One of the newest biocompatibility evaluation tools is extractable and leachable (E&L) testing. A correctly run E&L study, with an accompanying toxicological evaluation, can be used to replace traditional tests like systemic toxicity, genotoxicity, reproductive toxicity, and carcinogenicity. The data gained from these studies can help understand the total risk of your device to an intended population of users; but unlike the traditional animal tests, it comes with separate risks. These tests are not your typical “stamped” tests, where every lab gives a similar quality of results. Because of this, FDA has refined a strict, detailed, list of parameters that should be included in every test. This list is very dynamic and is changing rapidly; the best way to make sure you are performing the correct version of the test is to learn from the most recent FDA feedback on studies.
TAKEAWAY ITEMS:
• Understand recent FDA feedback and dissect what FDA is asking/looking for
• Learn how to address these concerns and develop a protocol to make sure you don’t receive similar questions
• Recognize how FDA is using the new ISO 10993-18 and where they deviate from that standard
This session took place live at the Greenlight Guru True Quality Virtual Summit, a three-day event for medical device professionals to learn to get their devices to market faster, stay ahead of regulatory changes, and use quality as their multiplier to grow their device business.
ISO 10993-4 Biological Evaluation of Medical Devices - Tests for Interactions...NAMSA
ISO 10993-4 Biological Evaluation of Medical Devices - Tests for Interactions with Blood provides a structured test-selection system based on the intended use of the device. Although it does not provide detailed test methods or evaluation criteria, it cites various applicable references.
This presentation gives an idea about extractable and leachables, Analytical techniques used for conducting studies. importance of conducting E&L studies.
Challenges using Multiple Single-use Systems: Functionality versus Extractabl...Merck Life Sciences
As single-use technologies continue to expand in pharmaceutical manufacturing processes, the risk assessment for extractables and leachables becomes increasingly complex. Join this webinar to obtain guidance on how to perform risk evaluation on a process with multiple single-use components.
A Single-Use System (SUS) is typically designed for a specific process step. In many cases, single-use components are chosen based on their functionality. The challenge arises when there are multiple processing steps-- as the different applications and product matrices are evaluated, the complexity of the risk assessment increases. Complexity includes component evaluation, process conditions, and model solvents streams which ultimately relates to the patient safety risk.
This webinar will evaluate the different single-use components with respect to compatibility and extractables and leachables. A case study will be used to demonstrate the complexity and potential concerns when performing a risk evaluation on the manufacturing process.
In this webinar, you will learn:
- Risk assessment of extractables
- Single-use component evaluation
- Complexity when evaluating multiple assemblies
ISO 10993-4 Biological Evaluation of Medical Devices - Tests for Interactions...NAMSA
ISO 10993-4 Biological Evaluation of Medical Devices - Tests for Interactions with Blood provides a structured test-selection system based on the intended use of the device. Although it does not provide detailed test methods or evaluation criteria, it cites various applicable references.
This presentation gives an idea about extractable and leachables, Analytical techniques used for conducting studies. importance of conducting E&L studies.
Challenges using Multiple Single-use Systems: Functionality versus Extractabl...Merck Life Sciences
As single-use technologies continue to expand in pharmaceutical manufacturing processes, the risk assessment for extractables and leachables becomes increasingly complex. Join this webinar to obtain guidance on how to perform risk evaluation on a process with multiple single-use components.
A Single-Use System (SUS) is typically designed for a specific process step. In many cases, single-use components are chosen based on their functionality. The challenge arises when there are multiple processing steps-- as the different applications and product matrices are evaluated, the complexity of the risk assessment increases. Complexity includes component evaluation, process conditions, and model solvents streams which ultimately relates to the patient safety risk.
This webinar will evaluate the different single-use components with respect to compatibility and extractables and leachables. A case study will be used to demonstrate the complexity and potential concerns when performing a risk evaluation on the manufacturing process.
In this webinar, you will learn:
- Risk assessment of extractables
- Single-use component evaluation
- Complexity when evaluating multiple assemblies
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...MilliporeSigma
Register for the interactive, on-demand webinar now: https://bit.ly/USP665
Single-use plastic systems are being utilized more frequently especially for COVID-19 vaccine manufacturing. However, there are issues regarding standardization of quality information that limits implementation efficiencies. One of the challenges is the evaluation of leachables derived from a variety of different plastic components in a timely manner.
Since the USP <665> highlights a risk assessment approach with no typical pass/fail limit, approaches to decision-making based on the extractables data package will be reviewed. In addition, we will highlight legacy testing requirements which may not be necessary once USP <665> is implemented.
In this webinar, we will discuss:
- Regulatory expectations of extractables and leachables assessment today and tomorrow
- The right criteria that need to be assessed to select the type and quality of plastic materials for use in biopharmaceutical manufacturing
Considerations to Extractables and Leachables Testing SGS
How to organize Extractables Assessments? FDA continues to issue Warning Letters to companies that fail to properly complete Design Verification, Design Validation, and Process Validation, and recently to include failures of manufacturers in Risk Management. The evaluation of extractables and leachables has become an increasingly important aspect in the Quality by Design (QbD) initiative of the FDA in the area of drug product design, including materials used in the drug product production process and container and closure systems used for product packaging. This presentation provides general approaches and practical aspects in E&L testing.
Integration of Risk Assessment and Chemical Characterization (MD&M Minn. 2017)Russell Sloboda
The Toxicological Risk Assessment (TRA) is an important tool in the safety assessment of biomedical devices, providing a chemical-based approach which complements a traditional animal-based testing program. The need for TRA is growing and in some cases, may be considered as a means of circumventing animal testing in the safety evaluation of devices.
Based on results of the chemical characterization, the TRA provides context to the chemistry data and the leachable compounds identified therein, which includes compounds expected to be found and compounds that are unexpected. The objective of the chemical characterization study is to identify and quantify substances that may be released from the test article during clinical use and in practical terms, is comprised of incubations of the test article in various media, e.g., water, ethanol, or hexane, at specific temperatures and durations.
By considering the end use of the characterization data in the TRA during the design of the chemical characterization study it can be assured that the study provides the most useful and informative data. Considering the needs of the TRA can also help in determining appropriate detection limits for the analysis, which in turn can help in determining the amount of test material needed for the study. Further, coordinating with the risk assessment team during the design of characterization study helps ensure that the data are usable and presented in the most suitable manner. By working together, the TRA and chemical characterization study provide an understanding of the impact of potential exposures on the overall safety of a device.
This document is intended to provide guidance for registration applications on the content and qualification of impurities in new drug substances produced by chemical syntheses and not previously registered in a region or member state.
ISO 10993 Series Part 1: Evaluation and Testing In The Risk Management ProcessNAMSA
ISO 10993 Series Part 1: Evaluation and Testing In The Risk Management Process discusses what ISO 10993-1 addresses, as well as the general principles governing the biological evaluation of medical devices within a risk management process.
THE PRESENTATIONS DESCRIBES THE ICH GUIDELINE FOR RESIDUAL SOLVENTS i.e Q3C.
IT contains the basic of ICH and the complete description about the ICH guideline Q3C and its classification,limits,acceptance criteria in Pharma industries and the standards.
#Pharmaceuticalguideline
#medicine
#healthandmedicine
drug execipent compatibilty studies is of prime importance for the better formulation of the new drug and also for reducing cost by verfication of the data at the earlier atage.
this presentation will give the brief explanation of the goal, importance, dteps involve to studi the drug execient compatibility studies with different examples suitable accordiingly.
The importance of extractable/leachable testing in Pharmaceutical Dosage forms has grown considerably in the last few years.Recent USP general chapters <1663>, <1664> states the requirements for extractables and leachables in regulatory submissions. There were several criticalities associated in the container closure system assessment in identifying the probable leachables that could impact the
quality of the Drug product. Control extractions studies provide an insight based on the technical characteristics and logical conclusions made. Technology advancements and bundles of literature provided major insights in understanding the analytical evaluation limits,specifications and procedural things conducting extractable and leachable studies. This presentation provides a summary and overview of regulatory requirements for extractables and leachables with the current trend of FDA deficiencies for the drug products.
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...MilliporeSigma
Register for the interactive, on-demand webinar now: https://bit.ly/USP665
Single-use plastic systems are being utilized more frequently especially for COVID-19 vaccine manufacturing. However, there are issues regarding standardization of quality information that limits implementation efficiencies. One of the challenges is the evaluation of leachables derived from a variety of different plastic components in a timely manner.
Since the USP <665> highlights a risk assessment approach with no typical pass/fail limit, approaches to decision-making based on the extractables data package will be reviewed. In addition, we will highlight legacy testing requirements which may not be necessary once USP <665> is implemented.
In this webinar, we will discuss:
- Regulatory expectations of extractables and leachables assessment today and tomorrow
- The right criteria that need to be assessed to select the type and quality of plastic materials for use in biopharmaceutical manufacturing
Considerations to Extractables and Leachables Testing SGS
How to organize Extractables Assessments? FDA continues to issue Warning Letters to companies that fail to properly complete Design Verification, Design Validation, and Process Validation, and recently to include failures of manufacturers in Risk Management. The evaluation of extractables and leachables has become an increasingly important aspect in the Quality by Design (QbD) initiative of the FDA in the area of drug product design, including materials used in the drug product production process and container and closure systems used for product packaging. This presentation provides general approaches and practical aspects in E&L testing.
Integration of Risk Assessment and Chemical Characterization (MD&M Minn. 2017)Russell Sloboda
The Toxicological Risk Assessment (TRA) is an important tool in the safety assessment of biomedical devices, providing a chemical-based approach which complements a traditional animal-based testing program. The need for TRA is growing and in some cases, may be considered as a means of circumventing animal testing in the safety evaluation of devices.
Based on results of the chemical characterization, the TRA provides context to the chemistry data and the leachable compounds identified therein, which includes compounds expected to be found and compounds that are unexpected. The objective of the chemical characterization study is to identify and quantify substances that may be released from the test article during clinical use and in practical terms, is comprised of incubations of the test article in various media, e.g., water, ethanol, or hexane, at specific temperatures and durations.
By considering the end use of the characterization data in the TRA during the design of the chemical characterization study it can be assured that the study provides the most useful and informative data. Considering the needs of the TRA can also help in determining appropriate detection limits for the analysis, which in turn can help in determining the amount of test material needed for the study. Further, coordinating with the risk assessment team during the design of characterization study helps ensure that the data are usable and presented in the most suitable manner. By working together, the TRA and chemical characterization study provide an understanding of the impact of potential exposures on the overall safety of a device.
This document is intended to provide guidance for registration applications on the content and qualification of impurities in new drug substances produced by chemical syntheses and not previously registered in a region or member state.
ISO 10993 Series Part 1: Evaluation and Testing In The Risk Management ProcessNAMSA
ISO 10993 Series Part 1: Evaluation and Testing In The Risk Management Process discusses what ISO 10993-1 addresses, as well as the general principles governing the biological evaluation of medical devices within a risk management process.
THE PRESENTATIONS DESCRIBES THE ICH GUIDELINE FOR RESIDUAL SOLVENTS i.e Q3C.
IT contains the basic of ICH and the complete description about the ICH guideline Q3C and its classification,limits,acceptance criteria in Pharma industries and the standards.
#Pharmaceuticalguideline
#medicine
#healthandmedicine
drug execipent compatibilty studies is of prime importance for the better formulation of the new drug and also for reducing cost by verfication of the data at the earlier atage.
this presentation will give the brief explanation of the goal, importance, dteps involve to studi the drug execient compatibility studies with different examples suitable accordiingly.
The importance of extractable/leachable testing in Pharmaceutical Dosage forms has grown considerably in the last few years.Recent USP general chapters <1663>, <1664> states the requirements for extractables and leachables in regulatory submissions. There were several criticalities associated in the container closure system assessment in identifying the probable leachables that could impact the
quality of the Drug product. Control extractions studies provide an insight based on the technical characteristics and logical conclusions made. Technology advancements and bundles of literature provided major insights in understanding the analytical evaluation limits,specifications and procedural things conducting extractable and leachable studies. This presentation provides a summary and overview of regulatory requirements for extractables and leachables with the current trend of FDA deficiencies for the drug products.
Humans are potentially exposed to tens of thousands of man-made chemicals in the environment. It is well known that some environmental chemicals mimic natural hormones and thus have the potential to be endocrine disruptors. Most of these environmental chemicals have never been tested for their ability to disrupt the endocrine system, in particular, their ability to interact with the estrogen receptor. EPA needs tools to prioritize thousands of chemicals, for instance in the Endocrine Disruptor Screening Program (EDSP). This project was intended to be a demonstration of the use of predictive computational models on HTS data including ToxCast and Tox21 assays to prioritize a large chemical universe of 32464 unique structures for one specific molecular target – the estrogen receptor. CERAPP combined multiple computational models for prediction of estrogen receptor activity, and used the predicted results to build a unique consensus model. Models were developed in collaboration between 17 groups in the U.S. and Europe and applied to predict the common set of chemicals. Structure-based techniques such as docking and several QSAR modeling approaches were employed, mostly using a common training set of 1677 compounds provided by U.S. EPA, to build a total of 42 classification models and 8 regression models for binding, agonist and antagonist activity. All predictions were evaluated on ToxCast data and on an external validation set collected from the literature. In order to overcome the limitations of single models, a consensus was built weighting models based on their prediction accuracy scores (including sensitivity and specificity against training and external sets). Individual model scores ranged from 0.69 to 0.85, showing high prediction reliabilities. The final consensus predicted 4001 chemicals as actives to be considered as high priority for further testing and 6742 as suspicious chemicals. This abstract does not necessarily reflect U.S. EPA policy
CCK Discussion Forum on Impurity Emergence: A Wake Up Call for Drug Safety & Quality - 13 Oct 2019 at ICCBS, University of Karachi. Session largely participated by qualified and experienced pharmaceutical professionals having diversified educational background and experience.
APVMA outcome-focussed approach to data requirements to support registration ...OECD Environment
The seminar on Problem Formulation for the Risk Assessment of Biopesticides stemmed from a previous CRP-sponsored event on Innovating Microbial Pesticide Testing that identified the need for an overarching guidance document to determine when in vivo tests are necessary. Problem Formulation, a common practice in pesticide risk assessment, was highlighted as a useful approach for addressing uncertainties in data requirements for biopesticides.
The seminar featured presentations from various perspectives, including industry, regulatory bodies, and academia. Topics included the history and principles of Problem Formulation, industry perspectives on Problem Formulation and how it is applied internally for microbial pesticides, regulatory approaches, and specific case studies. The seminar provided an overview of the challenges, considerations, and potential solutions in harmonising Problem Formulation for biopesticide risk assessment. It emphasised the need for collaboration and discussion to develop Problem Formulation guidance for biopesticides.
The Compliance Concern: Challenges and Roadblocks for Ensuring Compliance in ...Greenlight Guru
The medical device industry is doubling down on compliance readiness. This is a significant shift from last year when we saw accelerating product development as the main goal. Ensuring compliance is a requirement for continued success, and most importantly, patient safety. The panelists will discuss the challenges device companies face as they manage compliance throughout the product lifecycle.
How Electronic Data Capture Is Transforming the MedTech IndustryGreenlight Guru
Clinical research is crucial to the life science industry. But did you know that medical device companies require a different approach? In this discussion, our panelists will talk about the challenges of clinical operations for MedTech, the benefits of leveraging MedTech-specific Electronic Data Capture (EDC) systems, the pitfalls of using outdated clinical data collection methods, such as paper, and much more!
The ROI of Shifting Mindset From Compliance to QualityGreenlight Guru
Many MedTech companies focus on compliance without considering the importance of quality. In this session, panelists will dive into the differences between compliance vs. quality, the benefits of shifting mindset towards quality, and tips on how to start embedding quality into your organization.
Leveraging Modern Software Technologies: MedTech’s Best Kept SecretGreenlight Guru
There are several moving pieces that influence a medical device company’s time-to-market and continued success. An often overlooked (yet critical) one is the tools used to manage the product lifecycle. Are your tools working for you or slowing down your success? In this session, panelists will discuss trends from the 2023 survey results, common challenges with disjointed software solutions, the impact of modernizing, and the power of a modern QMS.
Behind the Stats: Expectations vs. Reality of Bringing a Device to MarketGreenlight Guru
Learn about what’s currently impacting the broader medical device industry. Our panelists will kick off the week by going over all the trends, statistics, and themes uncovered from the 2023 MedTech Industry Benchmark Survey. The session will uncover major shifts in industry goals, the use of modern Medtech software tools, major gaps in product lifecycle processes, and more. Discover how you can apply these findings as you make decisions within your organization in 2023 and beyond.
Common Misconceptions on Medical Device Risk & Design ControlsGreenlight Guru
Learn about common misconceptions on medical device risk and design controls.
This presentation originally aired during the 2022 Future of QMS Requirements Virtual Summit.
QMSR Harmonization: The Future of FDA's Quality Management System RegulationGreenlight Guru
Learn about the future of FDA's Quality Management System regulation.
This presentation originally aired during the 2022 Future of QMS Requirements Virtual Summit.
Today we will discuss why a QMS is the backbone of Regulatory through the lens of ISO 13845. The presentation will cover the importance of starting a QMS early and ahead of a regulatory strategy.
This presentation originally aired during the 2022 Future of QMS Requirements Virtual Summit.
Modernizing your QMS to keep up with the Modern Age of RequirementsGreenlight Guru
Learn about the importance of a modern QMS to keep up with changing requirements in the MedTech industry.
This presentation originally aired during the 2022 Future of QMS Requirements Virtual Summit.
In this session we will learn about the Why, the What, the Who, and the How for Medical Device Reporting to FDA through eMDR Submissions.
This presentation originally aired during the 2022 Future of QMS Requirements Virtual Summit.
Moving up to the State of the Art in Risk ManagementGreenlight Guru
During this presentation we will explore where Medical Device Risk Management Systems are today. We will look at the quickly upcoming deadlines for implementing the ISO 14971:2019 3rd Edition, and EN ISO 14971:2019/A11:2021 standards. We will also mention the potential next (4th) edition of ISO 14971, and how the industry may influence the next edition.
This presentation originally aired during the 2022 Future of QMS Requirements Virtual Summit.
While ISO 13485 is written in black and white, the alignment between the standard's requirements and expectations is not always clear - especially in regards to SaMD (software as a medical device). This session will discuss aligning ISO 13485 with best practices for SaMD, and how we can expect the shift of the industry to impact the anchor standard of the medical device industry.
This presentation originally aired during the 2022 Future of QMS Requirements Virtual Summit.
Computer Software Assurance (CSA): Understanding the FDA’s New Draft GuidanceGreenlight Guru
Understand the FDA's new draft guidance on Computer Software Assurance (CSA).
This presentation originally aired during the 2022 Future of QMS Requirements Virtual Summit.
Making Headway Despite the Turbulence: Regulatory Requirements, Quality, and ...Greenlight Guru
The European Union’s In Vitro Diagnostic Medical Devices Regulation, or IVDR, became effective May 26, 2022. In this session, you’ll get a glimpse of what’s changed since implementation day, the latest guidance available, and ways to keep your IVDD to IVDR transition moving forward.
This presentation originally aired during the 2022 Global MedTech Regulatory Trends Virtual Summit.
Reducing Friction Between Companies and Regulatory BodiesGreenlight Guru
We are operating in a complex environment, which is still undergoing changes. A lack of regulatory/quality management resources can be seen on both notified bodies and the industry. To overcome these hurdles, close collaboration and communication between companies and the notified body is necessary.
This presentation originally aired during the 2022 Global MedTech Regulatory Trends Virtual Summit.
Latin American Regulations - What you Don't KnowGreenlight Guru
Central and South America are emerging as hot new Medical Device markets. These two subject matter experts in the area break down everything from regulatory advantages and ethical dilemmas.
This presentation originally aired during the 2022 Global MedTech Regulatory Trends Virtual Summit.
Insights on the MedTech Regulatory and Clinical Environment in IsraelGreenlight Guru
Facts about the high-tech industry of Israel
The new medical device law in Israel
The regulatory landscape - requirements and market access
Performing clinical trials in Israel
This presentation originally aired during the 2022 Global MedTech Regulatory Trends Virtual Summit.
The Global Guide to Human Factors and Usability Engineering RegulationsGreenlight Guru
The regulatory landscape related to human factors and usability engineering has continued to evolve since FDA issued its draft guidance for human factors over ten years ago. In fact, the international standard for usability engineering, IEC 62366-1: 2015 was amended as recently as 2020. The good news is that the pathway to a successful regulatory strategy, in terms of human factors and usability engineering, has never been more clear. The regulators have spoken, by way of guidance and standards documents, all that is left to do is to make sense of it all as it relates to your specific device or product.
This presentation originally aired during the 2022 Global MedTech Regulatory Trends Virtual Summit.
Join industry expert, Danny Kroo, key takeaways from the session include: 1. What is MDSAP and when should you consider it? 2. How to prepare for an MDSAP certification audit 3. What are common nonconformities issued by auditing organizations
This presentation originally aired during the 2022 Global MedTech Regulatory Trends Virtual Summit.
QMSR Harmonization - The Good the Bad and the UglyGreenlight Guru
Learn about the proposed QMSR rule, intended benefits of MDSAP for the regulatory authorities, benefits for the manufacturer, and similarities between ISO 13485 and FDA Regulations, and more!
This presentation originally aired during the 2022 Global MedTech Regulatory Trends Virtual Summit.
The world of search engine optimization (SEO) is buzzing with discussions after Google confirmed that around 2,500 leaked internal documents related to its Search feature are indeed authentic. The revelation has sparked significant concerns within the SEO community. The leaked documents were initially reported by SEO experts Rand Fishkin and Mike King, igniting widespread analysis and discourse. For More Info:- https://news.arihantwebtech.com/search-disrupted-googles-leaked-documents-rock-the-seo-world/
Putting the SPARK into Virtual Training.pptxCynthia Clay
This 60-minute webinar, sponsored by Adobe, was delivered for the Training Mag Network. It explored the five elements of SPARK: Storytelling, Purpose, Action, Relationships, and Kudos. Knowing how to tell a well-structured story is key to building long-term memory. Stating a clear purpose that doesn't take away from the discovery learning process is critical. Ensuring that people move from theory to practical application is imperative. Creating strong social learning is the key to commitment and engagement. Validating and affirming participants' comments is the way to create a positive learning environment.
LA HUG - Video Testimonials with Chynna Morgan - June 2024Lital Barkan
Have you ever heard that user-generated content or video testimonials can take your brand to the next level? We will explore how you can effectively use video testimonials to leverage and boost your sales, content strategy, and increase your CRM data.🤯
We will dig deeper into:
1. How to capture video testimonials that convert from your audience 🎥
2. How to leverage your testimonials to boost your sales 💲
3. How you can capture more CRM data to understand your audience better through video testimonials. 📊
Company Valuation webinar series - Tuesday, 4 June 2024FelixPerez547899
This session provided an update as to the latest valuation data in the UK and then delved into a discussion on the upcoming election and the impacts on valuation. We finished, as always with a Q&A
Event Report - SAP Sapphire 2024 Orlando - lots of innovation and old challengesHolger Mueller
Holger Mueller of Constellation Research shares his key takeaways from SAP's Sapphire confernece, held in Orlando, June 3rd till 5th 2024, in the Orange Convention Center.
[Note: This is a partial preview. To download this presentation, visit:
https://www.oeconsulting.com.sg/training-presentations]
Sustainability has become an increasingly critical topic as the world recognizes the need to protect our planet and its resources for future generations. Sustainability means meeting our current needs without compromising the ability of future generations to meet theirs. It involves long-term planning and consideration of the consequences of our actions. The goal is to create strategies that ensure the long-term viability of People, Planet, and Profit.
Leading companies such as Nike, Toyota, and Siemens are prioritizing sustainable innovation in their business models, setting an example for others to follow. In this Sustainability training presentation, you will learn key concepts, principles, and practices of sustainability applicable across industries. This training aims to create awareness and educate employees, senior executives, consultants, and other key stakeholders, including investors, policymakers, and supply chain partners, on the importance and implementation of sustainability.
LEARNING OBJECTIVES
1. Develop a comprehensive understanding of the fundamental principles and concepts that form the foundation of sustainability within corporate environments.
2. Explore the sustainability implementation model, focusing on effective measures and reporting strategies to track and communicate sustainability efforts.
3. Identify and define best practices and critical success factors essential for achieving sustainability goals within organizations.
CONTENTS
1. Introduction and Key Concepts of Sustainability
2. Principles and Practices of Sustainability
3. Measures and Reporting in Sustainability
4. Sustainability Implementation & Best Practices
To download the complete presentation, visit: https://www.oeconsulting.com.sg/training-presentations
Implicitly or explicitly all competing businesses employ a strategy to select a mix
of marketing resources. Formulating such competitive strategies fundamentally
involves recognizing relationships between elements of the marketing mix (e.g.,
price and product quality), as well as assessing competitive and market conditions
(i.e., industry structure in the language of economics).
Understanding User Needs and Satisfying ThemAggregage
https://www.productmanagementtoday.com/frs/26903918/understanding-user-needs-and-satisfying-them
We know we want to create products which our customers find to be valuable. Whether we label it as customer-centric or product-led depends on how long we've been doing product management. There are three challenges we face when doing this. The obvious challenge is figuring out what our users need; the non-obvious challenges are in creating a shared understanding of those needs and in sensing if what we're doing is meeting those needs.
In this webinar, we won't focus on the research methods for discovering user-needs. We will focus on synthesis of the needs we discover, communication and alignment tools, and how we operationalize addressing those needs.
Industry expert Scott Sehlhorst will:
• Introduce a taxonomy for user goals with real world examples
• Present the Onion Diagram, a tool for contextualizing task-level goals
• Illustrate how customer journey maps capture activity-level and task-level goals
• Demonstrate the best approach to selection and prioritization of user-goals to address
• Highlight the crucial benchmarks, observable changes, in ensuring fulfillment of customer needs
Building Your Employer Brand with Social MediaLuanWise
Presented at The Global HR Summit, 6th June 2024
In this keynote, Luan Wise will provide invaluable insights to elevate your employer brand on social media platforms including LinkedIn, Facebook, Instagram, X (formerly Twitter) and TikTok. You'll learn how compelling content can authentically showcase your company culture, values, and employee experiences to support your talent acquisition and retention objectives. Additionally, you'll understand the power of employee advocacy to amplify reach and engagement – helping to position your organization as an employer of choice in today's competitive talent landscape.
FDA Feedback Regarding Chemistry for Toxicological Risk Assessment – How to Make Sure FDA will Accept Your Protocol
1. FDA Feedback Regarding Chemistry for
Toxicological Risk Assessment –
How to Make Sure FDA will Accept Your Protocol
Matthew R. Jorgensen, PhD, DABT
Chemist, Materials Scientist, Toxicologist
mjorgensen@nelsonlabs.com
Thor Rollins, BS, RM(NRCM)
Director, Toxicology and E&L Consulting
trollins@nelsonlabs.com
2. “Greenlight Guru Software is the handrail for Medical Device
Development and Documentation”
FEATURED
IN
75
years
industry
experience
275k
podcast listeners
#1
blog and
podcast in the
industry
90k
look to us for the
latest in medical
device quality
MEDICAL DEVICE QUALITY IS ALL WE DO, AND WE’RE ALWAYS AHEAD OF THE
GAME.
“My QMS is world class”
“One stop shop for MDQMS”
3. Toxicology Consulting Group
Thor Rollins
Director of Consulting
Biocompatibility Wizard
Dr. Matt Jorgensen, DABT
Chemist, Materials Scientist,
and Board Certified Toxicologist
Mtn Dew Enthusiast
4. Outline
3
What is ChemTox?
• One Slide Overview of Fundamentals of Toxicology
• Basic Principles of Chemistry for Toxicology
FDA Feedback Outlining Changes to Expectations
• Extractions (solvents, exaggerated/exhaustive conditions)
• Sample Preparation (solvent exchange and concentrations)
• Method Suitability (reference standards, spike and recovery)
How to Address FDA Concerns
• Overlap Between Expectations and 10993-18
• Development of an FDA Approvable Protocol
7. One Slide Intro to Toxicology
6
Seeks an answer to a fundamental question:
How much of a good thing is too much?
• Route of exposure
• Duration of exposure
• Potential negative outcomes
Oral Caffeine mg/kg to Dr Dew
(Acidic, Aqueous, Delicious Vehicle)
Irritability
New “Normal”
Arrythmia
Tremors
50% Chance
of Death
Death
Hallucinations
~150 mg/kg
11.5 g or 100 Red Bulls
8. Dose/Response Curves: Xenobiotics
7
Dose mg/kg, Oral, Rat
PercentResponse
AdverseEffect
Highest Dose
Where Nothing Bad
Happened
(NOAEL) LOAEL
Dose Where Something Bad
Happened 50% of the Time
Max
Response
10. • ANY substance that could
realistically leave the device during
use and enter the body
– Metals
– Production oils and other residuals
– Plastic additives
– Byproducts
• Ignore substances that are
impossible/improbable
Chemistry Strategy Framed by Problem
11. Suite of Analytical Methods
ANY Substance
(That Could Leave The Device)
Inorganic
(not carbon based)
Metals
And
Metal Oxides
Organic
(carbon based)
Very Small Molecules -
Volatile Organics (VOCs)
Small Molecules - Semi-
Volatile Organics (SVOCs)
Big Molecules – Non-
Volatile Organics (NVOCs)
Small molecules
evaporate easily,
great for
gas chromatography
(GC)
Big molecules
do not evaporate easily,
great for
liquid chromatography
(LC)
12. Critical Criteria for Chemistry: Sufficient Breadth and Sensitivity
11
Dose mg/kg, Oral, Rat
PercentResponse
AdverseEffect
Highest Dose
Where Nothing Bad
Happened
(NOAEL) LOAEL
Dose Where Something Bad
Happened 50% of the Time
Max
Response
Where is the Point of
Departure (POD)?
14. Changed Expectations: Choice of Extraction Vehicles
13
Recent FDA Feedback
In your repeat testing, you conducted chemical characterization for the DEVICE using
exhaustive extraction conditions in polar (ultra purified water, UPW), non-polar (hexane), and
mixed polarity (40% ethanol in ultra purified water) solvents with analysis by HS-GC-MS, GC-
MS, UHPLC-HRAM, ICP-OES, and ICP-MS.
The polarity of 40% ethanol in water is very close to the polarity of water and therefore FDA
does not consider 40% ethanol in water to be a mid-polar solvent. Please repeat exhaustive
extractions using isopropanol as your mid-polar solvent as was done in your original chemical
characterization report.
Yet, in the new 10993-18,
15. Changed Expectations: Choice of Extraction Vehicles
14
Recent FDA Feedback
We recommend that for implants with permanent contact (> 30 days), exhaustive
extraction should be conducted with polar, mid polar, and non-polar solvents to
generate worst-case extractables profiles. Therefore, we recommend that you
conduct exhaustive extraction with final finished implantable devices using
appropriate solvents (e.g., water, isopropyl alcohol, and hexane).
Lack of flexibility on this point observed across many device classes, including
limited contact devices and gas-path devices.
“Leachables may leave the device and remain in the body, therefore the
device is permanent”
17. Changed Expectations: Exhaustive Extractions
16
• NVR can still be used to demonstrate exhaustively
• TOC, THC, and ICP/MS have been successfully used
• Full work-up at 24 hour intervals by GC/MS, LC/MS, and ICP/MS have been successful
Recent FDA Feedback
You state that the total mass of Non-Volatile Residue water extracts was 40.1 mg. However,
based on the information provided, FDA calculates that there was a total water extract amount
of 3.12 mg for semi-volatile organic compounds as determined by GC-MS and 7.42 mg for non-
volatile organic compounds as determined by UHPLC-MS. Based on your data, FDA calculates
that there is 81% of unaccounted mass for the water extracts. FDA is concerned that there is a
significant amount of mass that is unaccounted for...
18. Changed Expectations: Method Suitability
17
• FDA has been requesting evidence of method suitability that is becoming more close to
what is expected in an EPA study:
• Method validation including precision and accuracy for a wide range of compounds
• Matrix spike and recovery through analytical process (including solvent exchange)
• Laboratory control samples, calibration curve verifications, etc.
• Defense or explanation of accuracy of non-validated compounds
19. The Analytical Evaluation Threshold
Final AET
ISI
All compounds above the AET:
Reported, identified and
quantified
2
1
3 4 5 6
7
8
20. Determining the Required Analytical Sensitivity
• Goal is to minimize risk related to undetected
compounds below the analytical sensitivity
• Consideration must be given to uncertainty in
accuracy of measurement (generally a factor of
2 to 4)
21. The Analytical Evaluation Threshold
Recent FDA Feedback (in regards to AET calculation)
We asked you to justify the analytical Uncertainty Factor (UF) of 4. In response to this question,
your Q-sub refers to the papers by Jordi and Jenke to justify an uncertainty factor of 4. However,
the references do not unequivocally recommend using a UF of 4. According to paper by Jordi et
al, “It is recommended that the AET be lowered by applying either a 50% reduction or a
correction factor equal to the % RSD of the relative response factor database. The approach
which provides the largest reduction should be applied.” Although you used a conservative UF
value of 4, you did not provide any data to justify the UF of 4. You should provide calculations
you made based on the %RSD value of the relative response factors to justify using a UF of 4.
𝐴𝐸𝑇
𝜇𝑔
𝑑𝑒𝑣𝑖𝑐𝑒
=
𝐷𝐵𝑇
𝜇𝑔
𝑑𝑒𝑣𝑖𝑐𝑒
𝑈𝐹
22. How Does E&L Work: Identification and Quantification
• GC/MS: Electron Ionization (EI)
– Literally shooting molecules with an
electron machine gun
– Highly standardized and reproducible
• LC/MS and LC/HRAM
– More variable from lab to lab
– Atmospheric Pressure Chemical
Ionization (APCI±)
– Electrospray Ionization (ESI±)
– MS is “low resolution” and good for
targeted lists
– High resolution accurate mass (HRAM)
good for screening but requires special
expertise
23. Extra Caution Needed with Identifications
O
O
O
O
O
O
NIST, Automatic ID
Internal DB
With
Expert Review
25. Extra Caution Needed with Identifications
Regarding Identifications:
• We do not recommend choosing a structure associated with the highest
match factor without providing a justification for eliminating other
potential matches.
• All potential identifications should be provided so that they can be
considered in the toxicological risk assessment.
• Substances for which only partial structure data is available should be
designated as unknown in the test report and for toxicological risk
assessment.
• If a class of substances is to be listed as the identification, then all potential
members of the class should be provided.
26. Extra Caution Needed with Identifications
Regarding Identifications:
• If a class of substances is to be listed as the identification, then all potential
members of the class should be provided.
C4 Alkanes: 2 members
C5 Alkanes: 3 members
C6 Alkanes: 5 members
C12 Alkanes: 355 members
C32 Alkanes: 27.7 billion members
27. Leachables Studies: When to Conduct Them and How?
Typical Extractables Analytical Test Matrix
Analytical Method
Polar
(water)
Mid-Polar
(IPA)
Non-Polar
(hexane)
Elements
ICP/MS and ICP/OES
X N/A N/A
VOCs
Headspace GC/MS
X N/A N/A
SVOCs
Direct Injection GC/MS
X X X
NVOCs
HRAM-UPLC/MS, APCl ±
N/A X X
NVOCs
HRAM-UPLC/MS, APCI/ESI ±
X N/A N/A
• The device is extracted per ISO
10993 standards
– 50 °C for 72 hours
– Polar, Mid-Polar, and Non-Polar
Solvents
• If there are problems, then
non-standard conditions can
be used
– 37 °C for 24 hours
– 10% EtOH in water
– Other conditions which closely
mimic clinical use
Even if we know that an extractables study will “fail,” it
is still conducted, followed by a leachables (simulated
use extractable) study targeted to the problem.
28. Feedback from FDA on Reporting
Regarding Reporting, the Following Should be Included:
• Calibration data that demonstrates that suitability of the calibration
method across the range needed for quantification.
• Chromatographic data that includes labeling to discern retention time and
relative signal intensity.
• Substance information when higher than the AET:
– (1) Retention time, (2) proposed identity(ies), (3) chemical name (e.g. IUPAC name), (4)
CAS number, (5) structural descriptor (e.g. SMILEs), (6) identification confidence level, (7)
type of identification data (e.g. spectra library match), (8) quantification method (e.g.
fully quantitative using an authentic standard, semi-quantitative based on a relative
response factor, or semi-quantitative using a surrogate response factor), (9)
concentration (e.g. in μg/ml), and (10) quantity (μg/device).
30. Reports Include-
• Introduction and Study Standards: “This is a medical device extractables study conducted
per ISO 10993-18:2020”
• Photos of the devices before and after extraction
29
36. Conclusion on ChemTox and FDA
• It should be understood that ChemTox is often viewed as a requirement and
undergoing a period of intense scrutiny by regulators
• The process should begin with a collaboration between the toxicologist and
the chemistry lab; erring on the side of providing more detail
• A detailed testing plan is recommended; this should be given to the FDA as
part of their pre-sub program
• Goals: Save animal lives, save time, save money, and IMPROVE PATIENT
SAFETY!