Beginners Guide to Biocompatibility for Medical Device Adhesives

Adhesives are used in most industries, including the medical industry, to assemble components of finished devices.  Adhesives can provide value over traditional joining methods such as mechanical fasteners, ultrasonic welding and solvent welding by reducing hazardous solvent usage, distributing stresses more evenly or even increasing production throughput.  In the medical device industry, particular care is taken to formulate adhesives for biocompatibility – to make them safe for use on or in the human body. 

As defined by the FDA, a medical device is an instrument, machine, device, implant, or contrivance that is used to diagnose or treat a disease. Given the critical nature of medical devices, the FDA requires these devices to meet strict biocompatibility standards. Generally speaking, the FDA and other regulatory bodies do not require individual components of the finished device to carry any specific approvals. However, medical device manufacturers choose to use various biocompatible components including adhesives during the assembly for increased confidence that their products are reliable and safe. What are biocompatible adhesives and how do they differ from regular industrial adhesives? Read this post to find the answers. 

biocompatible adhesives, Medical Adhesives, KRYLEX, needle bonding
Needle Bonding – biocompatible adhesives

A Brief Introduction to Biocompatibility 

Biocompatibility refers to the compatibility of a material with a living system or living tissue, as many medical devices are used for internal and external examination and treatment. Biocompatible materials produce no toxic response when in contact with any body part or tissue. These materials are subjected to a variety of rigorous tests to confirm their compatibility towards bodily fluids or body parts. 

A Discussion on Various Types of Biocompatibility Tests Performed on Adhesives

A medical adhesive differs from other industrial adhesives because it has been tested to certain standards and deemed as biocompatible at the end of the tests.  The two main testing standards used today include USP Class VI Biocompatibility Testing and ISO 10993 Biocompatibility Testing. 

  • USP Class VI Biocompatibility Testing: This testing is devised by the U.S. Pharmacopeial Convention (USP) that regulates standards for healthcare technologies, medications, food ingredients, polymers, as well as plastics used for building medical devices. The materials used in a product are distinguished into classes on the basis of their proximity with the human body and contact time. This contact time is taken as limited, prolonged and permanent on the basis of the product used. Adhesives tested by verified third parties and found to adhere to this classification are considered safe to use for medical device assembly. 

USP Class VI testing is comprised of the following three evaluations: 

  1. Implantation Test: In this testing, the material is implanted into the intramuscular tissue of the specimen. Toxicity, irritation, and infection response caused by this implantation is then measured over five days. 
  2. Acute Systemic Toxicity Test: The material or compound is orally administered, inhaled, or applied to the outer skin of the specimen. Toxicity and irritation response on the specimen is measured over several days.  
  3. Intracutaneous Test: The material is kept closer to subdermal tissue or the tissue to be accessed by the medical device. Toxicity and localized irritation produced by this contact in the specimen is measured and observed for several days.

The material extracts under evaluation for Toxicity and Intracutaneous testing are fixed at several time and temperature conditions.  The tests are administered and measured at 122°F for 72 hours, 158°F for 24 hours and finally at 250°F for one hour.

Adhesives that qualify USP Class VI biocompatibility testing are considered safe for bonding and assembly of medical devices.

  • ISO 10993 Biocompatibility Testing: In recent years USP testing has been superceded by the more robust ISO 10993 testing standards. These testing standards are developed by the International Standards Organization (ISO), which aims to standardize the evaluation of materials worldwide.  Like the USP standard, the ISO standard also distinguishes medical devices on the basis of their body contact and contact duration. The ISO 10993 series consists of over 20 standards that guide the biocompatibility testing of medical devices and components. ISO 10993 biocompatibility testing that is generally applicable to adhesives includes the following:
    • ISO 10993-4 Hemolysis
      • Selection of tests for interactions with blood
    • ISO 10993-5 Cytotoxicity
      • Tests for in vitro cytotoxicity
    • ISO 10993-6 Implantation
      • Tests for local effects after implantation
    • ISO 10993-10 Intracutaneous: Sensitization and Irritation
      • Tests for irritation and delayed-type hypersensitivity
    • ISO 10993-11 Systemic Toxicity
      • Tests for systemic toxicity

Generally, the minimum test method used in determining biocompatibility of an adhesive is ISO 10993-5 Cytotoxicity test. This test helps confirm if the adhesive has any negative impact on cells of mammals. It is important to note that the ISO 10993 standard is similar in many aspects to the methods described in the USP standard. However, the main difference is these methods from the USP methodology is the rigorous testing strategy. Medical adhesives testing to and found to pass ISO 10993 methodology are used in a wide range of medical devices including catheters, needles and syringes, connectors and tubes, imaging equipment, blood filtration equipment, smart health devices and wearable technologies. 

If you are a medical device manufacturer, it is important that you source biocompatible adhesives that are USP VI or ISO 10993 certified from a trusted supplier or manufacturer. The KRYLEX® range of medical adhesives have been developed specifically with biocompatibility in mind while maintaining the robust performance and quality associated with traditional industrial adhesives. Owing to their strong and reliable bonding characteristics, speed of cure, exceptional tensile properties and strict quality standards, these adhesives have emerged as an efficient, user-friendly, and easier alternative to traditional fasteners and welding.

PREMIER FARNELL LIST KRYLEX®

KRYLEX distributor's logo

Chemence® Ltd is pleased to announce the appointment of Premier Farnell plc as stockist & distributor for 28 carefully selected products from our KRYLEX® range.

Premier Farnell (part of Avnet, Inc) is a leading high service, multi-channel distributor of electronic and industrial products throughout the UK, Europe and Asia Pacific.

The listing of KRYLEX®products has been fully supported by onsite training of Premier Farnell’s technical sales team to guide and direct the selection of the most suitable KRYLEX® adhesive or sealant for any given application.

Premier Farnell aim to consolidate and reduce their supplier base for adhesives and sealants and were looking for a reputable manufacturer to replace several competing brands across a number of categories. They chose KRYLEX® due to the breadth of the range and the technical support that Chemence® can offer.

There are plans to further extend the range of KRYLEX® products offered throughout 2019.

Together, we are confident that the combination of the technical expertise of Chemence® combined with the global reach of Premier Farnell, will create a platform for further growth for our KRYLEX® adhesives and sealants range. 

UV-curing adhesives see the light

Adhesives require a chemical reaction to convert their structure from the liquid to the solid state. Once cured, the adhesive provides a high-strength bond between two substrates, which resists temperature or humidity changes and is impervious to many chemicals.

There are several ways to achieve the reactive curing process, such as light, heat, moisture or the combining of two reactive components. A UV-curing adhesive contains photo-initiators that start the chemical reaction when exposed to light of the appropriate wavelength and intensity, usually wavelengths of 250 nm to 400 nm. The UV-curing mechanism can be applied to several types of chemistries; there are UV-curing acrylics, epoxies, silicones and cyanoacrylates to name a few.

Strengths and weaknesses of UV-curing adhesives

Like any curing process, UV curing has its advantages and disadvantages.

The UV-curing process is flexible. Since it depends on the intensity of the UV light, the curing time can be controlled and can be as fast as a few seconds at high intensity or much longer at lower intensities.

ASTM tensile testing dog bones of Krylex KU9980-M fluoresce under UV light.
Figure 1. ASTM tensile testing dog bones of Krylex KU9980-M fluoresce under UV light. Source: Chemence

UV-curing adhesives are typically single-component formulations requiring no mixing, and generally low-viscosity formulations with minimal solvent content. The uncured adhesive has a relatively long shelf life, sometimes up to 24 months, and is easy to handle as long as appropriate precautions are taken to minimize ambient light.

Some UV-curing adhesive formulations contain fluorescing agents that will only shine when the product is fully cured. These allow manufacturers to perform in-line visual inspections of their processes, ensuring that bondlines are completely sealed between two substrates.

After curing, UV-curing adhesives are non-toxic and suitable for a wide range of applications, such as medical-grade adhesives to assemble needles and catheters, conformal coatings to protect sensitive electronic components or deep curing formulations used for encapsulation and potting of components.

UV-curing adhesives can be formulated with a secondary moisture-curing mechanism for use in shadowed areas that aren’t reachable by the UV lamp. The moisture comes from the air and best performance is achieved by combining both methods to fully crosslink the adhesive matrix. Dual-curing adhesives fixture rapidly after UV exposure and continue to build strength and environmental resistance as the adhesive cures over the course of several days.

On the other hand, there are a few disadvantages and limitations. Curing requires a light source that emits UV light at a wavelength that matches absorbance of the photo-initiator of the adhesive. All adhesives do not operate at the same wavelength. The source can be a mercury vapor lamp, a UV fluorescent lamp or a UV LED, but it represents an additional cost compared to other adhesive technologies. The light output slowly degrades as the lamp ages, increasing the curing time and eventually requiring replacement of capital equipment.

Unless the adhesive includes a secondary curing mechanism, the UV light from the lamp must illuminate the entire bond area; shadowed areas will not cure. It is important to note that not all substrates are usable with UV-curing adhesives. It will only be possible to cure the adhesive through materials that transmit light at the specific wavelength of the lamp. UV and visible light can only reach a certain depth, with the limit generally around 10 mm.

It should also be noted that exposure to UV light can be harmful to human operators, who need appropriate eye and skin protection.

Chemence® has developed UV-curing formulations that combat a majority of these issues. Broad-spectrum cured adhesives contain photo-initiators that respond to a range of wavelengths with a bell-shaped response curve over the 250 nm to 400 nm range. A medium-pressure mercury arc or metal halide bulb lamp provides optimum curing. LED optimized formulations have also been developed to work specifically with curing systems utilizing LED light sources in the 365 nm to 405 nm range.

A variety of formulations is available to provide tack-free curing – eliminating the potential for oxygen inhibition, which causes a permanent surface tackiness on adhesive exposed to the atmosphere. Chemence® has also developed several dual-cure formulations that rely on light for initial cure and then achieve full cross-linking after exposure to heat or moisture.

About Chemence® UV-Curing Adhesives

Chemence® has optimized an extensive range of UV-curing adhesives for bonding, tacking, sealing, coating, encapsulating, laminating and potting. The KRYLEX® UV-curing product line includes both acrylic and cyanoacrylate adhesives, with formulations for high-strength, tack-free, dual-cure and fast-bonding applications.

Chemence® also has a full line of UV-curing adhesives for medical devices, including needle, catheter and tube set assemblies under its KRYLEX® brand.

Making it stick: The many uses of cyanoacrylate adhesives

Krylex® Cyanoacrylate Adhesives blog
Figure 1. Cyanoacrylate: an adhesive for all seasons. Source: Krylex.com/Chemence

Cyanoacrylate, commonly known as superglue, is a one-part adhesive that can form strong bonds with a wider variety of materials than most other types of adhesives. It can join plastics such as ABS, polyester, polycarbonate, PVC and nylon; metals such as zinc, brass, aluminum, permalloys and iron; woods such as maple, balsa, plywood and rosewood; rubbers; and many other materials.

In its liquid form, cyanoacrylate consists of monomers of cyanoacrylate: ethyl 2-cyanoacrylate methyl cyanoacrylate, n-butyl cyanoacrylate, and others. Each formulation has different properties to meet end users’ needs. After application, the adhesive cures through anionic addition polymerization: the monomers react to the presence of a weak base and form long chains that join the surfaces together. Moisture in the air initiates this reaction. 

Advantages and disadvantages of cyanoacrylate adhesives

There are many advantages to a cyanoacrylate adhesives. When applied between two surfaces as a thin film, curing takes place rapidly at room temperature, forming a rigid thermoplastic with excellent adhesion to most surfaces. Light handling is possible within seconds at room temperature; the bond is fully cured in 24 hours, with very high strength. 

The one-component formulation reduces manufacturing costs by eliminating a mixing operation. In addition, cyanoacrylates can easily be stored and transported in bulk since they contain no solvents. There are also two-component products that provide unique properties not available in single component products.

A cyanoacrylate adhesive does have a few weaknesses. It’s unsuitable for bridging large gaps or bonding large surfaces in a single application. Standard formulations have relatively low impact resistance, low elasticity, a distinct odor and relatively poor resistance to extended high temperatures. A cyanoacrylate has a limited shelf life after opening, and care must be taking in handling, since it almost instantly bonds to skin. 

Cyanoacrylates are available in a range of viscosities: from water-thin liquids to thixotropic gels. A wide variety of formulations has been developed for specific applications and to address drawbacks:

  • Cyanoacrylates with rubber added offer higher peel strength and impact resistance. 
  • Thermally resistant cyanoacrylates offer excellent bond strength retention; in some cases for thousands of hours after exposure to temperatures as high as 121° C.
  • Surface-insensitive cyanoacrylates offer rapid fixture times and cure speeds on acidic surfaces, such as wood or dichromated metals, which could prolong curing time.

Guidelines for effective use

Cyanoacrylates are quite effective in bonding small parts that fit well together. They are therefore widely used in the electronics industry and in the assembly of small mechanical components. 

Cyanoacrylates can bond a wide range of similar and dissimilar substrates, but achieving the best performance requires careful attention to detail. The surfaces to be bonded must be clean, although roughness is not as critical since cyanoacrylate adhesives form strong bonds even on smooth surfaces. 

The relative humidity is important and should be kept between 40% and 70%. A low relative humidity (less than 30%) increases the setting time; conversely a high relative humidity (greater than 80%) leads to extremely short setting time and causes shock polymerization that leads to shrinking of the adhesive layer, reducing the bond strength.Temperature also influences the time of the chemical reaction. The speed of many chemical reactions doubles for every 10° C increase in temperature, following the Arrhenius equation: for cyanoacrylate adhesives, this corresponds to a halving of the polymerization time. The optimal curing temperature is between 20 and 24° C.

 Applications for Krylex® Cyanoacrylate Adhesives
Figure 2. Applications for KRYLEX cyanoacrylate adhesives. Source: Krylex.com

Figure 2 illustrates some of the uses for KRYLEX® products. Chemence® also supplies consumer cyanoacrylates for multiple applications. Glues for DIY and home use are sold under the Dewalt®, Black and Decker® and Craftsman® brand names; liquid bandages are sold under the Liquidskin® brand; and a range of cosmetics cyanoacrylates are sold as fingernail glues and eyelash adhesives.

About Chemence®

Chemence® has developed well over 150 grades of cyanoacrylates, many under the industrial-grade KRYLEX® brand based on a variety of technologies that include ethyl, methyl, n-propyl, isopropyl, n-butyl, isobutyl and alkoxy-ethyl formulations. 

The Chemence® product family includes high-purity medical-grade adhesives, high-performance rubber-toughened impact-resistant products, surface-insensitive and high-temperature formulations, and glues with low-odor and low-bloom characteristics.