The Facts About In Vitro Irritation

In this episode, our hosts are joined by Dr. Joe Carraway, co-author of the new research paper, “The suitability of reconstructed human epidermis models for medical device irritation assessment: A comparison of In Vitro and In Vivo testing results,” which discusses in vitro irritation assays and their viability for medical device testing. The three Rs in this type of experimentation, which stand for Replacement, Reduction and Refinement, are a concept always considered for new test development. In vitro irritation is one of the latest to reach the normative text of the ISO standards and manufactures and laboratories will need to be prepared to evaluate and utilize this test method. This episode provides in-depth details regarding the timing of the standard, the viability and accuracy of the test method and opportunities and challenges for laboratories and manufacturers related to the standard.

“The standards were written in such a way that it was still an option, and with the release of this new part 23… it essentially mandates what you really need to be doing, if you need to test for irritation {…} if you’ve determined that the next step says you do an in vitro model before going into an in vivo model.” – Dr. Carraway

“The concern with predictive assays is you don’t want to have false negatives. You can live with false positives because you are typically going to do further testing to confirm those.” – Dr. Carraway

“If you have a positive response, one of the approaches is to look at in vivo testing. Here, it’s a point to point comparison of irritation.” – Don Pohl

Discussion points include:

• When will an in vitro method be expected for irritation?
• What was the methodology of this comparison study?
• How does the in vitro method compare against the primary skin and intracutaneous study?
• What are some challenges of the in vitro study?
• What should manufacturers be doing now to prepare for the new ISO 10993-23

*Please note that the opinions discussed throughout the podcast are their own and do not reflect that of their current or former employers.

Also be sure to check out our Biocompatibility Strategy Navigator.

Meet the Speakers

Dr. Joseph Carraway, DVM, MS; Scientific Director, NAMSA

Dr. Joseph Carraway has over 38 years of experience in clinical medicine and surgery, biomedical science and testing procedures, and has worked at NAMSA since 1996. Dr. Carraway is actively involved in designing and conducting various in vivo studies to show “proof of concept,” efficacy, biocompatibility and safety for medical devices and combination productions. He works closely with sponsors and the FDA to design often-unique studies to meet research and regulatory requirements. His knowledge of in vivo models, research methods and regulatory requirements allows him to provide studies that most efficiently meet sponsors’ needs and regulatory approval.

Dr. Carraway has participated in numerous FDA meetings to discuss submission requirements, preclinical study design and interpretation of results. He has authored various publications on preclinical testing requirements for medical devices and has delivered numerous presentations on this subject as well as that of fulfilling ISO requirements within surgical implantation and genotoxicity studies. He is actively involved in ISO committee TC194, which is responsible for establishing the global testing guidelines and requirements for medical devices, ISO 10993: Biological Evaluation Medical Devices. He holds a Doctorate in Veterinary Medicine and an MS in Laboratory Animal Medicine.

Sheri Krajewski-Bibins; Product Marketing Manager – Biological Safety, NAMSA

Sheri joined NAMSA in 2003 and currently serves as Global Product Marketing Manager of Biological Safety. She has supported customers in a variety of commercial operations and management roles, and was an integral leader in the development of NAMSA’s biological safety consulting business. Additionally, Sheri created the much sought-after NAMSA Training Series for the biological evaluation of medical devices. Prior to NAMSA, Sheri was the marketing lead for a mechanical fatigue laboratory and consulting business where she worked primarily with cardiovascular implant manufacturers. Sheri holds a Bachelor’s Degree from the University of Nebraska.

Don Pohl; Principal Product Development Strategist, NAMSA

Don has over 25 years of experience in the preclinical evaluation of medical devices for biological safety. During his career, he has held a variety of positions ranging from laboratory supervision/management, GLP Study Director, Technical Specialist for Laboratory Information Management System, Technical Specialist and Project Manager for Biological Safety and Biological Risk Assessment consultation. He has specific expertise in the evaluation process outlined in ISO 10993-1, as well as the expectations of the USFDA and other countries in their interpretation of the biological safety evaluation of medical devices. Don holds a Bachelor’s degree from Ohio State University.