What does the biological evaluation under ISO 10993-1 mean in practice?
Biological evaluation according to ISO 10993-1 is not a single test, but a risk-based process in which chemical, biological, and clinical information are integrated to form a comprehensive picture. The starting point is the intended use, the type of contact, and the duration of exposure of the medical device to the patient and user. Based on this, the Biological Evaluation Plan (BEP) defines which existing data must be used and which tests need to be specifically added. This results in a transparent strategy that meets the requirements of ISO 10993-1 in both the European context (MDR) and – depending on the target market – the US context, in accordance with FDA expectations (including consideration of relevant FDA guidance on biocompatibility).
The starting point is the intended use, the type of contact, and the duration of exposure of the medical device to the patient and user. Chemical characterization according to ISO 10993-18 plays a central role in this process: it provides the list of identified and (semi-)quantified extractables/leachables for the subsequent Toxicological Risk Assessment (TRA) according to ISO 10993-17. Biological endpoints such as cytotoxicity, sensitization, irritation, and genotoxicity are tested in parallel. The results of these components are compiled in the Biological Evaluation Report (BER), which provides a transparent and verifiable explanation of whether the product is biologically safe for its intended use or whether residual risks remain that must be addressed through risk management.
As a testing laboratory, HygCen Germany provides methodologically sound, standards-compliant data: from sample processing according to ISO 10993-12 and the execution of the tests to QES-signed reports. The actual overall assessment is usually carried out by independent toxicologists who combine BEP, TRA, test data, and clinical information. Well-documented sample logic and clear interfaces between the laboratory, manufacturer, and external experts are crucial to ensure that the biological assessment is both scientifically sound and regulatory acceptable.
Key ISO 10993 building blocks (in-house & coordination)
- Cytotoxicity (ISO 10993-5) – in-house.
- Skin sensitization (ISO 10993-10) – in-house.
- Irritation (ISO 10993-23) – in-house.
- Chemical characterization (ISO 10993‑18) – coordinated via qualified partners.
- Sample preparation & reference materials (ISO 10993-12) – in-house
- Genotoxicity (ISO 10993-3) – in-house.
- Hemocompatibility (ISO 10993-4) – in-house.
- Pyrogenicity & endotoxin – in-house; ISO 10993-11 systemic toxicity coordinated via partners if required.
Advantages of biocompatibility testing of your medical devices
Determine registration requirements
A necessary aspect for obtaining regulatory approval of your medical device in the EU market.Risk minimization
An important part of your risk minimization plan, since as manufacturer you are liable for your product.Economization
We can support your product design at an early stage and test preproduction models.
Three reasons to evaluate biocompatibility with Hygcen
Professional evaluation for each test report
The evaluation by our scientific advisor categorizes and elucidates the results of your biocompatibility tests.Cutting-edge test methods
Using the Jena test method, we can determine cytotoxicity of compression stockings, bandages and similar elastic products.Accredited test laboratory
We test medical devices for manufacturers and end users according to European (EN) and international (ISO) standards. We are engaged world-wide and actively contribute to the quality assurance of medical devices.
This is how we test your medical device
- Request a quote - per telephone or online. Please provide the following information: What product would you like to test and which materials is it made of, if known.
- Once you have received our quote, send in your product.
- As soon as your product has arrived at our laboratory we will start the biocompatibility testing. We test your product as provided. Preferably your product should be in the state in which it will be marketed/sold later.
- We test according to ISO 10993 – and depending on the classification of your product. Initially we usually perform cytotoxicity testing. If your product does not pass this test, further testing is not sensible.
- You will receive a digital test report including a professional assessment, secured with a Qualified Electronic Signature (QES). This guarantees the legal validity, integrity, and immutability of your documents – recognized across the world. Our scientific director evaluates the results of the test reports.
Biological tests according to the ISO 10993 standard series
HygCen Germany offers all tests in of the ISO 10993 standard, which are not animal based (in vivo) tests. We test guaranteed cruelty-free, hence no animal testing. In addition, we test medical devices in original delivery condition. This implies that our tests will also detect potential contamination due to production residues, foreign substances and migration from packaging material.
In vitro tests are performed „in the test tube“. Animal welfare enjoys high priority as outlined in EN ISO 10993-1 and 10993-2. Your biocompatibility test plan should therefore focus on in vitro procedures. In vitro tests are rapid, animal friendly and low cost.
In vivo tests utilize living animals. These tests require a long time and incur high costs. If in vitro tests cannot fully assess the risk from a medical device, then in vivo tests become necessary. Implantable medical devices, or devices which come in contact with circulating blood, fall into this category. In vivo tests are used for acute, subchronic and chronic toxicity testing, which are used to judge systemic toxicity and implantation.
- A well-developed biocompatibility test plan is essential for reducing, or even obviate, the need for in vivo tests
HygCen Germany tests without animal tests!
Why ISO 10993‑2 matters within the biological evaluation
ISO 10993‑2 defines animal welfare requirements for biological testing and provides the ethical and procedural framework whenever in‑vivo studies are needed. It ensures that testing is scientifically justified, ethically responsible and aligned with the internationally recognized 3R Principle(Replace, Reduce, Refine).
For your medical device, this means:
- Replace: Whenever feasible, in‑vitro, in‑chemico or analytical methods (e.g., RhE models, AOP‑based sensitization assays, ISO 10993‑18 chemical characterization) are used instead of animal testing.
- Reduce: If in‑vivo studies become necessary, the number of animals is limited to the minimum required for scientifically meaningful results.
- Refine: Study designs are optimized to minimize suffering, apply humane endpoints and improve data quality.
For systemic toxicity testing performed by qualified partner laboratories (e.g., ISO 10993‑11), full ISO 10993‑2 compliance is ensured — including documentation of welfare measures, 3R implementation and standardized handling procedures. This keeps the overall Biological Evaluation ethically robust, scientifically credible and fully aligned with MDR expectations.
The BEP defines the strategy for biological evaluation: which existing data will be used, which additional tests are required and which endpoints can be waived with justification. It connects device characteristics, contact type and exposure duration with the relevant ISO 10993 modules. A well-documented BEP facilitates discussion with notified bodies and lays the groundwork for a consistent BER.
The BER consolidates all chemical, biological and toxicological evidence and answers the key question whether the device is biologically safe for its intended use. It documents assumptions, uncertainties and risk controls and therefore forms a central part of the MDR technical documentation. Without a clear and traceable BER, regulatory approval is generally not feasible.
TRA evaluates the substances identified during chemical characterization with respect to patient exposure and toxicological reference values. For each constituent, it is assessed whether expected exposure remains below acceptable levels or whether potential risk needs to be addressed. TRA conclusions feed directly into the BER and strongly influence the final statement on the chemical safety of the device.
HygCen Germany acts as a neutral testing laboratory, providing accredited test reports, methodological documentation and, where requested, coordination of the overall process. The final ISO 10993-1 Biological Evaluation and the BER are typically prepared by independent consulting toxicologists to ensure an objective assessment. HygCen Germany can involve suitable experts and manage interfaces so that all parties work from a consistent data set.
Sample strategy and extraction design follow ISO 10993-12 and are defined on a risk-based basis, taking into account contact type, exposure duration, materials and processing steps such as sterilization or reprocessing. The goal is to represent a realistic worst-case scenario without creating artificial overload conditions. This documented sample logic forms the methodological foundation for both biological testing and chemical characterization, and ultimately for TRA and BER.
Basic tests such as cytotoxicity can usually be completed within 5–10 days. Comprehensive ISO 10993 biocompatibility evaluations typically require 2–4 weeks after sample receipt, depending on scope.
Provide us with your product details and we will prepare an individual timeline.
Pricing varies depending on the testing scope, material characteristics and the required ISO 10993 strategy. Flat rates are not possible.
We are happy to prepare a non‑binding quotation once we receive key information about your device.
Yes. A stepwise testing strategy is often more cost‑efficient and significantly reduces project risk, especially when materials or design elements are not yet fully finalized. Early‑phase tests such as cytotoxicity, selected extracts or chemical characterization often reveal key issues before a full ISO 10993 test package is required.
We are happy to recommend an efficient test sequence that minimizes cost while meeting all regulatory requirements.
Related Links
ISO 10993-12 – Sample preparation & reference materials, ISO 10993-18 – Chemical characterization, ISO 10993-10 – Skin sensitization, ISO 10993-5 – Cytotoxicity, ISO 10993-23 – Irritation, ISO 10993-3 – Genotoxicity, ISO 10993-4 – Hemocompatibility, Pyrogenicity & endotoxin – incl. ISO 10993-11 coordination