Jerold Martin, Sr. VP, Global Scientific Affairs, Biopharmaceuticals, Pall Life Sciences – BPSA and Chairman at the Disposable Solutions for Biomanufacturing conference, which took place in Brussels, 19-20 February 2013, shares 6 hot topics in the single-use and disposable solutions industry in 2013.
Extractables and Leachables: Concerns about appropriate testing for E&L submissions to regulatory authorities continues to be a leading hot topic. Regulations and guidances are intentionally vague in stating that the drug sponsor must determine risk to product quality and safety. In many cases, vendor data may be sufficient if adequate. The variation in vendor data, however, makes comparison of components difficult. Several users have challenged suppliers to harmonize their test conditions to an industry "standard". While this can be possible for future studies, it raises the question of continued applicability of costly legacy data that may be technically adequate but will require greater understanding on the user side to determine applicability and sufficiency. The ISPE and BPSA are addressing these and looking to determine common test methods, extraction solvents, temperature and time conditions for harmonised supplier data suitability.
Biocontainer and Single-use system leak integrity: While some biocontainer suppliers have introduced 100% leak testing of biocontainers (bags), there are presently no 100% leak testing of assembled systems either by suppliers or available to users for pre-use or in-service confirmation of potential leak defects or damage. The desire for a 100% user pre-use/in-service leak test goes against principles of Quality by Design implemented by suppliers. Concerns about potential leaks are elevated by early implementation reports of high leakage rates. These rates have since been drastically reduced by supplier redesign of biocontainers and totes to eliminate potential leak sources and by operator training.
The application of "leak integrity" testing is complicated by the fact that SU biocontainers and systems cannot be pressure tested to the same pressures as rigid tanks and pipe systems, and contrary to common misperception, neither are actually correlated to microbial ingress. Even potential for liquid leakage is as much related to the size (especially fill height) of the container and surface tension of the fill liquid as it is to size and shape of hole or defect. Biocontainer and system suppliers individually and the BPSA are working with end users to find solutions and address exaggerated expectations.
Eliminating particles in single-use systems: This is important for final formulation and filling downstream of final filtration, or aseptic manufacturing of vaccines that cannot be 0.2 µm filtered, presence of particles in fluid paths that could be transferred to final dosage is a concern based on USP <788> which sets limits for subvisible particles and USP <1> requirement that injectable drug products be "essentially free of visible particles".. Demonstration of subvisible particle levels below USP <788> limits in SU biocontainer and system rinse effluents has been implemented by several suppliers and appears to be reasonably achievable when systems are assembled in Class 10,000 (ISO 5) cleanrooms.
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It is difficult for suppliers to make claims of "visible particle-free" because SUS are dry and many components are translucent or opaque. Users would prefer not to pre-rinse (as is done with traditional rigid stainless steel containers and systems) and pre-rinsing of SUS and biocontainers by suppliers is often not practical because drying and potential contamination of fluid contact pathways are technical challenges.
USP is developing a new monograph chapter <790> setting allowable limits for visible particles (instead of "0") and methods chapter <1790> for visual inspection. Once established, SUS biocontainer and system suppliers may be able to apply these limits to rinse effluents on a sampling basis to raise confidence that any undetected visible particles in SUS biocontainers and systems will not lead to rejection of filled drug product batches subject to USP particle standards.
Assurance of supply, single vs. multiple sourcing: End users are concerned about sourcing and resins and components that need to be put together, as equipment may have delivery issues, such as shipping breakdowns etc.
Ciaran Kelleher, Principal Engineer with Global Technical Services at Janssen Biologics agrees that supply chain reliability is an area that they have been aware of and working on for the past couple of years. “In the case of single-use, we’ve actually been working on strategies for dual source for components, without the need to do a complete turnover or complete changeover of equipment.” Ciaran explains. “It has proved successful and I would expect that's what we’re going to continue throughout the rest of the supply chain as time progresses,” he concludes.
Assurance of resin formulation consistency (extractable) and change notification: Migrant species from single-use components ultimately becoming leachables in final dosage formulations are primarily a function of the plastic resin formulations and processing. To ensure that no changes in resin or processing can impact process leachables and final dosage, it is imperative that users and suppliers establish appropriate quality agreements and change notification programs that also go back to the resin sub-suppliers. Negotiating quality agreements and change notification agreements can be cumbersome and time-consuming. BPSA is working on a consensus quality agreement template that will expedite negotiations and ensure key controls are put in place to minimize changes and communicate any that may impact the final drug product.
Disposal Waste Management Strategies: Disposal continues to be a hot topic, though primarily for social factors. Among waste management professionals, the impact of SU disposal is negligible and easily handled with facility and domestic plastic waste. Increasing implementation by municipalities and large users of waste-to-energy or pyrolysis technologies, which convert waste plastic into heat and electricity, or fuel oil respectively, will address "recycling" by linking it with recovery of the significant energy stored in plastics.
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