Accelerated Aging Testing For Medical Devices
What is accelerated aging?
Accelerated aging is a stability test for your product that allows you to determine the effect of the passage of time on the packaging protecting your product. The most common accelerated aging test methods allow you to determine the stability of a product in half the time real-time stability testing takes. Note that any data obtained through accelerated aging may be used to support the expiration date. However, this expiration date will not be confirmed until real-time stability testing has been performed. This is why most companies perform accelerated aging and real-time stability testing in parallel. Information on the accelerated aging formula and the accelerated aging of medical devices is detailed in this article.
Why is stability testing important?
Product packaging, also known as a sterile barrier system (SBS), breaks down over time. The loss of SBS integrity occurs due to packaging material or adhesive degradation over time. Product packaging is designed to provide sterility and product functionality until an item is at the point of use or until its expiration date. Stability testing allows validates SBS integrity and supports claims for a certain expiration date.
How does an accelerated aging test work?
Accelerated aging assumes that a particular packaging system is expected to age at the same rate regardless of the physical configuration of the package or what it contains inside. At its simplest, accelerated aging is the storage of samples at an increased temperature, which is used to simulate real-time aging in a shorter amount of time.
Accelerated aging is based on a particular theory. The theory is that a packaging system in storage exposed to external stress that is more severe than normal environmental stress for a shorter time is equal to the normal amount of stress the same packaging system experiences in storage over a longer time. This theory is based on an Arrhenius reaction rate function that predicts the deterioration of materials over time. The Arrhenius reaction rate states that a 10°C increase in temperature results in approximately two times the change rate of a chemical reaction. In other words, if you perform an accelerated aging study with a 10°C increase in temperature, you can get stability data equivalent to real-time data in half the time (ie. 6 months as opposed to 1 year). Thus, you will only need to store your packaging system for half of the time you would normally need to for a real-time stability study to validate expiration date time points. As an additional advantage, an accelerated aging study that accidentally goes below the specified temperature can be compensated for by increasing the total time of the accelerated aging test without invalidating the aging protocol. Note that the FDA still requires real-time stability studies to be performed to fully validate accelerated aging studies.
What is the Arrhenius equation?
Arrhenius Accelerated Aging Formula:
AAF= Q10[(TAA-TRT)/10]
Where:
AAF= accelerated aging factor
Q10= conservative aging factor (normally Q10 is 2.0)
TAA= accelerated aging temperature in °C (temperature aging study is conducted)
TRT= ambient temperature in (storage temperature for real-time aging, normally 25°C)
RT= required shelf life
Accelerated aging time (AAT) formula needed to establish equivalence to real-time aging is determined by dividing the required shelf life (RT) by the AAF.
AAT Accelerated Aging Formula:
AAT= RT/AAF
How Are aging studies performed?
First, you need to select a Q10 value, your conservative aging factor. For most studies, the Q10 is 2. At a Q10 of 2, every 10°C increase in temperature from ambient results in the rate of a chemical reaction doubling. Once you have your Q10 value, you can calculate your accelerated aging factor (AAF). Your AAF can be used to calculate your accelerated aging time based on the desired shelf life of the product. It is recommended that you set at least two desired shelf-life timepoints. This way you have a backup in case you do not meet your acceptance criteria for a particular timepoint. zero time point accelerated aging analysis.
Next, relative humidity and any tolerances will be set for the aging process. You will then define the material properties of the packaging system that you would like to test, such as seal strength integrity tests, sample sizes, and acceptance criteria. Your testing facility can support you with these criteria. Packaged products will then be sent to your testing facility. Make sure that you have enough samples for time zero and each accelerated aging timepoint. The physical properties of the time zero samples will be evaluated. These will provide a baseline for packaging later evaluated at aging time points.
Once you have reached one of your desired shelf-life time points, the packaging will be evaluated for acceptance criteria. If the stored packages meet the acceptance criteria (created based on time zero testing), the accelerated aging study is successful and the expiration date for this particular shelf-life time point is validated. This expiration date will still need to be confirmed with real-time stability testing for final regulatory approval. If your accelerated aging results fail to meet the acceptance criteria, then you can wait for the real-time aging studies to see if these meet the acceptance criteria period. You can also redesign your accelerated aging for medical devices by shortening shelf life, redesigning the product or packaging, or investigating any issues with the product production process. If the real-time aging studies meet the acceptance criteria, then the sterile barrier system shelf life is validated. If the real-time aging studies do not meet the acceptance criteria, then the shelf life must be reduced to the longest shelf life for which real-time testing has been a success.
Limitations to accelerated aging
Accelerated aging will not address environmental challenges due to extreme climatic conditions such as high humidity and high temperature. This is because the humidity is not included in accelerated aging and must be evaluated in a separate study. If humidity is a factor for product transport or storage, consider the material properties of your packaging and product carefully. Stability and aging studies are impacted by the material composition, morphology, thermal transitions, and material or adhesive additives. If you do perform humidity studies, the normal temperature (ambient temperature) will be 25°C.
Accelerating aging is not possible for all product-packaging systems. This is because the temperature for an aging study should be below the material transition temperature of the sterile barrier system. The material transition temperature is the temperature at which the materials and adhesives in a packaging system distort and experience non-linear changes (the creation of free radicals and peroxide degradation). Thus, if the material transition temperature of your packaging system is at 35°C or below, accelerated aging will not be a viable option and real-time studies are the only stability testing option.
Accelerated aging and stability testing are separate from performance testing. Performance tests assess the interaction between the packaging and the product in response to stresses that occur outside of storage, including manufacturing stress, stress from sterilization processes, handling stress, or environmental stresses.
MycoScience is a contract manufacturing organization specializing in sterile syringe and vial filling. MycoScience also offers Preservative Efficacy Testing, Sterilization Validations, Bioburden Testing, Cleaning Validations, Microbial Aerosol Challenge Testing, Accelerated Aging, Microbiology Testing, Cytotoxicity Testing, Bacterial Endotoxin Testing, EO Residual Testing, Package Integrity Testing & Environmental Monitoring services medical devices and allied industries. MycoScience is an ISO 13485 certified facility.
References
American Society for Testing and Materials. Standard Test Method For Determination Of Leaks In Flexible Packaging By Bubble Emission. West Conshohocken, PA, United States. (ASTM D3078-02).
