Medical Device Link.

MANUFACTURING

Meeting the challenge

As medical devices become more sophisticated, regulators and customers alike are seeking zero defects. Internationally, medical device packaging standards are being harmonised such as ISO 11607 2006, Packaging For Terminally Sterilised Medical Devices. The fear of product recall and litigation constantly exists and helps to focus minds on the need for defect-free medical device packaging systems.

One of the greatest potential risks to patient safety is the unwitting use of a sterilised device that is no longer sterile. Packages must protect these devices not only from physical damage and loss of sterility, but also, when appropriate, from uncontrolled changes to the gas concentration within their packages. Consequently, there is a need for packaging quality assurance and quality control teams to have effective inspection technologies. They need to verify that the protective environment provided by the packaging of each device is free from defects and continues to perform its intended function throughout distribution and storage, until the time the product is used.

When developing packaging for sterile medical devices it has always been a challenge to demonstrate, with the minimum of wasteful destructive testing, that each seal has been perfectly made with full closure integrity and to demonstrate prior to opening that the sterile barrier system has not been breached. The variety of techniques available to packaging specialists, particularly in the area of control and measurement, is advancing as new information technology comes to market. Two useful inspection tools have become available in recent times. The first employs ultrasound and computer graphics to display an image of the interface between the sealed layers of a heat-sealed package. The second relies on a noninvasive system that can measure the percentage of oxygen present in the interior of a package without damaging the product or the package.

Nondestructive seal checking

One technique is designed to perform nondestructive seal-integrity inspection on heat-sealed medical device pouches, sachets and the closure of thermoformed blisters.¹ The system can be used to check seals formed using Tyvek (DuPont), paper, foil, film and laminates, which are decorated or transparent. Using airborne ultrasound (high frequency sound waves) a transmitter fires focussed ultrasound pulses at 200 Hz through the seal area under inspection. A sensitive noncontact receiver detects and interprets the transmitted ultrasound signal. The resulting “opto-acoustic” display removes the need for destructive package opening to determine seal quality.

Traditional ultrasonic inspection technology generally requires that the test piece is placed in contact with a wet physical coupling. This novel ultrasound technology is noncontact and requires no coupling medium other than air and no product or package preparation prior to testing. The air-coupled ultrasonic technique avoids contamination of the package by the coupling liquid. Commenting on ultrasound, Wolfgang Hillger, an expert in nondestructiuve testing, states that, “The wave-length in water is about five times larger than in air, so that [using the same test frequency] the sound can be focussed in air much better than in water and also the resolution of materials with high sound attenuation is much better with air coupling.”²

Figure 1. (click to enlarge) Ultrasound display of pouch seal defects.

To use the ultrasonic inspection system described here effectively, it must be possible to pass all parts of the seal directly between a pair of transducers. Either the seal or the transducers will move to track the whole length of the seal. Ultrasound is partly transmitted and partly reflected at the transition from one medium to the next. The greater the acoustic difference between media (most evident at a gas-to-solid transition), the more sound is reflected and the less sound is transmitted through them. The ability of the ultrasonic pulses to propagate through the seal is used to characterise the overall quality and uniformity of the seal. It can also identify defects such as voids, delamination, foreign materials, inclusions in the seal and misaligned seals. Variations in material thickness have only a minor effect on the displayed result. The visual display of ultrasound images shows differing colours for sealed and nonsealed areas that can be used to nondestructively check pouch and blister seals for voids (Figures 1 and 2).

Figure 2. (click to enlarge) Photo of sachet with ultrasound image showing voids and channels in the seal area.

It has been forecast that airborne ultrasound systems will have a major impact on the packaging industry. Nondestructive verification of each pack’s sterile barrier system should prove of particular benefit to those device manufacturers packaging many small batches of high-value products in expensive thermoformed trays. Removing the need for destructive testing at the beginning and end of each short packaging run will save labour and materials and make available the capacity currently absorbed by the need for packaging rework.

Noninvasive oxygen measurement

Modified atmosphere packaging has facilitated a change in packaging materials from aluminium foils to clear, nonporous, high‑barrier plastic films. Oxidation is directly correlated to premature material wear in articulating joint prostheses, which consequently increases the risk of severe implant complications for the patient. There is a need to ensure the effectiveness of the gas flush for each package and to be able to check the oxygen content after sterilisation and throughout the product’s shelf life. A rapid and simple means of noninvasive, nondestructive measurement of oxygen has not been possible in the past. The introduction of oxygen and gas-fill sensing technology now makes this possible.¹

Sensors have the ability not only to withstand irradiation, but also to enable tests to be repeated and provide accurate information throughout the entire supply chain. This novel noninvasive oxygen measuring system consists of an oxygen analyser and patented sensors. When packaging the product, the sensor is attached to the interior of each sterile barrier system. This sensor can then be interrogated, noninvasively and nondestructively by an external analyser that verifies the effectiveness of the gas-flush system by displaying the level of residual oxygen in the package.

The oxygen analyser includes an optical head that uses a light-emitting diode (LED) to illuminate and excite the sensor with blue light. The re-emitted orange signal light from the sensor is detected using photodiodes and this information is then fed into the electronic circuitry that converts these signals into oxygen-concentration values. Specially developed software is used to display and record the readings.

The sensor is supplied in roll form as a printed self-adhesive label. It is placed within the sterile barrier system before gas flushing and sealing. The sensor can be scanned without physical penetration of the package using the analyser to measure oxygen concentration. The active ingredient of the sensor is a ruthenium complex that emits light when excited by the LED in the scanner’s optical head. The emitted light is sensitive to oxygen and detection of this light by the optical head allows the concentration of oxygen inside the enclosed area to be determined; neither the sensor nor oxygen is consumed in the measurement. The sensor is reportedly compatible with pick-and-place applicators and its size and shape can be tailored to meet user requirements.

The sensor can be interrogated repeatedly to measure gas-fill levels. This can be performed and recorded prior to bombardment by radiation and whenever required during the life of the packaging to verify the package integrity. Use of this system provides a tamper-evident indicator and enables verification of package integrity immediately prior to surgery.

The developers claim that the sensor’s reaction remains accurate throughout a product’s lifetime. Thus, the ability to monitor the integrity of the package along the entire supply chain for years after sterilisation can significantly increase patient safety and probably shelf life. There is the potential to increase shelf life because medical device manufacturers can now quantify the time it takes for external gases to leach back into the package.

Observations

The noninvasive evaluation of sterile barrier systems and their closure integrity is in its infancy. Yet, ultrasound testing of aircraft components is well established and accepted. Now that the technique has been adapted for use in packaging, medical device packagers can reap the benefits. Perhaps the next generation of ultrasound package inspection tools will use reflected sounds and accomplish the inspection test by one-sided package exposure to the transducers.

Nondestructive testing of oxygen levels has in the past been a time-consuming and expensive process. The availability of sensors in the form of a label that may be automatically applied changes that. This system is intended for verifying that the product has not been exposed to the risk of oxidation. However, when the pack is a gas barrier and the product is terminally sterilised, there is potential to use this measuring system as a noninvasive sterility check. Flushing with an inert gas could be used to remove all but trace remnants of oxygen, and then the oxygen level inside the closed pack could be used as a means of determining whether or not the sterile barrier has been breached. Future developments are awaited with interest.

Rolande E. Hall is a Consultant, Medical Pack Solutions, Pinewood Lodge, 16 Tullyvarraga Hill, Shannon, Co. Clare, Ireland. tel. + 353 61 364837, e-mail: rolande@medicalpackconsultant.com