Using Low Volume Gas Analysis to Ensure Package Integrity

FEATURE

FEATURE

Pack with confidence

Packaging fulfils a number of critical roles for medical devices; it ensures that a sterile environment is maintained and that the product is protected during storage and transport throughout the supply chain. It is essential that end-users have complete confidence in the device and its packaging because the consequences of failures can be incredibly expensive at best and fatal at worst. To help improve shelf life, for example, by preventing moisture ingress, many medical devices are packaged using high-barrier, gas flush packaging with modified atmospheric composition: the oxygen in the packaging is removed and replaced with nitrogen, carbon dioxide or argon.

The medical device industry uses a number of different packaging designs and materials, including blister packs and foam (usually made from polystyrene, polyurethane or latex) for use in peelable or tear-open pouches, heat-seal coated lidding and barrier packaging for orthopaedic devices. However, some manufacturers believe foam is too expensive and that the bubbles in the materials can lead to contamination. Alternatives are available, although these must be gas flushed because the foam is like a vacuum moulded cover and as a result of its construction, it eliminates air ingress.

Low volume gas analysis (LVGA) is a technique used to identify gases, vapours or residues, and it can help manufacturers ensure their gas flush systems are functioning correctly and that contaminants that cause process problems or product failures are eliminated. Conventional residual gas analysis requires a certain minimum gas volume to be presented for mass spectrometric analysis. Levels of gas between 1 to 5 mL do not allow sufficient accuracy for good quantitative composition determinations to be made for multicomponent gas mixtures, particularly when the component of interest may only be present in trace amounts. For sealed environments, and particularly for evacuated sealed environments, there is the added complication of extracting a sample from the container. LVGA methodology overcomes these difficulties by breaking the sealed container inside the analysis instrument and feeding the contents directly to the mass analyser. This article will describe the technique’s applications in monitoring the gases used in orthopaedic medical devices packaging.

Regulations

The United States Food and Drug Administration’s (FDA) guidance, “Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products” describes how device manufacturers must validate their processes (including sterilisation) for a device that purports to be sterile. It stresses that stability testing should be part of the design validation (21 Code of Federal Regulations 820 75, Process Validation), the purpose of which is to provide documented evidence on how the quality of a substance or product varies with time in relation to factors such as temperature, humidity and light. This helps manufacturers establish and/or modify the supply chain logistics, storage conditions and retest periods to ensure their devices remain in optimum condition.

Although there are no regulatory aspects to gas analysis as such, nor to the gas content of packages, FDA believes that the advantages of implementing integrity tests (including LVGA) within sterility and stability protocols include

■ detecting a breach of the container and/or closure system prior to product contamination

■ conserving samples that may be used for other stability tests

■ reducing the time taken to perform analysis

■ reducing false positive results.

LVGA of device packaging

LVGA is a high vacuum (or ultrahigh vacuum) technique that uses a mass spectrometer to detect leaks and outgassing. Molecules from the gas sample are ionised, analysed and identified via their charge:mass ratios. Typically, an LVGA instrument has three major components: an ioniser, the spectrometer and an ion detector.

A modified mass spectrometer, SIMSLAB IIIA Quadrupole SIMS (VG Ionex), enables residual gas from ruptured medical device packaging to be leaked in a controlled manner into the LVGA analyser in the main instrument chamber (Figure 1). The mechanism for in vacuo fracturing of medical device packaging is based on a modified ultrahigh vacuum (UHV) valve assembly in which the central sealing spindle is replaced by a diamond tipped shaft (Figure 2). This shaft is mechanically driven by rotation of the valve assembly, which brings the diamond tip into contact with the surface of the sample. Increasing the pressure on the tip causes rupturing of the sample and resultant release of the internal atmosphere into the evacuated chamber. A UHV leak valve is then used to bleed the gas into the main instrument chamber for mass spectral gas analysis.

The gas molecules in the sample are ionised and then analysed and the data represented as a graph with the mass:charge ratio on the x-axis and the relative intensity on the y-axis. Identifying the gases, vapours or residues can help to fix leaks in vacuum systems and identify contaminants. Figure 3 highlights the sensitivity of the LVGA technique in measuring gases commonly used in packaging orthopaedic devices, particularly nitrogen and argon.

Case study

A leading manufacturer of orthopaedic components commissioned a study to determine the extent of batch-to-batch variability in packaging gas composition following routine gas flushing and vacuum sealing of its ultrahigh molecular weight polyethylene implants. The gas composition of batches of packed products was compared with control samples (packaging with known gas composition) to ensure batches were within the acceptable range of gas concentrations. The products were routinely sealed under vacuum following flushing with an inert gas so that the residual gas volumes within the sealed pouch were appropriate, that is, to ensure an inert atmosphere with minimum air and particularly oxygen content as a precaution against product deterioration during storage.

The method of gas composition analysis was developed using a specially modified Quadrupole SIMS mass spectrometer. The instrument was fitted with a side chamber enabling in vacuo rupturing of the packaging combined with controlled leakage of the resulting internal atmosphere into a LVGA system. The mass of the gas fragments was measured in the LVGA to identify the whole pack gas composition. The benefit of this technique over more conventional gas sampling methods such as syringe extraction is the ability to analyse the small quantities of gas that remain once the packs have been evacuated following gas flushing.

A number of vacuum-packed pouches were analysed following flushing with inert gas (argon). High quality data were generated giving superior compositional accuracy for a five-gas mixture with trace level sensitivity down to less than 0.05 atomic percent. The variations in residual gas level were found to be consistent and acceptable. Only trace amounts of hydrogen, water vapour and oxygen were detectable, which demonstrates the technique’s capacity to detect extremely low gas levels.

The study confirmed that there were no differences in gas composition between the tested batches and the control batches. The manufacturer concluded, therefore, that the gas flushing process was operating correctly and consistently.

Valuable quality control step

Routine testing of packaging gas composition is an important element of quality control. In some instances testing of medical device packaging could supplement or even replace product stability and sterility testing. Issues with gas flush machinery or with packaging itself can result in costly product wastage for manufacturers. Regular confirmation of packaging gas integrity can improve customer confidence in product quality and safety. The recent rise in popularity of LVGA for use in testing the atmospheric content of gas flush medical device packaging is proving extremely valuable to manufacturers and end-users alike.

 

Dr Chris Pickles, PhD, is General Manager of Surface and Materials Analysis, CERAM, Queens Road, Penkhull, Stoke-on-Trent ST4 7LQ, UK, Tel. +44 1782 764 444, e-mail: chris.pickles@ceram.com [7] www.ceram.com [8]