Ready-to-fill syringes are increasingly being adopted by pharma, so what about ready-to-fill vials? Germana Molinari, manager of fill/finish process design in Foster Wheeler’s Milan Pharma division, looks at closed vial technology
Two essential questions currently preoccupy the pharmaceutical world. The first arises from considerable regulatory emphasis on assuring environ-mental safety in critical areas in aseptic filling. The question is: ‘Can the critical area that is to be strictly controlled (i.e. the filling/working area) be reduced as much as possible without introducing added issues of complexity and rigidity in operations often caused by the introduction of isolation technology?’
The pharmaceutical industry is also looking to achieve greater efficiency and effectiveness and to have a stronger focus on core business. This gives rise to the second question: ‘Is it possible to concentrate only on that which adds value to the product (i.e. formulation and filling) and to apply the same concept of ready-to-fill containers currently widely used for syringes to vials?’ In doing so, companies could remove the need for component preparation, which accounts for significant capital and operational costs, validation activities, daily manufacturing activities and is not an added-value step.
A possible answer could be the new concept of “closed vial technology”, based on a vial that is delivered clean and sterile with the stopper in place. This has the evident advantage of eliminating some complex operational steps that are required with traditional open vials, such as vial washing and depyrogenating as well as stopper washing, siliconisation and sterilisation.
This new filling technology is based on a needle that pierces the stopper and dispenses the liquid and then a laser re-sealing the pierce trace. It was developed by Aseptic Technologies of Belgium, with the aim of increasing quality for patients, but has also resulted in a simplification of the filling process itself.
The closed vial, registered under the name Crystal, is composed of five elements (see pic below):
•A polymer vial body, made of a copolymer based on cyclic and linear olefins (COC) that offers high transparency, low density, scratch resistance, excellent moisture barrier, resistance to aqueous and polar organic media, as well as ability to withstand the final steam sterilisation and gamma radiation
• A bottom ring that enhances vial stability and provides a tight hold of the vial during needle withdraw, avoiding the lifting up of the vial itself
• The stopper is made of thermoplastic elastomer which, by absorbing laser energy, melts without burning and allows pierce trace resealing after filling
• A top ring ensures closure integrity by means of a tight seal between vial body and the stopper
• A flip cap ensures protection of the piercing area until such time as the cap is opened.
Crystal is manufactured by moulding and immediately afterwards assembling the body and the stopper in a Grade A area; further assembly of the top and the bottom rings is performed in a Grade C environment. Then the assembled vials, arranged inside boxes on a pallet, are finally gamma sterilised.
A specific filling line has been designed for the Crystal vials and is composed of the following stations:
• A loading station protected by uni-directional flow provided with a semi-automatic device for box opening
• An optional mini e-beam for surface
re-sterilisation of the top of the vial, which will be in contact with the filling needle during piercing
• A filling station where a needle pierces the stopper, dispenses the liquid and is withdrawn
• A laser system that reseals the pierce trace on the stopper, fully restoring closure integrity
• A capping station based on snap-fit technology
Three major sizes of filling machines (all able to handle vial sizes ranging from 1 to 50ml) are available. The Laboratory version is for very small batches, with a maximum output of 7 vials/min. The Clinical version, designed for clinical batches and small commercial batches, is equipped with two or three needles with a maximum output of 75 vials/min. The Production model is designed for large commercial batches, equipped with 6 to 24 needles, with a maximum output of 600 vials/min.
Crystal vials can also be used for freeze-dried products, through the use of a special device with a funnel shape that is placed on the top of the vial after filling. At the start of the cycle, shelves are lowered to push down a “Penetrator”, which re-opens the stopper at the piercing trace. The Penetrator is maintained in that position by the shelves during the lyophilisation cycle. After unloading, the vials are resealed by laser and finally capped.
In summary, the key benefits of the closed vial technology are better sterility assurance and reduced particle presence through keeping the vial closed; a simple process, that is very focused on filling; easier handling of highly potent drugs; and easy container handling with very robust, rather than breakable vials.
Footnote
This article is based on a presentation given at a major pharmaceutical company’s internal seminar