C3.68 Failure to consider adequately how a pack is to be opened and the contents removed may significantly increase the chance of contamination occurring. With inadequate provision for aseptic opening a 10-3 probability of
contamination is easily possible which compares unfavourably with a 10-6 probability of sterility required as a minimum standard before labelling a product as sterile (BSEN 556).
C3.69 The means of sealing or closing the pack should be tamper evident in order that the user may rely upon the integrity of the contents.
C3.70 For sterile products the other major consideration at the point of use must be the ability to remove the product from the packaging without it becoming contaminated with micro-organisms, in other words the aseptic removal of the product.
C3.71 The provision of aseptic removal may be influenced by a number of elements in the design of the packaged product including:
• the type of product;
• the packaging system chosen;
• the method of closure or sealing;
• the number of layers of packaging material;
• the arrangement of the contents of the pack;
• the use of special equipment to remove the contents.
C3.72 Sterile medicinal products include both parenteral and topical preparations. The former are predominantly aqueous solutions whereas the latter may be aqueous solutions, oils, emulsions (ointments or creams), or dry powders. C3.73 The packaging system employed for sterile medicinal products will normally
consist of a closed rigid or flexible container as the primary pack. This may be closed by being hermetically sealed or by being sealed with a penetrable (or removable) elastomeric closure (such as a bung, stopper or disk) held in place with a screwed cap or crimped overseal.
C3.74 Sterile medicinal products are usually best presented in single-use form. Where a multi-use presentation is employed there will be a requirement for a suitable preservative to be included in the product formulation.
C3.75 The primary pack may need to be overwrapped if it is necessary to provide for aseptic handling of the primary pack.
C3.76 Sterile medical devices may be presented as single items such as individual instruments, dressings, etc. or, as a single pack containing multiple items;
the composition of which is designed so that contents comprise the items required for one (or more) particular procedure(s).
C3.77 These are commonly described in a variety of terms such as:
• Basic packs (dressing packs which may or may not contain instruments);
• Composite packs (instruments, dressings and other equipment/utensils);
• Supplementary packs (which include instruments, utensils, dressings for use with basic packs and composite packs);
• Procedure packs (which contain all the instruments, drapes, dressings and utensils required for a particular procedure);
• Linen packs (which contain all the drapes required for a particular procedure);
• Gown packs, dressing packs, etc.
C3.78 The packaging system employed for sterile medical devices may consist of flexible or rigid packaging, or the two types used in combination; and may be intended for single use, or be re-usable or be a combination of single use and re-usable.
C3.79 These may be closed by heat-seal, adhesive, compression gaskets, or tortuous path closures. A common format used in hospital SSDs is a pack formed from a rigid tray wrapped in a flexible packaging material. The tray may be re-usable metal or plastic, such as polypropylene, or single use, such as metal foil, moulded pulp, folded cardboard.
C3.80 For medical devices the arrangement of the pack contents will be of importance. The contents generally are arranged so that when the pack is opened they are available in an order convenient to the user for the intended purpose and suitable for aseptic removal.
C3.81 The method of opening the sealed or closed pack and/or removing the contents affects the aseptic removal capability. The various sealing and closing methods may involve particular risks with regard to transfer of contamination from the outside surface of the pack, or to transfer of fragments of the packaging.
C3.82 Tortuous path seals formed by the folding of flexible packaging material may be constructed so that they may be opened without touching the inner
surfaces.
C3.83 Pealable seals are used on heat sealed, and some adhesive-sealed, flexible packs and on many commercially produced packs, for example lidded blister packs. The construction of the seal should allow the opposing surfaces to be grasped easily and the seal on separating should not cause fibre shedding by, say, the splitting or tearing of either surface.
C3.84 Both flexible and rigid packaging systems are used which are intended to be broken, cut or torn open, for example ampoules, paper bags and pouches. It is important that this can be done without introducing contamination into the pack contents either from fragments of the packaging (for example glass particles from an ampoule), or from instruments used in the opening procedure, such as scissors for cutting open paper bags.
C3.85 Rigid re-usable containers for dry goods should have a tamper evident seal which must be broken before the container can be unlatched and the lid opened.
C3.86 Both single-use and re-usable containers for liquids, particularly those intended for topical administration or laboratory use, may have a seal which is formed from a compressible gasket (for example a rubber wad or stopper) held in place by, or as an integral part of, a screw capped lid. Aseptic
removal of the contents will depend not only on the ease with which the cap and gasket can be removed but also on the method used subsequently to dispense the contents, for example pipetting, pouring.
C3.87 Both single-use and re-usable containers for liquids, particularly those intended for parenteral administration, may have a seal which must be punctured and penetrated by a suitable device to remove the contents, for example using a hypodermic needle and syringe to remove the contents of a vial.
C3.88 The potential risk of introduction of contamination from surface of seal should be considered. The external surface of the seal may need protection (overseal) which can be removed immediately before use, or the instructions for use may require pre-treatment of the seal surface, for example by
swapping with a 70% m/v aqueous solution of spore-free isopropanol. C3.89 For re-usable systems the ability of the closure to re-seal after each
penetration will be an important consideration in the maintenance of sterility. C3.90 The seal for either single-use or re-usable systems must be of a material
which will not be damaged by the penetrating needle to the extent that fragments of the closure will contaminate the contents of the container. C3.91 Sealed packs should always be carefully inspected for seal integrity, or adventitious contamination, before being opened and this requirement should be drawn to the users’ attention both in the labelling of the pack and on any instructions for use or training programme which may be given.