Changes in main standard – biocompatibility trials for medical devices

At 1st of March standard GOST ISO 10993-1-2021 was updated, main changes in our review:

  1. The scope of application has been extended (previously the standard did not cover materials and/or medical devices which do not come into contact with the patient’s body, either directly or indirectly). The new scope of application:

This standard is applicable to medical devices (MD) and establishes the following:

  • general provisions for the assessment of the biological effect of MD as part of the risk management process;
  • classification of MDs on the basis of the nature and length of contact with the patient’s body;
  • requests for analysis of information supplied from various sources;
  • detection of gaps/inconsistencies in actual datasets on the basis of risk analysis (GAP analysis);
  • determination of additional datasets necessary for analysis of the MD’s biological safety;
  • general requirements for MD trials and studies.

This standard is applicable to the materials and MDs intended for direct or indirect contact:

  • with the patient’s body during clinical application;
  • with the user’s body when the MD is intended for personal protection (e.g. surgical gloves, masks etc.).

This standard is applicable to all types of MD, including active, passive, implanted and non-implanted MDs.

This standard contains guidelines for evaluations of biological hazards associated with:

  • risks such as changes occurring in the MD with the passage of time, as part of the general assessment of biological safety;
  • failure of the MD or its components, with the result that materials with certain new properties may come into contact with the body.

In other standards of ISO 10993, requirements are set for the evaluation of the biological effect of the MD in the course of specific studies. Methods for testing are detailed in the standards for the specific MD.

This standard is not applicable to hazards related to bacteria, molds, yeast, viruses, agents causing transmissive sponge-like encephalopathy (TSE) and other pathogens.

  1. Classification of medical devices by the type of contact has changed. The following descriptions are provided.

1) MDs not in contact with the human body. Non-contacting MDs are those without any direct or indirect contact with the human body and for which biocompatibility requirements are not stated. Example: diagnostic software, IVD diagnostic devices and blood collection tubes.

2) MDs in contact with the skin and mucosa. This category includes MDs which are intended for contact with the intact skin (e.g. electrode patches), or with intact mucous membranes (e.g. contact lenses), as well as with damaged or endangered skin and mucosa (e.g. occlusion bandages for burns or wounds).

3) Externally attached MDs. This category of MDs includes those contacting with the following systems and organs of the human body:

  1. a) with the blood and vasculature, indirect contact. MDs or components which are not necessarily intended for direct contact with the bloodstream, but are used as flow lines to deliver fluids to the blood vessels. (Example: infusion lines).
  2. b) with soft tissue, bones, dentine. MDs intended for contact with soft tissue, bones or canal-dentine systems. (Example: laparoscope), the MD or its components not necessarily intended for contact with the bone or tissue but may be used for delivery of fluids to the soft tissue or to the bones. (Example: irrigation tubes and MD components intended for contact with the fluid which in turn may come into contact with the patient).
  3. c) with the circulating blood in the bloodstream (example: intravascular catheters).

4) Implanted MDs. This category includes a MD intended for contact with the following tissues:

  1. a) with soft tissue and bones (example: bone prosthetics);
  2. b) with the blood (example: electrodes of cardiac pacemakers).
  3. Classification of the MD for the length of contact has been updated. 2 new types were introduced:
  4. MDs intended for short term contact.

Some short term contact MDs (category A) have really very short exposure times in relation to the human body (such as scalpels, injection needles or capillary tubes used for less than 1 minute). For those MDs, biocompatibility tests are not necessary. It shall be considered, however, that biocompatibility tests may be still necessary in the event of any cover or lubricant used which may remain in contact with the body’s tissues after removal of the MD itself. In this case, the total duration of MD use during application shall be considered.

  1. MDs belonging to several categories by the duration of the contact parameter.

When the length of contact allows the inclusion of a specific MD in several distinct categories at the same time, the studies and/or evaluation shall be conducted on the basis of the most stringent requirements. When multiple exposures of MDs are expected or intended, the decision on the certain category for such MD shall take into consideration the potential cumulative effects expected for the total time of exposure. If a MD changes its properties during contact with the body, e.g. undergoes polymerization and/or biodegradation in situ, separate studies shall be performed for each such MD condition. For example, for absorbable glue intended for polymerisation in situ, the study shall include different stages of the MD’s life cycle, including original components, products of the intermediate reaction, fully polymerized material and final degradation products.

  1. Appendix A has been reviewed “Endpoints used for the assessment of biological risks”, in table A new columns were added: “physical or chemical information”, “pyrogenicity mediated by the material concerned”, as well as columns “chronic toxicity”, “carcinogenicity”, “reproductive toxicity/development toxicity” and “degradation”, which designate “endpoints” for review as “E” (instead of “studies” to be performed, are designated as “X”).
  2. Appendix В has been replaced “Management risk process guidelines” has been replaced by “Guidelines for the assessment of the biological effect of medical devices during the process of risk management” (previously ISO/TR 15499).
  3. Additional information has been introduced for the evaluation of “non-contacting medical devices”, nanomaterials and absorbable materials, as well as new information regarding the assessment of “devices of short term contact”.