Originally published January 1997
Elastomers are used in many important and critical applications in medical devices and pharmaceutical packaging. As a class of materials, their unique characteristics--flexibility, resilience, extendability, and sealability--have proven particularly well suited for products such as gloves, catheters, syringe tips, drug vial closures, injection sites, tubing, and hoses. Estimates of the total consumption of elastomers in medical applications vary widely, but it is generally reported to be from 2 to 4% of total nontire industrial rubber consumption, or between 200,000 and 400,000 metric tons. This includes natural-rubber latex used in gloves and condoms.
There are three primary thermoset elastomers used in medical applications: natural rubber, silicone rubber, and butyl rubber. Each of the three offers a distinguishing set of characteristics that make it the material of choice for certain medical applications. With its resilience and high tensile and tear strength, natural rubber is unsurpassed for gloves and for septa applications requiring repeated needle penetration. Silicone rubber is selected for its clarity, its ability to withstand autoclaving, and, until recently, for its presumed biological inertness. Butyl rubber has been the most common choice for closures, given that its high permeation resistance enables it to protect oxygen- and water-sensitive drugs.
The use of thermoplastic elastomers (TPEs) in medical applications has also grown steadily, with 1996 estimated consumption of 27,000 metric tons and a 5-year average annual growth rate of 11%.1 Recently, there have been a number of dramatic changes that pose significant challenges to the medical device industry. Discussed in further detail below, many of these changes have had a substantial impact on medical materials, and in particular have caused device manufacturers to search for acceptable alternatives to conventional thermoset rubber.
In this regard, the class of TPEs known as thermoplastic vulcanizates (TPVs) has found steadily increasing acceptance in the medical industry as a thermoset rubber replacement. A TPV is a thermoplastic and rubber combination in which the rubber phase is highly vulcanized or cross-linked and finely dispersed in a continuous thermoplastic phase, in order to arrive at properties and performance values closely approaching those of a standard thermoset rubber material. For the medical-grade TPVs reviewed in this article, the thermoplastic phase is polypropylene and the elastomer is EPDM.
DEVICE INDUSTRY MATERIAL TRENDS
Natural-Rubber Latex Sensitivity. Natural rubber is the most widely used elastomer in medical applications. As a result of the heightened concern over bloodborne pathogens such as HIV and hepatitis B, the use of latex gloves has exploded. Within the same time period, reports of allergic reactions to latex proteins have also increased dramatically. Through September 1992, FDA had recorded over a thousand complaints of reactions to latex-containing medical products, reactions ranging from itching and swelling to asthma and even to death from anaphylactic shock.2 This topic is being investigated worldwide, with scientific studies under way to isolate the protein or proteins causing the reaction and to develop sensitivity tests to identify at-risk patients and health-care workers.3,4
FDA has proposed labeling requirements for all latex-containing devices, because at the moment there is nothing for a latex-sensitive person to do except to avoid natural-rubber latex. This proposal is being strongly resisted by many medical device manufacturers who object to the cost and find unpalatable the negative image of warning labels. In the meantime, companies are actively evaluating materials that do not contain natural rubber. To our knowledge, no medical-grade TPVs--or other medical-grade TPEs--contain natural rubber, and thus present no risk of latex-associated allergic reaction.
Table I. Mechanical properties of medical-grade thermoplastic vulcanizates (typical values).
Biocompatibility Concerns. The biocompatibility of materials used in medical devices has been a long-running concern of FDA. The level of the agency's concern has been heightened recently by the highly publicized problems with silicone breast implants, jaw implants, and Shiley heart valves. Many of these devices were approved through the 510(k) process, which has cast doubt on the ability of the existing system to effectively screen the safety of medical devices, particularly with regard to biocompatibility.
A recent flurry of activity has included some revision of FDA's processes for assessing device and material safety. First, the agency has added a request in the 510(k) process requiring the device manufacturer to certify that any materials used are identical in formulation, processing, and sterilization to those in the device already on the market to which the manufacturer is claiming equivalence. If this cannot be certified, FDA requests biocompatibility testing on the sterilized device on the basis of a modified version of ISO 10993, Biological Evaluation of Medical Devices.5 This standard outlines principles for evaluating devices according to three criteria: type of contact with the body (external, externally communicating, or internal); duration of body contact; and material type.
A matrix in the ISO standard lists 12 different biological test categories and indicates which tests are appropriate depending on the body-contact and material information.
These changes have already begun to lengthen the approval process in many cases, and pose a particular problem for products containing elastomers. The plastics industry has long been familiar with USP testing, which has been used for some time in the evaluation and approval of polymeric materials for medical devices. Although there are numerous materials that have met the most stringent Class VI requirements, many elastomers used in medical applications will not pass these tests. Natural rubber, for example, is known to display consistent cytotoxic and hemolytic responses. It is used nevertheless, primarily because there have been no alternatives that provide comparable performance characteristics. However, the increasing FDA scrutiny on biocompatibility is making it significantly more difficult to obtain approval for devices if there are any questions in this regard.6
Table II. Percent compression set of medical-grade thermoplastic vulcani-zates (ASTM D 395, Method B, 25% deflection, type-A compression-molded specimens).
Cost Reduction. Until recently, the attitude of manufacturers toward medical devices tended to be one of "safety at any cost." Compared with other markets, there was relatively little emphasis in the design and development of new devices on finding the most cost-effective solution. Rather, the emphasis was on achieving the lowest possible degree of risk. Once a device was approved, there was little interest on the part of its manufacturer in the kinds of cost-cutting programs typical in other industries, since the time and money involved in obtaining regulatory approval of a significant change was likely to outweigh any cost-reduction benefit.
Figure 1. Comparison of compressive stress relaxation.
Within the current context of ongoing health-care reform, however, medical device companies are beginning to carefully scrutinize product costs, especially during the design and development phase. Everything from fabrication techniques to packaging to disposal is now being examined with the goal of providing a safe and effective product at a minimum cost.7
For a variety of reasons, elastomer parts present a clear opportunity for cost reduction in medical manufacturing. Although elastomeric components typically make up only a small percentage of the total product in weight, they tend to represent a much larger percentage of total cost.8 For a product such as a 5-ml hypodermic syringe tip, a 55-Shore-A TPV can offer as much as a 25% savings over the thermoset rubber equivalent. Given the high volumes in which disposable syringes are produced, this can be a significant savings.
Table III. Biocompatibility testing results for medical grades of thermoplastic vulcanizates. (Products not recommended for use in human implants.)
A second opportunity for cost savings derives from the fact that thermoplastics manufacturing methods, such as injection molding or extrusion, produce parts with much tighter tolerances than does thermoset processing. For example, a typical injection-molded TPE part may have tolerances of ±3 mil, whereas the same part in thermoset rubber can only be specified to ±10 mil. The tighter tolerance of thermoplastic parts allows for increased line and assembly speeds, in addition to permitting reduced thickness in thin-wall parts such as septa. The ability to comold or coextrude TPVs with more rigid thermoplastics such as polypropylene provides design flexibility that can also help reduce total assembly cost.
Table IV. ISO 10993 test results. (The products tested are not recommended for implants.)
In light of the above-mentioned industry trends, the general performance characteristics of TPVs are certain to be of interest to device manufacturers. However, the requirements for medical devices are demanding and specific. Significant testing in several areas has been required in order to demonstrate the performance of TPVs in medical elastomeric applications.
Figure 2. Property retention following ethylene oxide (EtO) sterilization of 73-Shore-A TPV.
Mechanical Properties. Basic mechanical properties were measured for six hardness grades of TPV. Testing was carried out according to the ASTM tests referenced in Table I. In most cases, the test specimens were cut from injection-molded plaques perpendicular to the material flow (strong direction). In addition, the compression set and the stress-relaxation ratio versus time--two measures of sealing performance--were also tested.
Figure 3. Ultimate tensile strength of 73-Shore-A TPV following gamma irradiation.
Biocompatibility. Medical-grade TPVs were tested according to ISO 10993 through the stage including short-term implant testing. The materials were tested for mouse embryo toxicity by Micro Biological Associates (Rockville, MD). This extremely stringent test is needed to assess the effect of materials used for in vitro fertilization procedures.
Sterilization. Material samples were sterilized by the three most common sterilization techniques: steam autoclaving, gamma irradiation, and ethylene oxide exposure. Property retention following sterilization by each method was measured. Gamma irradiation was performed by Gamma Radiation Sterilization, Inc. (Westerville, OH), while the steam autoclave tests were conducted by the Akron Rubber Development Laboratory (Akron, OH), and the ethylene oxide sterilization and residual analysis were performed by North American Science Associates (Toledo, OH).
Table V. Property retention of thermoplastic vulcanizate following successive cycles of exposure in live steam autoclave (cycle: live steam--5-minute rise to 134°C (274°F), 5-minute hold, 5-minute cool to ambient).
Medical-Fluid Resistance. Resistance of the medical-grade TPVs to a variety of disinfecting solutions and common medical fluid analogs was also measured.
RESULTS AND DISCUSSION
The results of the above experiments are presented in Tables IVII and Figures 13.
Mechanical Properties. As seen in Table I, the TPVs meet the flexibility requirements for many medical elastomer applications, offering hardnesses ranging from 45 Shore A to 40 Shore D. Table II presents the results for compression set versus time and temperature for six hardness grades of TPV. These results show that compression set increases with both time and temperature. Softer grades provide better compression set, particularly at elevated temperatures.
Table VI. Resistance of 73-Shore-A medical-grade thermoplastic vulcanizates to fluids of medical significance. Testing was conducted for 168 hours at 23°C (73°F).
Figure 1 compares the compressive stress relaxation of 55- and 64-Shore-A TPVs to two typical thermoset rubber compounds, a natural rubber and a styrene-butadiene rubber (SBR). Compressive stress relaxation is measured by placing a specimen under a constant compressive strain. At equilibrium, the initial applied stress (F0) will be opposed by the rubber with a force equal to the compression force. As time passes, this opposing force (F) will decrease in response to the viscoelastic nature of the rubber, and thus represents a direct measure of the sealing capacity of the rubber as a function of time. The plot of the decay of F versus the logarithm of time for the TPVs and thermoset elastomers shows that the TPVs possess sealing characteristics comparable to the thermosets, indicating that they should provide adequate sealing performance in similar applications.
Table VII. Resistance of 55- and 64-Shore-A thermoplastic vulcanizates to sterilizing solution at 23°C (73°F).
Biocompatibility. In this area, the medical-grade TPVs showed exceptional performance. The ability of the materials to pass the full battery of ISO 10993 tests, as seen in Tables III and IV, offers medical device manufacturers a real improvement in performance over currently available thermoset rubber compounds. These medical-grade materials are not recommended, however, for long-term human implants.
Sterilization. As seen in Table V and Figures 2 and 3, the medical-grade TPVs tested performed acceptably in all three common sterilization methods. Of particular note is the ability of the materials to withstand repeated steam autoclaving cycles, an area of concern with early TPEs. One autoclave steam cycle is defined as a 5-minute rise to 134°C (274°F), a 5-minute hold, and a 5-minute cool to ambient.
TPV materials can be injection molded or extruded.
Medical-Fluid Resistance. When exposed to a wide variety of medical disinfectants and fluids, the TPVs demonstrated minimal change in physical properties, as shown in Tables VI and VII. This superior resistance is largely due to the fully vulcanized rubber phase in the TPV matrix.
The test results presented in this work demonstrate that medical-grade TPVs possess the required characteristics for replacing thermoset elastomers such as natural or silicone rubbers in many medical products. Although the mechanical performance and sterilizability of TPVs are certainly acceptable for most applications, where the materials seem to offer real benefit to medical device designers is in the areas of biocompatibility and cost reduction. TPVs will not meet the needs of all applications: lacking the extraordinary resilience of natural rubber, for example, they do not perform as well in applications for which repeated needle penetration is crucial. However, they do seem to resolve some of the major materials problems experienced by the medical industry and warrant serious evaluation for use in a wide range of products.
1. Medical Plastics in the 1990s, Multiclient Study, Cleveland, OH, The Freedonia Group, Inc., 1995.
2. Maguire P, and Curry W, "Sensitrivity to Latex Rubbers: Problems and Opportunities for the Plastics Industry," in Society of Plastics Engineers, Inc., Technical Papers, vol XXXIX (ANTEC 93), Brookfield, CT, Society of Plastics Engineers, pp 994997, 1993.
3. Moore, "Canadians Consider Latex Product Labeling," Rubber & Plastics News, 3 October, p 7, 1994.
4. Moore, "Latex Allergy Research Making Some Strides," Rubber & Plastics News, 3 October, p 7, 1994.
5. Biological Evaluation of Medical Devices--Part I: Guidance on Selection of Tests, ISO 10993-1, Geneva, Switzerland, International Organization for Standardization, pp 67, 1992.
6. Wallin RF, "Scoring Biological Safety Tests: What's a Pass or a Fail?," Medical Plastics and Biomaterials, 1(2):3842, 1994.
7. McConnell, "Medical Products--Costs on Critical List," Plastics Design Forum, November, p 28, 1993.
8. Williams JL, "Medical Applications for Thermoplastic Elastomers," in Proceedings of the Society of Plastics Engineers Regional Technical Conference, Brookfield, CT, Society of Plastics Engineers, 1993.
Nancy L. Boschert is a marketing technical services representative for the applications engineering team at Advanced Elastomer Systems L.P. (Akron, OH), a worldwide supplier of thermoplastic elastomers formed as a joint venture of Monsanto and Exxon. Her responsibilities include supporting medical applications and aiding customers in the selection of appropriate TPVs.