Manufacturing

How To Meet Biocompatibility Needs Of Polymeric Medical Components

The steps involved the selection of materials and their evaluation and testing is as follows:

1. Risk Assessment

The intended use and application of the final device is first identified. The initial design concepts can be used to conduct an initial risk assessment of the device design, the material and component characteristics, the manufacturing processes including sterilization, the clinical use of the device, and the nature and duration of  contact with human tissue.

The nature of contact falls into three categories per the standard.

• Surface contacting devices – Those devices contacting skin, mucosal membranes or breached and compromised surfaces (broken skin)
• External contacting devices – Those devices that contact blood paths indirectly, tissue/bone/dentin and circulating devices
• Implantable devices – Those devices that come into long term contact with tissue and bone, and blood

The durations of contact are:

• Limited Exposure – Contact up to 24 hours
• Prolonged exposure - Contact between 24 hours and <29 days
• Permanent contact – Contact e” 30 days

This information should be used to identify potential risks with respect to biocompatibility and the types of biocompatibility tests that need to be conducted. The standard and the guidance document allow for the use of historical data and information to make informed decisions before committing to extensive biocompatibility  testing..

2. Identification of Potential Risks and Exposure Assessment

The physical and chemical characteristic of the materials under evaluation should be listed. Before conducting any biocompatibility tests the potential risks can be
evaluated using methods like literature and historical data. Sources of information on potential biocompatibility risks can include previous experience with the same material(s) that have been used in the same or similar devices in the same anatomical location. In addition post market data for similar devices and applications can  also provide a rich source of data as an initial risk assessment for biocompatibility.

3. Material selection

When selecting materials to be used in a specific device design, manufacture and use, consideration should be given to the fitness for the device’s intended use with respect to chemical, toxicological, physical, electrical, morphological and mechanical properties. With respect to the biological evaluation of the device, the
following should be considered:

i. The properties of the base resin

The choice of the base resin can be constrained by the application and process needs of the device. For example, hydrolytically unstable resins cannot be used in implants. Highly porous materials may not be suitable under ethylene oxide sterilization because unremoved residuals from ethylene oxide could impact patient safety. Thermally unstable grades cannot be used in applications where high temperature autoclave sterilization is required. In addition to physical and mechanical
instability, degradation products could affect the material’s biocompatibility.

ii. The material formulation

Additives, catalysts, colorants, fillers, nanoparticles, plasticizers and other materials either alone or by interactions with each other can significantly affect biocompatibility. If each individual component of the formulation is claimed to be biocompatible, it does not automatically mean that the complete, formulated material is biocompatible. Compounders should evaluate the breadth of additives and a range of levels in their formulations to gain maximum flexibility of biocompatible materials in their portfolio.

iii. Manufacturing Processes – Degradation and Residues

Excessive heat and shear during the manufacturing of plastic parts can change the levels of extractables and leachables in the final part and thus significantly affect
biocompatibility. Joining and cleaning of parts and residues from materials used in facilitating production (e.g. mold release) can also change a product’s biological properties. Processors should define the process ranges that will not affect biocompatibility.

iv. Master Files

In the case where formulations are proprietary, Device Master Files (MAF) of the product can be used. Material suppliers can submit a Device Master File that is privy only to the FDA for review and evaluation of final device submissions. Device Master Files typically contain the name of the product, its formulation (ingredients and levels), manufacturing conditions, sterilization compatibility, physical and mechanical properties, known impurities and chemical characterization. Included are also biocompatibility screening studies.

4. Biological Evaluation

In order to reduce unnecessary testing, including animal testing, manufacturers should first consider all available relevant information from literature and test data For example, in some circumstances, a chemical analysis can demonstrate that the extractables and leachables using a specific solvent have not changed compared to a baseline material, eliminating the need for additional biocompatibility testing using that type of solvent. In addition, chemical analyses can be used to assess the toxicological risk of the chemicals that elute from devices. For example, chemical analysis using exhaustive extraction techniques can also be helpful to evaluate long-term toxicity endpoints such as potential carcinogens.

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