Biological evaluation
Background
According to the MDD 93/42/EEC Annex I “Essential requirements” Clause 7 and EU Member State regulations, every medical device manufacturer has to demonstrate that their devices will not cause potential biological risks. This applies to medical devices that have direct or indirect contact with the human body. The standard EN ISO 10993-1 “Evaluation and testing within a risk management process” and the US FDA Guidance “Use of International Standard ISO 10993-1, Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process (June 2016)” give a pathway to achieve this requirements within a risk management process, as part of the overall evaluation and development of each device.
According to the MDD 93/42/EEC Annex I “Essential requirements” Clause 7 and EU Member State regulations, every medical device manufacturer has to demonstrate that their devices will not cause potential biological risks. This applies to medical devices that have direct or indirect contact with the human body. The standard EN ISO 10993-1 “Evaluation and testing within a risk management process” and the US FDA Guidance “Use of International Standard ISO 10993-1, Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process (June 2016)” give a pathway to achieve this requirements within a risk management process, as part of the overall evaluation and development of each device.
To avoid unwelcome surprises with the final product to be used for the biological investigations, the material selection should begin during the development process. The selection of material(s) to be used in device manufacture and its biocompatibility evaluation should initially take into account the likelihood of direct or indirect tissue contact, and any available information about the materials of manufacture, for example, chemical formulation for each component material, including adhesives, known and suspected impurities, and constituents associated with processing. The device in its final finished form as well as possible leachable chemicals or degradation products should be considered for their relevance to the overall biocompatibility evaluation of the device.
The manufacturer should use materials that are well-known to be appropriate for the intended use and assumed to be biocompatible. Depending on the material, the manufacturing process and the intended use, some of the required investigations can be met through literature search and animal testing can be limited, this is the whole point of the new biological evaluation process.
How it should be performed
EN ISO 14971:2012, Medical devices – Application of risk management to medical devices states that toxicological risk assessment shall be based on:
- The physical and chemical characteristics of the device components and materials;
- Any history of clinical use or human exposure data;
- Any existing toxicology and other biological safety data on the product components and materials;
- Test procedures and results.
Collectively, knowledge of the composition of a medical device, including additives and processing aids, prior use of the relevant material(s) in a predicate device or similar device, and biological safety tests should provide predictive evidence of potential hazards to users of the device. This initial step is essential in the process of biological evaluation.
Evaluation of the chemical nature of the material can take the form of experimental data and/or information on the chemistry of the materials/components involved. Literature studies conducted on the materials help evaluate the biological response and are useful in assessing a finished medical device for its intended use/intended purpose. Some factors that affect the biocompatibility of the material include the identity, concentration, availability, and toxicity of all constituents such as additives, processing aids, and monomers.
To evaluate prior use, information on previous uses of the device/materials or intended additives, and any adverse reactions encountered, should be reviewed. Account should be taken of the intended use, the concentration of the ingredients, and current toxicological information. Biological safety should be considered giving special attention to the ISO 10993 series for a particular application in the context of a biological evaluation. The need for testing should be reviewed on a case-by-case basis.
The amount of data required on a material, and the depth of the investigation, is dependent upon the intended use in manufacturing of devices and the function and duration of patient contact. Knowledge of a material’s composition and potential leachable compounds, combined with results from biological safety testing, should provide predictive evidence of any potential toxicological risk to patients.
Medical devices must be designed and manufactured in such a way as to reduce to a minimum the risks posed by substances leaching from the device. Special attention shall be given to substances, which are carcinogenic, mutagenic, or toxic to reproduction, in accordance with Annex I to Council Directive 67/548/EEC of 27 June 1967 on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labeling of dangerous substances.[i]
International Standards Organization 10993-1:2009: Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process includes the recommended biological testing and the principles governing the biological evaluation of medical devices. ISO 10993-1:2009 applies to the non-clinical or pre-clinical testing of devices.
Our Service
Our Services include the following:
- Consultation : best strategy to develop for the biological evaluation plan
- Review of your report for compliance according to the state of the art
- Toxicological risk assessment : material characterization, research from a wide range of sources (books, databases etc…)
- Preparation of literature search protocol
- Preparation of literature research report
- Residual chemical analysis : tolerable intake levels
- Toxicological risk assessment
- Biological Evaluation Report preparation: overall summary of material characterization, toxicology and biocompatibility
If you wish to prepare some or all of the above, get in touch with us on our contact page.
You may also review our page about CE marking and FDA compliance.
[i] Council Directive 67/548/EEC, Annex I, of 27 June 1967 on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances.