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The effects of radiation on various materials and the qualification tests required for their use in medical devices
Rad~t. Phys. Chem. Vol.15, pp.34-45. Pergamon Press Ltd. ]980. Printed in Great Britain.
THE EFFECTS OF RADIATION ON VARIOUS MATERIALS AND THE QUALIFICATION TESTS REQUIRED FOR THEIR USE IN MEDICAL DEVICES
Harry Landfleld Abbott Laboratories 14th Street and Sheridan Road Abbott Park North Chicago, Illinois 60064
ABSTRACT (Many polymers used in the medical field show various degrees of degradation after radiation exposure either by visual or physical measurements. The general effects of radiation on such medical polymers are reviewed and discussed as well as the tests used to qualify their performance.) There has recently been a further marked swing towards radiation in the U.S. for the sterilization of medical devices encouraged by the problems that have arisen with ETO residuals and the EPA interest in the environment. Since its introduction in about 1960, the use of radiation for the sterilization of medical products has increased rapidly in Europe where about half of the installations are located and considerable practical experience has accumulated. Table i covers some of the most important polymers now accepted for use in medical applications from bone replacement to syringes.
TABLE i
PolFmers Accepted for use in Medical Applications
Polymer
Appllcatlon
Acrylfcs
Hemostatlc agents, bone replacement, Corneas
Cellulose Acetate
Nerve regeneration, packaging material
Fluorocarbons
Blood vessels, reconstructive surgery
Polycarbonates
Syringes, containers
Polyethylene
Tubing, Syringes, heart valves
Polypropylene
Syringes
Polyurethanes
Plastic Surgery
Polyvlnyl Chloride
Surgical tubing, blood collection and administration sets
Silicones
Tubing catheters, lubricants, tissue substitutes
Many polymers used in the medical field show various degrees of degradation after radiation exposure either by visual or physical measurements. For example the discoloration of PVC is known to be caused by the development of conjugated double bonds producing chromophorous o~ color producing groups which may have little or no effect on the physical properties. In many cases, slight cross linking results increasing the toughness of the vlnyl polymer. 39
40
H. Landfield
Polypropylene on the other hand may show little or no color changes but embrittlement take place initially or on aging especially due to trapped "free radicals".
can
The development of new stabilizer systems has done much to improve the properties of many polymers previously sensitive to radiation sterilization. Desensitization of polymers to radiation can be further enhanced by carrying out the radiation exposure cycle under a blanket of an inert gas. Table 2 reviews the limitations of the most common methods of sterilization in use with medical devices today.(1) Depending on the polymers' softening point, as well as chemical structure, each available sterilization method has its advantages and disadvantages.
TABLE 2
Limitations
of the Most Common Methods of Sterilization Used in Medical Devices
i.
Heat - Generally unsuitable with plastics having low softening points causing distortion and changes in properties.
2.
Ethylene Oxide - Still most widely used method in the U.S. as it is relatively harmless to plastic materials. However, surface glazing is possible as well as temporary retention of the gas by plastics.
3.
Radiation - Very effective with high penetration levels. In the past, has been more widely used in Europe but interest now growing in the U.S. Some polymers are attacked causing embrittlement and discoloration while others require special stabilization techniques to protect polymers from degradation. If embrittlement occurs, mechanical failures of medical devices on aging is possible.
Table 3 depicts the overall sterilization methods available plastic materials as well as some problem areas.
TABLE 3 Polymer
for various medically used
Sterilization Methods for Various Plastics Materials Sterilization Methods
Acrylics
Soften with autoclaving. Radiation may cause chemical degradation but satisfactory with a single radiation sterilization dose. ETO unsatisfactory for molded articles as poor gas penetration results.
Cellulose Acetate
ETO method satisfactory. reduce strength.
Fluorocarbons
Heat and gas may be used safely. Radiation unsuitable with PTFE. Fluorinated ethylene/propylene copolymers---more radiation resistant.
Polypropylene
May be autoclaved and gas sterilized. Newer types more resistant to radiation.
Silicones
Gaseous methods generally result in slow diffusion of gas out of material. M o d e r a ~ l y stable to radiation.
Polyvinyl Chloride
ETO gas satisfactory. Generally discolors and some x-linking with radiation unless properly stabilized.
Radiation may
Effect of Radiation on Various Materials
4!
In the U.S., there is presently interest in the possiblity of using a lower radiation sterilization dose than 2.5 Mrads if the "bloburden" is sufficiently low. While there may be some merit in this approach, it does bring in its train a number of control and plant operating difficulties which Europe has thought best to avoid by as wide acceptance as possible of sterilizing dose (2.5 Mrads) with a very large built-in safety margin. It is known, however, that with very lightly contaminated products, it is possible to get adequate sterilization with 1.5 Mrads or less. The radiation resistance of common polymeric materials is shown in Table 4. Generally, polystyrene and natural rubber have the most radiation resistance. The type of antloxldant in the rubber, however, has an affect on its stability.
TABLE 4
The Radiation Resistance of Common Polymeric Materials
Material
Stability Effect
Acrylonltrile-ButadieneStyrene (ABS)
Stable for single dose of 2.5 Mrads.
Polyamides
Suitable for single doses of 2.5 Mrad level.
Polyethylene
Stable under ordinary conditions at 2.5 Mrads.
Polypropylene
Embrlttles--newer variations more resistant.
Polyvlnyl Chloride
Withstands single dose radiation cycle-but dlscolors--some HCI llberated.
Poly (tetrafluoroethylene)
Poor resistance to radiation. Copolymers less e f f e c t e d .
Polystyrene
Most radlatlon--stable of common polymers
As previously mentioned, with new technology and research, polyvinyl chloride and polypropylene polymers (commonly used in medical devices) have been developed which, with the help of additives, result in improved radiation stabillty.(2) Polyvlnylchloride resins when properly stabilized can be made quite resistant to radiation exposure retaining both good color and heat stability. This paper also covers some of the specifications, qualifications and test methods which enable us to determine the feasibility of using specific materials and components for medical applications after a radiation sterilization cycle. A specification is generally a detailed description of requirements, dimensions, materials, including test references needed to cover a proposed component or object, as in this specific case a medical device by which it is possible to determine its suitability for an end use performance. A material specification generally consists of: i.
Description of material
2.
Acceptance Requirements: (a)
Qualification tests for approval of raw materlal (physical and visual)
(b)
Test references - ie - ASTM, SPI
(c)
Packaging and Marking requirements
42
H. Landfield
A typical material specification for a polyvinylchloride resin is shown in Table 5. Using the previously discussed typical polyvinylchloride resin specification, we should first consider both short and long range tests on the raw materials themselves.
TABLE 5
Description
Material Specificatio n Green Bay Medical Laboratory
- Randel PVC 1200
No. 5781 28 March 1979 Description
A medium molecular weight resin used in formulations and extrusion operations Acceptance
for injection,
molding,
Requirements Standard Test Method
Specificat%on i.
Appearance
- fine white powder
2.
Total Volatiles
3.
I.R. Identification
4.
Inherent Viscosity -
- not more than 0.2% - Sample spectrum must be qualitatively identical to Standard Spectrum Between 1.0 and 1.05
Packing:
Shipper to be corrugated
Markings:
Each container marking on label must include:
ASTM-D-1203 SPI-2
ASTM-D-1243
or fiber drum with polyethylene
i.
Greenbay Medical Lab. Spec. No.
2.
Greenbay Medical Purchase Order No.
3.
Quantity in the container
liner
The stability of PVC resins can best be determined by a Brabender or oven heat stability (short range test) after incorporating the resin into a typical standard PVC formulation. With the successful completion of the heat stability test, long range programs can then be instigated, preparing films, tubing or whatever medical component for a particular end use is required. To assure ourselves that the raw materials used in the Medical Devices as well as the Devices themselves are unaffected performance wise after exposure to radiation sterilization, it is necessary to run Qualification tests. In developing a medical device for radiation sterilization, the first concern should be with the identification and screening of materials that are compatible with Cobalt 60 radiation. A typical protocol for evaluating a raw material for its radiation resistance is shown in Table 6. A plastic film or sheet is prepared using the polymer under evaluation, compounded if necessary, and the samples are exposed at various radiation levels (le - i-I0 Mrads). The test protocol is carried out using a non-lrradlated specimen as a control. Since medical sets are being developed with increasing design complexity, a single protocol to cover the parameters of all medical devices would be impractical. As most devices contain basic co.~mon components such as plastic tubing and cannulas, a suggested general protocol for evaluating the most common irradiated sets is depicted in Table 7. To cover possible basic Governmental regulations and requirements for approvals, stability tests are also considered as part of the test protocols discussed above to develop additional
Effect of Radiation on Various Materials
43
information. In conjunction with room temperature stability studies, many evaluations will include aging programs covering both low temperature and elevated temperature cycles. In the development of a suitable medlcal device, in addition to the primary selection of the proper polymer and additives, e versatile package must also be included which will maintain its principle properties after irradiation exposure. Table 8 lists some of the most commonly used materials today for packaging medical devices.
TABLE 6
Typical Protocol for Evaluatln 8 an Irradiated Specimen (Raw Material Evaluation)
Plastic Film or Sheet Tests 1.
2.
Physical A.
Visual/physical inspection
B.
Tensile Strength properties 1.
100Z Modulus
2.
Ultimate tensile
3.
Ultimate elongation
C.
Exudation and bloom
D.
Ultraviolet bleed
E.
Melt-index (when applicable to polymer)
Animal Tests A.
U.S.P. biological tests (3) i.
2.
Acute systemic a.
Saline
b.
Alcohol
c.
PEG 400
d.
Oil
Intracutaneous reactivity a.
Saline
b.
Alcohol
c.
PEG 400
d.
Oil
Soma of the parameters to consider in the evaluation of irradiated packaging materials are: i. 2. 3. 4. 5.
Long-term stability Packaging strength retention Seal strength Discoloration of the package and printing inks Durability for shipment.
44
H. Landfield
TABLE 7 I.
Physical A.
Visual/physlcal
B.
Bond strengths
C.
II.
Typical Protocol for Evaluation of Irradiated Medical Devices
properties
i.
Tubing areas
2.
Cannula areas
3.
Other bonded components
Tensile properties
of tubing
i.
100% modulus
2.
Ultimate tensile
3.
Ultimate elongation
D.
Cannula characteristics
E.
Ultraviolet
F.
Leakage test
G.
Exudation and bloom
bleed
Animal tests A.
U.S.P. biological I.
2.
3. B.
tests
(3)
Acute systemic a.
Saline
b.
Alcohol
c.
PEG 400
d.
Oil
Intracutaneous a.
Saline
b.
Alcohol
c.
PEG 400
d.
0il
Implantation
reactivity
test
U.S.P. pyrogen test
Effect of Radiation on Various Materials
TABLE 8 Substrate
45
Medical Device Packaging Properties
Spun-bonded polyolefin
Tear and puncture resistant web. Readily allows penetration of ETO gas. More expensive than most packaging materials.
Plastic film and sheets
Semi-rlglds (i.e., PVC) used in kits, sets and trays. Includes coextrusion and copolymer systems. Variations in sterilization methods depending on polymer type and thickness of material.
Surgical grade papers
Very economical but generally poor anesthetlcally. Protection sometimes inadequate during shipping and handling of medical devices. More widely used in Europe than U.S. Readily adaptable to radiation sterilization.
CONCLUSIONS I.
An update has been presented on the effects of Radiation on various polymers and the Qualification tests required for their use in medical devices.
2.
With newly developed technology, polymer manufacturers are learning how to modify and protect most polymers from degradation due to radiation exposure.
3.
Typical protocols are presented as a guide for the evaluation of raw materials, components and medical devices which have been radiation sterilized.
BIBLIOGRAPHY i.
Landfield, H. (Nov. 8, 1977). Selective Parameters for the use of Plastics in Medical Devices. NATEC 1977 SPE, Denver, Colorado.
2.
Private Connnunicatlons with European and U.S. Polymer Producers and Personnel at Radiation Installations.
3.
United States Pharmacopeia XIX Containers/Physlcal Tests pp. 644-647.
R.P.C. 15/I--D
THE EFFECTS OF RADIATION ON VARIOUS MATERIALS AND THE QUALIFICATION TESTS REQUIRED FOR THEIR USE IN MEDICAL DEVICES
Harry Landfleld Abbott Laboratories 14th Street and Sheridan Road Abbott Park North Chicago, Illinois 60064
ABSTRACT (Many polymers used in the medical field show various degrees of degradation after radiation exposure either by visual or physical measurements. The general effects of radiation on such medical polymers are reviewed and discussed as well as the tests used to qualify their performance.) There has recently been a further marked swing towards radiation in the U.S. for the sterilization of medical devices encouraged by the problems that have arisen with ETO residuals and the EPA interest in the environment. Since its introduction in about 1960, the use of radiation for the sterilization of medical products has increased rapidly in Europe where about half of the installations are located and considerable practical experience has accumulated. Table i covers some of the most important polymers now accepted for use in medical applications from bone replacement to syringes.
TABLE i
PolFmers Accepted for use in Medical Applications
Polymer
Appllcatlon
Acrylfcs
Hemostatlc agents, bone replacement, Corneas
Cellulose Acetate
Nerve regeneration, packaging material
Fluorocarbons
Blood vessels, reconstructive surgery
Polycarbonates
Syringes, containers
Polyethylene
Tubing, Syringes, heart valves
Polypropylene
Syringes
Polyurethanes
Plastic Surgery
Polyvlnyl Chloride
Surgical tubing, blood collection and administration sets
Silicones
Tubing catheters, lubricants, tissue substitutes
Many polymers used in the medical field show various degrees of degradation after radiation exposure either by visual or physical measurements. For example the discoloration of PVC is known to be caused by the development of conjugated double bonds producing chromophorous o~ color producing groups which may have little or no effect on the physical properties. In many cases, slight cross linking results increasing the toughness of the vlnyl polymer. 39
40
H. Landfield
Polypropylene on the other hand may show little or no color changes but embrittlement take place initially or on aging especially due to trapped "free radicals".
can
The development of new stabilizer systems has done much to improve the properties of many polymers previously sensitive to radiation sterilization. Desensitization of polymers to radiation can be further enhanced by carrying out the radiation exposure cycle under a blanket of an inert gas. Table 2 reviews the limitations of the most common methods of sterilization in use with medical devices today.(1) Depending on the polymers' softening point, as well as chemical structure, each available sterilization method has its advantages and disadvantages.
TABLE 2
Limitations
of the Most Common Methods of Sterilization Used in Medical Devices
i.
Heat - Generally unsuitable with plastics having low softening points causing distortion and changes in properties.
2.
Ethylene Oxide - Still most widely used method in the U.S. as it is relatively harmless to plastic materials. However, surface glazing is possible as well as temporary retention of the gas by plastics.
3.
Radiation - Very effective with high penetration levels. In the past, has been more widely used in Europe but interest now growing in the U.S. Some polymers are attacked causing embrittlement and discoloration while others require special stabilization techniques to protect polymers from degradation. If embrittlement occurs, mechanical failures of medical devices on aging is possible.
Table 3 depicts the overall sterilization methods available plastic materials as well as some problem areas.
TABLE 3 Polymer
for various medically used
Sterilization Methods for Various Plastics Materials Sterilization Methods
Acrylics
Soften with autoclaving. Radiation may cause chemical degradation but satisfactory with a single radiation sterilization dose. ETO unsatisfactory for molded articles as poor gas penetration results.
Cellulose Acetate
ETO method satisfactory. reduce strength.
Fluorocarbons
Heat and gas may be used safely. Radiation unsuitable with PTFE. Fluorinated ethylene/propylene copolymers---more radiation resistant.
Polypropylene
May be autoclaved and gas sterilized. Newer types more resistant to radiation.
Silicones
Gaseous methods generally result in slow diffusion of gas out of material. M o d e r a ~ l y stable to radiation.
Polyvinyl Chloride
ETO gas satisfactory. Generally discolors and some x-linking with radiation unless properly stabilized.
Radiation may
Effect of Radiation on Various Materials
4!
In the U.S., there is presently interest in the possiblity of using a lower radiation sterilization dose than 2.5 Mrads if the "bloburden" is sufficiently low. While there may be some merit in this approach, it does bring in its train a number of control and plant operating difficulties which Europe has thought best to avoid by as wide acceptance as possible of sterilizing dose (2.5 Mrads) with a very large built-in safety margin. It is known, however, that with very lightly contaminated products, it is possible to get adequate sterilization with 1.5 Mrads or less. The radiation resistance of common polymeric materials is shown in Table 4. Generally, polystyrene and natural rubber have the most radiation resistance. The type of antloxldant in the rubber, however, has an affect on its stability.
TABLE 4
The Radiation Resistance of Common Polymeric Materials
Material
Stability Effect
Acrylonltrile-ButadieneStyrene (ABS)
Stable for single dose of 2.5 Mrads.
Polyamides
Suitable for single doses of 2.5 Mrad level.
Polyethylene
Stable under ordinary conditions at 2.5 Mrads.
Polypropylene
Embrlttles--newer variations more resistant.
Polyvlnyl Chloride
Withstands single dose radiation cycle-but dlscolors--some HCI llberated.
Poly (tetrafluoroethylene)
Poor resistance to radiation. Copolymers less e f f e c t e d .
Polystyrene
Most radlatlon--stable of common polymers
As previously mentioned, with new technology and research, polyvinyl chloride and polypropylene polymers (commonly used in medical devices) have been developed which, with the help of additives, result in improved radiation stabillty.(2) Polyvlnylchloride resins when properly stabilized can be made quite resistant to radiation exposure retaining both good color and heat stability. This paper also covers some of the specifications, qualifications and test methods which enable us to determine the feasibility of using specific materials and components for medical applications after a radiation sterilization cycle. A specification is generally a detailed description of requirements, dimensions, materials, including test references needed to cover a proposed component or object, as in this specific case a medical device by which it is possible to determine its suitability for an end use performance. A material specification generally consists of: i.
Description of material
2.
Acceptance Requirements: (a)
Qualification tests for approval of raw materlal (physical and visual)
(b)
Test references - ie - ASTM, SPI
(c)
Packaging and Marking requirements
42
H. Landfield
A typical material specification for a polyvinylchloride resin is shown in Table 5. Using the previously discussed typical polyvinylchloride resin specification, we should first consider both short and long range tests on the raw materials themselves.
TABLE 5
Description
Material Specificatio n Green Bay Medical Laboratory
- Randel PVC 1200
No. 5781 28 March 1979 Description
A medium molecular weight resin used in formulations and extrusion operations Acceptance
for injection,
molding,
Requirements Standard Test Method
Specificat%on i.
Appearance
- fine white powder
2.
Total Volatiles
3.
I.R. Identification
4.
Inherent Viscosity -
- not more than 0.2% - Sample spectrum must be qualitatively identical to Standard Spectrum Between 1.0 and 1.05
Packing:
Shipper to be corrugated
Markings:
Each container marking on label must include:
ASTM-D-1203 SPI-2
ASTM-D-1243
or fiber drum with polyethylene
i.
Greenbay Medical Lab. Spec. No.
2.
Greenbay Medical Purchase Order No.
3.
Quantity in the container
liner
The stability of PVC resins can best be determined by a Brabender or oven heat stability (short range test) after incorporating the resin into a typical standard PVC formulation. With the successful completion of the heat stability test, long range programs can then be instigated, preparing films, tubing or whatever medical component for a particular end use is required. To assure ourselves that the raw materials used in the Medical Devices as well as the Devices themselves are unaffected performance wise after exposure to radiation sterilization, it is necessary to run Qualification tests. In developing a medical device for radiation sterilization, the first concern should be with the identification and screening of materials that are compatible with Cobalt 60 radiation. A typical protocol for evaluating a raw material for its radiation resistance is shown in Table 6. A plastic film or sheet is prepared using the polymer under evaluation, compounded if necessary, and the samples are exposed at various radiation levels (le - i-I0 Mrads). The test protocol is carried out using a non-lrradlated specimen as a control. Since medical sets are being developed with increasing design complexity, a single protocol to cover the parameters of all medical devices would be impractical. As most devices contain basic co.~mon components such as plastic tubing and cannulas, a suggested general protocol for evaluating the most common irradiated sets is depicted in Table 7. To cover possible basic Governmental regulations and requirements for approvals, stability tests are also considered as part of the test protocols discussed above to develop additional
Effect of Radiation on Various Materials
43
information. In conjunction with room temperature stability studies, many evaluations will include aging programs covering both low temperature and elevated temperature cycles. In the development of a suitable medlcal device, in addition to the primary selection of the proper polymer and additives, e versatile package must also be included which will maintain its principle properties after irradiation exposure. Table 8 lists some of the most commonly used materials today for packaging medical devices.
TABLE 6
Typical Protocol for Evaluatln 8 an Irradiated Specimen (Raw Material Evaluation)
Plastic Film or Sheet Tests 1.
2.
Physical A.
Visual/physical inspection
B.
Tensile Strength properties 1.
100Z Modulus
2.
Ultimate tensile
3.
Ultimate elongation
C.
Exudation and bloom
D.
Ultraviolet bleed
E.
Melt-index (when applicable to polymer)
Animal Tests A.
U.S.P. biological tests (3) i.
2.
Acute systemic a.
Saline
b.
Alcohol
c.
PEG 400
d.
Oil
Intracutaneous reactivity a.
Saline
b.
Alcohol
c.
PEG 400
d.
Oil
Soma of the parameters to consider in the evaluation of irradiated packaging materials are: i. 2. 3. 4. 5.
Long-term stability Packaging strength retention Seal strength Discoloration of the package and printing inks Durability for shipment.
44
H. Landfield
TABLE 7 I.
Physical A.
Visual/physlcal
B.
Bond strengths
C.
II.
Typical Protocol for Evaluation of Irradiated Medical Devices
properties
i.
Tubing areas
2.
Cannula areas
3.
Other bonded components
Tensile properties
of tubing
i.
100% modulus
2.
Ultimate tensile
3.
Ultimate elongation
D.
Cannula characteristics
E.
Ultraviolet
F.
Leakage test
G.
Exudation and bloom
bleed
Animal tests A.
U.S.P. biological I.
2.
3. B.
tests
(3)
Acute systemic a.
Saline
b.
Alcohol
c.
PEG 400
d.
Oil
Intracutaneous a.
Saline
b.
Alcohol
c.
PEG 400
d.
0il
Implantation
reactivity
test
U.S.P. pyrogen test
Effect of Radiation on Various Materials
TABLE 8 Substrate
45
Medical Device Packaging Properties
Spun-bonded polyolefin
Tear and puncture resistant web. Readily allows penetration of ETO gas. More expensive than most packaging materials.
Plastic film and sheets
Semi-rlglds (i.e., PVC) used in kits, sets and trays. Includes coextrusion and copolymer systems. Variations in sterilization methods depending on polymer type and thickness of material.
Surgical grade papers
Very economical but generally poor anesthetlcally. Protection sometimes inadequate during shipping and handling of medical devices. More widely used in Europe than U.S. Readily adaptable to radiation sterilization.
CONCLUSIONS I.
An update has been presented on the effects of Radiation on various polymers and the Qualification tests required for their use in medical devices.
2.
With newly developed technology, polymer manufacturers are learning how to modify and protect most polymers from degradation due to radiation exposure.
3.
Typical protocols are presented as a guide for the evaluation of raw materials, components and medical devices which have been radiation sterilized.
BIBLIOGRAPHY i.
Landfield, H. (Nov. 8, 1977). Selective Parameters for the use of Plastics in Medical Devices. NATEC 1977 SPE, Denver, Colorado.
2.
Private Connnunicatlons with European and U.S. Polymer Producers and Personnel at Radiation Installations.
3.
United States Pharmacopeia XIX Containers/Physlcal Tests pp. 644-647.
R.P.C. 15/I--D