The phrase “First, do no harm” embodies the idea—with threads scattered back through the history of medicine—that when it comes to patient care, safety comes first. It is in defense of this idea that governments have founded regulatory bodies to protect public health in medical matters. Protecting patient safety by ensuring that new medical devices do no harm is also a calling applicable to manufacturers.

Unintended harm inflicted by a medical device can originate from a variety of routes. Consider an implant immediately after implantation: If it is not clean and sterile, it can cause a life-threatening fever or infection. On a longer time scale, there are a variety of adverse effects that can happen, ranging from irritation of local tissues to cancer possibly arising from material issues. Demonstration of biocompatibility is meant to screen for possible adverse reactions a patient may have to medical devices and therefore ensure that first, the device does no harm.

Biocompatibility of medical devices is a complex and evolving subject, the backbone of which is an international standard (actually a suite of documents), ISO 10993. The first chapter, ISO 10993-1, provides an overview of biocompatibility and the suggested approach for risk mitigation from the perspective of materials and processing. The remaining chapters dive deep into topics touching on risk mitigation, from sample preparation to animal studies and how to perform a toxicological risk assessment. FDA generally recognizes ISO 10993 for medical devices submitted for market clearance, and the agency recently released a guidance document on how it recommends ISO 10993 be applied.

Both ISO 10993-1 and FDA’s guidance on its application been updated within the last two years. These updates strongly emphasize using a risk-based approach to biocompatibility, which is in some ways an ideological shift from approaches in the past where biocompatibility could be demonstrated by simply executing a checklist of tests. Now, manufacturers must first understand their device materials and the way they could interact with the body, so that potential risks are identified. Tests to address those risks must be justified when they are selected. Understanding device materials and their potential risks can be challenging, as the formulation of materials may be unknown or proprietary, and identifying potential risks can require specialized knowledge. FDA recommends a process for demonstrating biocompatibility that includes getting and incorporating FDA reviewer feedback.

Demonstrating biocompatibility should proceed in three steps:

• First, a Biological Evaluation Plan (BEP) is created to review device materials, identify potential risks, and suggest possible evaluations and testing to address the risks identified based on the nature of patient contact of the device. This serves as an initial risk assessment outlined in ISO 10993-1 and provides good internal documentation of the approach used to address biocompatibility. This plan can be shared with FDA during a free pre-submission discussion.
   
• Second, the device is evaluated and tested using a variety of methods to address the potential risks identified in the BEP. These risks (and associated tests) include those listed in Annex A of ISO 10993-1. Often, this is accomplished using a combination of the following:
   
  • Traditional in vivo or in vitro biological tests.
     
  • Chemistry tests followed by toxicological risk assessment.
     
  • Written assessment based on scientific literature information and clinical use of the materials.
     
• Third, the results of all tests and written evaluations should be summarized in a capstone Biological Evaluation Report (BER) that is submitted along with test results to FDA.

From:MDDI