The success of a medical device depends on both the details of its design and the proper selection of materials from which it is fabricated, taking in to account its final use and regulatory requirements. Success also depends on how it is manufactured, and a critical feature of medical device manufacturing is ensuring a suitably clean product. Cleaning is almost always performed in the final stages of manufacturing, but some manufacturing processes may include intermediate cleaning steps.
To ensure that the cleaning process is doing its job, manufacturers will perform cleanliness measurements on their devices to determine how much manufacturing residue remains on the part, and the nature of that manufacturing residue. Simply quantifying the presence of residues is not sufficient however, because this does not account for how sensitive the design is to that residue. For example, residual sodium chloride may be acceptable at gram quantities, whereas arsenic may not be acceptable at any level. A critical step in clean-line validation that is often missed is therefore to assess what is an allowable amount of residue while still ensuring a good clinical outcome of the device. Often this involves are considered cost-benefit analysis between the effort to clean, and the risk associated with that residue.
Cleanliness measurements are either performed by removing the residue from the part and quantifying the residue with various analytical assays, or by measuring the residue in situ on the part. The latter technique is less suitable for quantification measurements, but is useful for identifying where on the part the residue is residing, which may assist in modifying either the cleaning process or the part design. Cleanliness measurements include residue weighing, FTIR, GC and LC/MS, ICP, UV-Vis, and SEM-EDS to quantify and identify sources of residue.
To assess what levels of residues may remain on the part without impacting the clinical performance, manufacturers often look at devices on the market already in the same application area with good clinical history, and measure their residue levels. These levels can serve as guidance for establishing acceptable manufacturing residues. Alternatively, toxicological studies can be carried out, or some animal studies.
The manufacturers clean-line can then be validated using the cleaning assays discussed above, along with the allowable residue levels the manufacturer previously determined. To validate a clean-line, a representative number of devices are tested under normal operating conditions as well as the extremes of the operating conditions, to see if the process is in control.
ASTM offers several standards for testing the cleanliness of medical devices, and new standards are being developed for clean-line validation and establishing allowable residue levels. Cambridge Polymer Group performs these standards for clients, and assists with clean-line validation.
Case studies on medical device cleanliness can be found here.
Car owners are advised to change their engine oil every 3000-5000 miles. But what is actually happening to the oil over time in the engine? We have heard about the benefits of antioxidants in the body. Antioxidants also help engine oil. In use, engine oil is subjected to high temperatures and high shear stresses which can act to break apart the oil molecules, affecting its viscosity and performance. This chemical reaction occurs through the generation of free radicals, or unpaired electrons on the oil molecules. By monitoring the free radical content, it is possible to monitor the change in the oil.
CPG used electron spin resonance spectroscopy to monitor the change in oil in a 6 cylinder gasoline engine, taking samples every 500-1300 miles. Free radical production started around 400 miles, and changed as the free radicals were either stabilized by the antioxidant package in the oil, or reacted to form other radical species. This method is useful for monitoring the chemical changes in the oil, and to see the efficacy of the additives package.
Princeton scientists Alban Sauret, Francois Boulonge, Emilie Dressaire, and Howard Stone have applied fluid dynamics and rheology to help long-suffering beer drinkers understand why beer with a head of foam are less likely to slosh and spill compared to their counterparts with less foam. Simple experiments, like the images shown above, indicate that reducing the thickness of the head of foam increases the sloshing potential when the glass is agitated. Stone and colleagues modeled this behavior, and demonstrated that the foam in beer dampens the sloshing effect of the beer through viscous dissipation. The viscous force scales with the Capillary number, which relates the relative contributions of surface tension and viscosity. The viscosity of the foam is related to the velocity of the bubbles in the foam. The foam dissipates the energy of sloshing to the walls of the glass. Stone and colleagues suggest this is why it is easier to carry a glass of beer versus a cup of coffee without sloshing, although the study would suggest that cappuccinos may be recommended for those on the go.
In the design of a new device, a good manufacturer will follow quality management principles to ensure the device meets the requirements of the end-user. What does this have to do with Swedish warships? History can provide us with useful lessons on quality management systems. The Vasa was a warship built in 1626 that holds the unfortunate reputation of sinking on her maiden voyage after sailing less than a mile. From a modern perspective, the construction and launch of the Vasa suffered from one primary problem. The lack of a quality management system during her design meant that a good design team was not assembled and new design concepts were not adequately tested and verified during construction. As a result, design changes were instituted “on the fly” after the nominal design freeze, and contradicting results from final verification tests were ignored, or never reached the right people. As a consequence, she was unable to meet the specifications required to be sea-worthy, and sank quickly when a gust of wind hit her when leaving Stockholm’s harbor an incorrect weight balance resulting from overly complex superstructure. An adequate quality management system might have provided the checks and balances and gating necessary to any good design process, perhaps avoiding her sinking.
As an aside of a more polymeric nature, she was raised piece by piece from the sea floor in 1961, and currently sits in a museum in Stockholm, where she is in surprisingly good shape. She is being impregnated with polyethylene glycol as a preservative, although recent studies are suggesting that PEG application to wood in an acidic environment (the Vasa was in acidic water for centuries) will form formic acid, which could damage the wood.
Plastic components subjected to cyclical loading cycles during their use can sometimes failure through fatigue crack formation. A plastic that shows good toughness in static testing may have brittle behavior when exposed to millions of fatigue cycles, particularly in parts with a sharp notch. Fatigue crack propagation testing helps to determine if a material is resistant to crack formation, and to compare different formulations of materials.
ASTM E647 describes the general protocol for fatigue crack propagation testing in materials using a pre-notched compact tensile specimen. The test requires simultaneous measurements of crack propagation after the application of tensile fatigue cycles. CPG engineers have developed an automated optical system that captures thousands of images of the propagating crack during the fatigue experiment from a dual camera system. The accompanying analysis software then determines the crack length in each image, outputting the da/dN vs. DK curve described in ASTM E647. The system provides a high density of data, in full compliance with E647, with greatly reduced labor.
More information on the system can be found here.
Contact CPG for more information on this system, which is available for purchase.
Many drugs used for the induction and maintenance of general anesthesia are volatile organic compounds that are delivered to the patient via inhalation. The low boiling point and high volatility of these compounds make them ideally suited for analysis by gas chromatography with mass spectroscopy (for example, as part of an in-process or QC check for material purity). Unfortunately, most commonly employed chromatographic methods are often unable to detect the presence of trace impurities due to limited instrument sensitivity. However, often the manufacturer is aware of the potential impurities or contaminants that may be present in a given anesthetic agent, and in such cases a targeted GC-MS method may be developed which maximizes sensitivity to these compounds. Cambridge Polymer Group has developed such chromatographic methods that can detect and quantify suspected anesthesia contaminants at levels in the parts per billion range.
Contact us for more information on this technique.
Two articles recently appeared in Qmed that discuss medical device cleanliness. The first discusses the effects of cleanliness on the application of coatings on guidewires. Guidewires are used to help steer catheters and other cardiovascular equipment through blood vessels. PTFE is often applied to improve lubricity of the guidewires. When problematic flaking of the PTFE from guidewires was observed, Surface Solutions modified their cleaning process to help adhesion. Even contamination on the atomic level can interfere with adhesion of the PTFE, resulting in the need for ultraclean processing conditions.
The second article mentions the Sulzer InterOp recall, which was previously discussed in this blog. The article discusses manufacturing decisions in medical devices, including cleaning and sterilization, and how the materials used in the device need to be considered when selecting a sterilization modality.
Manufacturers of medical devices and food products will often use packaging with a reduced oxygen level in the region of the product to minimize oxidation of the product and increase shelf-life. Inert gas, such as nitrogen or argon, may be flushed through the packaging, or vacuum may be pulled on the packaging.
Alternatively, an iron-based oxygen scavenger can be placed in the packaging. The packaging often uses a barrier film to inhibit the diffusion of oxygen through the packaging. This film is often a composite structure of multiple layers of plastics and metals.
Determination of the oxygen level in the packaging is a useful way to determine the efficacy of the
packaging process, and to monitor the packaging integrity over time. CPG has developed a technique to quantify the oxygen content in packaged components down to oxygen concentrations in the parts per million. This technique is discussed in this application note.
Some of the staff at Cambridge Polymer Group and their spouses participated in Boston’s annual Hub on Wheels, a 50 mile bike ride that winds through the Boston and its surrounding communities. The ride raises money for the Special Olympics, the Boston Parks and Recreation Fund, and Boston Bikes, an organization set up to encourage cycling in Boston.
An article recently appeared that discuss the use of extensional rheometry to characterize natural polymer systems. The study, published in Food Hydrocolloids by Choi and co-workers, considers the effect of saliva on food products thickened with either xantham gum or carboxymethyl cellulose. These authors used a CaBER extensional rheometer, developed by Cambridge Polymer Group, to demonstrate that filament breakup kinetics of xantham gum is greatly influenced by the presence of saliva, whereas carboxymethyl cellulose is not as affected.
The significance of this study relates to the concept of psychorheology, or how our perception of a product can be influenced by its rheology. In the present study, the extensional viscosity can influence our perception of taste and flavor, as well as general mouth feel, when the xantham gum’s viscosity is modified by the presence of saliva.
