Packaging Material Selection

Device and Packaging Materials Qualification

This annex gives guidance only for the qualification of medical devices and is particularly relevant to medical devices fabricated from synthetic polymeric materials. For other health care products the effects of exposure to radiation on properties other than those outlined in this annex will need to be addressed.
The indicators may be used to show that the products have been exposed to a radiation source. They should be used only to provide a qualitative indication of radiation exposure and may be used to distinguish process loads that have been irradiated from unirradiated process loads.

Prior to selecting the radiation sterilization process for a medical device, it is important to consider the effect that radiation will have on the stability of the materials that make up the devices or device components. While some materials such as polystyrene are inherently less affected by radiation than others such as polytetrafluoroethylene (PTFE) or polyoxymethylene, the radiation stability of any device will be a function both of the materials and the design (table A.1). Therefore, a programme to demonstrate functional stability of the device throughout its shelf life should be carried out.

Testing should include any specific property essential to the intended function of the device, such as strength, clarity, colour, biocompatibility and package integrity. The test programme should encompass all variations in manufacturing processes, tolerances radiation doses, radiation source, raw materials and storage conditions. Based upon the above considerations the maximum dose for each device shall be specified.

The effects of radiation dose on materials might not be immediately apparent. Therefore, the test programme may include accelerated ageing at extreme conditions for initial indication of material suitability, as well as ambient real-time ageing. The accelerated testing may include doses above those required simply to achieve sterilization, combined with storage at extreme environmental conditions. However, in most cases, ambient, real-time and non-irradiated control samples should be part of the test programme.

A typical testing protocol can require devices or material samples to be exposed to radiation at various dose levels between 10kGy and 100 kGy. The irradiation of test samples should be in accordance with C.1.5.4.

Although there is no substitute for long-term shelf stability studies, an accelerated ageing study can be used for screening of materials. In this case, the same test protocol for material testing is employed, but the temperature is held at 60oC. In the absence of a more accurate relationship, seven days at 60oC may be considered equivalent to 180 days of ageing at ambient conditions. A suggested time interval for accelerated testing is one week to 30 days. At ambient conditions, the suggested time intervals are 0, 3, 6, 9 and 12 months [2]. In all cases, non-irradiated material should be maintained as a control for the intended life of the device.

There are many tests employed in materials evaluation. Once a material is selected on the basis of these tests, final qualification to demonstrate functional stability of the device should be carried out on fully processed components, complete devices and packages, as appropriate. If testing of individual device components is done, a demonstration that the components are compatible with each other in a complete device should be part of the testing.

In addition to the physical and mechanical qualification testing some materials might need to undergo biocompatibility testing. Changes in the chemical structure of the polymer and/or its additives, as well as gaseous by products liberated during irradiation, can alter the material’s biocompatibility for medical device applications. This testing should also demonstrate biocompatibility throughout the intended life of the device ISO 10993-1 [1] gives a description of basic biological screening testing that may be used for predicting the safety of irradiated materials for use in medical devices. Specific tests might be required depending upon the end use of the device.

In summary, careful adherence to the guidelines in this International Standard will help the primary manufacturer to avoid problems encountered with radiation sterilization of medical devices. It is the responsibility of the device designer and primary manufacturer to ensure the suitability of the material, design and packaging for irradiation. The irradiator operator can only, if requested, advise in general terms and perform test irradiations. Primary manufacturers of medical devices are also responsible for ensuring that they are informed by suppliers of materials and components of any changes in the formulation and/or manufacturing process that could affect radiation stability.

Table A.2 lists some typical materials with good radiation stability. Table A.3 gives general guidelines to radiation stable materials.

Table A.1 – General guidelines for selection of radiation-stable materials

There are several rules that apply toward selecting or designing radiation-stable materials. A general rule, however, is that all plastics can be classified as materials whose molecules either a) predominantly degrade with irradiation or b) predominantly crosslink with irradiation. Materials that crosslink with irradiation tend to have higher radiation stability. The physical properties of some materials are affected differently by the mode of radiation. More specific guidelines are:

  1. Aromatic materials are more stable than aliphatic materials.

  2. Phenolic antioxidants contained in most plastics are a cause of discoloration. The use of non-phenolic additives may eliminate the problem.

  3. Most polypropylenes and polytetrafluoroethylene are unstable with irradiation. Polyvinylchloride and polypropylene should be especially stabilized to improve radiation compatibility.

  4. Polymer processing conditions and materials that lead to embrittlement of medical devices should be carefully evaluated for radiation sterilization (for example, the use of plastic regrind or nucleated polymers; the us of high temperatures during moulding; the creation of high levels of crystallinity in semi-crystalline polymers in slow cooling and autoclaves).

  5. High levels of antioxidants help radiation stability. In general, the level of antioxidant should be doubled if the device is going to be radiation-sterilized.

  6. For semi-crystalline polymers, processing conditions that lead to low degrees of crystallinity will improve stability.

  7. The elastic modulus of plastics is not significantly affected with a sterilizing dose of irradiation.

  8. Carefully evaluate the use of low molecular mass polymers.

  9. Within a given polymer class, the lower the density the greater the radiation stability.

Table A.2 – Examples of radiation-stable materials (in sterilizing dose range)


The following generic materials, which are readily available, are naturally radiation-stable, and can be used in most sterile device applications:

  Acrylonitrile/Butadiene; Styrene (ABS)
  Polystyrene
  Polystyrene-Acrylonitrile (SAN)
  Polyethylene (all densities and UHMW)
  Polyamides
  Polysulfones
  Polyimides
  Polyurethane
  Polyphenylene sulfide
  Polyesters
  Poly(ethylene-vinyl acetate)
  Poly(ethylene-acrylate)
  Phenolics
  Epoxies
  Natural rubber
  Silicone
  Most synthetic elastomers (except Butyl or Polyacrylic).


Table A.3 – General Guide to radiation stability of materials


Materials Radiation Stability Comments
Thermoplastics:
Polystyrene Excellent  
Polyethylene Excellent  
Polyamides Excellent  
Polyamides Excellent  
Polysulfone Excellent Natural Material is Yellow.
Polyphenylene sulfide Excellent  
Polyvinylchloride (PVC) Good Yellow – antioxidants and stabilizers prevent yellowing. High molecular weight organotin stabilizers improve radiation stability.
Polyvinylchloride - Polyvinylacetate Good Less resistant than PVC
Polyvinylidene chloride Good Less resistant than PVC
Polyvinyl Formal Good Less resistant than PVC
Polyvinylbutyral Good Less resistant than PVC
Styrene/Acrylonitrile (SAN) Good  
Polycarbonate Good Yellows – mechanical properties not greatly affected
Polypropylene Poor Must be stabilized – physical properties greatly reduced when irradiated.
Fluoropolymers:

Polytetrafluoroethylene (PTFE)
Polychlorotrifluoroethylene (PCTFE)
Polyvinyl fluoride Polyvinylidene fluoride
Ethylene- Tetrafluoroethylene (ETFE)
Fluorinated ethylene propylene (FEP)
Poor When irradiated PTFE and PCTFE are significantly damaged. The others show better stability.
Cellulosics: Esters Cellulose Poor Esters degrade less than does cellulose.
Polyacetals Poor Irradiation causes embrittlement – colour changes have been noted (yellow to green).
Thermosets:
Phenolics Good Very good with the addition of mineral fillers.
Epoxies Good Very good with the use of aromatic curing agents.
Polyesters Good Very good with the addition of mineral or glass fibres.
Allyl Diglycol carbonate (Polyester) Excellent Maintains its excellent optical properties after radiation.
Polyurethanes Aliphatic Aromatic
Excellent
Good
 
Darkening can occur. Possible breakdown products could be derived.
Elastomers:
Urethane Excellent  
EPDM Excellent  
Natural rubber Good  
Nitrile Good Discolours.
Polychloroprene (neoprene) Good Discolours – the addition of aromatic plasticizers renders the material more stable to irradiation.
Silicone Good Phenyl-methyl silicones are more stable than are methyl silicones.
Styrene-butadiene Good  
Polyacrylic Poor  
Chlorosulfonated Polyethylene Poor  

Source: ISO 11137:1995(E)
 
 
 
 
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