Biological Safety Testing, Biocompatibility

For medical devices with direct or indirect patient contact, the biological safety of the device considering its intended use should be considered. Typically, biocompatibility evaluation studies are performed, where necessary, in accordance to ISO 10993-1:2009 “Biological evaluation of medical devices – Part 1: Evaluation and testing”. With regard to an US FDA registration of the device further tests may be necessary as specified in the FDA guidance document “Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process”, issued on June 16, 2016. Both documents classify medical devices regarding their nature of body contact and contact duration and lists the biological test methods applicable for the respective device category. However, the tables showing the applicable biological test methods should not be used as a check box. The biological tests can be divided into in vitro and in vivo tests.

However, before starting several biological tests ISO 10993-1 requests to carry out extensive physicochemical analyses in order to identify and quantify at least leachable substances to be expected during regular intended use. Such tests are performed under the umbrella of the material characterization as described in ISO 10993-18:2005 (see Chapter “Physical and Chemical Testing“)

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. For devices with an invasive application endotoxin testing is necessary in order to evaluate the potential risk that the device may cause fever reaction during application.

The microbiological basic tests of “UL MDT” inform the manufacturer about the microbiological status of their products, determine anti-infective properties of materials and disinfectants and help to control manufacturing processes and sterilization procedures.

What we offer:

  • Bioburden Determinations
  • Sterility Testing
  • Differentiation and Detection of Pathogenic Microorganisms
  • Endotoxin Testing (LAL Test)
  • 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 (ISO 17664)

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. All processes need to be subjected to validation studies.

What we offer:

  • Cleaning and sterilization of medical devices delivered in a sterile state
  • Cleaning, reprocessing and sterilization 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 ISO 22442 series of standards, in order to establish their virological safety. Based on the classification rules of the Medical Device Directive, such devices are classified in Class III (except contact to intact skin) 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

The standard ISO 10993-1:2009 “Biological evaluation of medical devices – Part 1: Evaluation and testing” describes the strategy for the biological safety evaluation of a medical device with direct or indirect body contact. However, according to this standard first the suitability of a material regarding the physical and chemical characteristics should be evaluated: „In the selection of materials to be used in device manufacture, the first consideration shall be fitness for purpose with regard to characteristics and properties of the material, which include chemical, toxicological, physical, electrical, morphological and mechanical properties. […] Identification of material chemical constituents and consideration of chemical characterization (see ISO 10993-18) shall precede any biological testing […]”.

For the material characterization of medical devices ISO 10993-18:2005 “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 ISO 10993-9, ISO 10993-13 (polymers), ISO 10993-14 (ceramics) and ISO 10993-15 (metals and alloys). All identified leachable and degradation products should be subjected to a toxicological evaluation in order to estimate its toxicological risk during application of the device under evaluation.

After launching a device, 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.

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 offer:

  • Material Characterization of Medical Devices
  • Physicochemical Analyses of Polymeric Materials
  • Metal and Ceramic Analyses
  • Residue Analyses
  • Toxicological Evaluation of Leachables and Degradation Products

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, sterilized and final packed test devices are subjected to a thermal and regular ageing and to a transport simulation (pursuant ISTA or ASTM standards). Afterwards, the products can be subjected to the various test systems in order to evaluate the performance of the packaging system (aseptic presentation and microbial barrier properties) as well as the performance of the containing medical device (functionality and biocompatibility).

Following test system may be applicable for the packaging system: dye test for seal integrity, peel test, burst test, bubble test, air permeability test and test for microbiological tightness. Furthermore, the stressed medical devices are subjected to specific performance tests as well as to a biological evaluation test strategy.

What we offer:

  • 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
  • Evaluation of the Shelf-Life of the Sterile Packed Medical Device

Investigations of Ophthalmic Devices

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

The main focus of the investigations for intraocular lenses, contact lenses, capsular tension rings, viscosurgical devices and endotamponades is to verify the product properties and shelf-life assumptions as specified in the respective standards.

What we offer:

  • Intraocular lenses
  • Contact lenses
  • Contact lens care products
  • Compatibility between contact lenses and contact lens care products or eye drops
  • Capsular tension rings
  • Viscosurgical devices and endotamponades