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Recording the risk

Since the first reported outbreak of bovine spongiform encephalopathy (BSE) in the United Kingdom in 1986, suppliers of health-care products and global health-care agencies have diligently worked to reduce the threat of this disease. BSE is a progressive neurological disorder of cattle that can be transmitted to humans.

Because the plastics content of medical devices continues to increase, it is important to ensure that these products are in regulatory compliance. Plastic resins often use beef tallow as a lubricant in the manufacturing process. Tallow is derived from meat, bone, hooves and horns, rather than from the nervous-system components that are generally of concern, thus tallow is considered low risk for BSE transmission. However, the regulatory agencies regulate tallow and an understanding of the implication of this and knowledge about all the components within a medical product that may contain animal derivatives is an important consideration for any medical device manufacturer.

Worldwide health-care agencies have recommended a number of steps to reduce the risk of BSE transmission to humans. In Europe, any bovine-derived material used in the manufacture of a medicinal product is regulated according to the Note for Guidance (NG) on “Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products,” which was adopted by the Committee for Proprietary Medicinal Products (CPMP). The NG came into force in 1992 and was referenced in section 2.4, Tallow Derivatives, of Guidelines for Medical Devices, taking into account the European Directive 2003/32/EC.¹ In the United States (US), the BSE regulations are found in the US 21 Code of Federal Regulations (CFR) Parts 189 and 700.

The NG, Directive 2003/32/EC and Part 189 recognise that the risk associated with using animal derivatives is related to the source of the animals, the type of animal tissue involved and the production process that is utilised. Both the CPMP and the Food and Drug Administration (FDA) state that tallow is generally considered low risk for BSE transmission. However, it is not that simple.

FDA states in 21 CFR Part 189 that tallow is defined as the “rendered fat of cattle obtained by pressing or by applying any other extraction process to tissues derived directly from discrete adipose tissue masses or to other carcass parts and tissues.” To be exempt from regulation, “tallow must be free of prohibited cattle material or must contain not more than 0.15% of hexane-insoluble impurities.” Because plastics resin suppliers do not typically perform this level of testing, this exemption is generally a moot point in terms of the use of tallow in plastic products.

The NG states that “materials such as cleaning agents, softeners and lubricants that come into contact with the medicinal product during its routine manufacture or in the finishing stage or in the primary packaging are considered in compliance with this Note for Guidance if they are derived from tallow under the conditions described in section 6.” Section 6 describes examples of “rigorous processes” such as high heat. The NG goes on to state, “for the purposes of regulatory compliance, the Marketing Authorisation holder/applicant shall verify with the tallow derivative supplier/manufacturer that these conditions are met.” Because plastic components are often produced under high heat and pressure, the case could possibly be made that this meets the criteria of a “rigorous process.”

Both FDA and the CPMP recognise that one means of reducing the risk is to acquire material from BSE-free countries. FDA has added an additional step requiring documentation to be kept that certifies the source of the animal material. These regulations are found in 189.5(c)(5) and 700.27(c)(5). The impact of these rather detailed regulations is that medical device manufacturers are required to maintain extensive documentation demonstrating compliance, at significant expense for themselves and each supplier in the chain.

Alternative approach

Another option is to employ plastic resins that do not utilise beef tallow and FDA has encouraged manufacturers to use nonbovine materials whenever possible. In the past this has been difficult particularly because polypropylene, one of the most popular resins, was not available in animal-free versions. However, some resin manufacturers have begun producing animal-free polypropylene. Examples of other popular materials that can be found in animal-free versions are polyvinylidene fluoride, poly(vinyl chloride), polycarbonate, polyethylene, polysulphone, nylon, acetal copolymer and polybutylene terephthalate.

It is also important to ensure that the entire flow path of a fluid meets FDA and CPMP requirements, that is, everything that comes into contact with a fluid that will ultimately come into patient contact. For example, a blood bag may be made out of animal-free plastic and the tubing may be from an animal-free material. However, manufacturers often do not recognise that the connectors and the fittings that connect to the tubing may contain material that is not animal free. Admittedly, the risk is lower because the total contact surface area of a connector is low compared with the tubing or the bag. However, if the intent is to offer an entire animal-free solution, the entire flow path, including the fittings and connectors, must be animal free. Silicone tubing and specialised tubing are available in animal-free versions. Fittings and connectors such as luers, tube-to-tube fittings and quick disconnect connectors can all be found as animal-free products.

Choose the best route

In summary, if the plastic resin contains beef tallow, it must be documented that the resin in every plastic component in a medical device that may come into contact with patients is sourced from a BSE-free country or, that it has been verified that the tallow used in the resin meets the technical requirements established in the NG, Directive 2003/32/E and CFR Part 189. An alternative approach is to specify animal-free materials and avoid the issue altogether, although this may not be possible in all cases. However, many new options for animal-free materials are emerging and seeking these out may well be the best approach for manufacturers in the long term.

Mark Rosneck is Market Development Manager at Value Plastics Inc., 3325 South Timberline Road, Fort Collins, Colorado 80525 USA.
tel. +1 970 226 8250, e-mail: mark.rosneck@valueplastics.com