By Tina May and Brent Shelley, Nelson Laboratories
Standard sterility and biocompatibility tests are already an essential part of many manufacturers’ protocols. What may not be as commonly understood, however, are the different ways a product can be contaminated during production, packaging and even cleaning processes. To avoid detrimental contamination, manufacturers should test their devices for, what Nelson Laboratories calls, Residual Manufacturing Materials (RMM).
Contaminants, such as oils, lubricants, releasing agents and detergents, transferred to the product during the manufacturing or cleaning process are RMM. Device contamination can occur just about anywhere along the production process. Residues that remain on a product can potentially be cytotoxic and harmful.
Manufacturers can use RMM Analysis as a tool to monitor the cleanliness of production at any point, including the final product. Knowing how much residue is on a device or component allows for the establishment of effective cleaning procedures, which are crucial to the release of clean and safe medical devices.
RMM Analysis uses three analytical methods to evaluate the different phases of manufacturing and cleaning: gravimetric analysis, Total Organic Carbon (TOC) analysis, and detergent residual analysis by Ultraviolet/Visible (UV/VIS) Spectroscopy. All three tests are designed to remove surface contamination and are not intended to remove or assess leachable components from a device.
Quantification of Extractable Residue by Gravimetric Analysis ASTM F2459-05
Quantification of extractible residue by Gravimetric Analysis uses aqueous and non-aqueous solvents to extract contaminants such as oils, salts and other materials from the surface of medical devices. After the device is extracted, the solvent is evaporated and the remaining residuals are weighed and quantified. Gravimetric Analysis does not determine the specific elements making up the residue, but will measure the quantity of the total amount of residue coming off the device.
Total Organic Carbon Analysis
Total Organic Carbon (TOC) analysis is the most sensitive of the RMM series of tests. The analysis is quantitative and detects carbon-based materials on the product like oils, adhesives and detergents, but will not pick up inorganic residue such as metals and salts.
TOC analysis involves extracting devices in USP purified water by sonicating or shaking to remove surface contaminants. An aliquot of the extraction solvent is analyzed on a TOC instrument to determine how much organic carbon is on a device or component. Alternatively, the manufacturer can use swabs to evaluate clean-in-place components and equipment. After swabbing the targeted component, the swab is sent to the lab to be immersed in USP purified water and then analyzed.
Detergent Residual Analysis
Cleaning agents can leave behind potentially harmful residual material. Detergent Residual Analysis detects detergents by Ultraviolet/Visible (UV/VIS) Spectroscopy.
For this testing manufacturers must provide a full strength sample of detergent used in the cleaning process. Detergent residual analysis also uses water extraction and sonication to identify the detergent left on a device. The lab then compares device extracts to the detergents calibration curve for quantification.
There are no established regulatory limits of cleanliness for residual analysis. It is up to the manufacturer to perform a risk assessment to determine acceptable levels of residue based on the application and patient contact duration. It is the responsibility of the manufacturer to establish limits for the cleanliness and safety of its medical products.
Simply put, medical device manufacturers can save time and money down the road if they will have their devices analyzed for RMM. Doing so can streamline and enhance their process efficiency, ensure safety, and reduce product and regulatory liabilities. Each of which will help to keep manufacturing from halting when an issue or changes in the process arises.