Due to inherent low toxicity, pure silicones present a low risk for unfavorable biological reactions and have gained wide industrial and medical recognition and acceptance. There are several basic manufacturers of silicones suitable for use in health care applications; General Electric, Wacker, Bayer, Dow Corning, Rhone Poulenc, Shin Etsu, Nusil Technologies and Applied Silicone Corporation.

The primary difference between suppliers is the level of testing and commitment to serving a particular application.  Historically, most large silicone manufacturers have chosen to aggressively exclude themselves from uses of silicone in the human body for over 30 days due to the potential liabilities.  To my knowledge only two suppliers are willing to continue serving the long term implantable silicone market; Nusil Technologies and Applied Silicone Corporation.

When referring to silicones, the industry often uses terms such as "Industrial Grade", "Medical Grade", "Health Care Grade" and even "Implant Grade" which are not universally accepted and typically depend on a particular supplier's definition.  When using these terms, be sure that the context matches the intent of the supplier.  There are four levels of testing which are often recognized in the medical products business:

1.  "Food Grade" which is defined under CFR 177.2710.  This calls out a list of approved generic ingredients and additives and some test methods to evaluate candidate materials.  "Food Grade", while it has in the past given a level of security in the medical products business, is currently not widely used or accepted to assess silicones for medical application.

2.  "USP Class 6" is a battery of biological tests defined in USP XXII, Part 88, which was primarily designed for evaluating  plastics used in packaging drugs.  Any "Food Grade" material, which means most silicones, which will pass this test series can be called " USP Class 6".  It is a four part evaluation involving animal (rat and rabbit)  testing extracts of saline, cottonseed oil and alcohol along with a 5 day rabbit intramuscular implantation test.  While this level of testing is widely used and accepted in the medical products business, the meaning of the results and the level of safety assurance for medical devices is limited.  For instance, it would be possible to pass USP Class 6 while still showing up as cytotoxic, mutagenic, hemolytic or sensitizing in other biological testing.

3.  The next level of testing is sometimes called "Medical Grade" as defined by Dow Corning and is based on widely accepted industry practice.  In addition to performing USP Class 5 biological testing, tissue cell culture testing and a 90 day rabbit intramuscular implantation test with histopathology are performed.  Additional tests sometimes include skin sensitization, pyrogenicity, and hemolysis.  What is not obvious, but clearly true, is that Dow Corning performed a host of other mechanical, chemical, animal, biochemical, cell culture tests and clinical evaluations to create the data base for determining that their silicone formulations were safe for human implantation and that the tests listed were just confirmatory and not intended to be a universally accepted criterion to be used by any other vendor of silicones or other biomaterials.

4.  The next level of accepted testing, sometimes called "Dow Corning Medical Grade Equivalent", was created by the Silicone Task Force which was created in 1992 by HIMA with the co-operation and participation of the FDA which wanted to make sure that a continuing supply of implantable silicones was available after Dow Corning announced they were withdrawing these materials from general distribution effective March, 1993.  The objective of the Silicone Task Force was to create a data base on silicones which were "not substantially different" from Dow Corning medical silicones which are widely recognized as biocompatable and were the predominant implantable silicones.  The Guidelines were published by the FDA as a supplement to the Federal Register, Volume 58, N. 127 published in July, 1993.  The required testing is very extensive and requires special equipment and training.  A copy of the results of a typical test summary comparing a Dow Corning Medical Grade 50 Durometer Silicone to an Applied Silicone 50 Durometer alternative is shown below.  The test methods, test results and other information has been assembled into Master Files by the raw material manufacturers and filed with the FDA.  By authorization of the raw material supplier, device manufacturers can reference this data to support the safety and efficacy of their products.

FDA Material Master Files have been around for a long time and many suppliers of health care silicones have provided such files to the FDA.  The difference between most material master files and those that comply with the May 1993 Guidelines is that the files are in a format that is almost universally acceptable for all silicone devices submitted to the FDA.  The FDA can be accurately quoted as saying "we only want to look at the data once."  Thus, device manufacturers do not have to repeat expensive and time consuming preclinical physical, chemical and  biocompatability testing and can concentrate on device design and performance.   Preclinical testing of the chemical and toxilogical properties will only address the biocompatability of a silicone material. When selecting or changing vendors of an implant quality silicone,  the device manufacturer must carefully evaluate the required clinical performance of the completed device.

The latest FDA endorsed level of testing was published in May 1995 and is often called the "Blue Book Memorandum" and is based on ISO 10993 Part 1 "Biological Evaluation of Medical Devices".  The Blue Book Memorandum covers a variety of biomaterials from IV tubing sets to dental cements to long term implantable devices made of metals, ceramics, plastics and elastomers.  This testing guide replaced the "Tripartite Guidance" which was a sometimes confusing and often misinterpreted document.  ISO 10993 allows a multidisciplined approach to materials qualification.  Where extensive valid scientific data and clinical experience has clearly established the suitability of a material, such as pure silicone compounds, for medical devices, some tests can be avoided.  A typical cancer/long term toxicity takes four years and $250,000 to complete and should not be entered into lightly.  A reputable toxicologist should be consulted and can often demonstrate safety for a given application from an existing data base.  Often, the required testing can be accessed through the raw material supplier's Material Master File.

When evaluating what level of testing is needed, you must consider:

1.  Will this device reside in the human body over 30 days?
2.  What FDA regulations apply?
3.  What qualification testing and lot to lot testing is needed by the user and the FDA?
4.  What testing is available from the raw material supplier and what testing must the device manufacturer generate?
5.  What will the qualification cost?
6.  How long will it take?

When selecting a supplier for a health care application, there are several aspects to consider:

1.  Is the vendor willing to serve the market application?
2.  Does the vendor have required the staff and facilities?
3.  Does the Vendor understand and follow Good Manufacturing Procedures as defined by CFR 21.820.
4.  Does the Vendor have an adequate Quality System such as ISO 9000?
5.  Is the vendor willing to formulate a product to meet your physical and processing requirements?
6.  Is the vendor willing and able to provide the information required to perform the qualification testing and evaluation?

If the answers to these questions are not clear, find a consultant with direct experience in qualifying materials for medical devices.  Poorly qualified consultants can cause unnecessary delays and expenses so check references and monitor performance carefully.  When in doubt ask for a second opinion.  Often competent advise can be obtained from the raw material supplier or biological test laboratories at minimal cost.  A new resource is also available.  At the HIMA Device Workshop in July 1995, Dr. Bruce Burlington and his reorganized FDA staff also demonstrated both the commitment and ability to support medical device manufacturers.  Do not burden the FDA or your company with unnecessary or redundant testing.

In conclusion, I would like to reiterate a point made by President Clinton after the Oklahoma City tragedy when he said we must speak out against the "purveyor's of paranoia".  The implantable silicone business, and particularly Dow Corning, has been subjected to the vicious and unfounded criticism by the legal community.  It is highly unlikely that hundreds of scientists working over a period of 50 years have overlooked obvious problems with silicones.  I have had the honor of working with the best and most conscientious professionals from Dow Corning and the medical device industry for over twenty years.  As additional valid science becomes available, the alleged silicone-autoimmune disease connection has been found to be as real as cold fusion.  Recent reports from the Journal of Epidemiology, National Cancer Institute, New England Journal of Medicine and British Institute of Health (Ref.1,2,3,4) confirm that properly formulated silicones are among the most biocompatible materials available.

References:

1. Medical Device Directorate, Number 92/42, February 1993
2. New England Journal of Medicine, Volume 330, Number 24, June 16, 1994
3. Silicones in the System, Discovery, December 1995
4. Statement of the American College of Hematology, October 22, 1995

About the author:  Alastair Winn received a Bachelors Degree in Biochemistry and Molecular Biology from the University of California at Santa Barbara, California in 1973.  He was employed as a materials scientist at the Heyer-Schulte Division of American Hospital Supply, a world leader in implantable silicone medical devices, from 1974 to 1980 and has been in the business of manufacturing silicone for medical device manufacturers since 1980.  He is president of Applied Silicone Corporation and has been an active member of the HIMA Silicone Task Force and ASTM F04.