Hygienic disposable syringes, blood bags, infusion bottles and gloves are made of plastic, as are contact lenses and artificial heart valves too. Plastic packaging is highly suitable for medical applications in particular – thanks to its exceptional barrier properties, low weight, low costs, durability, transparency and compatibility with other materials. If necessary, it keeps the contents packaged sterile. (Photo: istockphoto)
This is attributable to the fact that plastics have an ideal property profile. According to the Fraunhofer IGB, plastics are
• light (density between 0.8 g/cm³ and 2.2 g/cm³)
• and flexible (wide range of elastic modulus and strength).
• Plastics have a low processing temperature (from room temperature to 250°C, in exceptional cases up to as much as 400°C).
• Plastics can be modified effectively during processing via additives (incorporation of fillers and reinforcement materials, foaming agents, colourants and active substances) and reaction.
• Plastics are suitable for large-scale manufacturing,
• provide tremendous design freedom,
• are highly biocompatible,
• are radiolucent and compatible with magnetic resonance tomography (MRT).
It goes without saying that medical polymers are not conventional plastics; they are instead functionalised products that have generally been subjected to sophisticated manufacturing, processing and finishing operations. The aim is, after all, to guarantee that the material integrated in the human body does its job perfectly for years and is at the same time not the source of any health risks, i.e. that no additives – for example – escape from the polymers, reach the organism and cause problems there. Quality assurance is responsible for making sure that implants work flawlessly, in order to eliminate any health risk. In this context, quality assurance experts do not, however, have access to defined, validated (i.e. generally tested) and established standards of the kind that have been available for a long time in – for example – the pharmaceutical industry. Manufacturers of prostheses and implants really are entering virgin territory in the product control field; for simplicity’s sake, however, they base their operations on experience and procedures in the pharmaceutical manufacturing industry, which carries out special studies for this purpose.
Also worth reading in this context: Packaging: Food and pharmaceutical packaging on the trail
The German Plastics Museum reports about polymer materials in medical applications
Testing is essential
A look behind the scenes in the pharmaceutical industry: the purpose of medical drugs and the substances they contain is to maintain or improve health and not to make patients ill. There is a risk of this, however, when chemicals or harmful substances from the packaging migrate into the drug or develop directly in the product. It is the pharmaceutical manufacturer’s responsibility to detect such problems at an early stage: in what are known as “extractable studies”, pharmaceutical packaging is investigated to determine migrating and/or leaching chemicals in simulated worst-case scenarios. This involves extraction of undamaged packaging using solvents of varying polarity and high temperatures. The extracts and the analytes they contain are analysed to obtain an insight into what compounds might contaminate the drug. The substances that are classified as critical are, finally determined in “leachable studies” using the pharmaceutical itself and applying validated methods. 
Doctors only started to use plastic on a large scale in the middle of the last century. The potential of plastic has been recognised in the course of time and nowadays it is mainly specially manufactured polymers that are used in medical engineering. Plastics are used today for orthopedic purposes, where they straighten, support, correct and improve or even replace the function of moving body parts. Plastic prostheses or orthoses can replace a body part and take over its main function. (photo: istockphoto)
Implants need to be safe too
Manufacturers of medical implants and prostheses face a similar challenge to the pharmaceutical industry; they too are required to check their products, which frequently consist of material combinations of metal and plastic, for the presence or development of compounds that migrate in-vivo, i.e. inside the human organism, during their use and may lead to harm or danger to the patient. This fact makes implants and prostheses the object of E&L studies as well.
In contrast to pharmaceuticals, however, there are no binding directives or specifications for carrying out E&L studies on implants and prostheses, as Gyorgy Vas points out. For this reason, the scientist – who works for the company intertek in the USA – bases his implant research (which is outlined below) on the way the pharmaceutical industry carries out E&L studies in accordance with existing standards and rules as well as on the specifications of the Product Quality Research Institute (PQRI), a US non-profit organisation which considers 150 nanograms per day to be the acceptable migration limit for genotoxic and/or carcinogenic leachables .
Modern medicine would not be possible without plastic: hygienic disposable syringes, blood bags, infusion bottles and gloves are made of plastic, as are contact lenses and artificial heart valves too. Plastic packaging is highly suitable for medical applications in particular – thanks to its exceptional barrier properties, low weight, low costs, durability, transparency and compatibility with other materials. If necessary, it keeps the contents packaged sterile. (Photo: istockphoto)
Not identical but comparable
Although the PQRI refers in its specification to results that were obtained in the course of the testing of inhalation products, Vas and his colleagues considered this approach to be “conservative” in the sense of maximum possible safety for the patient and thus an effective basis for their own research project, as Vas et al. write in the Journal of Pharmaceutical and Biomedical Analysis . In their article, the scientists report how they determined leachables from medical implants (tibia knee inserts) using analytical separation and analysis technology – gas chromatography in connection with mass spectrometry (GS/MS), to be exact – and special enrichment technology. They say that the purpose of their work was “to develop systematic procedure for the identification and quantification of antioxidant-related leachables from polymer knee implants that are given gamma ray treatment.”
About additives and general conditions
The tibia knee inserts tested by Vas et al. are made from polyethylene with an ultrahigh molecular weight (UHMWPE), which is cross-linked and sterilised with a very high dosage of gamma rays after the forming process. While the mechanical properties of the plastic are improved by the cross-linking, free radicals – i.e. extremely reactive compounds that damage cells – can be formed in the course of this process that attack the material and reduce its long-term chemical and mechanical stability. In order to prevent an oxidation process in the plastic and to improve product stability, an antioxidant – for example pentaerythritol-tetrakis [3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate](PBHP) – is added to the polymer. The purpose of the PBHP is to remove the free radicals that form, to prevent oxidation reactions in the plastic and to improve the long-term stability of the product.
Synthetic material also plays a vital role with sick arteries that cannot be treated with a stent. A sick section of the aorta is removed and the gap is closed with the help of a flexible plastic prosthesis. The main artery of the body is fully functional again. (Photo: istockphoto)
It’s not all sunshine ...
PBHP itself can be subject to a degradation process, however, in the course of which products from the implant can migrate into the surrounding tissue. The scientists stress that it is absolutely essential to identify and determine such PBHP degradation or by-products – a total of 16 have been detected – in simulated in-vivo experiments in knee implants, the useful life of which is estimated to be between 10 and 30 years.
However, large-format products, i.e. implants in this particular case, require large volumes of biologically relevant and thus aqueous media to carry out tests for leachables, in order in the final analysis to obtain solutions that contain the targeted components in very low concentrations. Vas and his colleagues write that the analytes need to be concentrated to enable quantification in accordance with the PQRI specification. They point out in an aside that sample preparation in this context is carried out by conventional means, is time-consuming and is both economically and environmentally dubious in view of the large amounts of organic solvents needed.
Quantification of leachables requires an enrichment operation, due to the low content of extractable substances in the aqueous medium. An obvious solution would be to evaporate the solvent, which might – however – lead to the loss of volatile components and the formation of contaminants. In addition to this, the aqueous extracts that are used to simulate in-vivo systems in studies of leachables are hardly if at all GC/MS-compatible, which at the end of the day means that a second extraction operation with an apolar, GC-compatible solvent would be necessary.
People with severe hearing problems can be fitted nowadays with a plastic implant that restores their hearing. This implant consists of numerous components – a microphone, a transmission device that is connected to a microcomputer worn on the body, a stimulator and an electrode array with 16 electrodes for 16 different frequency ranges. Since it converts the acoustic impulses into electrical impulses, it avoids the damaged cells and stimulates the vestibulocochlear nerve directly. (Photo: istockphoto)
All’s well that ends well
In order to meet the complex analytical challenges, Vas et al. chose and validated stir bar sorptive extraction (SBSE) with a patented extraction medium jacketed with polydimethylsiloxane (PDMS) and subsequent GC-MS/MS analysis for their project, following appropriate comparison of the methods available.
In contrast to other extraction techniques, SBSE enables the leachable substances to be extracted and concentrated in a single operation – without further extensive sample preparation before GC/MS analysis. The twister is also said to have a much higher PDMS / sorbent content than solid phase micro extraction (SPME): the research scientists conclude that “on a case-by-case basis, SBSE is significantly more sensitive at detecting organic compounds in aqueous matrices than SPME”.
With their work, Gyorgy Vas and his colleagues have closed a major gap in the quality assurance of implants and prostheses that contain polymers. With the help of the analytical method they have developed and validated, they have succeeded in determining traces (< 150 ng/day) of leachable components in medical implants. The method is said to be specific for the PHBP degradation products identified, sensitive and precise. The SBSE GC-MS/MS method was applied to eleven tibia knee implants of different sizes, that were extracted in their entirety rather than only in fragments after manipulation, as is frequently standard procedure. The scientists also emphasise that “most of the sample preparation is automated or requires only minimal manual work”. No solvents that are aggressive or harmful to health are used for extraction purposes, which – it is claimed – also lowers the demands made on the operating environment and thus the laboratory personnel while delivering impressive added value.
By the way: If you want to learn more about plastics and polymere on medical engineering please visit COMPAMED and MEDICA and enjoy.
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