BiocompCHATibility

In this episode of NAMSA's BiocompCHATibility Podcast, our hosts discuss early feasibility studies and the scope of biocompatibility necessary to get started. They highlight the importance of controlling device response in a small patient group and how this approach shapes biocompatibility considerations within the framework of risk management.“The control measure of just having a few patients is definitely used as a reason why, in part Biocompatibility doesn't need to be as extensive as it needs to be for a pivotal where you have hundreds of people and commercialization where you lose practically all control.” – Don Pohl“I want to make sure I'm choosing materials that I can support in my plan that I know have a general knowledge of safety.” – Sheri Krajewski“There's no specific guidance that tells you what you have to do in terms of testing and what you don't, but the concept is you're going to creep up on everything you'll do. You'll do some biocomp for early feasibility.” – Don PohlKey Discussion Points:Crafting a dynamic biological safety plan that evolves over timeEstablishing a robust evaluation strategy from the beginning to prevent missing important tests laterDesigning studies for high-risk cardiovascular implants and the importance of addressing biocompatibility and safety concerns

n this episode of NAMSA's BiocompCHATibility podcast, we welcome back Dr. Phil Smiraldo (Principal Toxicologist, NAMSA) for his third appearance as an honorary host. The discussion centers on the complexities of equivalency in biocompatibility, examining how equivalency can range from simple to complex and how a predicate device does not always equal equivalency.Listen in as we explore these topics with Dr. Smiraldo and gain insights into the intricate world of biocompatibility and the challenges faced when trying to establish equivalence between medical devices. “The world of equivalency runs the spectrum from incredibly simple to probably way too complex.” – Don Pohl“When we do these types of extractions on, we'll say prior devices and change to device, we're going to have variability within our experiments.” – Phil Smiraldo“You know whether you call it an equivalency assessment or change control assessment. Whatever you want to call it, I mean [10993] part one tells us if there's a change, you have to evaluate it.” – Don Pohl“I guess long story short, you could theoretically go through this whole exercise and end up with the two devices that are equivalent from a systemic toxicity perspective and that's it.” – Phil Smiraldo Key Discussion PointsImportance of confirming identical materials of construction, device categorization, and the IFU to ensure that the device remains equivalentThe detailed process required to establish proof of equivalenceThe critical role of adhering to standards in biocompatibility assessments

In this episode, our hosts are joined by Charles Ducker, PhD (NAMSA's Senior Director of Analytical Services) who recently returned from Korea, where he provided training to the MFDS (Ministry of Food and Drug Safety) about ISO 10993-18. Throughout this discussion, we review the use of the standard and how it is adopted by Korean authorities. We also explore the challenges that lie ahead for device developers and testing labs.“I think they [MFDS] were maybe surprised at the complexity. Laying out the information you have on your materials and the knowledge that you already have that may not lead to doing testing.” – Dr. Charles Ducker“They were interested in how to apply ISO 10993-1 and how you apply ISO 10993-18 to the standard. And they want to know how to assess whether a laboratory has conducted the test appropriately.” – Dr. Charles Ducker“One of the things I thought was very interesting… around Part 18, was what is different now versus the outdated version, and what changes came about. We had a lot of discussion about what is required and one of the big ones was AET [Analytical Evaluation Threshold] and how we calculate it.” – Dr. Charles Ducker“Also, about how we qualify methods, what components go into that and what data you have to have behind the scenes to support the fact that your methods are appropriate for the intended use.” – Dr. Charles DuckerTopics include:Korea's current position with the use of ISO 10993-18Qualification of a laboratory for chemical characterization testingSolvents and temperatures, and the justifications for each

On the latest installment of the BiocompCHATibility podcastis episode, our hosts are joined by Dr. Phil Smiraldo for his third feature3-peat episode on the podcast.The conversation throughout this episode focuses and we discuss on the new recently published FDA biocompatibility guidance document —issued onn September 7, 2023.“My favorite nuance is that annex A has slightly been updated because now the X's and O's are almost all gone.” – Don Pohl“Of these materials, you touch them every day, and your clothes are made out of them... Why would we need to do biocompatibility testing as a device? At a high level, that is what [(Attachment G)] says.” – Don Pohl “There are a few caveats, such as devices made for neonates… they are going to want to see the data. And similar type wording for pregnant woman.” – Phil Smiraldo“We are not saying it's never possible, but you're going to have to really convince us if you only look at Part 1 and not our guidance” – Sheri Krajewski-Bibins“One thing that I do like about this FDA document is it uses the same language from the ISO 10993 series.” – Phil SmiraldoDiscussion points include:Verbiage updates to legally market devices and the fineprint.The Addition of Appendix G and how it can be utilized.A general overview of other changes by the FDA from their previous document.

In this first BiocompCHATibility Podcast episode of 2023, our hosts are happy to introducea new podcast to the NAMSA family, and talk a little bit to the hosts about the insightfultopics to come.This new, conversational podcast will feature a new set of hosts who dedicate eachepisode to trending regulatory and quality affairs topics within the MedTech industry.Future topics include:Refuse to Accept Policy for 510(k)s – This episode will delve into the proceduresand criteria FDA intends to use in assessing whether a premarket notification(510(k)) submission meets a minimum threshold of acceptability and if it shouldbe accepted for substantive review.FDA Releases Draft Guidance: Content of Premarket Submissions for DeviceSoftware Functions – As a follow-up to one of NAMSA's recent blog posts, ourhosts will describe information that the FDA deems important during itsevaluation of the safety and effectiveness of device software with one or moredevice functions.Compliance Pitfalls (Start-up Focus) – This episode will focus on commoncompliance obstacles faced when dealing with documenting procedures,complaint handling processes, supplier controls, audit & training, laboratorycontrols, monitoring and calibration and more.

In this episode, Dr. Phil Smiraldo (NAMSA's Senior Toxicologist) joins us to discuss the test article and the many challenges with identification and preparation. Throughout this discussion, we explore the many different types of test articles and help define what is considered patient contact and what is not? We also review how you can best work with your laboratory to define your test article preparation and make certain the test article definition is clear to the regulatory agency Listeners can expect to learn: How to easily define their test article Key points to consider when separating patient contacting and non-patient contacting devices The risks of including non-patient contacting components in an extract “One of the things we thought we'd elaborate on today is how do I define my test article.” -Sheri Krajewski “We are not going to jump into the GLP regulations and jump into that definition, but we will help define the test article as it relates to biocompatibility.”– Don Pohl “I've even worked through a scenario for a particular device where the customer in fact came onsite to help take it apart.” – Phil Smiraldo “This stuff [prep instructions] needs to be written down clearly so anyone can follow.” – Don Pohl

In this episode, our hosts are joined by NAMSA Associate, Dr. Darin Kent, and second-time guest, Dr Ted Heise, to discuss the new paper released by the FDA and the American Chemical Society. The intention of this latest FDA publication is to examine specific topics that promote continuous discussion around the disparities between where the industry currently stands and how alignment and proper development may occur. Listen in as these industry experts explore the topics covered by the FDA within this document, as well as the challenges faced by medical device manufacturers and testing laboratories regarding chemical characterization testing. They also examine how the FDA fared in the attempt to answer many industry questions. Discussion points include: Thoughts on where to go from here FDA's perspective on alignment in the industry “State-of-the-art” and where that has us today with the chemical characterization of medical devices “The paper really is more about what is being done in devices and what is known about the work in devices.” – Ted Heise “It's striking really, the lack of literature out there about how these technologies and ideas could be used in an NTA [non-targeted analysis] type situation.” – Darin Kent “There's a fundamental need for basic research.” – Darin Kent “In terms of giving solutions of how to deal with the challenges, I think it's less true and part of that is simply that the state-of-the-art is just not well enough developed.” – Ted Heise “It provides arrows pointing to potential solutions.” – Darin Kent “Does current state-of-the-art product devices that are safe or are there areas we have not uncovered yet?” – Don Pohl “What we do better in characterizing medical devices has to bring additional value.” – Ted Heise “One of the concerns is the level of burden that is imposed by the expectations wrapped up in this work.” – Ted Heise You can access the full FDA publication for a fee through here: https://pubs.acs.org/doi/10.1021/acsbiomaterials.1c01119 (Chemical Characterization and Non-targeted Analysis of Medical Device Extracts: A Review of Current Approaches, Gaps, and Emerging Practices.)

In this episode, NAMSA's Senior Product Development Specialist, Ed Arscott, joins our hosts to examine the relationship between packaging and biocompatibility, including: how to evaluate primary packaging for biological safety. The discussion also focuses on the direction provided in ASTM F2475-05 Standard Guide for Biocompatibility Evaluation of Medical Device Packaging Materials. Listeners can expect to learn: Where to look for guidance on packaging evaluation for medical devices Key points to consider when looking at material contact to medical devices Evaluating device/package interaction Assessing cases or primary packaging for reusable devices “I'm happy to help join between the two realms of biocompatibility and packaging.” – Ed Arscott “One common thing in the past was that you saw a lot of cytos being performed on primary packaging.” – Don Pohl “The way that packaging interacts especially with implants; things can occur with packaging and implants that relate directly to product safety.” – Ed Arscott “Part of figuring out what to do or not to do is based on device/packaging interaction.” – Don Pohl “Let's discuss metal trays for instruments; A form of packaging to evaluate as well.” – Sheri Krajewski “Your level of evaluating for the packaging shouldn't exceed the evaluation of your device.” – Don Pohl

In this episode, our hosts are joined by NAMSA Toxicologist, Michelle Kelly, to discuss the ever-elusive biological equivalency claim. The discussion focuses on how to maintain the balance of the risk and benefit of a medical device without stalling innovation. We also explore equivalency and how it is not only a key concept to the risk analysis but also a challenging concept to prove. “This is often a controversial topic.” – Sheri Krajewski “You not only have to think about equivalency per 10993-1, but also think about it as one aspect of equivalency that is sitting in the MDR.” – Don Pohl “Equivalency is one of the key principles that sits in 10993-1.” – Don Pohl “To think of equivalence as a concept rather than an equation is the best thing to do.” – Michelle Kelly “We have that word “same” sneaking up on us. I can see that being interpreted differently by reviewers and regulators.” – Don Pohl “When we developed it [Annex C of 10993-18], we were trying to define toxicological equivalence to help out the working group writing 10993-17.” – Michelle Kelly   Discussion points include:       Equivalence in the 10993 Series, including ISO 10993-18 Annex C       Equivalence under the MDR       Variances in the EU from one Notified Body to another       Challenges with demonstrating and establishing overall MDR equivalence       The concept of “same” and how it is interpreted by regulators

In this episode, our hosts are joined by the QB1 (or 4 of them) of GLP (Good Laboratory Practice), NAMSA's Study Directors. Throughout this podcast, the team delves into the role of the Study Director in biocompatibility and chemical characterization studies, discussing day-to-day activities, legalities, key factors manufacturers should know about working with a Study Director, and the qualifications needed to be an effective Study Director. Discussion points include: GLP and what it means for biocompatibility studies The role of the Study Director in the GLP program The history of adopting GLP guidance from pharmaceutical studies and how they transfer to medical devices “GLP is front and center when submitting to global regulators.” – Sheri Krajewski “GLP is for conducting non-clinical lab studies that support applications and submissions to regulatory bodies with the intent that these studies assure quality integrity of studies.” – Alison Shaffer “We wear a lot of hats both externally with our customers and with the labs.” – Brandon Hahnlen “We like to drive things. Not a lot of people know about this industry {and role of a Study Director} and a lot of us take a fortuitous route to get here.” – Theresa Ford-Wells “One exciting thing is seeing the variety of medical devices. It's neat to see over the years the trends and types of devices coming that we get to work on prior to anyone knowing they exist.” – William Adamiak

In its third year, the North American Biocompatibility Summit (NABS) is a limited-seating event that provides industry insights and expertise sharing on the biocompatibility of medical devices. This year, sessions will include the latest regulatory updates, biological evaluation strategies, and best practices that lead to successful biocompatibility programs in 2021 and beyond.  In this episode, our hosts discuss this upcoming event and what attendees can expect. This includes details on the NABS Scientific Advisory Board, abstract submissions, and how the Board determined what educational opportunities to offer. Listeners will learn more about featured topics, including the overall theme that emerged from the abstracts. “The topics are universal to all medical devices.” Don Pohl “We receive enough abstracts that we have more than enough to choose from and it's interesting to see the trends in the industry of what people are struggling or dealing with.” Don Pohl “There are no cupcake topics at this event, that's for sure.” Sheri Krajewski “It's great to have this opportunity to get out and hear what everyone else is experiencing.” Don Pohl “This is not just a Minneapolis event; anyone from anywhere is welcome to join us.” Sheri Krajewski Discussion points include:What is the North American Biocompatibility Summit and how can one register Expectations attendees can have from this event; from education to networking time. The topics of the event including chemical characterization, toxicological risk assessment and alternative test methods Registration details for the event

NAMSA is pleased to announce that the U.S. Food and Drug Administration (FDA) granted the organization Accreditation Scheme for Conformity Assessment (ASCA) status on July 23. The ASCA Pilot Program, a first-of-its-kind assessment created by the U.S. FDA, reduces the regulatory burden on medical device manufacturers through consensus of biocompatibility testing requirements for efficiency. In this episode, our hosts are joined once again by Lisa Olson, NAMSA's Senior Vice President of Global Laboratory Operations to discuss the importance of this accreditation and what it means to NAMSA. But perhaps most importantly, what this status means for manufacturers who choose to do their testing with ASCA accredited laboratories. “It's the first time the FDA has done this for a biocompatibility lab.” Sheri Krajewski “I believe the FDA was really looking at the value of the tests. There are certain tests like cytotoxicity that are incredibly standardized. In essence, many labs are doing them the same. The FDA did a great job of picking out the studies are well established and many labs know how to do them and have established protocolsfor them.” Lisa Olson “NAMSA is accredited for biocompatibility testing and people would say, aren't you already? NAMSA has submitted biocompatibility testing for many years. Yes, we have. The difference here is the FDA has taken steps to pre-qualify certain tests.” Sheri Krajewski “There might be for ASCA studies limited deficiencies and limited review time. Hopefully none (deficiencies) for these (ASCA) studies.” Don Pohl “What you really care about is the data. And, by having these summary reports, you get rid of all the marketing part of it and some of the ‘fluff' and get a clean report of results. I think it's a great way to have both reviewers and labs focus on the most important part.” Lisa Olson Discussion points include: What biocompatibility tests are included in ASCA accreditation? How can manufactures capitalize on utilizing an ASCA laboratory for their biocompatibility testing? What types of devices are disqualified from ASCA testing? What are the potential challenges when implementing ASCA? How do manufacturers “order” ASCA Testing? Is everything ASCA?

Over the last year, the BiocompCHATibility Podcast hosts have been compiling questions asked by our listeners and training series attendees. In this episode, we will answer your frequently asked questions about all things biocompatibility—and no, we did not answer why Don is funnier than Sheri (it is definitely a growth opportunity for her). Highlights include: The use of clinical data in the biological evaluation Completing chemistry testing before in vitro/in vivo studies Gathering historic data -and how much is useful to the evaluation U.S. FDA and DBT (dose base threshold) values The truth about “whole lifecycle” evaluation “I can certainly do a preliminary risk assessment and not have any extractables testing because part of my plan might be to go do extractables testing; but that doesn’t mean I always need it.” – Don Pohl “If you have clinical data and you are doing a preliminary risk assessment to evaluate the safety of this device, it is general information and cannot be ignored. But, if you are going to use the data to offset the need for a test, it better speak to the endpoint very specifically.” – Don Pohl “For manufacturing, I make sure to understand what was there and what wasn’t there. Mapping the process out is important for the reader of the assessment to understand I have performed the evaluation of the manufacturing and any impact it has on biological safety.” – Don Pohl

In this episode, our hosts are joined by APS’s Senior Director of Biocompatibility Services, Dr. Yan Chen, to discuss NAMSA’s acquisition of APS and the importance of preclinical studies in the biological evaluation of medical devices. This podcast discussion revolves around the many synergies of the combined companies, as well as a technical discussion regarding preclinical studies, preclinical study biocompatibility endpoints, and of course, an energetic game of ‘2 Truths and a Lie’ that will surely bring you a laugh. “We have expanded the possibilities of people who can join us now.”-Sheri Krajewski “We are very excited. We firmly believe that both companies share the same goals to provide high-quality, comprehensive services for medical device development.” – Dr. Chen “Companies are beginning to think about biocompatibility when they should early-on with studies like these. These [preclinical] studies can be so powerful in so many ways.” – Don Pohl “The local tissue response is the most commonly used (biocomp endpoint) in the preclinical study. Sometimes you want a clinically relevant implant site. That is something to keep in mind to combine (preclinical and biocomp) studies.” – Dr. Chen Discussion points include: The importance of preclinical testing to the biological evaluation Early-stage preclinical studies vs. GLP studies and the value they bring to medical device regulatory submissions The challenges of combining preclinical and biocomp studies

In this episode, our hosts answer listener questions regarding the new ISO 10993-23:2021 from NAMSA’s February 3, 2021 webinar. The standard recommends that In Vitro testing be completed prior to In Vivo testing, warranting many questions about how to deal with legacy data, regulatory acceptance and timelines. Our hosts will provide podcasters a full episode of responses, possible scenarios and potential recommendations. “This is an extraction-based evaluation and you will be creating and dosing extracts in most cases. There is not a direct contact equivalent for the In Vitro like there is In Vivo.” Don Pohl “In the past, you used the intracutaneous or primary skin appropriately, then this In Vitro test is for you.” Don Pohl “We have heard from one Notified Body that they are going to be giving a one-year grace period, [meaning the standard just issued in January 2021], they are giving folks until January 2022 to switch to the In Vitro method.” Sheri Krajewski-Bibins “Similar concept to Part 1, if you already have your data collected, it might be worth mentioning in your biological evaluation report. If you feel like you need to [mention] regarding the timing of events, that testing was already planned, executed and performed prior to -23 issuing, therefore, the In Vivo method was utilized.” Don Pohl “If you are having a pre-sub with the FDA, maybe have that conversation too that you would like to do the In Vitro method, and see what they tell you even though there is no official position.” Sheri Krajewski-Bibins “The standard has the one sentence that says In Vivo may be needed post In Vitro to clarify, but it doesn’t necessarily say because you failed or found an irritant….. I think you need to still be careful on your due diligence. Look at your failure in the In Vitro level, understand the materials, your manufacturing process, and confirm you didn’t miss anything.” Don Pohl Discussion points include:What is in the new 10993-23 and what is it not? How do you know if an In Vitro irritation test is right for an implant? Regulatory agency answers on when they will expect In Vitro irritation Limitations of the In Vitro assay What to do if you receive an irritant response in the In Vitro assay

In this episode, our guests are joined by Syntactx’s Dr. Valerie Merkle, Associate Director – Regulatory Strategy, to discuss NAMSA’s recent acquisition of Syntactx. During this one-hour installment, Dr. Merkle discusses her deep-rooted experience at the FDA and the importance of proper biological safety planning to achieve biomechanical efficiency and successful clinical trial execution. Examples will be provided regarding how and when biocompatibility programs go wrong, which often result in derailment of development efforts. How can manufacturers create biocompatibility programs that are observed favorably by the FDA? Learn helpful tips and strategies to help ensure a successful FDA submission. “We really wanted to mirror what we were doing at the FDA.” – Valerie Merkle “You just never know what is going to come in next. It keeps you on your toes for sure.” – Don Pohl “People think biocomp is just a checklist, but there are a lot of rabbit holes you can go down—a lot of ways you can stray off the path unnecessarily. Definitely not a checklist item.” – Valerie Merkle “Make good decisions early-on to not derail yourself later.” – Sheri Krajewski-Bibins “A lot of companies don’t want to provide their thought process. They spend years and years developing and making decisions, FDA only sees what is in front of them and if the background is not there, we see lots of questions.” – Valerie Merkle Discussion points include: Syntactx company overview and strengths they bring to NAMSA Material selection and its importance in avoiding derailment of biocompatibility projects FDA experiences with manufacturers overlooking material testing FDA biocompatibility guidance and its role in regulatory submissions

In this episode, our guests are joined my NAMSA’s Melissa Cadaret to discuss the ever-confusing cytotoxicity failure.  Manufacturers can have more questions created when encountering an unexpected cytotoxicity result and these podcast experts have seen thousands of various cytotoxicity results.  The information provided from a cytotoxicity test can be useful and stressful, so what do manufacturers need to know to navigate the cyto failure, whether expected or unexpected. “I would say we generally see some type of cytotoxicity failure weekly.” –Melissa Cadaret  “Cytotoxicity is not really an end point. It’s a screen.” – Sheri Krajewski-Bibins “It is what it is and it is what it’s not.” – Don Pohl “It’s the only biological effect listed as an overall screen for biocompatibility.” – Don Pohl “Things like copper, and antimicrobials really wreak havoc and contribute to a lot of cytotoxicity failures.  Some of your residues from your cleaning and in processing aspect are also a huge culprit.”  Melissa Cadaret  “It might have been expected.  You can get pretty good at predicting cytotoxicity.” – Don Pohl Discussion points include:  What does it mean when one receives a failed cyto result  What is the useful information you can gather from a cytotoxicity test What typical materials and devices may have problems with a cytotoxicity test What to do if you know your material is going to fail cyto

In this episode, our hosts are joined by Allison C. Komiyama, Ph.D., R.A.C., Owner and Consultant at AcKnowledge Regulatory Strategies and former U.S. FDA reviewer, to discuss the U.S. FDA’s latest draft guidance, “Select Updates for Biocompatibility of Certain Devices in Contact with Intact Skin.”  The FDA has determined the biocompatibility risk of various polymers and fabrics to be low based upon a safe history of use in medical devices for this categorization. Our hosts dive into the list of materials as well as the nuances of this guidance that will ideally help manufacturers with these types of devices receive market access with fewer questions.   “There might be some unnecessary testing going on in some cases.” –Don Pohl “The long history of safe use. U.S. FDA uses a lot of resources to not only review the tests themselves, but they mention they spend resources on review of rationale and justifications; and I think that may be harder than reviewing test reports.” – Allison Komiyama “It was very exciting when we saw this guidance document. We all felt like this was a long time coming.” – Allison Komiyama “Class VI testing might become useful again.” – Sheri Krajewski-Bibins “People are going to be googling Type 4 Sensitivity to figure out what that is because its sitting on a label.” – Don Pohl “I commend the biocomp group on this document.” – Allison Komiyama “I was thinking about a device I’m reviewing right now. I look back at that device and it has stainless steel and aluminum, and if I look at all those polymers, I have co-polymers as well. If I look at this guidance now, I would be left wondering if I can apply everything here or am I going to have to do cyto, sensitization and irritation because I have metals and some co-polymers that aren’t necessarily defined.” – Don Pohl “Guidance is U.S. FDA’s current thinking, and even if it is a draft, we’ve had many reviewers say “there’s a new draft guidance, look at that”.” –Allison Komiyama Discussion points include:  Complete overview of the guidance and implementation Inclusions and exclusions for materials and devices Submission guidelines when applying this guidance Information needed to submit for these types of devices immediately Precautionary labeling instructions that may be necessary

In this episode, our hosts are joined by Lisa Olson (NAMSA’s Vice President, North American Lab Services) to discuss the U.S. FDA’s new Accreditation Scheme for Conformity Assessment (ASCA). This pilot program, launched September 24, 2020 with a https://www.fda.gov/regulatory-information/search-fda-guidance-documents/accreditation-scheme-conformity-assessment-asca-pilot-program (new guidance document), is designed to accredit laboratories for certain biocompatibility tests, allowing for decreased paperwork and time for certain regulatory submissions, among other things. Although this is not specific to the device manufacturer unless they have an in-house laboratory, it is important for manufacturers to understand what ASCA is, how it is implemented and how important it may be when selecting a laboratory testing facility in the future. “For the first time in medical device regulation history in the U.S., the U.S. FDA is going to accredit laboratories.” – Sheri Krajewski-Bibins “If things were inconsistently reported by different laboratories, they [the U.S. FDA] had the responsibility to ask things. So if you can imagine them having to ask the same type of question on a basic cytotox assay for example, how much extra work that created because they [the U.S. FDA] can’t just assume it was done correctly.” – Lisa Olson “They [the U.S. FDA] certainly won’t have to in all cases, review the complete testing report anymore.” – Don Pohl “There’s the founding basis that you have a robust quality system, and that is the basis of the whole 17025 certification, but now the ASCA program allows or requires, however you want to look at, to allow you to get yourself [a lab] accredited to a certain test.” – Lisa Olson “I could certainly see the benefit in trying to normalize that [training] across the industry.” – Don Pohl “It’s an easier button, not an easy button, and manufacturers need to think about then do they go with labs that have no exposure to this program, simply because I think the Agency is going to use that [ASCA] in the background in how they are looking at data, no matter what it is.” – Lisa Olson Discussion points include: When will the program be implemented? How does a laboratory qualify for the accreditation? How can manufactures capitalize on utilizing an ASCA laboratory for their biocompatibility testing? What are the challenges with implementing ASCA?

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

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 SoucyDiscussion points include:How this role is the “famed unicorn” of medical device developmentHow on-the-job training is a critical component to successful assessorsHow long until an assessor is able to work independently on a plan and assessmentChallenges with regulators utilizing an assessment properlyWhat 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 PorterDiscussion points include:How is a presub meeting useful in evaluating the biological safety of medical devicesWhat types of questions are useful to include in a presub What can you expect the FDA to provide to you in a presubHow can you insure the data you are getting from extractables/leachables program will be most usefulWhat can you do to insure the proper FDA personnel is present to answer the questions you have in a Presub meeting

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 PohlDiscussion points include:When to perform a biological evaluation strategy in the product development processMaterial selection and biocompatibilityHow a “passing” test does not mean there won’t be reviewer questionsHow the scope of biocompatibility reaches into the development cycle and planning for biocomp can alleviate challenges down the roadIt’s never too early to start planning for the biological safety of the device

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-BibinsDiscussion points include:Difference between respirators and ventilators and their evaluation processOverview of the US and UK guidance documents for ventilatorsSelecting materials to help control the chemical possibly releasedParticles – and how to produce in a “relatively clean” environmentThe use of these short term ventilators for acute, life-saving care until a CE Mark device could be used

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 TaylorDiscussion 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.

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 occurredAET: How to calculate the number of devices used in clinical use for a chronic device that can be used during someone’s lifetimeWhether NVR used to establish exhaustive conditions affect the AET calculation for analysisWhether the same replicates (single, duplicate, and triplicate) apply to NVRWith 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/

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 “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/

Our hosts are joined this week by Dr. Ted Heise, convenor of TC 194/WG 14 responsible for the re-write and release 10993-18 Biological evaluation of medical devices —Chemical characterization of medical device materials within a risk management process. This much-anticipated standard is expected to provide greater detail and guidance to the use of characterization within the biological evaluation of medical devices.“There are no technical changes allowed when FDIS is translated to International standard” – Ted Heise“The distinction between chemical information and analytical testing is one of the important changes in the new document.” -Ted Heise“You can use this standard to answer different types of questions and that a well-documented plan can justify an approach to answer one question. “ – Don Pohl“The document includes a tabulation of solvents with varying degrees of polarity…. It also emphasizes that your solvents should not degrade your test article.” – Ted Heise Discussion points include:High level overview of the changes to the standardDiscussion of the most significant changes and what it means to manufacturersThe differentiation between material and chemical characterizationDiscussion of degradation of materials and the importance of selecting proper solvents for extractionDiscussion of AET (Analytical Evaluation Threshold)

Our hosts are joined this week by Dr. Jean Pierre Boutrand, VP of North American Laboratory Services at NAMSA.  During this episode the team discusses the new book, Biocompatibility and Performance of Medical Devices.  Jean Pierre is the Editor of this collection of experiences by esteemed authors in the biocompatibility and medical device profession.  This is the second edition of the book, originally published in 2012 and the focus of the new edition is how to accelerate a product to market and ways to plan for evaluation. From the book cover “Biocompatibility and Performance of Medical Devices, Second Edition, brings an understanding of evaluation strategies for ensuring that medical devices and biomaterials are safe and effective and will perform s expected in the biological environments.  This second edition is updated and expanded to include the latest developments in nonclinical research to support rapid market introduction of innovative medical devices and biomaterials.”Discussion points include:Pertinent changes since the 2012 edition that effect today’s marketHow experts and topics were chosen for this edition of the bookHow listeners can win a free copy of the new bookThe inspiration and motivation for this type of book in the industryEnter to win a book at www2.namsa.com/freebook

Our hosts are joined this week by NAMSA colleagues, Dr. Sylvie Framery and Dr. Nicolas Martin  – LIVE from the NAMSA training series event in Frankfurt, Germany.  Sheri, Dr. Martin and Dr. Framery have spent the week conducting NAMSA’s biocompatibility training, and discuss the week’s events, the specific questions that seemed to drive the training this week, and any new awareness received from hearing attendee stories and experiences. “The MDR mentions that the manufacturer must demonstrate, amongst other things, the safety of its device but does not provide any technical solutions.. that’s why we will use the ISO 10993 series” – Sylvie Framery“Regarding using post market data - We can always try… it depends on the quality of the data and device as well… we have to have more precise data to cover biocompatibility endpoints” – Nicolas Martin“If we know the data are out there; to be in compliance with the standard we have to at least look at the data.“ – Don Pohl“What’s the alternative… I’m not doing biocompatibility after 10 years and waiting 10 years” –  Sheri Krajewski-BibinsDiscussion points include:EU harmonization of 10993-1: 2018The Medical Device Regulation (MDR) and biocompatibilityThe use of post market surveillanceHow to prove biological safety for the “lifetime of the device”Access NAMSA testing resources here at www2.namsa.com/MDR

Our hosts are joined this week by NAMSA colleague, Dr. Phil Smiraldo – LIVE from the NAMSA training series event in Philadelphia.  Sheri, Don and Phil have spent the week conducting NAMSA’s biocompatibility training, and discuss the week’s events, the specific questions that seemed to drive the training this week, and any new awareness received from hearing attendee stories and experiences. Discussion points include:Material information and its usefulnessHow to use clinical data for biocomp evaluationMulti component devicesThe hosts each give a main takeaway from the weekAnd ...Dr Smiraldo joins on his first visit to bicompchatibility for 2 truths and a lieTo connect with Dr Smiraldohttps://www.linkedin.com/in/phillip-smiraldo-phd-dabt-9a976717/Access NAMSA testing resources here at www2.namsa.com/biocomptraining

Lisa Olson, NAMSA’s Global Director of Analytical Services joins Sheri and Don on this special episode.  As Lisa is a recent addition to the NAMSA team, our hosts ask about her background, her thoughts on the future and present state of biocompatibility, and most specifically the use of chemical characterization in the biological evaluation strategy.  The hosts also introduce a new game of 2 truths and a lie, for biocompatibility. To connect with Lisa, you can find her here athttps://www.linkedin.com/in/lisa-olson-09659511/

Access NAMSA testing resources here at www2.namsa.com/csipodcast. There are many mentions of extractions throughout international testing standards and regulations. In this episode, ISO 10993-12 for sample preparations and extraction conditions is discussed. What happens to a sample when it’s received at a lab prior to testing? How does the lab actually extract a piece of plastic and when has the extraction gone too far?

Cytotoxicity, sensitization and irritation, sometimes known as CSI, are three of the most common tests performed on medical devices. In this episode, our hosts discuss these tests, common pitfalls and how to address regulatory expectations

In this first episode of BiocompCHATibility, hosts Sheri Bibins (Product Marketing Manager) and Don Pohl (Principal Product Development Strategist) of NAMSA discuss this first-of-its-kind podcast dedicated to all things medical device biocompatibility. Access NAMSA podcasts and transcripts here at www.namsa.com/resources/podcasts