Introduction

The majority of Sterile Medical Devices are transported by air or sea or rail, all will travel by road for at least part of their journey from manufacturer to the eventual user.

Further package handling takes place as pallet loads are first broken down into smaller units for stacking on shelves in distribution warehouses and then picked off the shelves to assemble mixed product loads that meet customer needs.

This means that packages and their contents will be subjected to: -

• Vibration and shock
• Temperature fluctuations and humidity changes
• Variation in atmospheric pressure

 All sterile packages must meet, inter-alia, the criteria listed below: 

• Sterility must be maintained for the duration of the specified shelf life.

• Normal distribution hazards must be tolerated without product or package damage.

• Product must tolerate physical contact with the package without adverse reaction.

• Packages must not impede product sterilisation nor be significantly adversely affected by the process. 

• Packages must tolerate the climatic conditions that prevail in the market area.

• The package surface must be of suitable material to accept labelling and have sufficient area.  

• Labelling must meet regulatory requirements.

• Comply with Environmental impact regulations.

Sterility must be maintained

Medical Devices are generally first packaged then terminally sterilised. Sterility is maintained by the use of package materials and closure mechanisms that resist the passage of microorganisms. Materials used for the sterile barrier system generally fall into one of two categories e.g. Gas ‘barriers’ or a filter material.

Pinhole free aluminium foil and plastic films may act as gas ‘barriers’.

Dupont's Tyvek® and appropriate medical grade papers both function as filters that resist the passage of microorganisms when used as a pouch component or as a blister pack lid. 

Distribution hazards must be tolerated

Packages must tolerate the vibration and shock hazards that will be encountered during distribution without allowing this vibration to cause oscillation of the product.

Product oscillation can lead to seal failure and cracking of blisters. Scuffing of labels and decorated surfaces due to the effects of vibration can be a problem. Shrink-wrapping the cartons readily prevents this.

Some years ago I tracked a consignment of devices from Shannon Ireland via Heathrow Airport to a London distribution warehouse. En-route some cases fell eight feet onto the tarmac. As a result of this experience, I now recommend that sterile device packages be designed to tolerate a 3-metre drop test. 

Product must tolerate physical contact with the package

Sharp points on a product should be protected to remove the risk of penetration of the sterile barrier. The package must locate the device so that product movement is not allowed to abrade the internal package surface and thus avoid the generation of undesirable debris.

Plastics must not contain any additive that may be subject to migration or leaching on to the product. 

Sterilisation needs

• If sterilisation is to be by Gamma or Electron beam radiation then plastic packaging materials should be chosen that have a good resistance to irradiation.

• For Eto sterilisation consideration must be given to the rate of penetration of water vapour.

• Eto sterilisation does not work in a very low humidity environment.

• Cellulose based materials are not compatible with Gas Plasma sterilistion methods.

Packages must tolerate the climatic conditions

The reduction in atmospheric pressure that occurs at high altitudes should not be overlooked. Medical devices may be used in an emergency at a mountain rescue site. Hospitals exist at high altitudes such as prevail in the Bolivian mountains.Packages may be stressed during an emergency ascent to avoid bad weather when being conveyed in an unpressurised aircraft. See Fig 1 below for table of altitude and mean atmospheric pressure. 

IATA Dangerous Goods  'Regulations' advise those shipping dangerous goods by Air:

·        A) That "the extremes of temperature that may be encountered in international transportation are in the order of minus 40°C and plus 55°C".

·        B) "due to altitude, pressure reductions will be experienced under flight conditions which may in extreme conditions be in the order of 68kPa        (0.68 bar, 10lb/ sq. in.)"  Such pressure reductions may lead to "bursting of the receptacles or packages during flight".

If a package is to tolerate such conditions then the design must either allow for equalisation of the internal and external pressure or the seal must be of such strength that the closure will remain in place despite the pressure differential.If products are to be transported or stored under high altitude conditions then the package designer must consider the potential for seal creep or even package explosion.

Peelable seals on film pouches or blister packs with an impervious lid of foil or film must only be specified after consideration of the potential bursting force that will be encountered. Multiplying the area of a blister opening by the expected pressure reduction enables an estimation of the force that the package seals must resist to prevent failure.

The seal strength chosen should not exceed the opening force that it is reasonable to expect a nurse to apply when wearing two pairs of surgical gloves with the added impediment of body fluid contamination.

Generally the strength of peel seals falls in the range of 400 to 1500 mg per 25mm width (measured at 180° peel angle and 300mm crosshead speed).

 There are two approaches to avoid seal stress when a none breathable package will be subjected to major changes in altitude: -

• Minimise the presence of air within the package. In the food industry, when packaging a liquid into a plastic pot with an impermeable lid, a common approach to prevent lids blowing, is to totally fill the pot so that there isn't any air to expand.

• Design the package so that its capacity can increase to accommodate expansion of its contained air.

Some years ago, a UK yoghurt producer took delivery of a new production line for filling and sealing his product. Following successful trials he was dismayed to find a high percentage of seal failures during air transport. Initially the blister sealing machine manufacturer was held to be responsible. The real cause was soon found to be a decision to improve the profit margin by reducing the amount of yoghurt in each pot. An air filled space was left above the Yoghurt. The trapped air expanded when the air pressure on the outside of the lid was reduced as the aircraft climbed. The messy result was spilt Yoghurt in an aircraft's hold when the lids blew open. Filling each pot completely without headspace eliminated leakage problems.

An example of a package that can change volume as its contents expand is a loose fitting pouch from which the air is partially evacuated after the product is inserted and before sealing the closure. With this type of flexible package, when the internal pressure exceeds the external atmospheric pressure, the pouch will inflate thus reducing the internal pressure and minimising the strain on the pouch seals.

Elevated temperatures during distribution may cause a reduction in the strength of peel seals (see Fig.2).

Normal seal strength generally returns when the temperature falls. If packages are closed by welded seals, then temperatures below the plastics melting point are not likely to affect the seal.Many plastics become more brittle as their temperature falls, leading to brittle packages that regain their usual strength when normal temperature is restored. 

The package surface must be of suitable material to accept labelling and have sufficient area.

Space and a suitable surface is needed for label application. Labels must remain legible and firmly attached for the life of the product; often this is five years. Paper labels like to stay flat! Contact adhesives tend to allow creep. Be careful that labels applied to a curved surface are produced from material that will not lead to ‘flagging’ in long term storage.   

Labelling must meet regulatory requirements.     

EU labelling requirements are defined in the Medical Device Directives, whilst the FDA defines the US requirements.Other countries requirements are similar to these. There is a general requirement for strict product traceability, the use of Bar Codes facilitates automatic identification.           

Comply with Environmental impact regulations.

The EU Packaging and Packaging Waste Directive applies to our industry.

  Fig. 1

Table showing relationship between Altitude above Sea level and Atmospheric Pressure.       

 Fig.2

Peel seal strength of available samples, measured at three different temperatures.