An MD&DI February 1997 Column
When selecting materials, medical device manufacturers must perform biocompatibility tests, even if material suppliers claim their materials are biocompatible. Paul Sordellini, a consultant with Quality Solutions, Inc. (Annandale, NJ), and a member of the Ethylene Oxide Sterilization Association, explains why such tests are necessary.
Q. Our firm is developing a device, molded in-house, that will incorporate medical-grade polymers. The device, to be part of a more complex surgical kit, will be in contact with blood and compromised tissue. We have a certificate from each of the polymer suppliers attesting that the raw materials are medical grade and biocompatible. Do we need to perform any additional biocompatibility studies on the finished device?
Sordellini: During the design phase of device manufacturing, biocompatibility studies serve to eliminate materials that, when placed in a certain environment, such as in contact with blood, may produce an adverse biological response (e.g., releasing harmful substances into the blood or reacting with any blood component). Presently, the industry lacks a universally accepted definition of biocompatible.
As a result, certification by a raw material manufacturer or supplier should not be the sole criterion for the use of any material. Even those substances generally recognized as safe according to the list provided by 21 CFR 182 should not be automatically assumed to be safe without empirical confirmation by the device manufacturer.
As part of the design process, companies should perform a complete biocompatibility study on finished and sterilized device samples. Because a raw material may undergo chemical changes during manufacturing, the samples must be exactly what firms intend to market--not simulated product samples. Heat applied during molding can induce chemical mutations and toxic substances, or particulates may be deposited on the device during manufacturing.
In addition, biocompatibility studies on finished, sterile devices demonstrate that the sterilization process did not induce harmful bioincompatibility. For example, irradiation is the application of pure energy that can cause almost any material to react or cause two components within a device to react with each other. The high temperature of steam sterilization can also induce chemical reactions among some materials that, at normal ambient conditions, seem inert. Ethylene oxide, as well as other types of reactive gas sterilants, can alter bonds on a molecular level or react with the materials, producing harmful by-products.
Choosing materials that have already been determined by the supplier to be medical grade or biocompatible is a good starting place in the design of medical devices. But manufacturers are ultimately responsible for demonstrating the safety and efficacy of their devices (i.e., biocompatibility). Companies need to select and perform the biocompatibility studies most appropriate for their devices, based on the devices' components and their intended use.
For additional information, firms can refer to the following documents:
ISO 10993--Biological Evaluation of Medical Devices, Part I: Evaluation and Testing, Geneva, International Organization for Standardization, January 1994.
Park JJ, Biocompatibility of Medical Devices, Rockville, MD, FDA, Center for Devices and Radiological Health, April 15, 1993.
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