Biocompatibility: Material Pains

10 January 2011 (Last Updated January 10th, 2011 18:30)

Choosing the right polymer to use in a medical device doesn’t have to be a headache. Len Czuba, president of Czuba Enterprises and the chairman of the Medical Plastics Division of the Society of Plastics Engineers, explains the importance of making sure that medical devices are biocompatible, and flags up the tests that designers and engineers need to pass if they want their devices to earn regulatory approval.

Biocompatibility: Material Pains

Although the process of selecting the right polymer for new medical devices has not changed much in the past ten to 15 years, the degree of complication seems to have grown exponentially. The variety of specially designed materials, the number of suppliers, some under the same name and some with a new corporate moniker, and the availability of reference databases puts a glut of information into the hands of the design engineers.

But how does one successfully navigate through this information and decide on the one material that is best for their particular application?

It is difficult to access live technical support from suppliers or database providers. With staff reductions and department consolidations, many companies have also lost the experts from their own library of specialists who would have led the polymer selection for new applications in the past. No longer do companies have the historical databank of material expertise or on-staff resources to guide new project efforts. The level of experience in many companies is down, while the breadth of knowledge is much more focused.

This, coupled with the evolution of complicated devices that often combine advances in multiple new technologies such as conductive polymers, shape memory materials, drug-eluting devices and polymers that dissolve in the body, all complicate the process of selecting the right polymer for a particular application.

Medical device designers and engineers have to keep in mind the various requirements that must be satisfied, including functional, chemical, biological, manufacturing, assembly and sterilisation. Collectively, the results of the evaluation of the materials used in the construction of a medical device and its function contribute to what many refer to as its biocompatibility.

Biocompatibility laid bare

When a material is selected for a medical device, biocompatibility is one of the first things considered. In a broad sense, biocompatibility is defined as having properties that make a material or a device compatible with the human body. For example, an indwelling catheter that does not trigger blood clotting or another thrombogenic reaction as a result of its contact with the bloodstream is considered to be biocompatible.

Suture materials that are able to support tissue healing without triggering an inflammatory response, and other long-term implements constructed in a way that does not interfere with the body’s normal functions, are also considered to be biocompatible.

Likewise, a polymeric material that can store blood cells effectively is said to be biocompatible, since the blood will be re-introduced into a patient and it must not be adversely affected by the material of the storage container.

"Broadly, biocompatibility is defined as having properties that make a material or a device compatible with the human body."

Bio-interactive materials

In other applications, implantable, resorbable polymers such as those based on polylactides, glycolides and their copolymers are considered the truest forms of biocompatible materials because they interact with bone and tissue, sometimes even promoting growth. In many cases, the materials are digested and resorbed as the affected area heals; the device completes its lifecycle and the polymer is excreted as by-products of the digested starches or sugars.

Some meshes or membranes are also designed to be ‘recognised’ by the body. Devices made of these materials can, for example, elicit a response, perhaps to allow cell seeding in a blood vessel graft or the incorporation of muscle tissue into a hernia repair mesh. Specially designed membranes will permit blood cleansing during haemodialysis while reducing the complement activation that often occurs when blood comes into contact with synthetic surfaces. These engineered materials, known as biocompatible surfaces, are incorporated into products that are broadly called biocompatible devices.

Biocompatible devices

Beyond the materials of construction, the design of the medical device dictates its biocompatible properties. For example, cardiac stents, small reinforcing meshes that are often made of metal, are deployed into restricted blood vessels to increase blood flow and maintain an enlarged opening.

Some of the first stents were bare metal; the development of drug-eluting stents followed and, more recently, the development of stents made from resorbable materials. The effectiveness of these devices is often ranked in terms of biocompatibility. Although long-term outcomes seem a better way to compare materials and devices, biocompatibility is frequently used to rank devices and product designs.

Types of devices

The US Pharmacopeia has categorised medical devices into three classes.

  • Class I – peripheral devices, which are usually non-contact items.
  • Class II – short-term contact devices that are in contact with body tissue for less than 30 days.
  • Class III – long-term contact devices that are in contact with body tissue for 30 days or longer.

These general categories dictate the extent of testing each material and each device undergoes to demonstrate its safety. The test requirements generally focus on the biological testing needed on the material or device. In order for either to be judged safe for use, test results need to come in with negative (acceptable) response.

Depending on the type of device being made, the polymeric material should be chosen with the final product requirements in mind; because Class II and III devices will be in contact with tissue for longer, biocompatibility considerations are more important.

More rigorous chemical testing will be required as well. By far the most comprehensive listing of test requirements is found in the ISO 10993 standard, which for the most part details the testing needed for each class of medical device. The results of these evaluations, often with additional testing, collectively help to determine if the material and the product is biocompatible or simply acceptable for use.

"Depending on the type of device being made, the polymeric material should be chosen with the final product requirements in mind."

A comprehensive approach

Three distinct sets of requirements must be considered when designing medical devices and selecting the materials to build them: physical and functional compatibility, chemical compatibility and biological compatibility.

Engineers typically think about what material properties are needed to allow a medical device or instrument to function properly as it is designed and developed. For instance, if it is a minimally invasive surgical instrument such as a tissue retractor, then plastic components will need to have the strength and the ability to be moulded and assembled to the high-precision requirements needed for these types of devices.

If the product is a cap, then the requirements for the material’s physical properties are less stringent. Whichever category the device is in, the materials need to support the design and intended use.

Physical and functional testing

Many physical properties are evaluated as an indicator of whether a material is suited for a particular application, including hardness, temperature properties, tensile strength, modulus of elasticity, impact strength and how the material would survive the intended manufacturing process. Is the material suitable for the intended assembly methods, and will it survive the sterilisation process for the final device? After sterilisation, will the materials maintain their physical properties until the product is used? The results of this testing gives an indication as to the suitability of the material for the intended application.

Testing specific to the polymer

A quick review of any material’s physical property data sheet will reveal its basic characteristics. Among the most familiar of these are:

  • tensile strength
  • tear strength
  • modulus of elasticity
  • hardness
  • temperature properties – melting point if semi-crystalline, softening range if amorphous
  • melt rheological properties such as melt-flow rate.  

More extensive testing may be needed in certain applications; these include heat flow and molecular weight distribution.

Testing specific to the device

Each device needs to be tested for functionality. For example, intravenous tubing needs to be tested for clarity, flexibility, kink and stretch resistance, surface friction or tack, surface durability and its tendency to scuff. Other questions need answering: will a clamped tube rebound and open when clamp force is removed? Do the inner surfaces stick together? Does the tube become coloured when sterilised?

A completely different set of questions needs to be asked of a surgical biopsy tool:  it needs to be lightweight, non-slip when wet, have good electrical resistance, be resistant to solvents and chemicals, have good adhesion to metal and have a clean surface finish with readable print.

Chemical testing

In addition to the engineering functionality of the medical device, the materials selected will need to pass the battery of chemical and biological testing required for whatever type of product is being made. These tests check that the material and the final product are safe for use.

"Additional chemical testing is usually performed to obtain complete assurance that devices are being made from the specified and qualified materials."

Why chemical testing? The first reason is to be assured that the material is what is intended in the product. Obtaining a fingerprint of the material by infrared analysis is usually sufficient for a general identification, though many device manufacturers and their suppliers are beginning to rely on material certifications to assure proper identification. Some suppliers will measure melt-flow rate properties, chemical additive package levels and any of a number of additional properties that may be important.

For medical device manufacturers, additional testing is usually performed to obtain complete assurance that its devices are definitely being made from the specified and qualified materials. If the device has critical function or unique property requirements, then usually there will be tight specifications put on the materials used in its construction, to eliminate any variability in material properties that could lead to product performance failures.

A thorough programme of product performance qualification must be carried out during the final phase of development of any new device or product. This includes testing a device’s performance in exaggerated-use conditions, and in ways that may be different than the originally intended method.

A properly developed and qualified device, with a complete specification package of well-designed components and carefully selected construction materials, can support a regulatory approval application. Engineering study results, together with chemical and biological test results, show that the device is indeed suited for safe use in the marketplace.

A note of caution

In addition to preliminary testing of any device, component or component material, all final testing must be done on the product in its ready-for-use condition. This means all polymers should be processed as they will be in the final device, and all devices or components should be subjected to the same sterilisation process that will be used for the final product. Components can be tested independently, but the finished device must ultimately be shown as safe for use as it would be in its final form.

Many polymer suppliers offer their materials as already qualified for use in medical devices; however, there is still a requirement for the device manufacturer to repeat the testing after the materials have been processed into a finished device and sterilised, to simulate the final form of the products.

Supplier testing can be used as additional supporting documentation of the safety of the selected materials, but other than giving device designers and manufacturers a degree of assurance that the materials will ultimately pass later testing, it has little additional value.

Biological testing

This final realm of testing ranges from simple tissue culture evaluations to eluate testing. It is designed to show that there is nothing in the material that may lead to a reaction within the body once it is being used. The types of testing that need to be done are well documented; virtually every laboratory, whether it is a company’s in-house team or an accredited contract laboratory, can help to define what testing needs to be done for each product.

Prepare for submission

"A properly designed medical device will be made with the polymers best suited for the product."

The process of developing a new medical device, together with the challenges of choosing the best polymers for their construction, should be done in a way that assures each manufacturer that the product will be safe and effective in use. A submission to any regulatory body should clearly include all the data necessary to show that the product meets these requirements. If the evaluations have been done properly and the process has been thorough, there should be no surprises from the reviewers, and whatever questions they have should easily be addressed.

A properly designed medical device will be made with the polymers best suited for the product. In each case, the polymer will meet all the requirements for physical and functional, chemical and biological properties, and still meet the multiple objectives of manufacturability, safety and functionality.

By the time the product is ready for market, the manufacturer should be confident that the materials are well suited to the device’s application, and that the product will function well in the marketplace.