German pharmaceutical firm Fresenius Kabi is expanding its pharmaceutical manufacturing facility in Wilson, North Carolina.
The aseptic filling of injectable drugs has always been very challenging for the pharmaceutical industry. Contamination accidents, although rare, are still significantly recorded among the 20 billion injections and infusions made every year. In recent market research, 6% of hospital professionals in the US and in Europe reported that they have faced at least one contaminated vial.
Authorities have taken a radical turn to strongly support the most advanced aseptic filling technologies while recommending withdrawal of preservatives agent whenever possible from injectables.
Aseptic pharmaceutical products
Aseptic Technologies develops and manufactures innovative aseptic processing technologies for the pharmaceutical industry. The Crystal® closed vial technology is designed to provide safer and easier sterility assurance for liquid aseptic filling operations.
Our main product is the Crystal closed vial technology consisting in a range of closed vials and a range of filling lines able to process it. It is a very attractive alternative to current aseptic filling technologies.
Closed vial concept
The Crystal closed vial concept is based on a vial that is provided clean and sterile, with the stopper in place and secured. Thanks to this container design, the most complex filling operations of classical open vials (vial washing, stopper washing, sterilisation, stoppering and crimping) are simply eliminated.
Filling of a Crystal closed vial is performed by means of a specific needle that pierces the stopper and dispenses the liquid. After withdrawal, the puncture trace is immediately resealed with a laser to restore closure integrity.
Closed vial filling properties
The five elements of the Crystal closed vial are:
- The vial body, which is made of cyclo-olefin copolymer (COC) to leverage its excellent barrier and transparency properties, making it one of the most used plastics for injectable containers
- The stopper is made of thermoplastic elastomer with specific absorbance properties to allow laser resealing. Under laser beam, the two lips on the puncture trace fuse to restore perfect closure integrity
- The top ring secures the assembly of the vial body and the stopper with non-return, right angle snap fits
- The bottom ring stabilises the vial and allows firm holding during piercing and needle withdrawal (1ml and 2ml only)
- The cap, designed with a circular rib that presses on the stopper surface, maintains the piercing area in ISO5 condition until use by the healthcare professional
The manufacturing of the vial is completely innovative as the two elements in contact with the drug (body and stopper) are moulded and assembled together by robots in Grade A/ISO 5 clean rooms before being sterilised by gamma-irradiation. This process provides vials with extremely high quality in terms of sterility, particle presence and endotoxin contamination.
Our range of vials covers nominal volumes from 1ml to 50ml plus overfills.
Closed vial filling lines
The filling is performed on a dedicated filling line which is made of only three steps performed in ISO 5 (aseptic) conditions:
- Loading of the vials from polyethylene boxes by an operator using semi-automatic equipment
- Top surface sterilisation of the stopper by e-beam (beta-irradiation at 25 kGray) prior to entering Class 100 barrier for filling and closing operations
- Filling is performed by a specially designed 13-gauge needle that pierces the stopper, dispenses the liquid, and comes out by lifting. The needle has been specifically developed to eliminate a coring effect in the stopper and to minimise particle generation
- Laser resealing with a low energy shot to melt the elastomer that then fuses and restores closure integrity. The melted stopper material fully recovers its initial elasticity and resistance characteristics
- Capping is done by simple snap-fit technology
Five equipment have been developed to cover capacities from manual scale up to 600 vials a minute.
To ensure optimal ISO5 environment for the filling operations, a new barrier concept has been developed: the closed vial filling system (CVFS) containment.
This containment is suitable for installation in ISO8 surrounding and has been recently approved by the European Medicines Agency (EMA).
Benefits of closed vial aseptic filling
The key benefits of the Crystal closed vial technology are:
- Better sterility assurance level and reduced particle contamination
- Simplified operations leading to cost reduction
- Safer supply chain due to closed sterile containers resistant to damages
- Clear preference expressed by healthcare practitioners and end users; preference which can boost sales compared to products in classical containers
Approval status of closed vial technology
The European authorities have recently approved Synflorix, the pneumococcal vaccine of GSK Biologicals, filled with the Crystal closed vial technology.
Several sites located in US and Europe have already performed filling of stability batches to support approval of additional drugs.
Support services for closed vial aseptic filling
Aseptic Technologies serves the whole pharmaceutical industry and offers complete services for its equipment. Aseptic Technologies provides assistance with studies of the stability of your products in the Crystal closed vial. Filling can be carried out according to your specifications.
Our equipment comes with full back-up services, including installation, qualification and training for your personnel, while our local network provides after-sales service, available spare parts as well as preventive maintenance.
Our engineering team is at your disposal to configure equipment according to your specific requirements.
Do not hesitate to contact us for more information or if you want perform a product fill in our GMP approved facility.
Allergan is a global pharmaceutical company based in Ireland, which produces eye-care and dermatological products. It began expanding its manufacturing facility in April in Waco's Texas Central Park in the US.