Closed –Vial Technology

By –

Kuldeepak Pandey

Closed –Vial Technology

1.0 Parenteral are preparations intended for injection through the skin or other external boundary tissue rather than alimentary canal so that the active substance reached directly into blood stream and to increase bioavailability of the drug.

As many drugs can be administered only through systemic way due to patient condition or bioavailability of drug.

Requirement for injectable drugs –

Provide sterility throughout operation. Provide security against counter fitting and bioterrorism. Ease of filling and use.

There are two ways to eliminate contamination –

Better air quality control in filling and packaging area. New container design

Closed –Vial technology as name suggests it is a closed container that can be filled through a heat resalable stopper the major advantage is that these containers remains closed during filling as compared to existing stopper Vials and prefilled syringes which reduces the chances of contamination of the product from environment.

1.1 Principal of closed vial technology-

Body of closed vial is made up of Cyclo-oleofin copolymer (COC) that can be moulded into shapes that are not feasible with glass providing a tighter seal between parts of vial providing closure integrity.

Closed vial eliminates washing& dehydrogenization step in filling. During filling a need le penetrates through the stopper and the needle path is resealed after

filling.

2.0 Closed vial – a closed vial consist of five major elements –

Vial body – COC plastic body which is already been used to contain parental drugs it provides minimum transmission rate for water and various gases and excellent optical performance.COC is hydrophobic and therefore does not require siliconization to allow easy liquid collection.Vials are available in sizes ranging from 2ml to 100ml.

For light sensitive drugs amber color vials can be used.

Stopper – stopper is made up of thermoplastic elastomer that can absorb laser energy to melt and fuse without burning it is highly flexible allowing it to maintain closed contact with needle during the filling process. Both vail body and stopper must meet USP Class VI criteria.

Top ring – it ensures tight seal between the vial body and stopper.

Bottom Ring- allows the vial to be held tightly with clamps during needle withdraw step at end of filling process.

Sterilized cap –it protects the piercing area until the flip top cap is opened the protection is obtained by circular rib that tightly covers the stopper surface.

Note – closed vial are moulded and assembled in a Class 100 environment to minimize the number of particles inside the vial after production.

3.0 Manufacturing of vials- Body and stopper – the vial body is made by injection molding with light pressure and slow and

precise motion for 2ml vials and injection stretch molding for more than 2 ml vial in class 100 environment.

Picked up by robotic arm and the components are assembled then they are transferred into class 10,0000 clean room for further process.

Top and bottom ring are applied by simple pressure. Packaging in polypropylene boxes and double wrapping in polyethylene bags Sterilization by gamma radiation (minimum of 25kGray).

4.0 Closed vial filling process-

Filling basically compromised of five steps -

Step 01- Loading of the vials from polypropylene boxes by an operator using semi-automatic equipment.

Step 02-Top surface sterilization of the stopper by e-beam (beta irradiation at 25kgray) prior to entering Class 100 filling area.

Step 03- Filling is done by a specially designed needle 13-guage that pierces the stopper, dispenses the liquid and comes out by lifting.

Step 04 –Laser resealing with a low energy shot to melt the elastomer that then fuses and restores closure integrity. The melted stopper material is fully recovers its initial elasticity and resistance characteristics.

Step 05 –Capping is done by simple snap- fit technology.

Sterilized vial Filling Laser resealing capping

Filling needle – a special needle to pierce the stopper pencil tip (2 to 3.1mm) with sharp edges to make a clear cut.

50 Process chart -

Clean room apparel recommendation-

6.0 Lyophilization using closed vial technology –

Lyophilization or freeze drying is a dehydration process typically used to preserve a perishable material ,

Preservation is possible because it greatly reduces water content which inhibits the actions of microorganism and enzymes that would normally spoil or degrade substance.

Lyophilization can be done in closed vial by using special equipment

7.0 Advantages of closed vial technology – Lyophilization completed

Lyo shell move down pushes the pentray and reopens

Penetray (funnel shaped)placed in line on vial top.

Vial filled but not resealed

Laminar airflow

Restricted Access Barrier System

Snap Capping

Laser resealing

Filling

Sterilization of top surface

Boxes are opened

Better sterility assurance combined with a lower level of particle contamination for patients the vial is never exposed to air and therefore has property similar to those of an isolator that is only disturbed during needle penetration.

Less investment is required by pharmaceutical manufacturer the closed vial filling eliminates (washing ,passing vials through a hot air tunnel and stoppering additionally other production cost is eliminated (eg.water for injection for washing, cleanroom space to install the line is reduce to half as compared to classical vial filling machine installed .

Eliminates the risk of breakage during filling, labeling and packaging . Reduces counterfeiting and bioterrorism risks.