Creating a Biological Evaluation Plan
Biological safety is a fundamental requirement for all medical devices. International standards such as ISO 10993-1 and ISO 14971 emphasize that every device must be supported by a Biological Evaluation Plan (BEP).
A BEP is more than a checklist of tests: it is a structured strategy within the risk management framework that identifies potential biological hazards, evaluates risks, and defines how to address them. Regulatory authorities and Notified Bodies increasingly expect to see a clear, scientifically justified BEP as part of submission packages.
When a BEP Should Be Written
A BEP is required at several critical stages in the device lifecycle:
- Before first human use or clinical trials – to demonstrate the safety of a new device before exposure to patients.
- During regulatory submissions for market approval – as part of the conformity assessment process with Notified Bodies.
- Whenever device changes occur, including:
- Raw material substitutions or supplier changes
- Modifications in manufacturing processes or sterilization techniques
- Shifts in intended use or duration of patient contact
- Introduction of new technologies or materials not previously used in similar devices
Examples of Devices Requiring a BEP
The specific requirements of a BEP vary depending on the type of medical device, its intended use, its materials of construction, and the nature and duration of patient contact. While the overall framework is consistent, each device type presents different biological safety challenges that must be addressed with appropriate testing strategies.
- Cardiovascular stent and delivery system – long-term implant requiring assessment of degradation products, material biocompatibility, and patient safety during extended contact.
- Blood pressure cuff – short-term skin contact device, where irritation, sensitization, or material safety must be addressed.
- Orthopedic pin made of implantable-grade titanium – although titanium is considered biocompatible, ISO 10993 requires documentation and evaluation of potential degradation or leachables.
- Dental implant – in addition to ISO 10993, further requirements may apply, such as ISO 7405, to address unique oral exposure conditions, mechanical wear, and potential interactions with the oral microbiome.
Challenges in Writing a BEP
Developing a BEP is complex. It requires:
- Complete knowledge of materials and additives used in device construction
- Assessment of chemical and toxicological data, including potential carcinogenic, mutagenic, or endocrine-disrupting properties
- Justification of testing decisions with clear, traceable documentation
- Evaluation of extractables and leachables, including their toxicological relevance
- Integration of chemical characterization data with biological endpoints, requiring expertise in toxicology and regulatory science
These challenges highlight that a BEP cannot be developed using a one-size-fits-all approach. It requires careful evaluation and input from experienced professionals who understand both the scientific and regulatory landscape.
A strong BEP not only supports regulatory approval but also demonstrates a manufacturer’s commitment to patient safety and product quality. By carefully tailoring the plan to the specific risks and characteristics of each device, companies can avoid unnecessary testing, accelerate time to market, and build confidence with regulators.
Given its complexity, preparing a BEP requires both technical expertise and regulatory insight—qualities best provided by experienced professionals who can ensure the plan meets international standards and withstands regulatory scrutiny.
