Aseptic Technologies - Crystal^® - A New Technology for Aseptic Filling of Injectable Drugs

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 already faced at least one contaminated vial.

Authorities have taken a radical turn to strongly support the most advanced aseptic filling technologies as well as recommending withdrawal of preservatives agent whenever possible from injectables.

THE CRYSTAL® ASEPTIC FILLING TECHNOLOGY

The Crystal® closed vial concept is based on a vial that is provided clean and sterile, with the stopper in place. Thanks to such container design, the most complex filling operations of classical open vials (vial washing, stopper washing, sterilization and stoppering) are simply eliminated.

Filling of Crystal® closed vial is done 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.

THE CLOSED VIAL

The five elements of the closed vial are:

• The vial body, this part of the container is made of Cyclo-Olefin Copolymer (COC) because of its excellent barrier and transparency properties, making it one of the most used plastic for injectable containers
• The stopper is made of thermoplastic elastomer with particular laser absorbance properties to allow laser resealing - under laser beam, the two sides 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 stabilizes the vial and allow firm holding during piercing and needle withdrawal
• The cap, designed with a circular rib that presses on the stopper surface, maintain the piercing area as Class 100 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 sterilized by γ-irradiation. This process provides vials with extremely high quality in terms of sterility, particle presence and endotoxin contamination.

THE CLOSED VIAL FILLING LINE

The filling is performed on a dedicated filling line which, thanks to Crystal® closed vial, is composed of only five steps:

• Loading of the vials from polyethylene boxes by an operator using semi-automatic equipment
• Top surface sterilization by e-beam (beta-irradiation at 25kGray) prior 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 minimize particles 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 in the barrier, by simple snap-fit technology

KEY ADVANTAGES

• Simplified operations
• Better sterility assurance and reduced particle presence
• Secured supply chain and easier handling