What’s the Point of a Biological Evaluation Report?What’s the Point of a Biological Evaluation Report?

What is the point of creating a report with the sole purpose of summarizing information already available in other documents? You already have a biological safety evaluation or biological evaluation plan (BSE/BEP) describing your device and laying out the testing plan. You also have the test reports summarizing the testing protocols and their results evaluating patient safety. Why do you need a document to summarize information that is all available in other documents? It seems like a waste of time and effort, and you have so many other things to complete in preparation for your upcoming submission. If you wonder why a biological evaluation report (BER) is necessary, then this article is for you.

Why a BER is Needed

The information provided in this article applies to all types of submissions, whether to FDA, a European Notified Body as a part of an EU submission, or any other regulatory agency around the world. While the specific requirements for evaluation of biocompatibility may differ around the world, the reasons for preparing a BER do not.

The first thing to keep in mind is your reviewers are human. Maybe they have an enormous pile of information to read and digest to evaluate your submission. Maybe they are tired or, worse yet, hangry. Maybe they have other things weighing on their minds. So, a report that summarizes all the available information regarding the biological safety of your device may be just the thing that your reviewer needs to get through your biological safety documents and have a full understanding of your device and its biocompatibility profile.

Think of your BER as performing these primary functions. It needs to lay out everything you know about your device pertaining to the relevant and current ISO 10993 standards (or, if applicable, ISO 7405 for dental devices or ISO 18562 for breathing gas pathway devices). Your BER also needs to summarize the information contained in other relevant documents (more on this point in a moment), and it needs to point to those documents so that the reader can review them in more depth, if necessary. The goal for your BER is to create a single document that can stand alone and explain all available information regarding the biological safety of your device. Think of the BER as the elevator pitch for your device’s biocompatibility profile.

Information to Include in a BER

At a minimum, the BER needs to include the intention for the submission (e.g., standard market-clearance submission, first-in-human study, de novo device submission), device description and categorization, summaries of test reports, and a conclusion of compliance with ISO 10993-1 or any other relevant standard for the device. Additional information may be needed based on your device and your situation.

If your device is minimally invasive (e.g.,  it involves tissue contact for under an hour ), has all passing results with no blemishes (e.g.,  particulates or elevated testing scores), involves testing that was done under the most recent ISO 10993 standards, and if your engineers have made zero changes to the materials and manufacturing processes since the test articles were created (don’t laugh, it could happen), then the information listed above is likely sufficient for your submission.

If your situation is more complex, additional information will be needed. Other possible sources of information to summarize and cite include the following:

Tips for Writing a Successful BER

My personal motto regarding reports is, “A happy reader is an agreeable reader.” When I am tired and do not want to re-review a reference document to make sure it aligns with the storyline of my current project or to find another reference source to bolster an argument, I remind myself of this motto. I always try to leave a nice trail of breadcrumbs through the document to help the reader stay on the path and to be trusting and agreeable with what has been written. Sometimes this requires additional references or extra legwork up front to make the reader’s job easier.

Next, the goal is to answer all questions before the reader ever asks them. It is also important to digest the often-complicated results or information and present them in a simple manner. It sounds easy, right? It can be, but often it is not. If your device’s test results have some abnormal or unexpected outcomes, provide evidence and sound reasoning to reassure the reader that your device is safe for its intended use. The sooner you do this, the better. For example, some materials (e.g., fabrics, hydrogels, or lubricity coatings) are known to elicit reactivity in a cytotoxicity test. If your device has any of these materials, mention the known cytotoxicity reactivities prior to describing your cytotoxicity report. This may require an extra sentence in your materials section citing a published source that describes the known reactivity. Your reader may be a seasoned veteran who has seen enough cytotoxicity test reports to be able to predict a failure based on a device materials list, or they may be doing their first submission review. Do not target your document to the seasoned professional; target it to the novice reader.

This leads me to the next point: Describe everything in simple terms that someone with a freshly printed college degree will be able to understand without the use of an internet or artificial intelligence search engine. At Nelson Labs, all biocompatibility documents undergo an internal review process. In the past, a colleague warned me that her device description or their storyline was really complicated. My response was (and is) this:, “You are not finished writing. Your device description and storyline should appear simple even to a novice reader.” I believe this issue is a common stumbling block for people who are too familiar with their devices. They often use technical or clinical terminology that is not commonly understood by those with less experience or expertise in the relevant fields. Remind yourself to explain everything in terms your grandparents would also be able to grasp—assuming your grandparents are not trained scientists.

Always perform the final proofreading step by reading your document from start to finish in a single sitting. This is especially important if multiple people have edited different sections. Make sure the storyline flows and no gaps in logic exist so the reader can easily stay with you from start to finish.

The last important point was mentioned earlier in this article. Cite all supporting information, make it available to the readers if they want a deep dive into areas of special interest, and describe the conclusion of these supporting documents. For example, if a toxicological risk assessment is needed to support a BER, include a quote from the conclusion of that document and cite the document number. Do not cite an important document without summarizing its content. That will encourage the reader to stop reading your BER, search for the cited document, and scan it for relevant content. Then the reader may lose track of your storyline. Your job as the writer is to make everything as easy as possible for your reader. Always remember our motto (yes, it should be your motto too now): A happy reader is an agreeable reader. Whether the storyline is simple or complicated with additional discussion points, the goal is the same: You want to keep the reviewer following along from start to finish and agreeing with your evidence and conclusion that the subject device is biocompatible according to ISO 10993-1. And that is the point of a BER.