By Glenn Petrie
Medical device manufacturers invest a great deal of time and money ensuring that their products meet both product performance needs and FDA guidelines. Choosing the appropriate plastic is critical for successfully bringing a combination product, such as a drug eluting stent or drug inhaler, to market. To decrease the time required for testing prior to device commercialization, manufacturers perform accelerated aging studies to determine physical aging. It is this essential test that is critical for documenting expiration dates for combination medical products.
The Need for Accelerated Aging TestingConsidering key variables at the beginning of product specification is essential to guaranteeing medical device integrity. Material aging information, including physical, thermal, and optical performance over time, is imperative for ensuring product integrity to meet stringent FDA validation requirements, including evidence of sterility and fitness-for-use over a product's life cycle.
| Package integrity is especially critical for delicate or expensive devices and implants. Sheet of Eastar™ Copolyester 6763 is the industry standard for rigid medical packaging, providing maximum performance with minimum risk. |
The American Society for Testing and Materials (ASTM) has established guidelines to contribute to the reliability of materials, promote public health, and improve quality of life. Accelerated aging testing is done based on ASTM F 1980-02[u1] standard guidelines and incorporates factors such as time at ambient (room) temperature, accelerated aging temperature, and ambient temperature into a test equation. Relative humidity is also noted as an important factor but is not included in the equation. While laboratory testing is normally accomplished at 23°C and 50% relative humidity, the guideline suggests that testing protocols might need to include low and high humidity environments. The ASTM guideline is currently under review so that humidity is taken into greater consideration.An integral part of this testing on plastics is physical aging. As a plastic is held below its glass transition (Tg) temperature, its physical properties can improve or deteriorate over time. It is essential that accelerated aging studies be performed properly since each plastic material ages differently. Failing to perform or improperly conducting accelerated aging testing on a drug/device combination can lead to incorrect data and quality issues that can affect the health and safety of the end user. In addition to looking at packaging, the unique characteristics of the drug, biologics, and the device must also be taken into consideration.
The Accelerated Physical Aging ProcessPhysical aging is a process of molecular relaxation that occurs in all amorphous polymers held at temperatures below their Tg temperature. Aging has been observed in polyvinyl chloride (PVC), polystyrene, styrene acrylonitrile, and polycarbonate, as well as in copolyester polymers. When a polymer is rapidly cooled to below its Tg, which occurs in all commercial melt phase processing techniques, it freezes into a non-equilibrium conformation with excess free volume. In an attempt to attain equilibrium, the molecular chains rearrange themselves into a more dense structure, reducing the free volume of the system. Although this densification is difficult to detect, it directly affects thermodynamic and mechanical properties that are easier to measure and can, therefore, be used to track the extent of aging over time.
| The chemical resistance of Eastar Copolyester 6763 makes it ideal for primary packaging for combination products like safety syringes. |
Accelerated Aging and CopolyestersCopolyester plastics possess excellent final application properties such as long-term clarity and toughness. Utilizing accelerated aging testing on copolyesters in combination medical products helps manufacturers to capitalize on these benefits. The ASTM guideline suggests using an accelerated aging (Q10) factor of 2.0 as a conservative estimate for aging the device. The guideline also states that materials such as polycarbonate, PVC, and copolyester have a unique Q10 factor. Other Q10 factors can and should be used if they are derived from proper research and experimentation.
To assist OEMs and medical device manufacturers in determining the proper Q10 factor, Eastman Chemical Company conducted a number of trials to induce accelerated aging on Eastar 6763. Testing this copolyester, which can be used for a wide range of medical devices and rigid medical packaging, illustrated how well the material’s physical characteristics are maintained during the aging cycle. Through this process, it has been shown that using the wrong Q10 factor can drastically alter the outcome and reliability of accelerated aging testing.
For example, if a medical device manufacturer wishes to age a package made of a sheet of Eastar Copolyester 6763 five years (43,800 hours) at 60°C prior to performing shipping validation testing with the Q10 set at 2.0, they will inadvertently age the material well past the intended time frame. Using the ASTM equation (t23=tT*Q10^((T-T23)/10) leads the manufacturer to deduce that the accelerated aging time duration will be 3,370 hours (140 days). Experimentation has shown that this process ages the copolyester almost 2,000 years. Based on this error, the product would not withstand additional testing.
However, by using the correct Q10 value for copolyester and taking relative humidity and aging temperature into consideration, the accelerated aging testing can be accurately completed in just 92 hours at 50°C with reliable results. Through extensive experimentation, Eastman has determined that the Q10 factor for Eastar Copolyester 6763 is 9.8.
Due to time-temperature superposition, it is possible to generate data as a function of time at different temperatures and then shift the data together on one common master curve. Eastman conducted numerous tests to determine the mechanical and thermal properties of copolyesters as a function of aging time and temperature.
Time-temperature superpositions were performed on the data generated from these experiments to create master curves for each material. These times and temperatures (Table) can be used to perform “accelerated aging” experiments. A product is aged at an elevated temperature for a short period of time to simulate aging at a lower temperature for an extended period of time.
The testing concludes that Eastar Copolyester provides the required properties to ensure product integrity for a minimum of five years if good manufacturing practices are followed during extrusion, package design, forming, and sterilization, and if the packaged device is stored at room temperature under normal conditions and humidity levels.
For example, using the Q10 factor of 9.8 for copolyester, 1 hour at 60°C is equivalent to 96 hours at 40°C or 4,700 hours at 23°C. Likewise, one hour at 40°C equals 48 hours at 23°C. Therefore, if manufacturers wanted to simulate the performance of a package after ten years of life (87,600 hours) at 23°C, it should be aged at either 50°C for 180 hours or 60°C for 19 hours. This aging protocol reasonably represents the lifetime of a typical copolyester application.
Testing Tips to ConsiderAging copolyesters at higher temperatures for longer periods of time is not generally recommended. For example, aging for 250 hours (ten days) at 60°C is equivalent to aging for 1,200,000 hours (133 years) at room temperature 23°C. Aging for this length of time or longer at 60°C may over-age the material and provide an unrealistic expectation of properties and aging at standard room temperature conditions.
The recommended conditions for copolyesters are to perform aging at 50°C and 50% relative humidity. At these conditions, 18 hours are equivalent to one year of actual aging at room temperature 23°C. Therefore, 92 hours of aging at accelerated conditions are equivalent to five years of actual aging at room temperature 23°C.
ConclusionThe plastic used in a combination product must ensure integrity over a long period of time. For this purpose, accelerated aging testing is performed to understand and determine a product’s expiration date. Proper testing is essential to maximize the benefits of copolyester material used to create a product and package that both meets regulatory guidelines and can be administered successfully to the individual.
Author’s Note: Eastman has published an industry technical tip as an educational resource on best practices and guidelines in aging testing, which can be accessed at the company’s web site .
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Glenn Petrie is the Field Marketing Development Manager for the Medical Packaging unit of Eastman Chemical Company. Petrie can be reached at 608-835-1632 or email@example.com .