Polymers used for medical devices must meet regulatory requirements specific to the application and geographic region. Engineers and product designers should be aware of these regulations when specifying polymers for use in medical devices.
21 CFR Color Additives
Color additives include dyes and pigments derived from vegetables, animals, minerals or other sources that impart color to device. This includes black, white and intermediate grays. The United States Food, Drugs & Cosmetics (FD&C) Act limits applicability of color additives that directly contact the human body.
Title 21 of the United States Code of Federal Regulations (21 CFR) part 73 and 74 provides nine pigments that are recognized and approved for use in medical devices. Polymer formulations that use these pigments do not need to be batch certified if previously tested by the pigment manufacturer to FDA specifications. However, device manufacturers are still responsible for FDA submission and final product testing. Batch certification exemption only applies to the testing of the color additive ingredient.
21 CFR parts 174 through 179 refer to pigments that are approved for food packaging. Medical device manufacturers often utilize pigments listed in these sections when a specific color is desired that is not obtainable using pigments listed in 21 CFR 73 and 74. Use of these pigments often requires additional documentation and testing for regulatory approval of a device.
Substances of Very High Concern (SVHC)
REACH is a regulation of the European Union, adopted to improve the protection of human health and the environment from the risks that can be posed by chemicals. The REACH regulation contains the list of SVHCs that may have serious and often irreversible effects on human health and the environment. SVHCs need to be reported if they are present in a material in concentrations exceeding 0.1% by weight.
Restriction of Hazardous Substances Directive (RoHS) was adopted by the European Union to ensure only small concentrations of hazardous substances are used in the manufacturing of electronics and electrical equipment. Any business that sells applicable electrical or electronic products, sub-assemblies or components directly or indirectly to RoHS countries is impacted if they use any of the restricted materials. Additionally, medical devices containing hazardous substances will no longer be allowed in RoHS countries for in-vitro diagnostic devices (IVD). Currently RoHS specifies maximum levels for the following ten restricted materials:
Lead (Pb): < 1000 ppm
Mercury (Hg): < 100 ppm
Cadmium (Cd): < 100 ppm
Hexavalent Chromium: (Cr VI) < 1000 ppm
Polybrominated Biphenyls (PBB): < 1000 ppm
Polybrominated Diphenyl Ethers (PBDE): < 1000 ppm
Bis(2-Ethylhexyl) phthalate (DEHP): < 1000 ppm
Benzyl butyl phthalate (BBP): < 1000 ppm
Dibutyl phthalate (DBP): < 1000 ppm
Diisobutyl phthalate (DIBP): < 1000 ppm
United States Dodd-Frank Consumer Protection Act (section 1502) requires public companies to ensure the raw materials used to manufacture products are not sourced or otherwise associated with the conflict in Congo. The most commonly mined conflict minerals include cassiterite (for tin), wolframite (for tungsten), coltan (for tantalum), and gold ore.
Carcinogenic and Toxic Chemicals
The Safe Drinking Water and Toxic Enforcement Act of 1986 (originally known as Proposition 65) requires the state of California to publish a list of chemicals known to cause cancer or birth defects or other reproductive harm. This list currently includes 800 chemicals. Common pigments used in plastics on this list are TiO2 and carbon black. In both cases, particles of respirable size have been known to cause cancer.
The United States Code of Federal Regulation (21 CFR 801.437) requires labeling of all devices, including device packaging, that contains natural rubber and is intended for contact with humans. Natural rubber includes natural rubber latex, dry natural rubber, and synthetic latex or synthetic rubber that contains natural rubber in its formulation. Natural rubber latex proteins have been associated with anaphylaxis, a severe allergic reaction, in some individuals.
Bisphenol A (BPA) is an industrial chemical that has been used to make certain polymers, including polycarbonate and epoxy. Some research has shown that BPA can seep into food or beverages from plastic containers and can health effects, particularly in fetuses and infants.
Phthalates are chemical plasticizers used to soften plastics, such as polyvinyl chloride (PVC). Phthalates are not chemically bound to the plastics and may be susceptible to extraction or leaching. The FDA has issued an advisory risk for DEHP, a common plasticizer in PVC, due to concerns related to reproduction. Common plasticizers used in plastics include:
DBP (dibutyl phthalate)
DnOP (di-n-octyl phthalate)
DiNP (diisononyl phthalate)
BBP (benzyl butyl phthalate)
DEHP (di 2-ethylhexl phthalate)
DiDP (diisodecyl phthalate)
DnHP (di-n-hexyl phthalate)
DIBP (diisobutyl phthalate)
Materials of Animal Origin
Materials of animal origin may induce risk of disease transmission from animals to humans, including brain and nervous system effecting transmissible spongiform encephalopathy (TSE). The Commission of the European Union (EU) has published a directive regarding the use of TSE-relevant animal tissues and products found in a wide range of medical devices. The regulations impose additional compliance requirements on medical device manufacturers, including rigorous risk assessment and risk management practices.