Biological Safety Testing, Biocompatibility

For medical devices, the biocompatibility of a product has to be evaluated in view of the harmonized standard EN ISO 10993-1 “Biological evaluation of medical devices – Part 1: Evaluation and testing”. The table below classifies medical devices regarding their nature of body contact and contact duration and lists the biological test methods applicable for the respective devices. With regard to international registrations, further tests may be necessary as specified in the “Blue book memorandum G95-1” of the American Food and Drug Administration (FDA).

Further to these biological tests, it is required in EN ISO 10993-1 to carry out extensive physicochemical tests and analyses in order to identify and quantify leachable substances to be expected during regular use.

For this, a separate standard, EN ISO 10993-18 has been developed. For reasons to avoid unnecessary animal tests, these investigations should be carried out before starting the biological tests. The tests which are actually performed for a certain product mainly depend on the type of material used for the respective devices and their intended use. In general, only those risks are tested which cannot be finally assessed by means of previous tests or scientific literature, as outlined in the diagrams below from EN ISO 10993-1.

What we do:

  • Cytotoxicity Testing
  • Tests for Sensitization
  • Tests for Irritation and Intracutaneous Reactivity
  • Systemic Toxicity
  • Genotoxicity Testing
  • Implantation Tests
  • USP Biological Reactivity Tests
  • Hemocompatibility Testing
  • Pyrogen Testing

Basic Microbiological Tests

Medical devices contaminated with pathogens may be a source of infection for humans. Therefore, according to the Medical Device Directive, devices must be designed and manufactured in such a way as to eliminate or reduce the risk of infection to the patient, user or third parties as far as possible.

Consequently, medical device manufacturers, in particular if they manufacture sterile devices, must produce their products under adequate and microbiologically monitored conditions involving a clear zone concept. Furthermore, the final products, and if necessary the starting and packaging materials, must be subjected to bioburden determinations in order to support the later sterilization success.

The microbiological basic tests of ‘mdt’ inform the manufacturer about the microbiological status of their products, determine antiinfective properties of materials and disinfectants and help to control manufacturing processes and sterilization procedures.

What we do:

  • Bioburden Determinations
  • Sterility Testing
  • Differentiation and Detection of Pathogenic Microorganisms
  • Antimicrobial Activity Testing
  • Microbiological Monitoring of Production

 

Validation of Cleaning, Reprocessing and Sterilization

The requirements of cleaning, reprocessing and sterilization procedures of medical devices can be divided into two product categories:

  1. Cleaning and sterilization of medical devices delivered in a sterile state
  2. Cleaning, reprocessing and sterilization of reusable medical devices

Both product categories have in common that validated sterilization processes can only be applied to devices which are clean and disinfected. Cleaning and disinfection are therefore prerequisites for any effective sterilization process.

What we do:

  • Cleaning and sterilization of medical devices delivered in a sterile state
  • Cleaning, reprocessing and sterilisation of reusable medical devices
  • Validation of sterilization processes

 

Virological Testing

Due to the significant risk that materials of animal or human origin may transfer pathogenic viruses or prions, all products containing such materials must be evaluated in accordance with the EN 22442 series of standards, in order to establish their virological safety. Based on the classification rules of the Medical Device Directive 93/42/EEC, such devices are classified in Class III and require a comprehensive design and safety review by the notified body.

Should the need arise to use medical devices repeatedly or by different persons, suitable cleaning, disinfection and sterilization processes must be applied in order to minimize the risk of viral transfer from person to person. Therefore, new cleaning and disinfection procedures must verify their virucidal efficacy. In particular cases it may even be necessary to investigate the elimination/inactivation of prions responsible for transmissible spongioform encephalopathia (TSE).

What we do:

  • Antiviral Activity of Disinfectants (Suspension Test)
  • Virological Testing of Final Products
  • Validation of Virus Reduction or Inactivation during Manufacturing
  • Tests for Antiviral Activity of Test Substances

Physical and Chemical Testing

According to the harmonized standard EN ISO 10993-1 “Biological evaluation of medical devices – Part 1: Evaluation and testing” the evaluation of the biological risk of medical devices must also take into account the non-biological attributes and properties of any materials used in a particular medical device. This includes chemical, physical, electrical, morphological and mechanical properties.

For the material characterization of new medical devices EN ISO 10993-18 “Biological evaluation of medical devices – Part 18: Chemical characterization of materials” was issued as a guideline. The material characterization supports the manufacturer at an early stage to evaluate the critical material properties or leachable chemical substances. Furthermore, during the development of new products an identification and quantification of possible degradation products has to be performed in accordance with EN ISO 10993-9, EN ISO 10993-13 (polymers), EN ISO 10993-14 (ceramics) and EN ISO 10993-15 (metals and alloys).

After launching new devices, accompanying inspections are necessary. This may include inspections of raw materials, in-process controls, final inspections of the product (e. g., residual monomer content, ‘fingerprint’ of extractable substances, sterilization residues) as well as tests of packaging materials.

To demonstrate the suitability of a medical device with patient contact a material characterization pursuant to ISO 10993-18 should be performed as requirement in ISO 10993-1. Materials can be characterized using chemical, physical, morphological and mechanical test methods. Also, volatile and leachable chemical substances can be identified and evaluated toxicologically. UL MDT uses numerous modern analytical test procedures, like GC/MS, HPLC, FTIR, ICP, XPS and SEM/EDX to help you perform the required physicochemical analyses.

What we do:

  • Material Characterization of Medical Devices
  • Physicochemical Analyses of Polymeric Materials
  • Metal and Ceramic Analyses
  • Residue Analyses

 

Shelf Life Testing of Devices and Packaging

According to ISO 11607-1, the specific properties of medical devices and their packaging systems must remain stable during their shelf life. Consequently, medical device manufacturers should perform appropriate validation studies in order to justify shelf life and transport stability of their devices. This includes also the validation of the packaging processes, like forming and sealing process of sterile barrier systems, pursuant to ISO 11607-2. In the course of a combined stability and packaging validation study, test devices are subjected to a thermal and regular ageing and to a transport simulation (pursuant ISTA or ASTM standards). Afterwards, the packages are subjected to the following test systems: dye test for seal integrity, peel test, burst test, creep test, bubble emission test, air permeability test and test for microbiological tightness. Furthermore, the stressed medical devices are subjected to specific performance tests.

What we do:

  • Qualification of Packaging Materials
  • Validation of the Forming, Sealing and Assembly Processes of Packaging for Terminally Sterilized Medical Devices
  • Validation of Final Packaging Systems for Sterile Medical Devices

 

Investigations of Ophthalmic Devices

Based on many years of practical testing and contribution to the standardization work in the respective technical committees, ‘mdt’ has gained special expertise in the experimental investigation and risk evaluation of ophthalmic devices.

The main focus of the below mentioned investigations for contact lenses, intraocular lenses, capsular tension rings, viscosurgical devices and endotamponades is to verify the product properties as specified in the respective standards. Due to the large variety of standards the several tests procedures mentioned in this chapter can not be described in detail. During precise test request we are willing to specify the respective test requirements as well as our practical procedure.

What we do:

  • Contact lenses
  • Contact lenses and contact lens care products
  • Contact lens care products
  • Intraocular lenses
  • Capsular tension rings
  • Viscosurgical devices and endotamponades