Packaging for medical devices, related products and materials is highly regulated and must meet very specific requirements. The most critical factor for medical device packaging is product sterility, which must be maintained throughout distribution and storage, allowing for safe and effective use of the device.
The primary standard governing medical device packaging and shelf life validation is ISO 11607-1. The intent behind this standard is “To provide designers and manufacturers of medical devices with a framework of laboratory tests and evaluations that can be used to qualify the overall performance of the package used to protect the device components during handling, distribution, and storage.”
The importance of material and design
There is more to medical device packaging than simply creating a flashy package that gets consumers’ attention. Package design, while being cost effective to the manufacturer, should be tailored to the end user for optimum ease of use, safety and product protection. The materials used in packaging devices play as important a role as the colours and design, protecting the device as much as providing quality packaging. The paper used to make folding carton packaging is an important part of medical device manufacturing.
The four main types of substrates used in folding cartons are: unbleached kraft paperboard; bleached kraft paperboard; recycled paperboard; and small flute corrugate.
– Unbleached kraft paperboard is the most common material used for folding cartons
– Bleached kraft, also called solid bleached sulfate, is the highest quality and most expensive paperboard substrate
– Recycled paperboard is made from recovered paper, and represents the single largest market for recovered paper in the United States
– Small flute corrugate has added strength and rigidity due to its construction, but this also adds cost to the converting process. It is usually used in high-end packaging where strength and stiffness are important
Packaging for terminally sterilised medical devices
The process of developing and constructing a packaging system for terminally sterilised medical devices is a convoluted and pressing endeavour. The definitive nature of the medical device, the intended sterilisation methods, the intended use, expiration date, transport, and storage all influence the packaging system design and choice of materials. The combination of the medical device and the packaging system should perform efficiently, safely, and adequately in the end user’s hands.
ISO 11607 details the requirements from the International Organization for Standardization (ISO) for this process. The standard is broken into two parts. Below is a summary of each of the two sections of the standard.
ISO 11607-1 details the elemental attributes demanded of materials and pre-formed systems intended for use in packaging systems for terminally sterilised medical devices. It takes into consideration the vast array of potential materials, medical devices, packaging system designs, and sterilisation methods.
ISO 11607-2 describes the validation requirements for forming, sealing and assembly processes. The development and validation of packaging processes are crucial to ensure that sterile barrier system integrity is maintained until opened by the users of sterile medical devices.
Beyond ISO there are also ASTM (Association for Testing and Materials) and ISTA (International Safe Transit Association) standards which must be followed, especially if you intend to achieve FDA (Food and Drug Administration) approval.
Medical package testing can be broadly categorised into:
1. Distribution simulation testing – Involves a series of tests specifically designed to measure the sturdiness of the outer/secondary packaging. This is to ensure that the packaging can meet industry standards and can safely contain the devices during shipping, handling and storage. Major standards involved are:
– ISTA Procedure 1A
– ISTA Procedure 2A
– ISTA Procedure 3A
– ASTM D4169
2. Package integrity testing – Focuses on the device’s primary packaging/pouch. Tests are designed to check the pouch’s ability to maintain sterility and its robustness. Standards utilised here are:
– Bubble Leak Test per ASTM F2096
– Peel Test per ASTM F88
– Burst Test per ASTM F1140
– Dye Penetration Test per ASTM F1929
– Visual Inspection per ASTM F1886
3. Stability testing/accelerated ageing – Includes accelerated ageing and real-time ageing. These tests are conducted to determine that the packaging configuration is sufficient to maintain product sterility for the intended shelf life period.
– Accelerated Aging per ASTM F1980
– Conditioning per ASTM D4332
Let’s delve into each of these in more detail.
Standards and regulations
Distribution simulation testing assesses a medical package’s ability to protect and maintain the sterility of the products within. There are numerous variables that medical packages and products will encounter when traveling from the point of manufacture to the sterilisation facility, distribution centre or healthcare facility. A medical package falling from a fork lift, swaying around a truck during transit, or being stacked on top of other packages or containers in a storage warehouse are all examples of distribution occurrences.
Distribution simulation is a systematic and repetitious way of testing shipping containers, using testing equipment which exposes these packaging systems to genuine, real life hazards that may ensue within the forthcoming distribution environment.
Distribution simulation is a large and quintessential component that complies with the ISO 11607-1 standard. The package or container and its contents are subjected to a test plan involving shock, compression, vibration and drop tests as per the guidelines set by ASTM D4169 and ISTA standards.
It may also be necessary to expose the medical packages and products to atmospheric conditioning in order to simulate particular field conditions that a packaged product or component may encounter during its expected life cycle or testing cycle. The ASTM D4322 standards cover this.
ASTM D4169 lists the ‘Standard Practice for Performance Testing of Shipping Containers and Systems’ as per current industry/government practises and experience. The container’s performance level is determined by putting it through a specified order/sequence of tests, throughout which the shipping unit must withstand the distribution environment.
The International Safe Transit Association (ISTA) is the author of test procedures that define how packages should perform to ensure protection of their contents. ISTA test procedures are internationally recognised because they are based on leading technology and the most current global transport environment data.
The organisation provides the final validation of package revisions through its packaged-product performance test procedures. The ISTA test procedures are acceptable in complying with the ISO 11607-1 standard.
ISTA testing standards include the following:
– ISTA-1A: Non-Simulation Integrity Performance Tests
– ISTA-2A: Partial Simulation Performance Tests
– ISTA-3A: General Simulation Performance Tests
Package integrity testing
Package validation testing is vital to ensure integrity of the package’s seal. Validation will provide assurance and security that a package is sealed properly, leak free, and secure from any number of outside contaminants. Accelerated ageing should take place after the integrity of the product and package has been determined.
The main culprit for feeble package strength is the seal heat-sealing parameters. If a formal validation of the heat sealer is not carried out, the medical device manufacturer can expect sterile barrier failure. Packages may also lose their integrity as a result of the various events that occur during processing and/or distribution. Package validation testing may be used to validate that the package integrity has been maintained throughout the package’s processing, expected shelf life, and handling.
Testing includes, but is not limited to, the following:
– ASTM F1886: Visual Inspection Test – Standard test method for determining integrity of seals for medical packaging by visual inspection
– ASTM F88: Peel Strength Test – Standard test method for seal strength of flexible barrier materials
– ASTM F1140: Burst Test – Standard test methods for internal pressurisation failure resistance of unrestrained packages
– ASTM F1929: Dye Penetration Test – Standard test method for detecting seal leaks in porous medical packaging by dye penetration
– ASTM F1140: Creep Test – Standard test methods for internal pressurisation failure resistance of unrestrained packages
– ASTM F2096: Bubble Leak Test – Standard test method for detecting gross leaks in packaging by internal pressurisation
Stability testing is done through accelerated ageing and real-time ageing tests. Accelerated ageing is a testing method used to estimate the useful lifespan of a product when actual lifespan data is unavailable. This occurs with products that have not existed long enough to have gone through their useful lifespan.
A product can be released to market based upon successful accelerated ageing of the package/product that simulates the period claimed for product expiration (e.g. one or two years). Accelerated ageing data is recognised by regulatory bodies as an acceptable means to generate data quickly, but is only accepted until those tests can be repeated on real time samples.
An accelerated ageing test is carried out by subjecting the packaged product to unusually high levels of stress (controlled temperature and humidity) designed to mimic the effects of normal storage.
Accelerated ageing techniques are based on the assumptions that the chemical reactions involved in the deterioration of materials follow the Arrhenius reaction rate function. This function states that a 10° C increase or decrease in the temperature of a homogenous process, results in approximately a two times or half time change in the rate of a chemical reaction. For example, at 55° C, 6.5 weeks is equivalent to one year on-the-shelf, two years would be equivalent to 13.0 weeks and five years would be 32.5 weeks (assumes ambient temp = 25° C, and Q10=2).
Testing includes, but not limited to, the following:
– ASTM F1980
Standard Guide for Accelerated Aging of Sterile Barrier Systems for Medical Devices
– ASTM D4332
Standard Practice for Conditioning Containers, Packages, or Packaging Components for Testing
The entire testing process is both costly and time consuming, lasting anywhere from 30 days to several months, so time and finances should be planned accordingly.
Before sterile medical device packaging validation begins, an ISO 11607-1 compliant protocol should be developed and signed-off.
After testing is complete, a final report is submitted which documents all test results, any corrective actions which were taken, and any other pertinent information regarding testing and packaging.
Finally, remember that although the ISO 11607-1 standard is the benchmark, each customer may have particular requests which exceed these standards, so it’s best to remain flexible and prepared for further testing if necessary.
For detailed knowledge on each standard and test procedure visit: https://lso-inc.com/medical-package-testing/