Starting from its successful business case of the EZ-fill syringes, Nuova Ompi (main company of Stevanato Group’s glass division) developed a standard to extend the ready to be filled containers range to vials and cartridges. The EZ-fill vials and cartridges solution is an innovative option because it allows pharma companies various advantages: lower time to market, higher quality and safety, Total Cost of Ownership (TCO) reduction, process standardisation and filling flexibility providing a common filling platform for vials, cartridges and syringes.
The manufacturing development process for new or existing drugs, especially for the emerging biotech needs or small batch needs such as orphan drugs, is very often in a stand-by phase or it is frequently delayed due to the limited availability of filling options and formats at existing aseptic lines.
The effective availability of containers for direct filling operations could represent a consistent reduction of the time-to-market cutting cost related to the manufacturing process.
Until few years ago, only syringes were available in the market in nest and tub in a steribag: a configuration that ensures a standard machinable format able to keep particle content below limits assuring sterility, thus preventing the PharmaCo from expensive treatments. The lack of different types of sterile containers does not always allow very specific production like clinical trials or orphan products and so it implies a huge investment in capitals for washing and the sterilisation of the container itself, resulting in a consistent TCO and increased time-to-market.
For this reason Stevanato Group, among the top leaders in the glass-tubing converter market, has been developing a new standardised production process to extend the existing ‘ready to be filled’ concept (already launched in 2007 for the syringes) to a wide range of glass containers for pharma use, including vials and cartridges: the ‘EZ-fill vials and cartridges.’
This kind of solution provides clean, sterile, not pyrogenic and ready to be filled glass containers for pharma use. These are different from syringes and which can be used in injection devices, simplifying and standardising the traditional production process. In fact, with EZ-fill vials and cartridges, PharmaCo and CMO can outsource even more ‘non-core’ manufacturing process, thereby reducing overall costs and concentrating resources on added value ‘core’ activities, such as aseptic finish and filling.
The development of the EZ-fill project represents a synchronised effort between the two divisions (Glass and Engineering) combining glass forming technology with engineering experience. In fact, the involvement of SPAMI (representing the Group’s Engineering Division), specialises in the design, manufacture, installation and after-sales support of high-speed precision machinery for the production and control of glass containers, as well as vision inspection systems, provided the technological support during the project. The application of SPAMI technology guarantees 100 per cent cosmetic control on vials and cartridges and no glass to glass contact. Moreover, an important point which needs to be considered is that the concept has been approved and developed with the main manufacturers of fill/finish machines and it can therefore be easily integrated into the already existing pharma manufacturing filling lines installed. Everyone of them may have format change parts already fully suitable and industrialised for the EZ-fill concept.
Machine manufacturers have been involved in the development of the packaging design and concepts for proper handling and machine-ability with a wide range of fill/finish units. In addition to that, EZ fill vials and cartridges can be easily managed in clinical trials and small batch productions thanks to new machines developed by the main filling machines manufacturers, designed to be used in sterile room applications, in accordance
with cGMP regulations. Changeover to different sizes can be carried out quickly, easily and without tools, by exchanging complete sets of format parts.
EZ-fill vials and cartridges process
The EZ-fill vials and cartridges process can be described in the following phases (see figure):
Incoming materials: Vials and cartridges are supplied to the EZ-Fill area (ISO7 and ISO5 under laminar flow);
Washing: Vials and cartridges are washed into the washing machine with WFI (Water For Injection);
Siliconisation: Cartridges are optionally siliconised with high performances layer distribution process;
Heating: Drying and depyrogenation in an oven. The cycle is optimised in order to reduce the timing and assure an optimal drying;
Packaging: The final steps place the vials and cartridges into two final packaging solutions:
- Tray: One piece box
- Nest&Tub: Standard nest&tub format as the PFS one
Both are sealed with a Tyvek lid, packaged in steribags and case-pack allowing for sterilisation. Key attention is given to the cleanliness of the packaging components as to the production of the glass container itself. Final configuration includes packaging in pallets.
Final sterilisation: Filled tubs/tray in steribags are sterilised by Ethylene Oxide (EtO). Ethylene Oxide sterilisation is mainly used to sterilise medical and pharma products that cannot support conventional high temperature steam sterilisation. This process is completed by aeration.
Further developments/validation of alternative terminal sterilisation methods are ongoing, as requested from most of the top pharma companies.
Capping: Cartridges can optionally (upon customers’ request) be pre-capped with selected rubber formulations.
Nuova Ompi has already launched an EZ-Fill industrial process. The second step after implementation of pilot process, and expansion of the same area. The EZ-fill process is GMP oriented, already approved by several main top pharma companies.
TCO: Total Cost of Ownership for pharma companies. In a traditional manufacturing approach using a bulk vial or cartridge, there is the need to wash and depyrogenate them before the filling and closing by capping and crimping. With EZ-fill, at the pharma environment there is still the filling and closing but no more the washing and depyrogenation tunnel. A further strength is keeping compatibility with existing equipment (minimum change) and filling lines but also process simplification at pharma site and reduced costs for production equipment (washing line, depyrogenation tunnel, etc.). Other strengths are a faster validation time, a saving on production area size, a saving on qualification operations and validated state management.
The result is that the EZ-fill approach has positive impact on the Total Cost of Ownership (TCO);
Cost of Packaging: At industrial quantities, same model of syringes;
Capital Investment: The concept allows a significant reduction of the capital investments because implementing the EZ-fill approach means less machines, less space, less clean rooms, less utilities, etc.;
Cost of Operations (for the PharmaCo): for the same reason this concept lower the costs associated to the acquisition, validation and maintenance of traditional lines (less operators, less variable costs, less maintenance, etc.);
Cost of NON Quality: considerable reduction of the breakage rate expected at PharmaCo and prevention of recall phenomenon in the market.
Flexibility
Fill finish flexibility
Combo machines carry out the following workflow: automatic steribag opening, surface decontamination, tyvek removal and a system to extract the glass container from the nest in order to process them in a segment transport system line in a conventional filling unit.
The use of this kind of machines allows an immediate saving and an optimisation of manufacturing operations and avoids the need to use several machines for each container. Therefore, the EZ-fill approach is particularly interesting for CMO and all pharma companies that need to support customers with different containers from early steps of clinical trial up to the product launch with the big advantage to save also time.
Two packaging options for an easy integration with the existing filling process: Tray or Nest and Tub
The possibility to have two different formats of packaging (nest&tub and tray) is also a good advantage point: the tray sealed with Tyvek lid and protected by a steribag is the ideal solution for existing linear filling line, on the other hand, the nest placed inside a tub (sealed with Tyvek lid and protected by a steribag) is suitable for existing x-y syringe filling processes. The nest and tub format is becoming the new industry standard that could be sub-licensed or subcontracted to the other pharma primary packaging producers in order to have a unique format solution.
Summarizing, the actual portfolio of EZ-fillTM Vials & Cartridges comprises the 3ml Cartridge in nest&tub format, the 2R, 4R, 6R, 8R and 10R Vials both in nest&tub and in tray configuration. More options are available upon request.
Conclusion
The extension of the EZ-fillTM range to different types of glass containers besides syringes has been permitted thanks to the strong exchange of information that Nuova Ompi had with all the leading machine manufacturers. It represents an example of direct co-development of a project by merging the skills of a manufacturer of glass containers for pharmaceutical use with the experience on aseptic filling with all the best known manufacturers of pharmaceutical equipment, in order to provide a high quality product. Thanks to all these synergies and the implementation of innovative approaches, Stevanato Group puts now on the market an extended range of clean, sterile, not pyrogenic glass containers, ready to be filled, with the following peculiarities:
WFI—washed glass containers, using a validated washing and drying cycle and a set of utilities and procedures for fast switch between different types of containers and formats; Glass containers arranged in innovative nest and tub which will prevent, as for the syringes today, the glass-to-glass friction, for the highest cosmetic quality of products; Packaging operations in Class ISO5/ISO7 environment; Packaging units subjected to a validated EtO sterilisation process.