The Importance of USP Class VI Testing

The United States Pharmacopeia (USP) group is a non-government, non-profit organization that sets the standards for the production of drugs (for both humans and animals), food ingredients, and dietary supplements. The USP organization typically is concerned with and sets the standards for purity, quality, strength, and consistency in biotechnology and pharmaceutical endeavors.

The standards set by the USP group are published in the USP-NF, a combined effort by the two compendia. The National Formulary (NF) is a list of formulas for preparations of commonly used pharmaceutical drugs within the United States. The USP-NF contains the standards for medicines, dosage forms, drug substances, excipients, biologics, compounded preparations, medical devices, dietary supplements, and other therapeutics. These standards are enforceable by the United States Foods and Drug Administration (USFDA).

The USP has six different classes of standards for plastics to test the biological reactivity of various types of plastic materials in vivo, or inside the body. These classes are used to certify materials with Class I being the simplest certification, and Class VI being the most rigorous and frequently requested certification.

The 3 biocompatibility tests

The tests required to pass a USP Class should help to determine how biocompatible the material will be. The aforementioned tests include a systemic injection test, an intracutaneous test, and the implantation test. The systemic injection and intracutaneous test will be able to determine the systemic and biological responses by the single injection of the sample material, while the implantation test will be able to determine the response of living tissue to the sample material.

The first test, the systemic injection test, is used to study any acute toxicity of the sample material. To determine acute toxicity, extracts from an alcohol saline solution, polyethylene glycol solution, 0.9% sodium chloride solution, and sesame oil are used as the control injection. The variable injection uses the same extraction solutions that are exposed to the sample material. All extraction solutions are injected into mice and then studied for behavioral changes and weight changes over the course of three days.

The second test, the intracutaneous test, uses the same extraction solutions as Test 1 but instead is looking for visual impacts to the injection site. All the extractions are injected into the skin of a rabbit along its spinal column and monitored for 72 hours looking for signs of erythema (reddening of the skin) and edema (swelling). To pass this portion of the test, the injection sites are graded on a scale of 0 (no sign of reddening or swelling) to 4 (severe reddening or swelling) and must achieve a score of 1 or lower on both tests.

The final test is a muscle implantation test to determine any reaction of living tissue to a test material. Control samples of high-density polyethylene rods as well as rods of the sample material are surgically implanted into a rabbit’s muscle tissue and then monitored for seven days. After the week, the rabbit is euthanized and the implantation sites are investigated looking for signs of tissue damage such as hemorrhages, necrosis, discoloration, and/or infection. If the implantation site shows no sign of damage, the sample material is considered to have passed this test.

Class VI testing extends beyond plastics

This rigorous form of biological compatibility testing helps to keep in-vivo parts and other biotechnology safe for human and animal use. While this test was originally designed for plastics, any material can be subject to USP Class VI certification.

For example, SilcoTek works with many pharmaceutical, medical device manufacturing, and medical packaging companies. The company takes customers' metal parts and, using a high-temperature chemical vapor deposition (CVD) process, deposits an ultra-thin, amorphous silicon-based surface coating. Those who employ this service typically require a bioinert, low surface energy coating called Dursan that helps to impede protein adhesions and assist in corrosion protection. While those surface improvements are helpful in these industries, the coating technology would be useless without a USP Class VI certification.

SilcoTek was able to send their Dursan-coated samples to the US Pharmacopeia group’s appointed lab and have all three of the required tests performed using the sample materials, easily passing each of them. The Dursan coating process makes stainless steel surfaces inert to numerous chemicals as well as creates a non-stick surface for the release of proteins, plastics, and many other materials.

Manufacturers interested in learning more about USP Class VI testing can visit www.usp.org or reach out to the author of this article. For manufacturers interested in learning more about SilcoTek’s CVD coating technology: Please visit www.SilcoTek.com or contact the author directly at [email protected].