With core expertise in toxicology, biocompatibility, quality assurance, and regulatory affairs, Medical Matters provides comprehensive solutions for medical device manufacturers throughout the development, approval, and production of biologically safe products. Our services encompass every stage, including:
Initiation, Strategic Planning, and Execution of Biological Safety Assessments (BSA)
Coordination of Chemical Analytical and Pre-clinical Testing
Documentation and Evaluation of results in Toxicological Risk Assessments (TRA), Systematic Literature Reviews, and Meta-analyses
Our scientifically sound, risk-based assessments align with regulatory standards and integrate seamlessly into quality management systems, supporting the complete life cycle of medical devices.
Regulatory support
Our services include integrating the biological safety process into the broader quality management system, developing procedures and templates, and performing gap assessments against the latest regulations for established processes.
We can also assist with regulatory body correspondence, including writing responses and developing gap fixes for deficiency reports at any stage of a submission. Developing an approval strategy for the biological safety component of your submission is one of our core competencies.
Biological safety assessments
We support you in biological safety evaluations of medical devices in compliance with the systematic approach outlined in ISO 10993, and relevant FDA and European guidelines, to help bring your device to market and ensure regulatory compliance over its entire lifecycle.
Document types such as the biological evaluation plan (BEP) and biological evaluation report (BER) are essential steps in the medical device development process. They ensure that all available data is considered and if testing is found necessary, that the test strategy is documented, scientifically sound and any outcomes are evaluated in compliance with regulatory guidelines. To cover the complete lifecycle, we further offer biological safety impact assessments (BSI) for changes, deviations or any other events with a potential effect on the biological safety profile of legally marketed devices.
BEPs and BERs are typically established for newly developed products or products undergoing an initial evaluation. Beyond that, our services include the preparation of biocompatibility dossiers (BCD) especially suitable for regulatory submissions. These documents are typically established on product family level and include all biocompatibility data, including impact assessments, generated over a products lifecycle. They allow to be updated continuously and can be reviewed periodically for emerging biological risks and regulatory compliance. They are therefore the ideal document type to document the biological safety of a product family over its lifecycle.
Chemical characterization
Medical Matters services encompass the chemical characterization of materials and final finished devices, following the guidelines set forth in ISO 10993-18. This process involves evaluating the materials’ suitability for their intended purposes.
Chemical characterization includes estimating the substances released by the medical device during clinical use through chemical analytical testing. Initially, we compare the subject devices to clinically established predicate devices, focusing on the hypothetical worst-case chemical release profiles. This comparison allows to determine whether further chemical analytical testing is necessary. If required, we proceed with extractable and/or leachable testing.
Toxicological risk assessments
As one of our core competencies we establish full toxicological risk assessment reports for extractables and leachables (E&L) found in your chemical analytical testing, including, if warranted a pre-screening and risk categorization of detected compounds. Documentation may either be in a standalone document or, for maximum coherence and reviewer friendliness, integrated in the corresponding biological safety assessment.
To provide the highest standard of chemical hazard and risk assessments, we compile toxicological profiles per compound and/or classes of compounds under consideration of all relevant endpoints. Relevant endpoints are evaluated contingent on the intended use of devices and route-specific exposure limits are established leveraging available literature and in silico Quantitative Structure Activity Relationship (QSAR) software tools.
Toxicological profiles
Medical Matters may further establish stand-alone toxicological profiles for any chemical constituent or particulates. These profiles can set acceptable limits for use in monitoring programms, cleanliness criteria, biological safety assessments of potential contaminants, and toxicological risk assessments of extractables and leachables (E&L), as well as other analytical outcomes such as particulates. Reviews to create these toxicological profiles can be either narrative scoping reviews or more exhaustive systematic reviews with a clearly defined search process to minimize bias. Systematic reviews may also be combined with a meta-analysis of the data extracted during the review process.
Hazardous substances
Based on material standards, material characterization, formulation data and/or chemical analytical testing data, it may be determined whether a hazardous substance as defined in MDR 2017/745 section 10.4.1 or any other regulation is present in a final finished device. If composition data is available, we offer to screen it against the latest version of hazardous substance lists as they are defined in MDR 2017/745 section 10.4.1.
If a carcinogenic, mutagenic, or reproductive toxicant (CMR) of category 1A or 1B and/or an endocrine disruptor as defined in the MDR regulation with potentially greater than 0.1% w/w has been identified on a final device in the course of a biological safety assessment or hazardous substance assessment, further justification, including an analysis of alternatives and a detailed risk assessment are necessary. Our services include the documentation for the presence/absence of such substances and if applicable establishment of a more detailed hazardous substance assessment, including further justification for the presence of the substance, an analysis of alternatives and a detailed risk assessment.
Similarly, if substances from other REACH lists, the California Proposition 65 list or any other regulatory hazardous substance list are identified as present during a biological safety assessment, we might support you with a more in-depth assessment.
Literature reviews & Statistical analyses
Medical Matters offers comprehensive solutions for literature reviews across a wide range of research topics. These reviews can either be:
1. Scoping or Narrative Reviews: These have no specific methodological approach defined, and the literature selection is mainly driven by the intended purpose of the review.
2. Systematic Literature Reviews: These are more exhaustive, with a clearly defined and documented research question, search process, eligibility criteria, and interpretation of findings. A systematic review is defined as a review using a systematic method to summarize evidence on specific questions, with a detailed and comprehensive study plan. It may also include a statistical meta-analysis of the extracted data.
With a profound background in statistics, epidemiology, as well as various fields of science and manufacturing processes, we can support you in the analysis, graphical visualization and interpretation of a wide range of data. We may support you in identifying appropriate statistical methods, study designs and the analysis and evaluation of cross sectional-, time-series- as well as panel-data. Additionally, we provide solutions for managing your leachable and extractable data based on risk management principles outlined in standards such as ISO 14971.
Training courses
We offer tailor-made training courses in any field of our expertise including biocompatibility evaluation, toxicological risk assessment and data handling, analysis and visualization with Excel, Minitab and R, respectively.