In this episode, two esteemed colleagues from Abbott, Tim Schatz and Ken Grove, join our hosts discuss ISO 10993-4:2017 Biological Evaluation Of Medical Devices - Part 4: Selection Of Tests For Interactions With Blood. Our experts highlight the general requirements of this very important and sometimes misunderstood segment of biological evaluations, including how to classify products requiring this test and how various products and scenarios may call testing evaluations. 

 “We are discussing specifically contact with circulating blood directly or contact with circulating blood indirectly at its most basic element.” –Don Pohl

“When assessing blood damage, we really use a battery approach to assess the overall interaction of the medical device with blood.” -Tim Schatz

“In the event with the thrombosis NAVI model, you do end seeing thrombosis, you are allowed to go into using anticoagulation model.” -Kent Grove

“(for platelets and leukocytes) You are trying to make sure that your new device or iteration performs at least as well as your marketed device – it’s a pretty quick test and definitely more sensitive than it used to be.” -Tim Schatz

“Now we have the ability to assess the variability in blood that can come in from one donor vs. the next and what’s interesting is that we have a true positive and true control – it helps us understand how the blood is behaving specifically from a thrombosis aspect.” -Kent Grove

Discussion points include:

• General overview of the standard and applicability to various medical devices
• Strategies for new devices and design iterations
• U.S. and EU approaches, and where they may differ
• Challenges with Non-Anticoagulation Venous Implant (NAVI) studies, including possible improvements for future evaluations
• The blood loop model and the future state of this evaluation

In this bonus episode, our hosts discuss the new FDA Supplementary Information Sheet (SIS) on ISO 10993-18:2020 and their extent of recognition. On July 6, 2020 the FDA released this document to help clarify how manufacturer’s should utilize ISO 10993-18:2020 for US submissions. With this release, may come more questions than answers, so we decided to try to clarify this document and highlight the items that have the most impact to manufacturers and their upcoming submissions.

“There’s certainly a lot to recognize or not recognize when it comes to part 18.” – Don Pohl

“What you’re hoping to see there is something that states complete standard {..} in this instance that is not the case.” -Don Pohl

“Myself and some of our colleagues were pretty much, if we were betting people, we were betting this would not be recognized by the FDA.” – Don Pohl

“Overall, I don’t see these {extent of recognition} as being huge show stoppers for anyone.” – Don Pohl

Discussion points include:

• What is an SIS and how is it helpful
• What does partial recognition really mean
• How do these changes impact the chemical testing we have ongoing
• What are the 5 main parts not recognized and what does that mean to manufacturers

In this episode, our hosts answer your questions about biocompatibility. After 15 episodes of discussing what we think is important surrounding this topic, we asked for your questions and created this special episode to answer them.

“A toxicological risk assessment is the process of focusing on the risk associated with the chemicals that are in or may come out of a device, that’s your primary focus.” –Don Pohl

“The first step to investigation is trying to understand root cause […] what went into to my device that might cause this response.” - Don Pohl

“I love the ever changing environment, and I’m excited about us (the industry) getting better at performing evaluations that minimize unnecessary testing,” – Sheri Krajewski-Bibins

“The reality is, if you look at the grand scheme of things, it (biological evaluation of medical devices) is relatively new in terms of what we are doing – it’s constantly evolving and changing.” - Don Pohl

Discussion points include:

• Updates on In Vitro alternative testing
• How to handle unexpected biocompatibility results
• What genotoxicity methods are preferred by the FDA
• Alternative extraction temperatures accepted by the FDA
• Differences between a toxicological risk assessment and a biological risk assessment
• The future of biological safety evaluations – an exciting outlook

In this episode, our hosts are joined by Nicole Soucy, PhD, DABT from Boston Scientific to discuss qualifications of expert assessors and other personnel qualified to make biological evaluation decisions for medical devices. Documents including ISO 10993-1, Medical Device Regulation (MDR) documentation submissions and BSI best practice guidelines recommend having a qualified individual make decisions for the biocompatibility of medical devices.

While many testing organizations claim to perform this work, what does “qualified” really mean and how do companies determine this qualification?

In this episode, our experts discuss hiring and training processes utilized to identify and grow qualified individuals within their organizations.

“What are the qualifications that a person needs to have to evaluate the biocompatibility of a device? We get questioned about it all the time.” –Don Pohl

“Anytime you have a position open…you’re looking for that needle in a haystack to find someone who is appropriately qualified and has a good, strong background.” -Nicole Soucy

“You are not going to go out and find someone who has a Bachelor’s or Master’s degree—or even a PhD—in medical device biocompatibility; those people don’t exist. There is definitely an on-the-job training component to growing and developing this skill set.” -Nicole Soucy

“A really critical partner in all of this is your analytical chemist. They need to be integrated into you team. You need to have strong chemistry support all the way through your project.” -Nicole Soucy

Discussion points include:

• How this role is the “famed unicorn” of medical device development
• How on-the-job training is a critical component to successful assessors
• How long until an assessor is able to work independently on a plan and assessment
• Challenges with regulators utilizing an assessment properly
• What someone looks for when choosing a qualified individual to perform this work

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

In this episode our hosts are joined by 2 esteemed colleagues from Abbott: Deanna Porter, Kent Grove to discuss the US FDA pre-sub meeting process as it pertains to the biocompatibility of Medical devices.

The group will review the current procedure for a pre-sub meeting and how this opportunity to obtain FDA feedback prior to an intended submission can be very useful, especially for programs containing chemical characterization or other complex testing protocols.

It’s a great opportunity to receive feedback and responses to specific questions, although not guaranteeing approval, the guests show today how using this process saves them valuable time in their biological evaluation.

“When you see 3 responses in a week with 15-17 questions about biocomp, it makes you wonder if there’s a way to make this process more effective.” – Don Pohl

“We focus the presubs and take advantage of this meeting with the FDA” – Kent Grove

“We like to focus the meeting on a specific need, so that we can really zero in on the responses and the guidance that we specifically need.” -Deanna Porter

“Little things can make a difference in profile.” -Kent Grove

“The key to a successful presub is knowing what you know and what you don’t know so you put the right detail into the presub.” -Don Pohl

“Have very pointed questions, not presenting a lot of ambiguity, making sure you understand what you want to get out of them, what answer you are seeking, so that it speaks specifically to the input that you are requiring them to provide.” -Deanna Porter

Discussion points include:

• How is a presub meeting useful in evaluating the biological safety of medical devices
• What types of questions are useful to include in a presub 
• What can you expect the FDA to provide to you in a presub
• How can you insure the data you are getting from extractables/leachables program will be most useful
• What can you do to insure the proper FDA personnel is present to answer the questions you have in a Presub meeting

Opinions are their own and do not reflect that of their current or former employers.

In this episode our hosts are joined by Jeremy Koehler, Director of R&D for Prescient Surgical. Prescient Surgical is a small medical device company in the San Francisco area, with a biocompatibility story to tell.

Their first product submitted to the FDA, although not a high risk device, encountered delays directly related to some biocompatibility testing and the program. As a young start-up this can be very time consuming and most of all expensive.

“As a small company, speed is everything and time is a precious commodity.” Jeremy Koehler

“Externally communicating, limited contact. What more is there to talk about? What gives? As it played out it got a little bit more interesting.” Don Pohl

“The challenge came when we didn’t really have a good scientific justification for what we’d done and why we did it and why it was appropriate and sufficient.” – Jeremy Koehler

“Kind of the moral here is to have a solid scientific plan to help you down the road.” Sheri Krajewski-Bibins

“It’s important to mention that not every change triggers new testing.” Jeremy Koehler

“There’s plenty of projects that I’m involved in where I tell people; You don’t have to do testing, you have to address biocomp but that doesn’t always mean testing.” Don Pohl

Discussion points include:

• When to perform a biological evaluation strategy in the product development process
• Material selection and biocompatibility
• How a “passing” test does not mean there won’t be reviewer questions
• How the scope of biocompatibility reaches into the development cycle and planning for biocomp can alleviate challenges down the road
• It’s never too early to start planning for the biological safety of the device

Opinions are their own and do not reflect that of their current or former employers.

In this special release episode, our hosts are joined by Dr. Phil Smiraldo, Toxicologist at NAMSA.

During this episode the team discusses the current pandemic situation of Covid 19 and the production of ventilators and respirators to help treat and prevent spread of this virus. With companies like Dyson, Ford, GMC and others discussing the design and/or manufacture of ventilators to meet the growing need of infected patients, how do we insure biological safety on a very short term?

Hosts will discuss some guidance put in place by the UK and USFDA alike that address these needs and offer some guidance and solutions.

This is a great example of the evaluation of risk/benefit and how using risk as your guide for biological safety is so critical. These documents go through risk mitigation through various means, which may address evaluation endpoints outlined in ISO 18562, the document that guides the evaluation of air pathway devices.

“Respirator is a protection piece of equipment… technically in the US may not even be a medical device – although a surgical mask is a medical device,” – Don Pohl

“This (ventilator) is an actual instrument that is helping you breathe - whether it’s provided a positive pressure situation or its doing your inhaling and exhaling for you. So these are very different than respirators.” -Dr. Phil Smiraldo

“Biocompatibility associated with all these different guidance (documents) as they pertain to ventilators, masks, respirators - it’s certainly interesting to at least ponder where biocompatibility falls in the grand scheme of things.” – Don Pohl

“The lungs are quite efficient at absorbing chemicals and putting those chemicals into systemic circulation.” – Dr. Phil Smiraldo

“It’s a risk evaluation. Is the short term solution more critical than any long term risks of exposure?” - Sheri Krajewski-Bibins

Discussion points include:

• Difference between respirators and ventilators and their evaluation process
• Overview of the US and UK guidance documents for ventilators
• Selecting materials to help control the chemical possibly released
• Particles – and how to produce in a “relatively clean” environment
• The use of these short term ventilators for acute, life-saving care until a CE Mark device could be used

Opinions are their own and do not reflect that of their current or former employers.

Our hosts are joined this week by Stephanie Taylor, Staff Scientist - Toxicology and Biocompatibility at DePuy Synthes Companies. During this episode the team discusses the reprocessing of reusable devices and the challenges of the ever- changing landscape of the biological evaluation of such devices.

There is activity requested both by the USDA and the EU that greatly impacts the timelines and costs of evaluating these devices for biological safety, so the team shares some strategies and practices used by manufacturers today to meet high regulatory expectations.

“The end goal is a defensible position.” -Stephanie Taylor

“The magic number 6? I don’t know if that’s justifiable.” - Don Pohl

“What’s your biocomp at the end of life – you have to be able to figure that out.” - Stephanie Taylor

“Biocomp is interesting, challenging and a little bit magical at times.” – Stephanie Taylor

Discussion points include:

• Why the great concern with such devices?
• The differentiation between an end of life evaluation and what might be expected currently by the USFDA.
• The great cost and time involved in such evaluations and burdens on manufacturers.

Opinions are their own and do not reflect that of their current or former employers.

During this episode, our hosts are joined by Andy Wyen, Toxicologist at NAMSA, to answer questions received during NAMSA’s live Webinar on the new ISO 10993-18:2020. As this new standard is a complete re-write from the 2005 version, it is stirring up industry and leaving many manufacturers confused and searching for the most efficient adoption methods.

Topics include:

• Triplicate testing and how to determine if there is low variability in a sample before extraction has occurred
• AET: How to calculate the number of devices used in clinical use for a chronic device that can be used during someone’s lifetime
• Whether NVR used to establish exhaustive conditions affect the AET calculation for analysis
• Whether the same replicates (single, duplicate, and triplicate) apply to NVR

With the release of 10993-18:2020 on January 15, 2020, it is crucial for professionals involved with the Biological Evaluation of medical devices to understand the standard’s use, interpretation and requirements, as well as how an effective link now exists to the overall Biocompatibility Evaluation as described in ISO 10993-1.

Connect with Andy: https://www.linkedin.com/in/andy-wyen-3448486/

Opinions are their own and do not reflect that of their current or former employers.

Our hosts are joined this week by David Parente, Director of Global Sterilization at and Biological Safety at Ecolab.  During this episode the team discusses Dave’s chapters in the new book, Biocompatibility and Performance of Medical Devices.  Dave has a long history with the biological evaluation process, including founding NAMSA’s first biological safety consulting team, NAMSA Advisory Services.  For many years Dave has been teaching and writing about the importance of a plan.  Additionally, Dave has years of experience as a manufacturer facing the challenges of meeting biological evaluation expectations from regulators.

“It all speaks to the importance of a plan.. plan, evaluate, plan, evaluate.  Things change and you have to do this continually” – Don Pohl

 “Every device does not fit on this table.”  Sheri Krajewski-Bibins

“If your truly understand the risks your device introduces udrin it’s intended use– that’s an active means in evaluating biocompatibility ” – Dave Parente

Opinions are their own and do not reflect that of their current or former employers.

“As a segue to the 2018 version of 10993-1 and it’s greater emphasis on one of the aspects of biocompatibility – manufacturing effects on the safety of a device” – Don Pohl

“Originally everyone just said this is a checklist – and credit to TC 194 they have slowly over the past 10 years or so transformed biocomp to what it should be – it’s risk assessment.  There are several degrees of risk..…  If I have to mitigate this risk, then what’s my plan for mitigation?”  Dave Parente

Connect with Dave here https://www.linkedin.com/in/davidmparente/