Medical Device Cleaning Validation

A medical device manufacturer produces medical devices for implants. Since these implants are for internal use in humans, it is essential for the devices to be devoid of any contaminants. The fluids and oils used in the cutting of the material as well as the cleaning of the finished devices could leave residues. These residues could be potentially cytotoxic and harmful, or hinder efficient integration of the device into the body.

One Eighty was contracted to carry out the necessary tests to validate the cleaning methods of the medical device manufacturer.

INVESTIGATION

As described in the standard ASTM F3127-16, “specific analytical methods” was employed to measure the presence of specific residues. MSDS certificates were provided for the compounds and thus specific residues could be tested for. Sampling methodology of the residues is critical to avoid contamination and to ensure the tests results are representative. Rinse sampling with agitation or sonication with an appropriate solvent in sterile sample bottles was used.

Table 1: Specific residues to test for with the method that was employed

 

GC-MS

GC-MS uses polarity to separate mixtures into their different components (in the GC column) and then analyses each fraction with MS. MS  is an analytical technique that ionizes chemical species and sorts the ions into a spectrum based on their mass-to-charge ratio. The atoms or molecules in the sample can be identified by correlating known masses (e.g. an entire molecule) to the identified masses or through a characteristic fragmentation pattern.

The samples were immersed in sterile containers in three different samples, namely chloroform, ethanol and hexane and sonicated for an hour. The solvents were then injected into the GC for analysis. The compounds used for manufacturing the implants were also dissolved in these solvents, filtered and analysed.

Instrument: Agilent 6890N Gas Chromatography–5973 MSD MS Detector System.

ICP

ICP (Inductively Coupled Plasma) Spectroscopy is an analytical method used to detect and measure elements in order to analyse the chemical composition of samples.  The process is based on the ionization of a sample by an extremely hot plasma, usually made from argon gas.  The sample ions are then evaluated using a spectroscopy instrument. Before analysis samples are filtered using a 1.2 μm filter. Silicon, aluminium and boron were the target analytes based on the information in Table 1. The filter paper was taken for SEM-EDS analysis.

SEM-EDS

Energy Dispersive X-Ray Spectroscopy (EDS or EDX) is a chemical microanalysis technique used in conjunction with scanning electron microscopy (SEM).  The EDS technique detects x-rays emitted from the sample during bombardment by an electron beam to characterize the elemental composition of the analysed volume. These x-rays released from the surface of the sample carry a unique energy signature that are specific to elements found in the sample.

FTIR

FTIR spectroscopy (Fourier Transform Infrared Spectroscopy) is a technique that uses infrared light to observe properties of a solid or liquid.  It is used in many different applications to measure the absorption, emission, and photo-conductivity of matter by shining a narrow beam of infrared light at the matter in various wavelengths and detecting how the different wavelengths are absorbed or transmitted. This response corresponds to the types of bonds and functional groups present.  Once the data has been obtained, it is converted into digital information using a mathematical algorithm known as the “Fourier transform” and is used in conjunction with other techniques to identify compounds.

The sample preparation of the medical implants was as follows: The implants were immersed in ethanol and sonicated for 5 minutes. The samples were left immersed for a further 30 minutes and sonicated again for 5 minutes. The liquid samples were then tested with ATR-FTIR. An ATR attachment was used with the FTIR instrument. The FTIR test method was as follows: The FTIR was blanked to the atmospheric air. A droplet of the samples was placed over the crystal block. The volatile solution was then allowed evaporated and the thin film left behind was analysed.

A series of dilutions of the two reference samples (Biokool and Tapmatic) was analysed to determine the limit of the detection of the FTIR for each solution.

RESULTS

GC-MS

The reference samples of Biokool, Tapmatic and Polishing compound were used as comparison compounds. The uncleaned implant sample solution of hexane showed no significant peaks and neither did the chloroform, hexane or ethanol solution used to wash the cleaned implants. This is shown below in Figures 1-4 by the flat line with some displaying solvent peaks. This indicates that no organic compounds were left after the initial manufacturing as well as after the cleaning process. The limit of detection was measured to be approximately 2ppm (50 x dilution of Tapmatic). This indicates that none of the organic residues are present above 2ppm even on the “uncleaned” reference sample.

Figure 1: Overlaid chromatograms of the uncleaned reference sample and sample 3 (in hexane) with hexane peak at 8.06 minutes

Figure 2: Overlaid chromatograms of the Biokool sample and sample 1 (in ethanol)

Figure 3: Overlaid chromatograms of the Polishing powder sample and sample 2 (in chloroform)

Figure 4: Overlaid chromatograms of the Tapmatic sample and sample 3 (in hexane)

 

ICP

The ICP results are shown in Table 2 where the silicon value differs between the cleaned and uncleaned sample. The cleaning method was effective enough to remove silicon residues.

The other elemental residues were not detected for both the uncleaned and cleaned sample. This may be due to reasons: the limit of detection does not allow for the very dilute concentrations to be detected or those residues did not stay on the implant even without cleaning.

Table 2: ICP results

SEM-EDS

SEM-EDS did not yield any valuable information because the quantities were so small, and it is suspected that contamination resulted in no significant difference. There was a difference in the visual observation of the filtrates and filter paper.

 

FTIR

FTIR LOD (limit of detection) for Biokool and Tapmatic was found to be 10 ppm for both. The spectra for the cleaned and uncleaned sample solutions are compared in  Figure 5.  There is obvious residue present in the uncleaned sample while the cleaned sample shows no peaks. It can be said that no residue above 10 ppm is present on the cleaned sample according to these results. Visible residues on the uncleaned sample could be observed before washing.

Figure 5: Uncleaned sample solution versus cleaned sample solution.

 

Figure 6 shows the spectra of the uncleaned and cleaned sample solutions relative to concentrations of Biokool and Tapmatic that appear similar to that of the uncleaned sample. The residue is estimated to be between 10 000 and 100 000 ppm.

Figure 6: Cleaned and uncleaned sample solutions compared to the Biokool and Tapmatic dilutions that fits the intensity of the uncleaned peaks.