Today's medical device marketplace is a dynamic environment where new instruments and therapies are developed daily. But the commercial introduction of new products carries with it the challenge of assigning to them an effective shelf life, as well as ensuring that the packaging chosen for them is appropriate for the intended sterilisation, transportation, storage and end use.
Since humidity may have a significant impact on the performance of some packaging materials, it is important to establish appropriate and realistic humidity levels when evaluating them. As a result, the Sterilization Packaging Manufacturers Council (SPMC) of the Flexible Packaging Association has become involved in providing guidance on the role of humidity in the accelerated ageing of sterilisable medical packaging.
SPMC is comprised of leading US manufacturers of sterilisable flexible packaging and materials. These companies work proactively and voluntarily as FPA-SPMC members to develop test methods and guidance documents for the US-based flexible sterilisation packaging of medical devices used in hospitals and other healthcare facilities. SPMC member companies include Alcan Packaging, Amcor Flexibles Healthcare, Beacon Converters, Inc, Oliver Medical, Perfecseal, Rollprint Packaging Products, Inc, Technipaq, Inc, and TOLAS Health Care Packaging.
ACCELERATED AGEING PROTOCOLS
Understanding the impact of time on the efficacy of a sterile medical device often relies on accelerated ageing protocols. Such protocols are generally accepted as valid for testing new product introductions, provided real-time ageing is in place to confirm accelerated ageing test results. Devices are generally regarded as sterile as long as package integrity has not been compromised.
Typically, during ageing studies, a series of tests are carried out to assess package integrity and the physical properties of the packaging materials, as well as its opening features (if applicable). Packages that have been sterilised and aged in this manner are then sometimes subjected to shipping studies.
Another approach involves a shipping study performed in advance of accelerated ageing, with material property and package testing used to measure the influence of time on shipped sterilised products. The use of the Arrhenius equation is recognised as a valid approach for defining the effect of elevated temperature on a homogeneous first order reaction rate. The Q10=2 calculation developed from this equation assumes that the ageing process is approximately doubled for each 10°C rise in temperature. In fact, the temperature for the study must be chosen carefully, so that materials are not damaged because of conditions that would not be expected to occur in real time or which are outside the recommended range of use for that material.
ASTM's F1980-02 standard, entitled Standard Guide for Accelerated Ageing of Sterile Medical Device Packages provides further guidance on this topic. However, while this standard notes briefly that: "The effects of humidity may need to be considered," it is fair to say that the impact of humidity on accelerated ageing continues to need more definition.
HUMIDITY AND ACCELERATED AGEING
How should humidity be handled in accelerated ageing? Current industry practices vary widely, but a good starting point is understanding the definition of Relative Humidity (RH), which is the ratio of the amount of water vapour in the air to the greatest amount the air could contain at the same temperature. The warmer the air, the more water vapour it can hold. For example, the water load in air at 25°C at 80% RH equates to about 25,000 parts per million (ppm). At 55°C, this same 25,000ppm is less than 21% RH. If the same RH (80%) is established at this higher temperature, the amount of water increases to more than 100,000ppm, a condition that must be created artificially.
So what RH should be used for accelerated ageing? One major medical device manufacturer uses a fixed absolute humidity of 27,500ppm, irrespective of the temperature chosen for the study. This humidity level corresponds to over 90% RH at 25°C and 18% RH at 55°C. The manufacturer further recommends that for simulating environmental exposure and/or for humidity sensitive materials, 37°C-40°C at 80% RH (~58,700ppm water) should be used, which is designed to cover conditions that approximate the temperature/humidity extremes that can be encountered during a product's life cycle. Other companies and independent testing laboratories conduct hot/cold cycling to mimic the seasonal extremes to which packaged medical devices may be subjected.
It is helpful to divide these different approaches into two categories: accelerated ageing, where the effects of time on packaging and its contents are being studied, and environmental challenging, where extremes of temperature and/or humidity are simulated to determine the impact of difficult environments on packaging systems.
In fact, the following two new definitions for these terms were recently balloted at ASTM as additions to ASTM F1327, Terminology Relating to Barrier Materials for Medical Packaging. The clarification of these terms is expected to be addressed within ASTM F1980 in the near future.
Accelerated ageing is a technique to simulate the effects of time on a package by subjecting the product/package system to elevated temperatures under conditions otherwise representative of controlled environment storage conditions. The equivalent time is generally estimated by assuming that the degradation of packaging materials follows the kinetics described by the Arrhenius reaction rate function, more discussion of which is available in ASTM Standard Guide F1980.
Environmental challenging is the process of subjecting a package to extremes of temperature and/or humidity with the goal of determining the sensitivity of the package to environmental stress. In contrast to accelerated ageing, environmental challenging often includes conditions and/or transitions of temperature/humidity that equal or exceed those that can be encountered in a package life cycle.
In accelerated ageing, the humidity level is chosen to avoid damage or changes to packaging materials that would not be expected during real-time ageing. With environmental challenging, the aim is either to assess package performance at the extreme conditions possible in a package life cycle, or (in the case of conditions unattainable except in the laboratory environment – conditions of 55°C at 80% RH, for example) to stress the material to near or past its failure point.
MAKING MATERIAL SELECTIONS
Different materials have different sensitivity to moisture, so conclusions regarding a given material's suitability as a packaging component may not be valid if humidity is not controlled. For example, paper is particularly sensitive to humidity. Excessive drying negatively impacts its strength properties, and excessive humidity can lead to mould growth. Some laminates commonly employed in medical packaging may fail under conditions of extreme humidity, despite the fact that such materials have been shown, historically, to provide excellent protection for medical devices. Specifically, PET extrusion coated with LDPE can often be induced to delaminate during environmental challenging, although real-time or controlled accelerated ageing either rarely or never produces such a result.
Ultimately, the medical device manufacturer must make the final decision regarding the suitability of a packaging material to ensure the efficacy of a sterilised medical device. Hopefully, this article will serve as a guide to choosing the conditions for testing a package so that informed judgments can be made regarding the performance of packaging over time, and to separate shelf life testing from the environmental impact of temperature and humidity.
For additional guidance, the Flexible Packaging Association publishes Sterilization Packaging Manufacturers Council Standards, a manual that includes SPMC's standard test methods, specifications and practices, and a guide for the design and evaluation of primary flexible packaging materials for medical products. This publication provides valuable information on test method selection, testing technique and troubleshooting.
SPMC also provides technical information through its website. The frequently asked questions section provides valuable guidance and information regarding the technical issues faced by the industry. The organisation's technical committee convenes regularly to answer questions of general interest to the industry and posts the answers on the website.