Use of Single-Use Assemblies for Aseptic Filling
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For some years now utilization of single-use assemblies has significantly developed for the production, purification, sterilization and aseptic filling of products such as vaccines, blood products, recombinant products and proteins. |
Single-use technology meets the needs of the pharmaceutical and biotech industries, as well as regulatory requirements. Nevertheless, some doubts may remain as to how reliable single-use assemblies are for critical phases such as aseptic filling.
1. New Challenges for the Pharmaceutical and Biotech Industries
With personalized medicine (smaller batch production, rapid change in procedure), the search to accelerate timer-to-market as well as stringent regulatory requirements mean that production costs have to be controlled.
2. The Advantages of Single-Use Systems
The flexibility of single-use equipment means production facilities are optimized, and as a result, production costs are too:
-reductions in preparation time and time for transfer and operator training
-multi-product flowpaths
-optimized production areas (surface area used, area classification)
-reduced energy use (autoclaves, SIP), fluids (CIP), etc.
Single-use therefore also makes sense in light of sustainability. Reduced energy use, optimized production and storage areas and tighter control of release rates for gases, fluids, chemical agents and waste, thereby reduce the carbon footprint.
The performances cited have been demonstrated in various articles comparing the environmental impact of classic and single-use systems .
3. Single-Use in the Aseptic Filling Phase
The use of single-use assemblies still meets with certain resistance for a phase as critical as aseptic filling, and concerns:
-reliability of the components and especially of their assembly
-risk due to extractible substances and salting-out/migrating/leachable substances in the plastics used
-equipment transfer in the filling area (ISO 5), or the transfer of only sterile fluid to the filling machine needles
4. Ensuring Reliability of Single-Use in Aseptic Filling
Maintaining fluid sterility, protecting operators, minimizing product waste, ensuring speed and ease of implementation while eliminating steps such as cleaning, sterilization, and process flexibility and reliability are all essential aspects.
Designing a process with single-use elements calls for as much consideration as for the so-called "classic" procedures:
-compatibility of the components used with procedure parameters
-compliance of the components
-assembly functionality
-reliability
-able to comply appropriately
With an advantage for single-use:
-methods for simple connection and disconnection permitting the maintenance of a high sterility level (SAL)
Transfer of the assembly or certain of its elements from the preparation area to within the filling area can take place with Alpha-Beta type transfer ports. This technology means all equipment can be transferred under sterile conditions from a controlled or non-controlled area to another.
4. Validation of Single-Use Assembly for the Filling Phase
Before validating the assembly for its use, compliance of each of its elements must be confirmed first:
-compliance of the plastics (tubing, connectors, bags, filters, etc.) with regulatory recommendations (see US and EU Pharmacopeia).
-component integrity if possible (batch release)
-compliance in terms of maintaining sterility of connectors and disconnection systems during handling
Then comes assembly validation consisting of in particular verification of its integrity, sterility (see ISO 111137 & 111737), packaging and shipping (see ISTA tests & ASTM 2O96-04).
Of course on-site validation with the fluid while taking process conditions into account should be conducted. Should extractible and/or leachable substances be identified, a pragmatic approach such as the “Threshold of Toxicological Concern” (TTC) makes it possible to determine whether the extractible substance rate presents a risk for the patient. A maximum concentration threshold should be defined prior (see PQRI, ICH Q3C(R4)). It is generally accepted that a daily dose (TTC) of 1.5 µg/patient/day is acceptable in terms of genotoxic compounds.
Conclusion:
Single-use assemblies have demonstrated their advantages in production capacity and flexibility. Today, knowledge on the construction materials for the various components as well as commitment to their compliance permits development of reliable assemblies, which may even be used for a phase as critical as that of aseptic filling. The expertise and experience of the various partners involved in the design, compliance, validation and integration of these single-use assemblies is crucially important in ensuring reliability and success.
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Guy Ravanat, European Services Manager - Single-Use Technologies This email address is being protected from spambots. You need JavaScript enabled to view it. |
