Ensuring Patient
Safety: A Comprehensive Guide to the
Biological Evaluation of Medical Devices
Dr. T S Kumaravel
Founder Chairman
GLR Laboratories, UK |
Dr. M R Murali, Dr. S S Murugan,
Dr. T S Kumaravel, GLR Laboratories Pvt. Ltd.
INTORODUCTION
The biological evaluation of
medical devices is a crucial part of the regulatory
framework aimed at ensuring patient safety. Experts
with the necessary knowledge and experience should
conduct this evaluation. According to Section B.3.1.4
of ISO 10993-1, “It is critical for the integrity of a
biological risk evaluation that it should be conducted
by assessors with the necessary knowledge and
expertise to determine the appropriate strategy for
the evaluation and ability to make a rigorous
assessment of the available data and to make sound
judgments on the requirements for any additional
testing” [1]. |
Successful biological evaluation depends on
collaboration among various stakeholders [Figure 1]. The
medical device manufacturer provides essential
information about components and materials, including
details on manufacturing and cleaning additives. The
material supplier offers comprehensive data on
composition, including MSDS and CoA. The biomedical
engineer selects suitable materials for device
construction and designs devices to minimize biological
risks. The toxicologist performs toxicological risk
assessments, evaluates data from biological tests, and
recommends strategies for risk mitigation. The
analytical chemist identifies the extraction strategy,
selects appropriate solvents, and conducts chemical
characterization studies to report extractables.
Additionally, the toxicologist, veterinarian, and
pathologist carry out standard biocompatibility tests,
analyze and report results, and provide scientific
interpretations.
Two essential documents in the biological evaluation
process are the Biological Evaluation Plan (BEP)
and the Biological Evaluation Report (BER). These
documents offer a systematic approach to assessing and
documenting the biocompatibility of medical devices,
ensuring that all potential biological risks are
identified, evaluated, and mitigated [Figure 2]. The
overall biological evaluation process should be seen as
an ongoing cycle of improvement. Post-market
surveillance data, feedback from clinical use, and new
scientific findings should be continuously integrated
into the BEP and BER. This iterative approach helps
maintain the relevance and accuracy of the biological
evaluation, ensuring the long-term safety and efficacy
of the medical device.
BIOLOGICAL EVALUATION PLAN
A biological evaluation plan (BEP) is a strategic
document that outlines the approach and rationale for
assessing the biological safety or biocompatibility of a
medical device. This plan is based on ISO 10993 1, which
provides guidelines for the biological evaluation of
medical devices within a risk management process. The
BEP identifies the necessary tests and evaluations to
determine the potential biological risks posed by the
device. It considers the materials used in the device,
its intended use, and existing data to prescribe a
risk-based approach to evaluating device safety. By
understanding these factors, the plan identifies
potential biological risks and outlines the necessary
steps to
address them. Leveraging existing data, including
historical data and previous studies, helps reduce
redundancy in testing. This strategic approach ensures
compliance with regulatory standards and promotes
efficiency and resource optimization in the evaluation
process.
ISO 10993-1 mandates that the biological evaluation of
any medical device intended for human use must be part
of a structured biological evaluation plan within a risk
management process, in accordance with ISO 14971. The
BEP is also instrumental in demonstrating that medical
devices comply with FDA and EU regulations. The FDA
recognizes ISO 10993-1 as a consensus standard that
manufacturers should follow when assessing medical
device biocompatibility. This recognition ensures that
the BEP aligns with the FDA’s stringent requirements for
medical devices, thereby facilitating smoother
regulatory approval processes. The FDA’s guidance
document on use of ISO 10993-1 further underscores the
necessity of developing a BEP to address any knowledge
gaps through biocompatibility testing or other
evaluations [2]. This approach ensures that all
potential risks are adequately assessed and mitigated.
While the Biological Evaluation Plan is not explicitly
mentioned in the EU Medical Device Regulation (MDR), the
regulation obligates manufacturers to provide detailed
information on their devices’ biocompatibility and the
methods used to evaluate it [3]. This requirement
ensures that all medical devices meet the necessary
safety and performance standards before being marketed
in the EU.
Key components of the BEP
A holistic approach to the BEP involves not only
evaluating individual components but also considering
the overall design and intended use of the device. This
includes understanding the clinical context in which the
device will be used, the duration of contact with the
body, and the specific tissues and organs that may be
affected. This broader perspective helps identify
potential risks that might not be apparent when focusing
solely on individual components. The plan starts with a
comprehensive review of the device's materials, design,
and intended use. By understanding these factors, the
BEP identifies potential biological risks and outlines
steps to address them, leveraging existing data to
reduce redundant testing [4]. Thus, the BEP should
include details on the following:
Device description: A comprehensive device
description is essential for the biological evaluation
plan. This section should provide detailed information
about the device, including its materials, manufacturing
processes, and intended use. It should also include a
description of the medical device family, if applicable
and the materials of construction. This information
forms the foundation for understanding the potential
biological interactions and risks associated with the
device.
Intended use: The intended use section outlines
the clinical context in which the device will be used.
This includes specifying the duration of contact with
the body and identifying the specific tissues or organs
that will be affected. Understanding the intended use is
crucial for selecting the appropriate biocompatibility
tests and ensuring that the device is safe for its
designated application.
Device categorization: Device categorization
involves classifying the device based on several
factors, including frequency and duration of contact
with the human body. The frequency of contact can be
categorized as single use, repeated use, or continuous
use. The duration of contact can be classified into
limited exposure (less than or equal to 1 day),
prolonged exposure (more than 1 day but not more than 30
days) and longterm exposure (more than 30 days). This
categorization helps in determining the specific
biocompatibility tests required for evaluating the
device’s safety.
Reasonably foreseeable misuse: Reasonably
foreseeable misuse refers to the use of a medical device
in a manner not intended by the manufacturer, but which
can result from readily predictable human behaviour.
This section addresses potential misuse scenarios to
ensure that the device remains safe and effective even
when used incorrectly.
Risk assessment: Risk assessment is a crucial
component of the biological evaluation plan. It involves
identifying potential biological risks based on the
device’s materials and intended use. This process
includes leveraging existing data to reduce redundant
testing, utilizing historical data and previous studies
to inform the evaluation. By systematically identifying
and assessing risks, the plan ensures that all potential
hazards are addressed and mitigated.
Testing strategy: The testing strategy section
outlines the selection of appropriate biocompatibility
tests to evaluate the device’s safety. This includes
tests for cytotoxicity, sensitization, irritation,
systemic toxicity, genotoxicity, implantation and
hemocompatibility. Additionally, chemical
characterization is performed to identify potential
hazards associated with the device’s materials. This
comprehensive testing approach ensures that all
potential biological risks are thoroughly evaluated,
providing a robust assessment of the device’s
biocompatibility.
Chemical characterization: BEP includes chemical
characterization to identify potential hazards
associated with the device’s materials. This step is
crucial for understanding the material composition and
identifying potential leachable and extractable
substances. By thoroughly analyzing the chemical makeup
of the device, the evaluation can pinpoint any
substances that might pose a risk to patient safety.
This detailed chemical characterization helps ensure
that all potential hazards are recognized and addressed
early in the evaluation process. |