ISO 10993

The Risk-Based “Big Three”

Incorporating Biocompatibility, Chemistry, and Toxicology into your Biological Risk Evaluation

In the past, biocompatibility consisted of determining the contact of your medical device, looking at the Table A.1 in ISO 10993-1 and running the test prescribed. This approach put too much emphasis on checking boxes of antiquated tests to screen the biocompatibility risk for modern-day complex devices.

PowerPoint Presentation

The better approach for biocompatibility is to assess the risk of the device through consideration of its materials, geometry, and process residuals. This creates a change to the “Big Three” of biocompatibility which were cytotoxicity, sensitization, and irritation.  The “Big Three” for this new risk based approach are:

  • Biocompatibility assessment can evaluate the impact of the geometry of the device, chemistry results, material research, intended use of the device, and toxicological evaluation to give an overview of risk and safety
  • Chemistry (e.g., chemical characterization, extractables/leachables) gives an understanding of the compounds that are released from a medical device. It provides insight on what the patient’s exposure would be from the use of the device.
  • Toxicological principles, chemistry results, genotoxicity, systemic toxicity, and carcinogenicity risks from the device are all evaluated.

Incorporating these new “Big Three” into your biocompatibility assessment will help to truly understand the risk associated with the medical device and allows the evaluation to be done with the least impact to cost and timelines.

LIVE Webinar: How to Develop a Risk-Based Safety Evaluation per New US FDA Guidance

Register HERE for the three-day live webinar series “How to Develop a Risk-Based Safety Evaluation per New US FDA Guidance” presented by Nelson Laboratories’ experts: Thor Rollins, Sarah Campbell, and Audrey Turley.

This three-day webinar will incorporate the new US FDA guidance on biocompatibility into the three main steps in developing a Biological Safety Evaluation (BSE): Biological Evaluation Plan (BEP), Testing Options, and Biological Evaluation Report (BER). Composed of three one-hour presentations followed by Q&A sessions, the webinar will cover each step in developing a BSE in detail. This webinar will provide insight into regulatory expectations when it comes to evaluating device safety.

The presenters for this three day webinar provide a combined 50 years of experience in their field of expertise. Thor Rollins is a leading biocompatibility expert and has worked closely with medical device companies and the FDA for over 15 years. Dr. Sarah Campbell is a board certified Toxicologist with an extensive 17 year background in practicing and using analytical chemistry for toxicological evaluation. This combination of expertise is important to in order to handle the important aspects of material/chemical characterization and toxicological risk assessment. Audrey Turley has 20 years of experience working in research, laboratory, and test design functions in the medical device industry.


The new FDA guidance document for ISO 10993-1 focuses on a risk based approach to biocompatibility. The first step is to develop a BEP. This webinar will go over the thought process and information needed to develop a useful testing plan.

Date: August 30, 2016
Time: 11:00 AM PDT | 2:00 PM EDT
Duration: 60-minutes


Thor S. Rollins, B.S., RM (NRCM)
Senior Scientist


Justifying out of testing using chemical characterization vs performing full biocompatibility testing. The first important step in determining the risk of a medical device to a patient is to know and understand your materials and processes. This webinar will go over the steps in evaluating device materials and an extractable/leachable chemical testing needed to demonstrate biocompatibility.

Date: August 31, 2016
Time: 11:00 AM PDT | 2:00 PM EDT
Duration: 60-minutes


Sarah Campbell, PhD, DABT


The ISO 10993-1 and new FDA guidance document asks you to write a BER to demonstrate that the identified risks have been mitigated. We will go over the information needed and the important points that should be included in the report.

Date: September 1, 2016
Time: 11:00 AM PDT | 2:00 PM EDT
Duration: 60-minutes


Audrey Turley, B.S., RM (NRCM), CBA (ASQ)
Research Scientist

New Approaches to Assessing Biocompatibility for Medical Devices

Audrey Turley

The regulatory environment for biological safety evaluation of medical devices is changing rapidly. Biological safety evaluations following ISO 10993 have typically been addressed with biocompatibility  testing on animals; however, alternate options are now available using literature research and chemical characterization tests when appropriate to reduce animal testing. Considerable progress is being made in the development and standardization of new in vitro test methods; particularly for cytotoxicity, sensitization and irritation, the basic tests performed for any medical device regardless of the device’s application. These alternative in vitro methods provide multiple benefits, including: less sample amount, less time required to perform the test, and reduced animal use.

Click here to view Research Scientist Audrey Turley’s presentation from MD&M West 2016.

What will be learned:
• Learn how to use a risk assessment approach for process and material changes
• Understand how to use material and chemical characterization to reduce animal testing
• Update on development of alternative in vitro testing methods for irritation and sensitization


Alternatives To In Vivo Biocompatibility Testing

Reconstructed human epidermis (RHE) for in vitro skin irritation and sensitization testing.

Reconstructed human epidermis (RHE) provides an accurate and reliable test system for in vitro skin irritation and sensitization testing.

By: Daniel Olsen, Senior Laboratory Analyst II, Nelson Laboratories

The landscape of biocompatibility assessment of medical devices is an ever-changing and evolving one. Recently, there has been a lot of effort put into the development of alternatives to in vivo biocompatibility testing. Expanding technological capability and increased scientific understanding of the key events in complex biological responses is making this shift to in vitro alternatives possible by enabling the development of accurate, sensitive, and reliable test methods.

Because of the large amount of toxicological data available and increased sensitivity compared to animal tests, the advanced chemical characterization of medical device extractables is largely being seen as a potential replacement for many in vivo systemic toxicity endpoints. This is reflected in Figure 1 of ISO 10993-1, which lists chemical characterization as a first step in the biological evaluation of a new medical device.

Another area that is making great progress in the transition to in vitro alternatives is that of skin irritation and sensitization testing. A number of in vitro test methods for assessing skin irritation and sensitization have been validated and approved for use in chemical, cosmetic and pharmaceutical testing1-3. Many of these methods are being successfully adapted for use in medical device assessment. The final preparations are currently underway for a round-robin validation of in vitro skin irritation testing for medical devices. In addition, recently published research shows promising results for in vitro sensitization using medical device extracts4.

Nelson Laboratories is committed to scientific advancement and is actively engaged in research to assist in the development of safe and reliable in vitro alternative methods. We believe that this transition will be largely beneficial to medical device manufacturers, testing laboratories, and end users.

For more information on these important developments Daniel recommends you read Evaluation of an In Vitro Human Dermal Sensitization Test for Use with Medical Device Extracts, Better Animal Testing Alternatives Are Coming to U.S., and review Nelson Labs’ 2015 SOT poster presentation, Extractable Positive Control for In Vitro Skin Irritation Testing of Medical Devices.


  1. OECD. Test No. 439: In Vitro Skin Irritation.  (OECD Publishing).
  2. OECD. Test No. 442C: In Chemico Skin Sensitisation.  (OECD Publishing).
  3. OECD. Test No. 442D: In Vitro Skin Sensitisation.  (OECD Publishing).
  4. Coleman, K. P. et al. Evaluation of an In Vitro Human Dermal Sensitization Test for Use with Medical Device Extracts. Applied In Vitro Toxicology 1, 118-130, doi:10.1089/aivt.2015.0007 (2015).

BIOMEDevice San Jose Focus On Biocompatibility

BIOMEDevice San Jose - Biocompatibility Training InvitationPlanning your BIOMEDevice conference schedule? Be sure to leave room for Nelson Laboratories, Inc. Nelson Labs will be offering a full schedule of biocompatibility focused lectures at BIOMEDevice San Jose, December 3 – 4, 2014, while also exhibiting in booth #321.

Bob Michaels’ recent Medical Product Manufacturing News (MPMN) Q&A interview with Nelson Laboratories’ biocompatibility expert, Thor Rollins, provides a sneak peek preview of the topics to be discussed in Rollins’ upcoming BIOMEDevice lectures. The following are excerpts from Mr. Michaels’ article, What Types of Biocompatibility Testing Do You Need To Perform? Visit to read the complete interview.

MPMN: Please go into ISO 10993-1 and why cytotoxicity testing is used for screening medical device materials.

Rollins: Cytotoxicity testing is used for screening materials because it is sensitive. In the body, body systems help protect against cytotoxins, protect the cells to wash away any pH imbalances, or even deal with some of the concentration issues or pressures that the cells cannot handle by themselves. Thus, to determine the potential impact of cytotoxicity testing, we take the device and put it right on the cells and then bombard the cells with pH, particulates, and osmotic issues. Thus, during testing, cells are subjected to substances that may not exhibit toxicity in the patient or that could only have a toxic effect if they are present in the body in large quantities. …

MPMN: How should a medical device manufacturer decide which tests are most appropriate for a given device?

Rollins: This is the $1 million question for most of the tests that we perform. …
The amount of data required about a material and the depth of the investigation depends on the intended use of the device and the processes used to manufacture it, in addition to its function and how long it will have contact with the patient. Thus, if you have knowledge of the materials that were used to make the device and data about the potential leachable compounds, this information can be used together with a biological safety evaluation to help pool which types of testing are necessary. In other words, you take the history of the history, the processing methods used to create it, and some chemistry analysis and then evaluate all of these endpoints to help decide which testing should be performed to show that the device is safe. Thus, instead of using ISO 10993-1 as a series of checkboxes, you approach the safety assessment of the device scientifically based on several factors.

Each of Thor Rollins’ BIOMEDevice lectures is slated to focus on a different aspect of the swiftly evolving biocompatibility testing landscape, providing MedTech professionals the knowledge they need to navigate the challenges inherent in contemporary biocompatibility testing. Mark your calendar for Thor Rollins’ three Tech Theater presentations Wednesday December 3rd, and register for his Conference Presentation Thursday December 4th. To learn more visit

Half-Day BIOMEDevice Biocompatibility Lecture Series:
Wednesday December 3, 2014

  • 12:30 pm – 1:15 pm: Rethinking The Big Three: Cytotoxicity, Sensitization, & Irritation
  • 1:30 pm – 2:15 pm: The Power of Chemical Characterization to Assess Changes in Your Medical Device
  • 2:30 pm – 3:15 pm: How the New FDA Guidance on ISO 10993 Could Affect You

Biocompatibility Conference Training (BIOMEDevice registration required):
Thursday December 4, 2014

  • 2:45 pm -4:00 pm: Material Selection and Sampling Techniques for Biocompatibility ISO 10993

Biocompatibility Advancements To Be Showcased At MD&M Minneapolis ǀ Nelson Laboratories

In the midst of an evolving biocompatibility testing and regulatory environment, MedTech professionals face the challenge of staying informed of biocompatibility testing and regulatory trends. Intended to provide MedTech professionals the knowledge and expertise to navigate the challenges inherent in contemporary biocompatibility testing, the upcoming MD&M Minneapolis tradeshow is slated to offer four lectures by Nelson Laboratories biocompatibility expert Thor Rollins.

“Right now we have a very exciting, dynamic, and sometimes challenging biocompatibility testing landscape. I have been on the ISO Committee for almost 12 years and we have never seen as much development in the 10993 standards as we have in the last several years.” Rollins said. “We are in what I would consider the new age of biocompatibility testing.”

Biocompatibility test methods and regulatory behavior have changed dramatically over the last four years. While the future of biocompatibility testing hints at faster, more accurate, cost effective test methods, the contemporary regulatory environment has become increasingly complex. Changes to the ISO standard and diverse regulatory interpretation and application means that merely establishing a testing scheme will be wrought with challenges. According to Rollins, it is not uncommon for regulators to request additional testing beyond the scope of the current ISO 10993 standard. It is these unforeseen complexities that make understanding current biocompatibility testing trends so important for MedTech professionals.

Courtesy of Nelson Laboratories, Thor will be presenting four consecutive biocompatibility testing and compliance focused lectures beginning Thursday October 30th at 10:30 am central time.

MD&M Minneapolis tradeshow participants will be given complimentary access to Mr. Rollins’ three Tech Theater presentations which will include discussion of the Big Three, the power of chemical characterization, and how the new FDA ISO 10993 guidance could affect you.

Thor’s final presentation will focus on the latest FDA trends in biocompatibility testing for cardiovascular devices. This is a conference presentation scheduled to begin Thursday October 30th at 2:45pm. Registration is required.

Half-Day MD&M Biocompatibility Lecture Series:

The Big Three: Cytotoxicity, Sensitization, & Irritation
10:30 am – 11:15 am, October 30th

The Power of Chemical Characterization to Assess Changes in Your Medical Device
11:30 am – 12:15 pm, October 30th

How the New FDA Guidance on ISO 10993 Could Affect You
12:30 pm – 1:15 pm, October 30th

Hemocompatibility and the FDA: The Latest Trends From The FDA
2:45 pm – 4:00 pm, October 30th
Requires MD&M Minneapolis registration. CLICK HERE to register.

Click here to learn more about Thor Rollins MD&M Lecture Series!