Session 3: Cleaning and Testing Part 2

Cleaning and Testing for Debris in Reusable Medical Devices

Shani Haugen, Vicki Hitchins, FDA, Silver Springs, MD

Residual organic material in reusable medical devices impedes proper sterilization, which can lead to outbreaks of infections. Thus, proper cleaning is an important first step in preparing a used reusable medical device for clinical use on the next patient. In the past, «visibly clean» was an acceptable endpoint for determining if a device was clean and ready for disinfection/sterilization. However, complex devices that have features such as narrow lumens, stopcocks, sheaths, acute angles, joints, or hinges are becoming increasingly common.  Such design features are not readily visualized by the naked eye; therefore, «visibly clean» is no longer an acceptable endpoint for «clean». Currently, there are several methods to detect residual debris on and within devices, however these methods are not optimized to detect insoluble clinical debris, such as tissue, cartilage, or bone. Unless the debris is completely digested or solubilized, such material may not be adequately sampled, and/or may not be accurately measured in a «cleaned» device.

To quantify insoluble debris, we have developed a filter-weighing approach to assess total residual debris in models of complex devices and actual medical devices. Briefly, after the device or model is inoculated with test soil and cleaned, the device is immersed in filtered water and agitated for two hours to extract debris. The extraction liquid is then filtered, and total debris on the filter is assessed. This method is simple, sensitive, and requires few pieces of specialized equipment. In some instances, the amount of protein in the extraction liquid was below the level of detection by the Bradford assay, however the filter-weighing approach was able to detect total debris (>100 micrograms). Additionally, the filtrate can be saved to assay for the presence of soluble protein, total organic carbon, etc. This method is flexible, and can be used with different devices, with different types of test soil, by manufacturers performing cleaning validation, or users who seek occasional verification of device cleanliness. Future experiments will use this assay to assess the impact of device design on retention of organic material in reusable medical devices.

Evaluation of the Cleaning Efficiency of a Aqueous Based Detergent System for Cleaning Metallic Medical Devices

B. Dhanapal¹,  N. Weiler¹ and J. Rufner², ¹Zimmer GmbH, Switzerland, ²Zimmer Inc, Warsaw, USA

Introduction

Cleaning orthopaedic implant devices commonly involves aqueous detergent based processes. The detergent solutions may be acidic, alkaline or neutral and ultrasonics may also be utilized. In this example system a series of baths using different detergents combination with sonication was used to evaluate the cleaning effectiveness for 100% metallic medical devices. Detergents of both alkaline and acidic nature were used for the removal of auxiliary processing materials used in the different manufacturing steps from the raw material to the final product (such as grinding, blasting, machining and others).  This system utilized five consecutive baths. The first two baths contained alkaline detergents at different concentrations; the fourth bath was an acidic detergent. The third and fifth baths were rinse baths containing highly purified water to minimize the carry-over of the detergents to subsequent baths. The concentration of the detergents were monitored and closely controlled in order to insure the removal of auxiliary materials and the chemical cleanliness of the device. Periodic adjustment of the detergent concentrations was necessary to ensure optimum concentration and cleaning potential at all times within the life cycle of the detergent baths.

Monitoring Approach

According to literature published by the supplier of the detergents, the respective detergent concentrations could be determined by performing an acidimetric titration of the solution. An empirical factor is provided by the manufacturer to calculate the detergent concentration (v/v %) from the volume of Hydrochloric Acid or Sodium Hydroxide used in the titration.  The weekly monitoring activities of the cleaning system were as follows:

• Sampling of baths No. 1, 2 and 4
• Acidimetric titration (colorimetric)
• Calculation of the difference between the current (measured) detergent concentration and the target concentration
• Based on the measured detergent concentration, addition of detergent as necessary to achieve the target concentration

The detergent baths are analyzed twice a week with regard to detergent concentration by acidimetric titration (direct monitoring). A calibrated automatic titrator was used (potentiometric titration) because this offered a higher accuracy and precision than visual titration techniques. After three full weeks of use, the detergent baths were completely renewed. This period defines the life cycle of the detergent baths.

The test parts were assayed for Carbon Tetrachloride (CCl₄) extractable residues by FTIR, water extractable residues by Total Organic Carbon (TOC), and for water extractable insoluble particulate matter gravimetrically.

Evaluation of the Cleaning Efficiency

In order for this defined detergent bath life cycle to be validated, the product cleanliness was used to define the acceptance criteria. It was analyzed for pre-defined worst-case conditions in the cleaning system.  Worst-case scenarios were defined by taking into account such things as: devices which possessed the most challenging size, surface texture, geometry etc, longest time period from bath renewal as well as from the detergent replenishment, and washing programs with the shortest dwell times, lowest ultrasonic power and lowest temperatures. After washing, the parts were removed from the system and analyzed using analytical methods.

Results

Three different worst-case devices were subjected to chemical cleanliness analyses (see Table 1).The following results wereobtained:

Table 1: Average Results: Total Organic Carbon (TOC),

Organic Residual, Ionic Residual, Particulate Residual

Total of 135 specimens were analyzed in the scope of this cleaning validation.

Discussion

During the direct monitoring of the detergent concentrations using potentiometric titrations, a significant drop in detergent concentration of up to 20 %(v/v) within a week was observed. Thus, the detergents were replenished twice a week to keep the concentrations within the specified limits. Using these standardized cleaning processes enabled us to obtain clean products in a reproducible and repeatable manner.

Conclusions

From the results shown in Table 1 for the predefined worst-case parts and worst-case conditions in terms of cleaning parameters, it is clear the system and operational parameters described were able to produce parts with very small amounts of chemical residuals.

Two-phase Flow Cleaning of Endoscope Channels

Mohamed E. Labib¹, Stanislav Dukhin¹, Joseph Murawski¹, Yacoob Tabani¹, Richard Lai¹ and Michelle Alfa²

¹Novaflux Technologies, Princeton, NJ 08540, USA, ²St. Boniface General Hospital, Winnipeg, MB R2H 2A6, Canada

Cleaning of flexible endoscopes has been traditionally done by flowing a cleaning liquid through endoscope channels. Because of the small diameter of the narrow lumens of flexible endoscopes, the magnitude of bulk shear created during liquid flow is low and the cleaning efficiency is usually limited. This is why manual cleaning is recommended before processing the endoscope in conventional AERs.

During our investigation of two-phase flow in hydrophobic narrow channels, we discovered a new hydrodynamic mode that can create shear stress orders of magnitude higher than the bulk shear generated by conventional liquid flow. This hydrodynamic mode was investigated in long Teflon tubes (about 200 cm) and in endoscopes, in the range of Reynolds number 6,000 to 30,000 at different water/air volumetric ratios (WAVR). High-speed video-microscopy techniques have allowed us to visualize a new mechanism of flow instabilities in endoscope channels. We were able to compare the cleaning of such channels with the two-phase flow and with conventional liquid flow.

We will review and analyze the fundamentals of cleaning long and narrow lumens with emphasis on flexible endoscopes. We will also discuss critical issues involved in removing macromolecules such as proteins and adhering organisms from the surface of endoscope channels. We will place emphasis on the novel two-phase flow process.

Assessment of Organic Residues on Medical Devices

B. Dhanapal¹, D. Zurbrügg,², J. Rufner³, R. Gsell⁴,

¹ Zimmer GmbH, Switzerland, ² Niutec AG, Switzerland, ³ Zimmer Inc, Warsaw, IN, USA,

Introduction

Although governmental agencies currently have not set limit values for residues on orthopaedic implant devices, it is the manufacturer’s responsibility to provide clean, safe and effective products. They must develop appropriate test methods and specify acceptance criteria.  Currently ASTM F 2459–05¹ is the only standard published which was developed specifically for medical implant devices.  It is limited to metallic devices using gravimetric quantification. A second medical implant cleanliness guide is being developed under ASTM WK15532². This guide describes a wide range of more specific and sensitive test methods for assessing implant cleanliness.

Methods

Fourier Transform Infrared spectroscopy (FTIR) method has been to quantify the amount of carbon tetrachloride (CCl₄) extractable residues on 100% metallic devices. The sum of organic residues is quantified against a calibration curve prepared using a hydrocarbon reference standard such as hexadecane.  Other reference materials, such as known manufacturing lubricants, may also be used. The FTIR technique is widely used for the quantification of organic residues in different fields like e.g. ASTM 1374-92(2005)³.

The test device is extracted with CCl₄ to dissolve the residues. The amount of organic material present in the resulting extract solution is then quantified (e.g., as mg equivalent of hexadecane per part) by measuring its maximum absorbance in the 2800-3000 cm^-1 region.  Using the appropriate calibration curve the absorbance readings are converted to extract solution concentrations and finally to mg/part readings.

Discussion

Based on our experience using ASTM F 2459–05¹ to quantify residuals gravimetrically the typical detection limit for soluble residues of 0.3 mg/part is more than a factor ten (0.02 mg/part) higher than the FTIR method describe here. Lower limit of detection (LOD) may be necessary to statistically assure a reliable assessment of the cleanliness of certain products. 

Using one or more of the specific methods proposed by WK15532² may be of benefit too.  For example, it may be possible to use techniques such as gas chromatography (GC) coupled with mass spectroscopy detection (MS), high-performance liquid chromatography (HPLC) coupled with such detector systems as MS, single or multi-channel or photo diode array ultraviolet (UV) detector systems or evaporative light scattering detection (ELSD). In some cases it is possible to not only quantify the total amount of extractable organic residue but to identify and quantify the specific components from specific lubricant and detergent systems used.

Based on our experience these techniques (e.g. ASTM F 2459–05¹ and FTIR) can also be applied to polymeric medical devices. However, one has to consider that the polymer itself might release materials which are by definition not residues. Such materials that are already present in the raw material must be considered when setting the extraction and analytical parameters and their acceptance criteria.

Conclusion

Although ASTM F 2459–05¹ has made a significant contribution to the orthopaedic industry in regards to evaluating the cleanliness of 100% metallic medical devices, more standardization is needed in application of the many different techniques available to the analyst. Additionally, application of these techniques to the many different types of polymeric materials used by the industry presents another major challenge. To assure the safety of the medical devices, their cleanliness using sensitive methods as proposed here and by ASTM F 2459-05¹ WK15532² are necessary.

Reference

[1] ASTM F 2459–05 Standard Test Method for Residue from Metallic Medical Components and Quantifying via Gravimetric Analysis

[2] ASTM Work Item: WK15532 - New Practice for Reporting and Assessment of Residues on Single-Use Implants

[3] ASTM 1374-92(2005) Standard Test Method for Ionic/Organic Extractables of Internal Surfaces-IC/GC/FTIR for Gas Distribution System Components (Ultra-High-Purity Gas Distribution Systems)

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