The preferred format for many sterile alcohol products is sprays. Magnus Hedman, Aurena Laboratories, outlines some additional benefits of using Bag-on-Valve aerosols
Sterile alcohol products in water for injection (WFI) are often available in spray presentations. Most common are different types of trigger sprays. However, double-bagged sterile disinfection sprays with isopropanol alcohol or ethanol are now available in innovative ‘Bag-on-Valve’ (BOV) packaging.
Using this packaging format, sterile alcohol products in WFI can be sprayed straight from the aerosol from any angle, in any direction, and they evaporate quickly and completely. Double-bagging and gamma irradiation also ensure sterility for easy administration in critical areas. BOV aerosol sprays offer continuous dispensing of their content and can be used from any angle without losing pace or force in the spray. The content can be sprayed smoothly and evenly, giving the user perfect control over the administration of the product, as opposed to pump or trigger sprays, which are more cumbersome to handle and offer a lower degree of control. The degree of emptying is also very high, close to 100% for many liquid products.
The BOV system offers microbiological safety for products as the contents come into contact only with the inside barrier film of the bag
The BOV system consists of a bag, to hold the contents, which is welded on a valve stem. Instead of mixing the propellant gas with the contents, the propellant is stored between the bag and the aluminium can wall. The valve is crimped onto the can while the propellant (compressed air or nitrogen) is filled into the space surrounding the bag.
This common pressurising process is called under the cup (UTC) gassing and creates an initial pressure of a few bars in the can. The final pressure, when the contents have been filled through the valve, is normally between 6 and 9 bars, depending on product configuration.
The BOV systems normally use standard aluminium aerosol cans ranging from 30ml to 500ml, with 1 inch can openings. The product content in the bag encompasses 60% of the can’s capacity (brim capacity), while the remaining 40% is occupied by the compressed gas.
The pouch or bag of a BOV system typically consists of four layers of barrier laminations of different materials with adhesives in between. Extensive research has gone into developing these laminates and each layer has a specific purpose that guarantees the chemical and mechanical resistance based on the filled product.
The innermost layer of a typical BOV product consists of polyethylene (PE) or polypropylene (PP). It is this sealing layer that gives the required weld strength to the valve. Then follows a polyamide (OPA) layer, which provides enhanced mechanical resistance to high pressures. The next layer is made of aluminium, providing a barrier to gases, moisture, aroma, light and other external factors. The outside layer is typically made of polyester (PET), which guarantees laminate integrity, as well as providing alufoil protection and mechanical resistance.
BOV offers complete oxygen protection, total integrity and a sterility that is maintained during its entire shelf life
The adhesives create a high strength bond between the layers, ensuring high mechanical resistance. Chemically resistant adhesives are also used to avoid delamination due to corrosive contents.
The BOV system offers microbiological safety for products as the contents come into contact only with the inside barrier film of the bag. As an airless, one-way valve system, no contamination will come from outside the bag. Thus, BOV offers complete oxygen protection, total integrity and a sterility that is maintained during its entire shelf life. With pre-sterilised bags and cleanroom production any bioburden can be minimised.
This hygienic format is well suited to sterile liquids used for disinfection and contamination control of equipment and surfaces in cleanrooms, as well as on the people operating in them; for example a sterile alcohol spray with an optimised efficacy at 70% dilution with WFI.
The four-step filling process involves placing the valve in the can, followed by gassing and crimping of the can, followed by product filling and finally actuator and cap replacement
For most sterile products in BOV, gamma irradiation of the final product is the preferred sterilisation since gamma rays are able to penetrate aluminium. For some, however, it is possible to arrange aseptic filling. For gamma irradiation of products that need to be classified as sterile, the most common irradiation dose is a minimum of 25kGy. Minimum and maximum doses need to be validated for each product. The gamma irradiation process is carried out by sterilisation contractors, some of whom offer full pallet sterilisation; however, sterilisation in ‘tote boxes’ is the more common procedure.
However, some products may not be suitable for gamma irradiation, such as gels containing carboxymethyl cellulose (CMC) as thickener. Products for wound care and eye washes are often sterile as well, as are medical devices for treating ear, nose and throat problems.
Provided the product itself does not contain flammable ingredients, a BOV system can be classified as a non-flammable aerosol
Since the BOV system propellant is compressed air or nitrogen, it is neither flammable nor hazardous to the environment. The propellant is not released to the atmosphere and once the product has been used up, the pack does not contain any flammable residue. Thus, provided that the product content itself does not contain flammable ingredients, a BOV system can be classified as a non-flammable aerosol.
The non-flammable classification offers obvious advantages regarding safety, transportation and storage. For transportation, BOV products are classified as aerosols (UN 1950). Since the propellant is not part of the formula, a product may be transferred from a tube application to a BOV system without changing the formula.
Internal view of the laminated multilayer bag expanding in the can
Some contract manufacturing organisations in the EU, such as Aurena Laboratories, offer medical device classified BOV products that are registered and approved (CE-marked) according to the European Medical Device Directive. To make the products available for marketing by a partner, Aurena has established a private labelling programme. This offers the possibility to market the products under a brand name owned by the distribution partner. This programme refers to markets that fully accept the MDD CE-mark as the passport to market access.
The brand name and artwork design of the new private label will be added to the technical file (dossier) of the registered product and become a part of the registered product. The procedures will differ, depending on the classification of product.The four-step filling process involves placing the valve in the can, followed by gassing and crimping of the can, followed by product filling and finally actuator and cap replacement Internal view of the laminated multilayer bag expanding in the can