ROLE OF PACKAGING

Packaging plays significant roles in maintaining product quality and promoting safe and effective use of a medical device, namely:

• It protects the product from the environment and vice versa: effective barrier to light, moisture, oxygen, bacteria; etc., protection from damage, maintain product integrity until its in-use phase is completed (or the expiry date has passed)
• It provides all necessary information for: identification of the article, safe use of the product (clearly worded instructions, pictograms) including precautions, storage and shelf life of in-use product, appropriate disposal of the unused product and the packaging itself.
• It enables accurate dosing and compliance: additional spoons or syringes for oral dose measurement and delivery, dropper tubes, applicators, dispensing devices, dose counters and calendar devices.
• It ensures supply-chain integrity of the product: “Track-and-Trace” systems, anti-counterfeiting measures.

A well-designed and correctly used sterilization pack provides effective sterilization, safe handling and storage of all items until the moment they are used. A pack must remain sealed against bacteria and facilitate aseptic presentation of the packaged product. The sterile state of a medical device is maintained with the help of an appropriate packaging. The design, materials and manufacture of the packaging materials have to be compatible with the medical device to be packed, the handling processes of the medical device, the sterilization method to be used, the labelling systems, and the distribution and storage conditions as well.

STANDARDS APPLICABLE TO PACKAGING

Directive (EU) 2018/852 on packaging and packaging waste must ensure that the packaging placed on the EU market meets the essential requirements:

• limit the weight and volume of packaging to a minimum to meet the required level of safety, hygiene and acceptability for consumers
• reduce the content of hazardous substances and materials in the packaging material and its components
• design reusable or recoverable packaging

Medical device packaging is highly regulated. Often medical devices are sterilized in the package (=terminal sterilization). A series of special packaging tests documents and ensures that packages meet regulations and end-use requirements. Manufacturing processes must be controlled and validated to ensure consistent performance.
ISO 11607-1:2018 – is the principal guidance document

• Part 1: Requirements for Materials, Sterile Barrier Systems and Packaging Systems. Details the elemental attributes demanded of materials and pre-formed systems intended for use in packaging systems. It takes into consideration the vast array of potential materials, packaging system designs and sterilisation methods. Specifies the requirements and test methods until the point of use.
• Part 2: Validation requirements for Forming, Sealing and Assembly Processes. The development and validation of the packaging processes are crucial to ensure that sterile barrier system integrity is maintained until opened by the users.

TERMINOLOGY

The following definitions can be found in EN868 or EN ISO 11607:

• Packaging material: any material used in the fabrication or sealing of the packaging system or a primary pack.
• Primary pack: sealed or closed packaging system which forms a microbial barrier, enclosing a medical device.
• Seal: result of joining of surfaces together (e.g. by use of adhesive, thermal fusion or gaskets).
• Seal integrity: characteristics of the seal which ensures that it presents a microbial barrier.
• Secondary pack: pack containing one or more medical devices, each in its primary pack.
• Sterile: condition of a medical device which is free from viable micro-organisms (EN 556 standard on sterility of medical devices)
• Terminally sterilized: term for medical devices which are sterilized after being completely sealed or enclosed in at least the primary pack.
• Transport pack (or tertiary pack): pack containing one or more primary and/or secondary packs intended to provide the necessary protection during the transport and storage.
• Sterile barrier system is defined as “the minimum packaging configuration that provides a microbial barrier and allows aseptic presentation of the product unit at the point of use”.
• A preformed sterile barrier system is a “partially assembled sterile barrier system prior to filling and final closure and sealing”.
• Protective packaging is the “packaging configuration designed to prevent damage to the sterile barrier system and its contents from the time of their assembly until the point of use”.
• Packaging system is the “combination of the sterile barrier system and protective packaging” and could include the transit packaging.

PACKAGING SEALING SYSTEM

Pouches are typically fabricated from two or more different materials with plastic, Tyvek, film, paper, and/or laminates of these materials sealed to form a peel-open or tear-open package. In general, peel pouches should be used for small, lightweight, low-profile items. For larger and heavier items, thermoformed trays provide a stronger, more protective package.
The regular pouches are manufactured of medical grade paper (allows penetration for sterilization process) and clear plastic film (allows the content to be seen) and are suitable for sterilization in steam and EO processes.
Dimensioning of pouches: outside dimensions are given: first the opening or width, secondly the length of the pouch.

Characteristics of packages closed by “heat sealing”:

• The MD may occupy at most 75 % of the pouch in order to allow the package to conform to air evacuation processing during sterilization
• The space between the MD upper end and the seal seam on the peeling side must be at least 3 cm with an excess of up to 3 cm above the seal seam to allow for un-impeded peeling as well as aseptic withdrawal
• A protective must be fitted to any pointed or sharp instruments before they are placed in pouches or reels.
• The opening of MDs with a cavity (e.g. kidney dish) will face the paper side.
• End of the article to be grasped is presented first when the package is opened.
• Each seal must extend along the total width and length of the seal lines with no channels, kinks, folds, air pockets or notches and no signs of burning or melting.
• Protective packaging in the form of an outer see through wrap: The pouch size must permit unimpeded introduction of the inner wrap. The inner see through foil must not be kinked or folded, the inner wrap is not sealed into the seal seam of the outer wrap and the paper side of inner pouches face the paper side of the outer pouches
• Labels should be affixed to the foil side. If the label is to be affixed to the paper side, the size of the label must not exceed 20% of the paper surface. Label only outside the seal seam and outside the area surrounding the sterile MD.

USE OF DESICCANTS

Desiccants are used to control the exposure of products to ingress of moisture. They vary in their capacity and the rate that they can adsorb/absorb moisture.
Silica gel is an amorphous and porous form of silicon dioxide (silica), consisting of an irregular tridimensional framework of alternating silicon and oxygen atoms with nanometer-scale voids and pores. The voids may contain water or some other liquids, or may be filled by gas or vacuum. Silica gel is usually commercialized as coarse granules or beads, a few millimeters in diameter. Some grains may contain small amounts of a substance that changes color when they have absorbed some water. Small paper envelopes containing silica gel pellets, usually with a “do not eat” warning, are often included in dry food packages to absorb any humidity that might cause spoilage of the food.
When a visible indication of the moisture content of the silica gel is required, ammonium tetrachlorocobaltate or cobalt chloride is added. This will cause the gel to be blue when dry and pink when hydrated. An alternative indicator is methyl violet which is orange when dry and green when hydrated. Due to the connection with cancer, cobalt chloride has been forbidden on silica gel in Europe.

KEY MESSAGES

• The packaging protects the medical device from the environment and maintains sterility
• Medical devices must be transported and stored in their original packaging
• Sterile medical devices must be stored at least in their secondary packaging
• Sterile medical devices must be packaged in easy handling pouches that can be opened while maintaining product sterility before use
• Nest paper to paper and plastic to plastic for steam penetration
• Basic control of the packaging before use of sterile medical devices :
• Expiry date
• Seal strength (sufficient peeling force)
• Packaging integrity (no holes)
• Validity of the desiccant when applicable