pH, temperature, and process duration) are covered by the model solvents and testing scheme used for extractables test- ing. Extractables testing should rep- resent a worst-case scenario. If the processing conditions fall outside of the range of the extractables test- ing, then process-specific testing may be required. Additionally, if there is an aspect of the equipment function that could change the leachables profile (contribute to or remove) of a single-use system, then those aspects should be qualified as a part of the overall process qualifi- cation activities. BioPharm: What are some steps manufacturers employ to minimize E&L so as to optimize the qualifica- tion process? Isberg (Entegris): Single-use sys- tems are offered in materials with a wide range of potential leach- able t y pes a nd concent rat ion. Many of these contaminants are additives used to help stabilize the material and make the material workable. When E&L is critical, manufacturers can choose single- use systems, which are made from high purity materials like f luo- ropolymers, and do not require additives for stability or workability. Manufacturers can also limit exposure of systems to chemistries and processes that may acceler- ate the breakdown of the material structure and add to the leachable profile. Choosing advanced materi- als that are compatible with these processes allows more flexibility in process chemistry, temperature, and exposure time. BPSA: Extractables and leachables have been the subject of intense scrutiny and analysis dating back to the advent of single-use in the late 1990s. Biopharmaceutical producers (end-users) demand safe, sterile, and inert systems. While plastics-based bio-processing meets those needs, the issues around analyzing E&L impact on cells and extractables uptake within bioprocess fluids, the debates have essentially centered on 'how much data is enough' in ensuring that single-use bioprocess- ing presents, in the context of E&L, no risk to the ultimate consumer, the patient. So, E&L minimization is key in all bioprocess systems. For a more efficient qualification process to minimize E&L, some of the following steps can be consid- ered, where feasible: • Sufficient supplier E&L data: Select single-use components/ assemblies that have sufficient E & L s u p p o r t i n g d a t a t h a t already cover the actual product/ ingredient contact conditions (i.e., components have been tested by supplier in accordance w i t h B P O G e x t r a c t a b l e / leachables recommendations). • Biopharm manufact urer uses pre-site E/L qualified materials/ components: select same film types, filters, and tubing every time, for example, so that when a new single-use assembly is designed and ordered, the user will often try to use the pre- qualif ied components. T hus, the assembly or components are bracketed by a pre-existing E&L study. • S u f f ic ie nt s up pl ie r pr o duc t compatibility and quality tests: purchase components that are commonly used polymers in the bioprocessing industry and/or follow expected testing matrices. Hower and Lu (SGS): T here a re several ways for manufacturers of single-use systems to minimize E&L risks in order to optimize the qualification process. One step is to reduce the number of plastic single-use systems that are used in the process, but this will also require that cleaning validation be performed on stainless-steel com- ponents. There are different types of materials of construction used in components of pharmaceutical manufacturing systems. If materi- als are well characterized per USP <661.1> (6), the selection and use of the materials can be optimized. Those testing parameters include biocompatibility, general physico- chemical properties, additives, and extractable metals testing. Bulpin (MilliporeSigma): As a sin- gle-use supplier, we start by using high purity polymeric materials and perform testing to characterize the chemical compatibility and extract- ables profiles. We try to limit the number of different fluid contact materials of construction (MOCs) used within our single-use compo- nent library and have aligned on a single fluid contact film layer to make it easier to qualify our systems across the entire biopharmaceutical process. In addition, we are in the process of performing extractables testing per the BPOG protocol for the most commonly used components within our library.

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