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Impact of 2017/745 EU Medical Device Regulation (MDR) on Biological Evaluation of Medical Device

Webinar Recording | Presentation Slides

Date and Time: Thursday, January 16, 2020 at 11:00 pm–12:00 pm (EST)

Speakers: Jeremy Tinkler, Director of Regulatory Consultancy and Quality Assurance, MedPass International SAS;
Varun Sukumaran, Senior Strategic Consultant, MedPass International SAS

Brief Abstract: This webinar will focus on the impact of the 2017/745 EU Medical Device Regulation (MDR) on biological evaluation of medical devices. The webinar will compare relevant MDR General Safety and Performance Requirements (GSPR) with the Medical Devices Directive (MDD) Essential Requirements; compare MDR GSPR with ISO 10993 and ISO 14971; and discuss the impact of changes in ISO 10993-1:2018 and other ISO standards. A generous Q&A session is planned to accommodate conversation with the speaker—Chairman of ISO/TC 194 Biological Evaluation and Director of Regulatory Consultancy and Quality Assurance at an EU Authorized Representative, regulatory consultancy, and CRO.

Biological Risk Assessments for Ocular Medical Devices

Webinar Recording | Presentation Slides

Date and Time: Wednesday, August 28th at 12:30 pm–1:30 pm (EST)

Speaker: Simona Bancos, Ph.D., Center for Devices and Radiological Health, U.S. Food and Drug Administration

Brief Abstract: This webinar will focus on reviewing the changes to the International Standard Organization (ISO) Fifth edition 10993-1:2018 and whether these changes have an impact on ophthalmic device biocompatibility assessments and on 2016 FDA Biocompatibility Guidance. The discussion will include an overview of relevant vertical standards and FDA guidance documents for ophthalmic devices including ISO 11979-5 Ophthalmic implants—Intraocular lenses- Part 5: Biocompatibility and Premarket notification (510(k)) FDA guidance document for daily wear contact lenses. The applicability of chemical characterization to the biological evaluation of ophthalmic medical devices will also be discussed.

CDRH Scientific Perspective on Analytical Testing and Toxicological Risk Assessment for Medical Devices

Webinar Recording | Presentation Slides

Date and Time: Wednesday, May 22, 2019 at 11:00 AM–12:30 PM (EST)

Speaker: Alan Hood, Berk Oktem, and Jennifer Goode, Center for Devices and Radiological Health, U.S. Food and Drug Administration

Brief Abstract: Analytical testing as part of chemical characterization is used to determine the extractable or leachable substances (E/L) including additives, degradants and impurities, present in patient contacting components of medical devices. Analytical testing generally involves one or more extractions followed by use of multiple analytical methods with sufficient sensitivity to identify and quantify E/L substances that could raise a toxicological concern. In this presentation, we will provide an overview of current regulatory review considerations for submissions to FDA/CDRH that contain analytical chemistry data and toxicological risk assessment information. Specific topics covered will include methodological approaches and reporting, including but not limited to, extraction design, analytical instrument/tool selection, sample manipulation, system suitability, calibration, identification/quantification, and data reporting. The selection and application of the analytical evaluation threshold (AET) will be discussed. There will also be discussion on when to conduct a toxicological risk assessment, the current state of reporting, and some considerations for assessing hazard, exposure, dose-response and risk characterization.

MDCPSS Sponsored Events at the 2019 SOT Annual Meeting and ToxExpo

  • MDCPSS Evening Reception: Wednesday, March 13, 2019 from 6:00 pm–7:30 pm (Hilton Baltimore Key 6)
  • MDCPSS Mentoring & Membership Mixer: Wednesday, March 13, 2019 from 8:00 pm–10:00 pm (the bar at Sullivan’s Steakhouse, 1 E. Pratt Street Suite 102, Baltimore, MD 21202)
  • Executive Committee Officers Meeting: Tuesday, March 12, 2019 from 8:00 am–9:00 am (Bistro 3000 Restaurant, Baltimore, MD)
  • Sponsored Workshop: Time for a Change: The ISO 10993 Standards and Irritation Testing of Medical Devices (Chaired by Kelly Coleman), Monday, March 11, 2019 from 2:00 pm–2:55 pm (CC Ballroom IV)
  • Exhibitor-Hosted Session: Case Studies and Challenges of Risk Assessments using Physical and/or Chemical Information Per ISO 10993 Part 1: Presented by WuXi AppTec, Wednesday, March 13, 2019 from 10:30 am–11:30 am (CC Room 339)
  • MDCPSS Poster Tour: Wednesday, March 13, 2019 from 1:30 pm–3:00 pm at the Medical Device Poster Session, Poster #371–392 (CC Exhibit Hall meet near poster #371).
    • A member of the mentoring committee will chaperon interested students/postdocs through the medical device posters, help with poster discussion, and explain the significance of posters to the medical device and combination product industry.
    • Students/postdocs interested in the poster tour please email Whitney Christian or Megan Hahn.
  • Mentoring Q&A Event: Wednesday, March 13, 2019 from 5:00 pm–6:00 pm (Hilton Baltimore Key 6)
    • Stop by to discuss what it means to be a medical device and combination product toxicologist.
    • This is a casual round table Q&A conversation between students, postdocs, and professional toxicologists interested/involved in the medical device and combination product industry.
    • Contact Whitney Christian.
  • MDCPSS Mock Interview/CV Review Session: Wednesday, March 13, 2019 from 5:00 pm–6:00 pm, (Hilton Baltimore Key 6)
    • Students/postdocs interested in undergoing a mock interview should email their CV to Whitney Christian or Sarah Campbell. The CV will be used to generate questions for the mock interview.
    • Spaces to participate in the mock interview are limited; please email as soon as possible to assist with scheduling.
  • After the mock interview, the interviewer(s) will review the CV of the interviewee and offer suggestions for improvement.

ISO 18562 biocompatibility evaluation of breathing gas pathways in healthcare applications, what does it cover and how to put it to use

Webinar Recording | Presentation Slides

Date and Time: Wednesday, November 14, 2018 at 11:00 AM–Noon (EST)

Speaker: James Morrison, Senior Consultant at Brandwood Biomedical

Brief Abstract: The ISO 18562 series of standards Biocompatibility evaluation of breathing gas pathways in healthcare application was published by ISO in 2017. The series includes four parts, which cover the current thinking on gas pathway requirements. On June 7th 2018, US FDA added the ISO 18562 standards to their list of Recognized Consensus Standards, with partial recognition. ISO 18562 standards are now referenced in the newly released ISO 10993–1:2018, as international acceptance of these standards increases.

Unlike the ISO 10993 series of biocompatibility standards, which is a set of biological test methods, ISO 18562 evaluates biocompatibility using a set of toxicol ogical risk analyses. These toxicological methods are not novel, but their application in this way will greatly expand the knowledge and use of these concepts.

In this webinar, we discuss the four published standards, their applications, and add commentary about putting them into practice in real word situations.

The Application of Reconstructed Human Epidermis (RhE) Models as an In Vitro Skin Irritation Test for Detection of Irritant Activity in Medical Device Extracts.

Webinar Recording | Presentation Slides

Date and Time: Wednesday, May 9, 2018 at 11 AM (EST)

Speaker: Dr. Wim De Jong of RIVM

Brief Abstract: Assessment of dermal irritation is an essential component of the safety evaluation of medical devices. Testing the irritant capacity of medical device extracts is currently performed by either topical or intradermal injection in rabbits. Attendees will learn about an international validation study that evaluated living human tissues as potential replacements for the rabbit irritation test. In the chemical industry, the RhE model as described in OECD Test Guideline 439 is used to identify irritant chemicals. Although the basic principles remain the same, for application in other domains, adaptation of the assay may be necessary. Therefore, the OECD 439 protocol was modified for testing of medical device extracts. This modified protocol was first evaluated to demonstrate the presence of spiked irritant chemicals added to medical device extracts to show the capability of the modified RhE test protocol to detect irritants in a complex extract mixture. The real proof of the test would be to detect irritants in extracts of medical devices or materials used in the production of medical devices. Therefore, specific polymer materials were prepared containing irritant chemicals within the polymer matrix. With these materials two RhE models, EpiDerm™ (MatTek, Inc.) and SkinEthicTM RHE (EpiSkin, SA), were evaluated in an international round robin study. The read-out endpoint was the same as in OECD 439, that being tissue viability by the MTT method; in addition, Interleukin 1a release was also considered. In order to enhance the impact and future implementation of the RhE assay for medical device safety testing, a broad range of stakeholders were encouraged to join the round robin. Participants included medical device companies, contract research organizations, university and governmental laboratories. The results of the round robin study showed that RhE tissue models could detect the presence of strong skin irritants at low levels in dilute medical device polymer extracts. Consequently, the protocol will now be adapted and proposed as a new ISO 10993 standard for medical device irritation testing.

Assessing the Hazards of Fluoropolymers, a Class of Per- and Polyfluoroalkyl Substances (PFAS)

Webinar Recording | Presentation Slides

Date and Time: Tuesday, February 27, 2018, 11:00 am–12:00 noon Eastern Time

Speaker: Barbara Henry, PhD, Toxicologist, W.L. Gore and Associates

Brief Abstract: This webinar will be of interest to all toxicologists who perform toxicological risk assessments. The regulation of per- and poly-fluoroalkyl substances (PFAS) is a growing topic of interest, due in part to the widespread detection of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Some believe the most appropriate approach to PFAS regulation or consideration of their potential risks is to lump together both polymeric and non-polymeric categories, treating them as if they were a single class of substances. Fluoropolymers become aggregated into the highly broad PFAS classification without regard to distinct characteristics that qualify them as meeting the globally accepted criteria for Polymers of Low Concern (OECD, 2009; BIO by Deloitte, 2015).

A new paper, in review for publication in Integrated Environmental Assessment and Management (IEAM), is intended to drive further clarity on the broad group of chemistry known as PFAS. The authors conducted a thorough review of the regulatory history of the hazard assessment of polymers and non-polymers, as well as the scientific foundation for the resulting paradigm ("polymers of low concern"), and they articulate a clear and compelling scientific basis for segregating fluoropolymers from other PFAS. Separation of fluoropolymers from the larger list of thousands of substances grouped into five different classes of PFAS is based upon the authors' demonstration that fluoropolymers constitute a distinct class within the PFAS group and, therefore, should be considered separately for hazard assessment or regulatory purposes. The paper further establishes that grouping fluoropolymers with all classes of PFASs for "read-across" or structure-activity relationship assessment is not scientifically appropriate, when a complete, good quality data set exists, as it does for fluoropolymers.

Quantitative Structure Activity Relationships: An Overview

Webinar Recording | Presentation Slides

Date and Time: Tuesday, November 14, 2017, 11:00 AM to 12:00 Noon EST

Speaker: Dr. Prachi Pradeep, US EPA/ORISE

Brief Abstract: Chemical risk assessment is often limited by the lack of experimental toxicity data for a large number of diverse chemicals. In the absence of experimental data, potential chemical hazard is often predicted using data gap filling techniques such as quantitative structure activity relationship (QSAR) models. QSARs are theoretical models that relate a quantitative measure of chemical structure to a physical property or a biological effect. QSAR tools are a widely utilized alternative to time-consuming clinical and animal testing methods, yet concerns over reliability and uncertainty limit application of QSAR models for regulatory chemical risk assessments. The reliability of a QSAR model depends on the quality and quantity of experimental training data and the applicability domain of the model. This talk will describe the basics concepts and best practices in QSAR modeling, principles associated with validation of QSAR models, summary of available QSAR tools, limitations and challenges in the acceptance of QSAR models within a regulatory framework, and the current status and prospects of QSAR modeling methods in the medical devices community.

Regulations, Standards and Practices for Biocompatibility & Toxicology Assessment in China

Webinar Recording | Presentation Slides

Date and Time: Friday, October 13, 2017 11:00 AM to 12:00 Noon EST

Speaker: Chenghu Liu, Director, Biological Evaluation Department, Shandong Quality Inspection Center for Medical Devices Jinan, China

Brief Abstract: The purpose of this webinar is to help participants learn about evaluating biocompatibility of medical devices in China. In recent years, the China Food and Drug Administration (CFDA) has released several important policies and regulations that impact local medical device submission and registration. At the same time, local biocompatibility evaluation standards have also evolved to align with advances in the global ISO 10993 standards. Technical Committee 248 of the Standardization Administration of the People’s Republic of China (SAC) is currently based at the Shandong Quality Inspection Center for Medical Devices and is chartered with establishing local biocompatibility standards. The current Chinese GB16886 standards were adopted from the ISO 10993 standards and are essential for biocompatibility evaluation in China. In addition, China has also developed specific test method standards to supplement the GB16886 standards. This webinar will provide an overview of the current status and future trends in biocompatibility evaluation, regulatory requirements, and best practices in China.

ISO 10993–1 Biological Evaluation—The Risk Management of Unstudied Extractables and Leachables (E&L) Impurities in Medical Devices and Combination Products

Date: April 10, 2017, 11:00 AM–12:30 PM EST

Use of In Silico Modelling in Preclinical Testing, Co-Sponsored with IVAMSS

Webinar Recording | Presentation Slides

Speaker: Kim Li, PhD, DABT, MPH, Amgen Inc. Thousand Oaks, CA

Abstract: In 2016, the FDA issued final guidance on the use of ISO 10993–1 “Biological evaluation of medical devices—Part 1: Evaluation and testing within a risk management process.” The guidance describes a framework whereby chemical characterization of device materials and the toxicology assessment of the extractables and leachables (E&L) impurities may reduce certain biocompatibility testing requirements.

The chemical characterization of the device materials and components is often a comprehensive profile with known as well as tentatively identified structures (TIS). TIS may result from degradation and/or fragmentation of the chemical additives and processing aids used in the production of polymeric materials. The polymeric materials of construction in medical devices are also common materials of construction for bioporocess materials and primary containers that have direct contact with drug product. Therefore the widespread use of polymeric materials underscores the need for a holistic approach in the evaluation of leachables in combination products. Protein therapeutics are more susceptible than chemically synthesized drug products to the leachables that may impact product safety and quality.

While the risk assessment of known chemical compounds is well established based on the known toxicity endpoints (e.g. target organ toxicity, mutagenicity, carcinogenicity and reproductive/developmental toxicity), TIS are unstudied chemicals for which the current risk assessment practices and threshold concepts may not apply. However, it is neither practical nor technically feasible to conduct animal testing on TIS. On the other hand, biocompatibility tests using extracts as described in ISO 10993–12 do not have the specificity nor sensitivity offered by chemical characterization and toxicology assessment of the E&L profiles of the test materials.

This presentation will examine the science- and risk-based decision analysis to integrate the current threshold concepts with in silico tools for the screening of TIS impurities. The presentation will discuss the three different modules of Toxtree (IdeaConsult): in vitro mutagenicity (Ames test) prediction, Cramer classification for systemic toxicity and protein binding alerts. When integrated into a systematic analysis, these modules offer understanding of the chemical reactivity and toxicity for the TIS, which may form the basis to reduce certain unnecessary biocompatibility testing.

Animal-Specific Modelling for the 3R in Preclinical Assessment: A Bone Drugs Example

Webinar Recording | Presentation Slides

Speaker: Marco Viceconti, Executive Director, Insigneo Institute for In Silico Medicine, The University of Sheffield and Sheffield Teaching Hospital NHS Foundation Trust

Date: April 10, 2017, 11:00 AM–12:30 PM EST

Abstract: There is a growing societal pressure toward the Reduction, Refinement, and Replacement (3R) of animal experimentation in most developed countries, primarily motivated by ethical considerations. But there is also a growing concern that the approach used to test the safety and the efficacy of products potentially affecting human health needs some serious revision: a 2014 report of the Tufts Center for the Study of Drug Development suggests that the cost to take to the market a new drug today exceed US$2.5bn; most of these money is spent during the clinical assessment, but it is probably the preclinical assessment to be blamed most, if (according to Pharmaceutical Research and Manufacturers of America) out of five compounds cleared in the preclinical phase, only one will survive the clinical trials. This means that pre-clinical trials, which are mostly based on animal experimentation, are wrong four times out of five, and this is clearly unacceptable.

Under these combined pressures, the drive for the 3R is combining with the need for the development of Non-Animal Alternatives that not only help to solve this delicate ethical conundrum, but also improve our ability to predict safety and efficacy of a new product before it is tested on humans. There are other industrial sectors that develop products potentially hazardous for human health; if a large airliner crashes, or a nuclear power plant blows, hundreds if not thousands of lives can be at risk, and the environmental damage could eventually affect many more. But in none of these sectors it is conceivable to evaluate safety by trial and error, which is at the basis of the preclinical testing of products affecting human health. These products are most entirely tested through laboratory experiments, and the massive use of modelling and simulation. However, until recently no human health products regulator would even consider in a submission evidences obtained with modelling and simulation.

Here we present the results of a research funded by the UK National Centre for the Reduction, Refinement, and Replacement of animal experimentation (NC3R), where a well establish murine model widely used to test preclinically the efficacy of bone drugs was critically revised using animal-specific modelling based on longitudinal imaging. The methods developed were able to reduce of 63% the number of animals required to achieve statistical significance. But more important, the possibility of observing the effect of the drug being tested over large anatomical volumes, and over time in the same animal non-invasively, has put in serious question the need for a series of interventions that if removed would significantly refine this animal experiment. Last, we will present some preliminary results where animal-specific models are used to partially replace animal experimentation altogether, using an approach call in silico augmented study. We will conclude by suggesting that animal-specific modelling, when combined with human-specific model could produce conclusive evidences on non-animal alternatives are better suited than animal models in predicting the response in humans.

Effects of Nanoscale Particles in the Brain

Webinar Recording | Presentation Slides

Speaker: Alison Elder, PhD, Associate Professor of Toxicology in the Department of Environmental Medicine at the University of Rochester Medical Center.
Date: January 23, 2017, 1:30 PM–2:30 PM Eastern Time

Research Focus: Toxicology of Inhaled Ultrafine Particles and Engineered Nanomaterials

Abstract: It is well understood that exposure to particulate matter is causally associated with adverse cardiopulmonary health effects that are related to the generation of inflammatory mediators, autonomic nervous system activation, and the delivery of particles or their constituents to target tissues (translocation). A growing body of work has explored the ability of inhaled particles—with a focus on nanoscale particles (<100 nm in diameter)—to also have adverse effects in the central nervous system via similar mechanistic pathways. Studies with very poorly-soluble nanoscale particles demonstrated translocation to distal tissues like the brain and that smaller particles accumulate more efficiently than larger particles, albeit at a small fraction of applied dose. Exposures via other routes have also shown the accumulation in various tissues of nanoscale particles. The consequences of particle accumulation in the brain, such as inflammation or the induction or exacerbation of neurodegenerative processes, are also being explored in animal models. Using poorly-soluble nanoscale Mn oxide particles, for example, we found that markers of oxidative stress and inflammatory cell activation were elevated in the same regions of the brain where Mn accumulated following whole-body inhalation exposure in rats. Using a mouse model of Alzheimer’s disease (AD), it was also demonstrated that exposure led to persistent microglial and astrocyte activation, elevations in amyloid β-42 protein, and decreases in synaptophysin staining. Similar findings have been reported in studies of the effects of other particle types like diesel exhaust. Taken collectively, the findings from these studies suggest that inhaled particles can be transported to the central nervous system and that they can elicit tissue responses that could contribute to the progression of pathology in those regions where accumulation occurs.

MDCPSS—ISO 10993-4 Biological Evaluation of Medical Devices: Selection of Tests for Interaction with Blood

Webinar Recording | Presentation Slides

Speaker: Michael Wolf, BS, MS, Medtronic Inc.
Date: December 14, 2016, 11:00 AM–12:15 PM EST

Abstract: For medical device companies with blood-contacting products, the ISO 10993-4 guidance document is important because it defines general requirements and considerations for evaluating interactions of concern between the devices and blood. The document describes: (1) classification of blood-contacting medical devices based upon intended use and duration of contact as defined in ISO 10993-1, (2) fundamental principles and scientific bases behind various methods of evaluating interactions of devices with blood, and (3) a structured selection of tests for consideration based upon intended use and blood contact duration. In short, this standard is a guide for start-up companies, established industry, and regulatory agencies to assess the apparent pre-clinical blood compatibility of candidate cardiovascular devices and materials intended for human blood contact applications.

The foundation of ISO 10993-4 has several sources. However, since its inception in 2002, the document has received only minor revision. Over the past several years the revision of this document has involved review of hundreds of comments from around the world, with the FDIS recommended for formal approval in 2016. Concisely, the new document provides a simplified process flow diagram for high level planning decisions, a reduced and simplified table of example devices vs. testing categories for consideration, and a streamlined table of actual tests for consideration in each test category.

Importantly, the standard suggests more opportunities for meaningful in vitro testing to supplement or replace certain animal testing. More emphasis is also placed on the importance of testing blood contacting devices for impact on thrombosis.

Evaluation of Medical Devices for Genetic Toxicity: A Global Perspective

Webinar Recording | Presentation Slides

Speaker: Robert Przygoda, PhD, Johnson & Johnson, Co-chair of AAMI Genotoxicity, Carcinogenicity and Reproductive Toxicity Working Group (U.S. Sub-TAG for ISO/TC 194/WG 6).
Date: October 19, 2016, 1:00 PM–2:00 PM Eastern Time

Abstract: Genotoxicity is a key safety evaluation endpoint of healthcare products including pharmaceuticals and medical devices. It is also an ever evolving area in terms of the advancement of science and regulation. The ISO 10993-3 standard governing genotoxocity testing for medical devices was recently updated in 2014. Furthermore, quite a few national regulatory agencies have issued their own guidance to use the ISO 10993-3 standard, such as the recently published US FDA, Use of International Standard ISO 10993-1, Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management.

The current presentation will discuss the topics below:

  1. What is different about evaluating the genotoxicity of medical devices?
  2. How to determine if genetic toxicity evaluation is needed.
  3. ISO 10993-3 (2014)—Requirements (Risk Based Approach, Chemical Characterization, Tests, Test Sample Preparation, Reports)
  4. ISO TR 10993-33 (2015)—Guidance on Tests to Evaluate Genotoxicity Supplement to ISO 10993-3.
  5. Challenges using ISO 10993-3 Globally accepted but subject to interpretation by national regulatory agencies: US FDA guidance, Japan guidance and considerations for China submissions.

Use of International Standard ISO 10993-1, “Biological Evaluation of Medical Devices—Part 1: Evaluation and Testing within a Risk Management Process”

Webinar Recording | Presentation Slides | Guidance Document

Hosted by: US FDA

Speakers: Jennifer Goode, Office of Device Evaluation, Center for Devices and Radiological Health
Date: Thursday, July 21, 2016, 1:00 PM–2:30 PM EST

Abbreviated Abstract: On July 21, 2016, the US FDA held a webinar for industry to review the Use of International Standard ISO 10993-1, “Biological Evaluation of Medical Devices—Part 1: Evaluation and Testing within a Risk Management Process” final guidance document. The recommendations in this final guidance clarify and update how medical device developers may use ISO 10993-1 standard in their premarket submission to determine the potential for an unacceptable adverse biological response resulting from contact of a medical device with the body. This final guidance replaces the Office of Device Evaluation (ODE) Blue Book Memorandum #G95-1 (1995), entitled “Use of International Standard ISO-10993, ’Biological Evaluation of Medical Devices—Part 1: Evaluation and Testing.”

Exploring Certifications in General Toxicology: An Introduction to ABT/ERT/ATS Certification

Hosted by: American College of Toxicology

Webinar Recording

Speakers: Bas Blaauboer, PhD, Emeritus Professor of Toxicology at the Division of Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Chair of the Registration Subcommittee of EUROTOX; Michael Holsapple, PhD, ATS, Director and Endowed Chair at the Center for Research on Ingredient Safety/Professor of Food Science & Human Nutrition at Michigan State University, President of ATS; and Christopher P. Weis, PhD, DABT, Toxicology Liaison/Senior Adviser, Office of the Director, National Institute of Environmental Health Sciences, Vice-President of ABT
Date: Wednesday, June 22, 2016, 11:00 AM–12:00 Noon EST

Abbreviated Abstract: Professional toxicologists across the world pursue certifications to add value to their credentials as part of their career development. There are three primary professional certifications in toxicology.

I. The American Board of Toxicology (ABT) offers Diplomate status to qualified individuals who demonstrate relevant education, actively practice in toxicology, and pass a comprehensive examination.

II. The European Registry of Toxicologists (ERT) includes toxicologists, who demonstrate knowledge of the major areas of toxicology. This knowledge can be acquired by either following an appropriate academic program, e.g. by attending courses, or by practical experience and on the job training. At least 5 years of relevant toxicological experience is needed.

III. The Academy of Toxicological Sciences (ATS) awards Fellow status to individuals with demonstrated contributions to the discipline of toxicology over their career, as judged by peer review of relevant education, professional practice in toxicology, and professional recognition.

Each of these three certifications is complementary, professionally valuable, and has unique requirements for eligibility. This webinar will provide a primer on eligibility, value, and maintenance for each certification followed by a Q&A session.

Webinar: SCENIHR Opinion on the Determination of Potential Health Effects of Nanomaterials Used in Medical Devices

Webinar Recording | Presentation

Speaker: Wim De Jong, DVM, PhD, Centre for Health Protection at the National Institute for Public Health and the Environment (RIVM)
Date: Thursday, January 21, 2016, 11:00 AM–12:00 Noon EST

Abbreviated Abstract: The use of nanomaterials in medical devices poses a challenge for the safety evaluation and risk assessment of these medical devices as the specific character of the nanomaterial used should be taken into consideration. The various aspects of safety evaluation and risk assessment of medical devices containing nanomaterials are addressed in this Guidance. The use of nanomaterials in medical devices can vary considerably. Examples are the use of free nanomaterials being a medical device and administered to the patient as such (e.g. iron oxide or gold nanomaterials for heat therapy against cancer), free nanomaterials in a paste-like formulation (e.g. dental filling composites), free nanomaterials added to a medical device (e.g. nanosilver as antibacterial agent in wound dressings), fixed nanomaterials forming a coating on implants to increase biocompatibility (e.g. nano-hydroxyapatite) or to prevent infection (e.g. nano-silver), or embedded nanomaterials to strengthen biomaterials (e.g. carbon nanotubes in a catheter wall). In all these cases the potential exposure to the nanomaterials should be considered. It is additionally recognised that wear-and-tear of medical devices may result in the generation of nanosized particles even when the medical device itself does not contain nanomaterials.

Guidance is provided on physico-chemical characterisation of nanomaterials, the determination of hazards associated with the use of nanomaterials, and risk assessment for the use of nanomaterials in medical devices. The safety evaluation of the nanomaterials used in medical devices is discussed in the context of the general framework for biological evaluation of medical devices as described in the ISO 10993-1:2009 standard. Therefore, the risk assessment should be performed taking into consideration the type of device, the type of tissue contact, and the contact duration, thus identifying the specific exposure scenario.

A phased approach is recommended for evaluating the risk of the use of nanomaterials in medical devices based on potential release and characteristics of the nanomaterials to avoid unnecessary testing. In phase 1 an evaluation of the potential for the device to release nanoparticles either directly or due to wear of the device during use should be carried out. In phase 2 the aim is to determine the distribution of the particles released and also their persistence potential. In phase 3 the hazard is assessed using appropriate toxicity tests taking account of the exposure characteristics and potential for persistence in specific organs. This will provide input for the final risk characterisation (phase 4). The estimated risk needs to be compared to the risk from the use of comparable devices not incorporating nanomaterials in judging the acceptability of the risk. In conclusion, the potential risk from the use of nanomaterials in medical devices is mainly associated with the possibility for release of free nanoparticles from the device and the duration of exposure.

Webinar: The Threshold of Toxicological Concern: Application to Medical Devices and Pharmaceuticals.

Webinar Recording | Dr. Brown’s Presentation | Dr. Ball’s Presentation |

Speakers: Ron Brown, FDA, CDRH, and Douglas Ball, Pfizer
Date: Monday, November 16, 2015, 11:00 AM–12:00 Noon

Abstract: Over the past 50 years, this question of assessing human health risk of unstudied or incompletely characterized chemicals has been the subject of many publications. The most widely accepted scientific approach to assess the risk of exposure to incompletely characterized chemicals is to consider a level of exposure for all chemicals below which there is no appreciable risk to human health; a threshold of toxicological concern (TTC). The concept of a TTC holds true across a wide spectrum of toxicity endpoints, such as genotoxicity, carcinogenicity, neurotoxicity, reproductive and developmental toxicity and acute and repeated dose systemic toxicity (Munro and Kroes [JECFA], 1998; Muller, 2006; Delaney et al., 2007; Bernauer et al., 2008; van Ravenzway, 2011). The literature provides evidence of the scientific community’s acceptance of the TTC concept, which many regulatory authorities around the world have also endorsed. The TTC concept has been applied to many applications including food packaging, food flavorings, pesticide metabolites in groundwater, pharmaceuticals, herbal substances and preparations and genotoxic drug impurities.

Application of the TTC to Pharmaceuticals: In 2013, the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) published a draft consensus guideline on the Assessment and Control of DNA Reactive (Mutagenic) impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk, M7. The ICH M7, which applies to products to the pharmaceutical market and to combination drug devices, was written “to provide a practical framework that can be applied for the identification, categorization, qualification, and control of these mutagenic impurities to limit potential carcinogenic risk.” The guideline also extends the TTC to less than lifetime patient exposures by allowing for higher thresholds for shorter exposure duration, such as during clinical drug trials. Douglas Ball (Pfizer) will provide background on the derivation of the TTC and how it is applied in pharmaceuticals and the pharmaceutical industry through case studies including a process-related mutagenic impurity and Leachable & Extractable qualification using a modified Cramer Classification strategy.

Application of the TTC to Medical Devices: Ron Brown will focus on how the proposed application of the TTC concept for Leachables & Extractables from medical device materials is similar to/different than the approach for impurities in drugs. The International Standards Organization (ISO) Technical Committee 121 has begun work on the development of a TTC approach for volatile compounds released from respiratory devices.

Webinar: Medical Device Color Additives: Legislative History and Regulatory Perspective

Webinar Recording | Webinar Presentation | Webinar Booklet

Presenter: Brenda Seidman, MS, PhD, RAC
Date: Wednesday, June 24, 2015, 11:00 AM

Description: Color additives in medical devices serve a range of purposes, from the reinforcement of a manufacturer’s branding to providing visual cues to health providers. Most regulatory toxicologists lack an understanding of either the Federal Food Drug and Cosmetic Act (FFDCA) or the 1976 Medical Device Amendments, the legislation that brought device premarket approval and notification into the Act. An understanding of color additives language in the FFDCA, and its 1976 amendments, is necessary in order to understand the CDRH’s recent, elevated interest in medical device color additive use. The CDRH’s concern with color additive use in medical device is rooted in the FFDCA, which dictates that the CDRH regulates medical device colors that have “direct contact with the body for a significant period of time.” It is also rooted in past policy, the regulations themselves, historical practices and institutional memory. The following topics will be discussed during the session:
  • Introduction to medical device color additive use and color additive legislation and regulation
    • Uses in Medical devices
    • The Wiley Act
    • FFDCA overview and applicable language
    • The Delaney Clause
    • FDA Regulations
  • CFSAN and CDRH medical device color additive practices
    • Historical practices
    • Borrowing color additives for use in devices that were approved for food uses?
    • Practices versus regulations
    • 510(k) versus PMA/IDE color additive regulations/practices
    • Borrowing color additives for use in one type of device that were approved for another type?
  • The CDRH’s draft guidance on the use of ISO 10993 (Section 7)
  • Suggestions for dealing with device color additives now and in future

MDCPSS 2015 Annual Reception

Date: Tuesday, March 24, 2015, 6:00 PM–7:30 PM
Location: Room 33A, San Diego Convention Center

Continuing Education Courses

Date: Sunday, March 22, 2015
Description: MDCPSS has endorsed two continuing education courses: “Toxicology and Regulatory Considerations for Combination Products” and “Advances in Safety Assessment of Medical Devices.” More information is available at the 2015 SOT Annual Meeting website.

MDCPSS Fall Webinar: Quantitative Risk Assessment of the Genotoxicity and Tumorigenicity of CoCr-Containing Hip Implants

Webinar Recording | Webinar Presentation

Date: September 24, 2014, 12:00 Noon

Description: Cobalt-chromium (CoCr) alloys have long been used in metal-containing hip implants because of their biocompatibility. Like all implant materials, CoCr alloys undergo some degree of wear and corrosion in vivo, and as a result implant patients experience blood and tissue Co and Cr(III) concentrations that are higher than background levels associated with dietary intake. Although to date epidemiology studies do not indicate an increased incidence of cancer in patients with hip implants, questions continue to be raised about the potential cancer risk posed by CoCr-containing implants. To address these concerns, the scientific literature investigating the genotoxic and tumorigenic effects of Co particles and ions, Cr particles and ions, CoCr alloy particles, as well as CoCr alloy implants was gathered, and NOAEL/LOAEL values were compared with body burdens of Co/Cr particles and ions that were calculated to exist in systemic tissues of hip implant patients under normal and excessive wear conditions. This presentation will illustrate the quantitative methods that were used to evaluate the weight-of-evidence regarding a causative relationship between CoCr-containing hip implants and increased cancer risk to determine whether the existing toxicology data support epidemiological findings.

Supporting Information: Toxicology-based cancer causation analysis of CoCr-containing hip implants: a quantitative assessment of genotoxicity and tumorigenicity studies. Christian WV, Oliver LD, Paustenbach DJ, Kreider ML, Finley BL. J Appl Toxicol. 2014 Sep;34(9):939–67.

Speaker Bio: Whitney V. Christian, PhD

Dr. Whitney V. Christian is a Health Scientist II with Cardno ChemRisk. He received a PhD in Molecular Toxicology from the Department of Environmental Medicine at the University of Rochester and a BA in Biology from Davidson College. Prior to attending graduate school he conducted cancer research in the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill.  Combining his experience with genetics and toxicology, Dr. Christian possesses a unique understanding of gene-environment interactions and their contribution to the development of human disease. Dr. Christian’s areas of expertise include applied toxicology involving the use of exposure assessment methods, such as physiologically-based pharmacokinetic (PBPK) models, for quantitative risk assessment as well as specific areas of toxicology, including toxicokinetics, endocrine-disruption, metal toxicology, nanotoxicology, neurotoxicology, and genotoxicology/carcinogenesis.

Webinar: Use of Computational Toxicology for the Biological Evaluation of Medical Devices

Webinar Recording | Webinar Slides

Presenter: Ron Brown, FDA CDRH OSEL

Recording Date: Monday, June 23, 2014, 12:00 Noon

Description: The biological safety of medical devices is typically assessed by conducting biocompatibility testing of an extract of the device or the device itself; however, there is growing interest in an alternate approach that involves characterizing the chemical composition of the device extract and conducting a risk assessment on the compounds identified in the extract. One limitation to the practical implementation of this chemical characterization/risk assessment approach is the lack of toxicity data for many compounds released from device materials. To address this need, computational toxicology models, such as Quantitative Structure-Activity Relationship (QSAR) models, are being increasingly used to predict the toxicity or carcinogenicity of compounds based on their chemical structure. Efforts are underway to validate the predictive ability of QSAR models for compounds that are known to be released from device materials. This webinar will describe the computational modeling approaches available to predict the toxicity, mutagenicity, and carcinogenicity of compounds released from device materials and will explore ways to use model-derived predictions as part of the biological evaluation of a device, notably, to determine when certain types of testing may not be necessary.

MDCPSS 2014 Annual Reception

Date: Monday, March 24, 2014, 6:00 PM–7:30 PM

Location: Sheraton Paradise Valley Room

Symposium: In Vitro Medical Device Testing

Date: December 10–11, 2013

Location: Johns Hopkins University, Mt. Washington Conference Center, Baltimore, Maryland

This symposium, hosted by the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), will examine how the National Academy of Sciences, Toxicity Testing in the 21st Century can be applied to Medical Devices. The program will examine current requirements and testing approaches, followed by an examination of in vitro assays useful in medical device testing. The agenda includes speakers from industry, academia, and government.

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Webinar: Medical Device Testing In Vitro—Pyrogenicity Testing and Beyond

Webinar Recording | Presentation Slides

Date: Friday, May 24, 2013, 11:59 AM

Speaker: Dr. Thomas Hartung

Description: In vitro methodologies are only slowly embraced by the field of medical device safety testing. The Limulus amebocyte lysate assay might be considered a forerunner for non-animal tests here as it is applied to eluates from medical devices in order to determine microbiological contaminations. However, this test is limited to Gram-negative bacterial endotoxin. More recently, assays based on the human fever reaction were developed. They make use of human white blood cells, which respond to many further stimuli. Especially the whole blood pyrogen assay allows to measure directly on the surface of the medical devices avoiding pyrogen eluation. Its adaptation to medical devices showed, that both eluation and depyrogenation by standard methodologies are not adequate to determine and remove pyrogen burden of medical devices. This test case is used to discuss opportunities and limitations for in vitro medical device testing in general. The webinar will benefit toxicologists involved with the safety assessment of medical devices, drugs, and combination devices.

Webinar: Current Testing and Alternative Methods for Assessment of Medical Device Blood-Material Interactions

Presentation Slides

Presenter: Michael Wolf, BS, MS, Medtronic Inc.

Date: Friday, February 8, 2013, 12:00 Noon

Description: One of the most complex organs in the body is blood. There is a rich diversity of cells, proteins, small signaling molecules, electrolytes, etc., in the blood, and maintaining equilibrium in the interconnected systems is critical for health. Materials utilized in medical devices can interact directly or indirectly with blood and related systems, and ensuring and verifying hemocompatibility is a primary concern in interventional health care products. Technologies and strategies for assessing hemocomaptibility have appreciably advanced over the last several years, and the webinar will address emerging approaches. Any toxicologist with particular interest in hemocompatibility, or working on projects or programs where the blood or blood components are potential targets or effectors will benefit from the discussion. It should be noted that the speaker, Dr. Michael Wolf is a recognized expert in hemocompatibility, and is the chairperson for the ISO 10993 committee responsible for the ISO 10993 standard on hemocompatibility.

Webinar: Polyphenol-Eluting Stent reduces Restenosis and Promotes Vascular Healing in a Rat Model of Arterial Angioplasty and Stenting

Date: November 2, 2011, 11:00 AM

Presenter: Jim Kleinedler, LSU Health Science Center

Webinar Recording | Webinar Presentation