When bringing a medical device to market, demonstrating biocompatibility is more than just a checkbox–it’s a critical part of ensuring patient safety. That’s where the Biological Evaluation Report (BER) comes in. Governed by ISO 10993-1: Evaluation and testing within a risk management process, the BER is the cornerstone of biological safety documentation for medical devices.
The question is, what exactly needs to go into a BER? Whether you’re writing your first report or revisiting your approach for a new device, this post breaks down the essential components you need to include, based on ISO 10993-1 in alignment with ISO 14971’s risk management framework.
1. Executive Summary
The executive summary provides a high-level snapshot, outlining the purpose, scope, and outcome of a biological evaluation. This includes a clear conclusion regarding the biological safety of the device based on all available data. The purpose of the executive summary is to give the reader an immediate understanding of:
- What the device is
- What the device is used for
- Whether the biological evaluation supports device safety
2. Device Description
This section includes specific details on the device:
- The intended purpose and use of the device and its clinical application
- A technical description (shape, size, material interfaces)
- Device classification (Class I, II, III, etc.)
- Illustrations or images, if relevant
A description of patient contacting components, anatomical site(s) of contact, and duration of exposure should be included in order to define the scope of biological evaluation per ISO 10993-1.
3. Materials of Construction
A list of all materials and components in direct or indirect contact with the body should be provided. Information should include:
- All material names and functions that contact the patient, directly or indirectly
- Information on material grade, processing aids, surface coatings, and adhesives
- If possible, supplier declarations or specifications
- Packaging materials that directly or indirectly contact the medical device
Understanding material composition is fundamental to predicting biological risks.
4. Contact Type and Duration
ISO 10993-1 categorizes biological risks based on type and duration of body contact, which helps determine which biological endpoints you must assess. The nature (e.g., surface, tissue/blood path, implant) and duration of patient contact (limited, prolonged, long-term) must be defined. These parameters determine the relevant biological endpoints per ISO 10993-1 Table A.1.
- Contact types: Surface (skin, mucosa), externally communicating (blood path, tissue), or implant
- Duration: Limited (<24 hours), prolonged (>24 hrs to 30 days), or long-term (>30 days)
This categorization drives testing requirements.
5. Risk Assessment and Testing Justification
This section identifies potential biological risks, compares existing data against ISO 10993 requirements, and justifies any testing omissions. It should align with the device’s risk management profile and consider:
- Historical data from predicate devices, if applicable
- Literature-based evidence
- A gap analysis comparing existing data with ISO 10993 recommendations if needed
- Rationale for which tests were (or weren’t) performed
If historical data is being leveraged, predicate devices or scientific literature can provide support for your conclusions.
6. Biological Endpoints Table
Each biological endpoint from ISO 10993-1 must be addressed. The evaluation basis can include:
- List all relevant endpoints, in vivo and in vitro
- Explain how each was addressed (e.g., via testing, literature, or justified omission)
- Chemical and toxicological data, if applicable
- Scientific literature or prior to use of equivalent materials
A summary table mapping endpoints to evaluation methods is recommended to enhance clarity and traceability.
7. Chemical Characterization Summary
A synopsis of analytical testing (per ISO 10993-18) used to identify extractables and leachables should be included (if applicable), and the points below should be included as well:
- Test conditions including methods used to detect extractables/leachables, as well as solvents, temperature and duration of extraction
- Detected substances and concentrations
- Relevance of findings to patient exposure
Where applicable, substances of concern must undergo further toxicological evaluation. Threshold of Toxicological Concern (TTC) or margin of safety (MoS) calculations should also be included, if applicable.
8. Summary of Biological Testing
If testing was done (e.g., cytotoxicity, sensitization, etc.), the report should include:
- A brief summary of methods and results
- Confirmation that testing followed GLP and relevant ISO standards (e.g., ISO 10993-5)
- References to full reports (usually in annexes or technical files)
It is ideal to make it easy for the reader to find what they need without repeating the full data.
9. Toxicological Risk Assessment (TRA)
This is often needed when chemical characterization identifies potentially toxic substances. Your TRA should include:
- Identity and toxicity profile of each substance
- Estimated patient exposure based on contact and leachables data
- Margin of safety (exposure vs. tolerable intake)
- A conclusion on biological risk
Sound science and clear logic are key here.
10. Integrated Evaluation of All Data
Pull everything together:
- Testing results
- Literature data
- Chemical and toxicological information
- Historical knowledge of materials or devices
This is an evaluation of whether all relevant risks have been identified and mitigated. If any residual risks remain, explain why they are acceptable within the device’s benefit-risk profile.
11. Conclusion
State it plainly: based on the data, is the device biologically safe for its intended use?
This should:
- Reference the endpoints considered
- Mention any limitations or ongoing evaluations
- Affirm that the risk is acceptable within the intended use and exposure context
12. References and Annexes
Last but not least, include:
- Full citations for all literature, standards, and technical references
- Appendices or annexes with supporting data, tables, and testing summaries
The BER is not merely a collection of test results, it is a structured scientific justification for the biological safety of a medical device. A well-documented BER supports regulatory submissions, facilitates market access, and most importantly, ensures that patient safety is appropriately evaluated through a risk-based framework.
Frequently Asked Questions (FAQ)
Is biological testing always required to complete a BER?
No. Biological testing is not always required if sufficient data exists such as material characterization, toxicological risk assessments, or historical data on the same materials in similar applications. This includes the use of predicate devices that are composed of identical materials, similar manufacturing and sterilization processes, and shares the same intended use and contact profile. ISO 10993-1 encourages a risk-based approach, emphasizing the use of existing data whenever possible to reduce unnecessary animal testing.
What are some common deficiencies seen in BERs during regulatory review?
Some common issues include incomplete material identification, lack of justification for omitted endpoints, unsupported use of historical or literature data, and the absence of toxicological assessments for identified extractables/leachables. Ensuring a clear rationale and comprehensive documentation for all conclusions is essential to avoid delays or regulatory rejections.
How is the BER different from a Toxicological Risk Assessment (TRA)?
The BER is a comprehensive report that may include a TRA as one component. The TRA focuses specifically on evaluating the biological risk of identified chemical constituents based on toxicological thresholds and exposure estimates. The BER integrates the TRA with other lines of evidence (e.g., test results, literature, historical use, etc.) to support a holistic safety conclusion.
Should the BER be updated after product changes?
Yes. Any material or process changes, or any modifications to contact duration or route of exposure may impact biological safety. In such cases, the BER must be reviewed and revised as needed to assess whether the previous conclusions remain valid or if additional testing/data is needed.
References
ISO 10993-1:2018: Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process.
ISO 10993-17:2023: Biological evaluation of medical devices – Part 17: Toxicological risk assessment of medical device constituents.
ISO 10993-18:2020/AMD 1:2022: Biological evaluation of medical devices – Part 18: Chemical characterization of medical device materials within a risk management process.
