Dr. Andreas Nixdorf presented on chemical characterization of plastics used in medical products according to ISO 10993 standards. He discussed the normative framework for chemical characterization and analytical methods for identifying extractables and leachables. Key points included sample preparation according to ISO 10993-12, using both exaggerated and accelerated extraction conditions. A variety of analytical techniques were outlined for separation and detection of extractable substances.
ISO 10993 Biological Evaluation of Medical Devices UpdateNAMSA
The ISO 10993 Biological Evaluation of Medical Devices Update covers the revisions/updates that were discussed at the TC194 meeting in Mishima, Japan in April of 2014.
ISO 10993 Biological Evaluation of Medical Devices UpdateNAMSA
The ISO 10993 Biological Evaluation of Medical Devices Update covers the revisions/updates that were discussed at the TC194 meeting in Mishima, Japan in April of 2014.
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.
ISO 10993-7 Biological Evaluation of Medical Devices - Ethylene Oxide Sterili...NAMSA
This presentation, ISO 10993-7 Biological Evaluation of Medical Devices - Ethylene Oxide Sterilization Residuals, discusses why it is necessary to test ethylene oxide (EO) and how to categorize your device.
Just providing the information on Impurities in drug substances & Drug products to share my view and the collected information from the web for knowledge purpose.
Use of Chemical Characterization to Assess the Equivalency of Medical Devices...NAMSA
Use of Chemical Characterization to Assess the Equivalency of Medical Devices and Materials describes chemical characterization techniques and why they are important.
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.
New legal obligations and liability under MDR and IVDRErik Vollebregt
Presentation at the MedTech Summit in Amsterdam on 19 June 2017 on the product liability regime under the MDR and IVDR, its nexus with the EU Product Liability Directive and its impact on other provisions in the MDR / IVDR
[Note: This is a partial preview. To download this presentation, visit:
https://www.oeconsulting.com.sg/training-presentations]
ISO 13485:2016 is an international standard that sets out the requirements for a quality management system (QMS) specific to the medical devices industry. The standard focuses on meeting customer and applicable regulatory requirements and is intended for any organization partially or fully involved in the medical device life-cycle.
This presentation can be used to brief your employees, new hires and potential auditees so as to create awareness of the ISO 13485:2016 standard. Alternatively, the presentation may be used to supplement your materials for the training of QA professionals and internal auditors in the medical devices industry.
It covers the what and why of ISO 13485, the QMS key clause structure, the audit approach and also offers practical tips on how to handle an audit session. When you are done teaching this material to your employees, they will be much more informed and comfortable with ISO 13485:2016.
LEARNING OBJECTIVES
1. Provide background knowledge on ISO 13485:2016
2. Gain an overview of ISO 13485:2016 structure and the certification process
3. Understand the audit approach
4. Gather useful tips on handling an audit session
CONTENTS
1. Overview of ISO 13485
About ISO
What are Standards?
Why are Standards Important?
What is ISO 13485?
Who is ISO 13485 For?
What is a Medical Device?
What is a Quality Management System?
How Does ISO 13485 Work?
Benefits that ISO 13485 Will Bring to the Organization
Advantages of Certification
Development of ISO 13485
Why Was ISO 13485 Revised?
Key Improvements to ISO 13485:2016
Relationship of ISO 13485 with ISO 9001
2. ISO 13485:2016 Structure
The ISO 13485:2016 Structure
The Plan-Do-Check-Act (PDCA) Process Model
ISO 13485:2016 Approach is Based on the PDCA Cycle
Documentation Requirements
ISO 13485:2016 Key Clause Structure (4-8)
Clause 4: Quality Management System
Clause 5: Management Responsibility
Clause 6: Resource Management
Clause 7: Product Realization
Clause 8: Measurement, Analysis & Improvement
3. ISO 13485:2016 Certification
Becoming ISO 13485:2016 Certified
ISO 13485:2016 Certification Process
4. Audit Approach
What is a Quality Audit?
What Are Audits Used For?
Types of Quality Audits
Internal Quality Audit
Principles of Auditing
Audit Focus
Audit Approach
Audit Emphasis
Document Review
Audit Findings
5. Handling an Audit Session
Rights of Auditee
Rights of Auditor
How to Handle an Audit Session?
Auditee's Conduct
Interacting with Auditors: Do's
Interacting with Auditors: Don'ts
Woodbay Ltd Takes Initiative by Transitioning to ISO 9001:2015SGS
Woodbay Ltd is a care home provider for elderly residents based in Scotland.
Due to the nature of a care home’s operations it is essential that high levels of quality and safety are maintained at all times. By cultivating a culture of continuous improvement alongside ISO 9001, Woodbay is committed to ensuring that these needs are met.
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.
ISO 10993-7 Biological Evaluation of Medical Devices - Ethylene Oxide Sterili...NAMSA
This presentation, ISO 10993-7 Biological Evaluation of Medical Devices - Ethylene Oxide Sterilization Residuals, discusses why it is necessary to test ethylene oxide (EO) and how to categorize your device.
Just providing the information on Impurities in drug substances & Drug products to share my view and the collected information from the web for knowledge purpose.
Use of Chemical Characterization to Assess the Equivalency of Medical Devices...NAMSA
Use of Chemical Characterization to Assess the Equivalency of Medical Devices and Materials describes chemical characterization techniques and why they are important.
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.
New legal obligations and liability under MDR and IVDRErik Vollebregt
Presentation at the MedTech Summit in Amsterdam on 19 June 2017 on the product liability regime under the MDR and IVDR, its nexus with the EU Product Liability Directive and its impact on other provisions in the MDR / IVDR
[Note: This is a partial preview. To download this presentation, visit:
https://www.oeconsulting.com.sg/training-presentations]
ISO 13485:2016 is an international standard that sets out the requirements for a quality management system (QMS) specific to the medical devices industry. The standard focuses on meeting customer and applicable regulatory requirements and is intended for any organization partially or fully involved in the medical device life-cycle.
This presentation can be used to brief your employees, new hires and potential auditees so as to create awareness of the ISO 13485:2016 standard. Alternatively, the presentation may be used to supplement your materials for the training of QA professionals and internal auditors in the medical devices industry.
It covers the what and why of ISO 13485, the QMS key clause structure, the audit approach and also offers practical tips on how to handle an audit session. When you are done teaching this material to your employees, they will be much more informed and comfortable with ISO 13485:2016.
LEARNING OBJECTIVES
1. Provide background knowledge on ISO 13485:2016
2. Gain an overview of ISO 13485:2016 structure and the certification process
3. Understand the audit approach
4. Gather useful tips on handling an audit session
CONTENTS
1. Overview of ISO 13485
About ISO
What are Standards?
Why are Standards Important?
What is ISO 13485?
Who is ISO 13485 For?
What is a Medical Device?
What is a Quality Management System?
How Does ISO 13485 Work?
Benefits that ISO 13485 Will Bring to the Organization
Advantages of Certification
Development of ISO 13485
Why Was ISO 13485 Revised?
Key Improvements to ISO 13485:2016
Relationship of ISO 13485 with ISO 9001
2. ISO 13485:2016 Structure
The ISO 13485:2016 Structure
The Plan-Do-Check-Act (PDCA) Process Model
ISO 13485:2016 Approach is Based on the PDCA Cycle
Documentation Requirements
ISO 13485:2016 Key Clause Structure (4-8)
Clause 4: Quality Management System
Clause 5: Management Responsibility
Clause 6: Resource Management
Clause 7: Product Realization
Clause 8: Measurement, Analysis & Improvement
3. ISO 13485:2016 Certification
Becoming ISO 13485:2016 Certified
ISO 13485:2016 Certification Process
4. Audit Approach
What is a Quality Audit?
What Are Audits Used For?
Types of Quality Audits
Internal Quality Audit
Principles of Auditing
Audit Focus
Audit Approach
Audit Emphasis
Document Review
Audit Findings
5. Handling an Audit Session
Rights of Auditee
Rights of Auditor
How to Handle an Audit Session?
Auditee's Conduct
Interacting with Auditors: Do's
Interacting with Auditors: Don'ts
Woodbay Ltd Takes Initiative by Transitioning to ISO 9001:2015SGS
Woodbay Ltd is a care home provider for elderly residents based in Scotland.
Due to the nature of a care home’s operations it is essential that high levels of quality and safety are maintained at all times. By cultivating a culture of continuous improvement alongside ISO 9001, Woodbay is committed to ensuring that these needs are met.
Understanding Pesticide Residue Risks in Food Products and Supply ChainsSGS
The aim of this presentation is to promote an understanding of the origins of pesticide residues, and current industry challenges due to increasing regulations for the management and compliance of food products destined for international markets.
Analytical Development of Biosimilar Mabs: From Vision to Reality SGS
The approval of the first biosimilar mAbs in Europe last June (Celltrion’s Remsima™ and Hospira’s Inflectra™ versions of infliximab) paves the way for the advent of more widespread access to biological treatments in indications such as rheumatology and oncology. One year on, lessons learned from these approvals will guide the global regulatory framework for such complex biomolecules. Indeed, several more biosimilar mAbs are currently in late-stage clinical trials and can be expected to be submitted to Regulatory Authorities shortly. Read more or listen to live streaming http://bit.ly/SGSBiosimilarWebinar
Presented by Fallbrook Engineering President/CEO Richard Meyst for UCSD's Overview of FDA Regulations for Medical Device Professionals and SDSU's Current Good Manufacturing Practices: Advanced Topics.
Impact of Sample Handling and Processing on Bioanalycial OutcomeSGS
Data from clinical assays (biomarkers, PK, PD, and immunogenicity) are often key outcomes from clinical trials. Implementing these endpoints in clinical trials is very costly and also time - and resource-consuming. Therefore, ensuring that appropriate measures are taken from the collection of samples until the completion of laboratory testing is paramount.
The purpose of this presentation is to discuss the challenges and potential pitfalls of sample collection, processing, and storage on the final bioanalytical endpoints and laboratory assays. Key parameters affecting various assay endpoints will be discussed and illustrated with specific examples, highlighting the SGS approach to handling and controlling these critical activities for the successful delivery of these studies outcomes.
Contact Us: clinicalresearch@sgs.com
Visit our Website: http://www.sgs.com/cro
Follow Us on LinkedIn: http://bit.ly/SGSLifeSciences
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.
In this presentation from CPhi 2014, Elise Gallais outlines the guidelines for cleaning validation: and focuses on analytical methods and their validation.
Meta Analysis of Medical Device Data Applications for Designing Studies and R...NAMSA
Meta Analysis of Medical Device Data Applications for Designing Studies and Reinforcing Clinical Evidence discusses what meta analysis is as well as the potential benefits.
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...Merck Life Sciences
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
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
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.
Assessing the Impact of Single-Use Systems on Patient Safety: A perspective ...MilliporeSigma
Presented at INTERPHEX on March 21-23, 2017.
Single use process technology is routinely used in the manufacture of pharmaceuticals and biopharmaceuticals. The potential for extractables and leachables from single use systems and their impact on patient safety are an important focus of drug manufacturers and regulators. While current regulatory guidelines and industry standards provide general direction on compound-specific safety assessments, they do not offer a comprehensive approach to safety evaluations of extractables and leachables. Smaller, emerging companies might not even be aware of the extent of the extractables and leachables data expected by regulatory authorities and that the FDA has issued warning letters in cases where the appropriate extractables and leachables studies were missing for a drug product. The author will describe a comprehensive approach to determine the impact single use process technology has on patient safety.
DESIGN OF IMPLANTABLE DEVICE – UNDERSTANDING THE PREMARKET REVIEW PROCESS AN...UBMCanon
Xin Fu, Ph.D., D.A.B.T.
Pharmacologist
FDA/CDRH/ODE/DRGUD/ULDB
Outline
-Overview of premarket review process of
medical devices, with emphasis on
biocompatibility evaluation
-Review of device materials
A Review on Step-by-Step Analytical Method Validationiosrphr_editor
When analytical method is utilized to generate results about the characteristics of drug related samples it is essential that the results are trustworthy. They may be utilized as the basis for decisions relating to administering the drug to patients. Analytical method validation required during drug development and manufacturing and these analytical methods are fit for their intended purpose. To comply with the requirements of GMP pharmaceutical industries should have an overall validation policy which documents how validation will be performed. The purpose of this validation is to show that processes involved in the development and manufacture of drug, production and analytical testing can be performed in an effective and reproducible manner. This review article provides guidance on how to perform validation characteristics for the analytical method which are utilized in pharmaceutical analysis.
Challenges using Multiple Single-use Systems: Functionality versus Extractabl...MilliporeSigma
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
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
SGS First Quarter 2024 Sales Update Presentation EN.pdfSGS
Get the financial highlights and an overview of our performance per business. You can view our financial reports here: https://www.sgs.com/en/investors/results
Get the financial highlights and an overview of our performance per business. You can view our financial reports here: www.sgs.com/en/our-company/investor-relations/reports-and-presentations
Get the financial highlights and an overview of our performance per business. You can view our financial reports here: www.sgs.com/en/our-company/investor-relations/reports-and-presentations
SGS 2022 Full Year Results Alternative Performance Measures ReportSGS
This document presents and defines the Group’s alternative performance measures (APMs), not defined by IFRS which are used
to evaluate financial and operational performance. Where relevant, a reconciliation to the information included in our IFRS consolidated
financial statements is presented. Management deems these performance measures as a useful source of information when taking
strategic decisions and managing the operations. These APMs are disclosed in the annual report, the half year report and other external
communications to investors, as well as available under: www.sgs.com/en/our-company/investor-relations/reports-and-presentations
Get the financial highlights and an overview of our performance per business. You can view our financial reports here: www.sgs.com/en/our-company/investor-relations/reports-and-presentations
Discover our Corporate Sustainability report to get an overview of how we contribute to sustainability, demonstrated by case studies from our operations and services, and a summary of performance.
We've delivered a strong financial performance in 2021, making significant progress on our new strategic plan.
#SGS #SGSGroup #WeAreSGS #FinancialResults
SGS 2021 Full Year Results Alternative Performance MeasuresSGS
We've delivered a strong financial performance in 2021, making significant progress on our new strategic plan.
#SGS #SGSGroup #WeAreSGS #FinancialResults
Learn about our collaboration on a range of innovative circular projects with Dutch Government.
Discussion with three experts on safe construction.
First recycled content declarations for manufacturers.
Get the financial highlights and an overview of our performance per business. You can view our financial reports here: www.sgs.com/en/our-company/investor-relations/reports-and-presentations
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Chemical Characterization of Plastic Used in Medical Products
1. CHEMICAL CHARACTERIZATION
OF PLASTIC USED IN MEDICAL
PRODUCTS
Dr. Andreas Nixdorf
China Medical Device Association, 2016 annual meeting
SGS - Life Sciences, Germany
Last changes: Jan. 19 2016
2. 2
AGENDA
Introduction of SGS E&L German team in brief
Chemical characterization per ISO 10993, the normative framework
General analytical methods, ISO 10993 part 18
Extractables & Leachables: Sample preparation, ISO 10993 part 12, Solvents,
analytical techniques
What influences material chemical profiles?
Physical and morphological characterization, ISO 10993 part 19
Factors influencing biocompatibility
Examples of surface characterization
Failure analysis of materials
3. 3
AGENDA
Introduction of SGS E&L German team in brief
Chemical characterization per ISO 10993, the normative framework
General analytical methods, ISO 10993 part 18
Extractables & Leachables: Sample preparation, ISO 10993 part 12, Solvents,
analytical techniques
What influences material chemical profiles?
Physical and morphological characterization, ISO 10993 part 19
Factors influencing biocompatibility
Examples of surface characterization
Failure analysis of materials
4. 4
SGS EXTRACTABLES TEAM – TAUNUSSTEIN
(GERMANY)
We have long term experience
• Increasing regulatory requirements need knowledge about
guidelines and cross-disciplinary skills
• E&L reports are submitted for product registration
• Assessment to satisfy regulatory authorities:
US-FDA and EMA
by following PQRI, BPOG, BPSA, and ISO 10993 recommendations
We are Extractables Center of Excellence in Taunusstein
• International client network
• Testing performed in cGMP compliant laboratory or ISO accredited laboratories
• Solid basis of trust and high degree of market acceptance
We are global partner from Risk Assessment to Toxicological Evaluation
• Customized study design
• Expertise in regulatory questions
• Close communication and exchange with our clients
• Professional and efficient project management
7. 7
THE NORMATIVE SYSTEM OF ISO 10993
Evaluation Strategy
ISO 10993 Part 1: Evaluation and testing within a risk management process
Biological Testing
Part 3: Tests for genotoxicity, carcinogenicity and
reproductive toxicity
Part 4: Selection of tests for interactions with blood
Part 5: Tests for in vitro cytotoxicity
Part 6: Tests for local effects after implantation
Part 10: Tests for irritation and skin sensitization
Part 11: Tests for systemic toxicity
Part 20: Principles and methods for immunotoxicology
testing of medical devices
Others / Administrative
Part 7: Ethylene oxide sterilization residuals
Part 2: Evaluation and testing within a risk
management process
Part 8: Selection and qualification of reference
materials for biological tests (has been
withdrawn by ISO steering committees)
Part 12: Sample preparation and reference
material
Material Characterization
Part 18: Chemical characterization of materials
Part 19: Physico-chemical, morphological and
topographical characterization of
materials
Degradation Products / Toxicological Evaluation
Part 9: Framework for identification and
quantification of potential degradation
products
Part 13: Identification and quantification of
degradation products from polymeric medical
devices
Part 14: Identification and quantification of
degradation products from ceramics
Part 15: Identification and quantification of
degradation products from metals and alloys
Part 16: Toxicokinetic study design for degradation
products and leachables
Part 17: Establishment of allowable limits for
leachable substances
8. 8
WHY CHEMICAL CHARCTERIZATION?
Chemical Characterization, ISO 10993-18 a useful and important
addition:
Regulatory bodies are increasingly asking for data on the material and
chemical components of devices
In Vitro and In Vivo biocompatibility studies are not so sensitive and often do
not allow the root cause of “irritation”
Complements in vivo biocompatibility studies for qualification of materials
selection
Analytical chemistry studies help to evaluate hazards that are associated with
the device or with the manufacturing process
Support process control in manufacturing
Demonstrate equivalency of proposed materials to a clinically established
material
9. 9
WHY CHEMICAL CHARCTERIZATION?
Chemical characterization information can be used for:
As part of an assessment of the overall biological safety (10993-1, 14971)
Measurement of the level of leachable substances in a medical device in order to
allow the assessment of compliance – allowable limits for safety risk assessment
Judging equivalence of a proposed material to clinically established material
Judging equivalence of a final device to a prototype device to check the
relevance of data on the latter to be used to support the assessment of the former
Screening of potential new materials for suitability in a medical device for a
proposed clinical application
NOTE: Part 18 does not address identification or quantitation of degradation
products, which is covered in part -9, -13, -14 and -15.
10. 10
CHEMICAL CHARCTERIZATION / ISO 10993-18
Materials characterization in 5+2 principal major steps (see also Dr. Stark in
2003)*:
1. Qualitative Information:
Describe material and its intended purpose within the device. Data may be taken from
suppliers
2. Material equivalence:
The new material is compared to an existing material that is used in a device with the
same clinical exposure
3. Quantitative data:
Quantitative data will be needed, if a risk assessment cannot be made purely on
qualitative information
4. Quantitative risk assessment (see also ISO 14971):
In The quantitative risk assessment of identified chemicals are compared to toxicological
information, rather than to another material
5. Estimate clinical exposure (see also ISO 14155):
Finally the amount of potentially harmful chemicals, the dose, is compared to the clinical
dose a patient might receive in a lifetime, a procedure, or other unit of time
6. Exposure of Risk Assessment:
As before, an evaluation for unacceptable toxicological risks shall be carried out
7. Biological evaluation Tests:
Where the evaluation indicates that there are still unacceptable risks then appropriate
biological evaluation tests shall be considered in line with part 1
*Stark NJ, Biocompatibility Testing & Management, Fourth Edition, Clinical Device Group Inc, Chicago, IL (2003).
11. 11
CHEMICAL CHARCTERIZATION (1/2) – FLOWCHART
OF RISK MANAGEMENT PROCESS ISO 10993-1*
~
*see FDA; Draft Guidance for Industry 2013, “Use of International Standard ISO 10993, Biological Evaluation of Medical Devices Part 1:
Evaluation and Testing”.
12. 12
CHEMICAL CHARCTERIZATION (2/2) – FLOWCHART
OF RISK MANAGEMENT PROCESS ISO 10993-1*
*see FDA; Draft Guidance for Industry 2013, “Use of International Standard ISO 10993, Biological Evaluation of Medical Devices Part 1:
Evaluation and Testing”.
~
13. 13
CHEMICAL CHARCTERIZATION / ISO 10993-18
Qualitative and Quantitative information:
Detailed description of the Material and it´s intended use.
Materials chemical composition:
Material constituents (Type of polymer, additives, processing aids, etc.)
Potential contaminants (unintentionally introduced via material handling)
The extent to which constituents are subjected to use conditions should be
assessed:
Perform extraction and migration experiments
Select analytical methods to give the required information for toxicological
evaluation
The scope of validation should correspond to the requirements and should become
part of the risk assessment
Starter materials should also be well characterized
Information should be provided by suppliers.
Used to identify toxic hazards arising from the chemical components of materials
Includes: technical data, specifications, certifications, literature data
14. 14
CHEMICAL CHARCTERIZATION (1/3) –ANALYTICAL
METHODS ISO 10993-18 AND OTHERS
General physico-chemical testing:
Analytical Technique Description Application
Dynamic mechanical thermal analysis
(DMTA)
Allows the material response to stress,
temperature, frequency and other values
to be studied
Changes in elastomers by dimension,
changes in stiffness and damping
Differential scanning calorimetry (DSC) Measures the heat capacity of a sample
by comparing the energy required to
change temperature compared wit
reference sample.
Characterization of polymers, change of
transitions and phase changes
Electron dispersal – X ray analysis-
Scanning electron microscopy (EDX-
SEM)
Electron microscopy combined with
elemental and compound analysis using
energetic electrons to liberate X rays for
analysis
Identification of materials in surfaces and
contaminants present. Useful for metals
and ceramics. Verification of deposition of
coatings
Three Dimensional Scanning Electron
Microscopy (3DSEM )
Combines the high resolution imaging of
SEM with quantitative surface metrology
information
Information about the sample's surface
topography and composition
X-ray photoelectron spectroscopy (XPS) Surface analysis by measuring energy of
electrons released by incident radiation.
Examination of surfaces for cleanness,
contaminants and coatings
X-ray fluorescence (XRF) Similar to XPS but delivered energy
results in secondary fluorescence.
Examination of surfaces for cleanness,
contaminants and coatings
Infra red spectroscopy (IR) Measures intra red transmission through
a thin film, or reflectance from a surface
Polymer identification and verification,
identification of particles
15. 15
CHEMICAL CHARCTERIZATION (2/3) –ANALYTICAL
METHODS ISO 10993-18 AND OTHERS
General physico-chemical testing :
Analytical Technique Description Application
Secondary ion mass spectrometry
(SIMS-ToF, static and dynamic)
Used to analyze the composition of
solid surfaces by sputtering the surface
of the specimen with a focused primary
ion beam and collecting and analyzing
ejected secondary ions
Elemental composition of materials from the
surface to depths of 100 microns and
beyond. SIMS is generally considered to be
a qualitative, very sensitive technique
White Light Interferometry (WLI) Makes use of the wave superposition
principle to combine waves in a way
that will cause the result of their
combination to extract information from
those instantaneous wave fronts
Topographical information from the surface
including 2D, 3D images and profilometry as
well as roughness parameters including
surface roughness, peak height and valley
depth
Atomic Force Microscopy (AFM) Arguably the most versatile and
powerful microscopy technology for
studying samples where an extremely
sharp inert tip is scanned over a surface
Images in three-dimensional topography, it
also provides various types of surface
measurements. Can generate images at
atomic resolution with angstrom scale
Inductively charge plasma (ICP)
combined with MS or OES
Measures the masses of the element
ions (MS) or the light emitted at
element-specific characteristic
wavelengths (OES) from thermally
excited analyte ions generated by the
high temperature argon plasma
Detection of trace metals in extracts
16. 16
CHEMICAL CHARCTERIZATION (3/3) –ANALYTICAL
METHODS ISO 10993-18 AND OTHERS
General physico-chemical testing :
Analytical Technique
(Chromatography)
Description Application
Mass spectrometry combined with
different ion sources
Identification of compounds by measuring
mass to charge ratios of ions
Elemental composition, identification of
chemical structure, quantitation of substances
Ultraviolet spectroscopy (UV) Absorption of light Analysis of extractions for organic substances
(Leachables) and others
Electrochemical detection (ECD) Amperometric electrochemical detection
the electrical current is measured
resulting from oxidation or reduction
reactions.
Electrochemically active substances
Gel permeation chromatography (GPC) Separation of polymers by transit time
through a gel by size.
Distribution of polymers of different chain
length. GPC is often used to determine the
relative molecular weight of polymer samples
as well as the distribution of molecular
weights
High performance liquid chromatography
(HPLC)
Liquid phase separation and quantitation
of chemical mixtures
Analysis of extractions for organic substances
(Leachables) or cation and anions
Gas chromatography (GC) Separation and quantitation of volatile
substances
Analysis of extractions for organic substances
(Leachables)
Nuclear magnetic resonance (NMR) Detailed analysis structure of complex
molecules by energy measurement of
nuclear environment
Structural analysis of molecules
17. 17
CHEMEICAL CHARACTERIZAION – SAMPLE
PREPARATION ISO 10993 -12 (E&L)
Some important definitions:
Extractables: Soluble substances that are removed from a device using
exaggerated conditions
Leachables: Soluble substances that are removed from a device using
conditions of simulated use
Exaggerated extraction (e.g. by solvent): ..results in a greater amount of a
chemical constituent being released (for identification) as compared to the
amount generated under simulated use conditions
Accelerated extraction (e.g. by temperature): “…using conditions that
shorten the time for leaching of the substances into the extraction vehicle…”
18. 18
CHEMEICAL CHARACTERIZAION – SAMPLE
PREPARATION ISO 10993 -12 (E&L)
Extraction conditions (justify the selection):
(37 ±1)°C for (72 ±2)h
(50 ±2)°C for (72 ±2)h
(70 ±2)°C for (24 ±2)h
(121 ±2)°C for (1 ±0.1)h
Other conditions may be used but shall be described and justfied.
Complete dissolution of material may be appropriate (e.g. Oxidative
digestion of polymer to determine total amount of metals by ICP-MS)
20. 20
CHEMEICAL CHARACTERIZAION – SOLVENTS
ISO 10993 -12 (E&L)
Soft solvents:
Polar Water, Saline, Culture media (no serum)
Non-polar vegetable oil (may be replaced by pure solvents such as octane,
hexane,…)
Additional extraction vehicles ethanol/water, ethanol/saline, PEG 400, DMSO
and culture medium with serum
Harsh conditions could damage material, avoid it´s dissolution!
Do extraction under circulation or agitation!
Maximize the amount of extractables
Do the extraction with treated (e.g. sterilization) material, if included in your
material process.
21. 21
CHOOSE APPROPRIATE TOOLS FOR
SEPARATION & DETECTION
Volatiles organics by GC
Head-space technique, TDMS, FID and MS –detector
Semi-Volatiles organics by liquid injection GC
FID and MS detector
Non-Volatiles organics by HPLC
DAD, LC-MS/(MS) with accurate mass assignments
Metals / Elements
ICP-MS, ICP-OES
Cations, Anions
Ion chromatography
Special Techniques for critical compounds
GC-TEA for Nitrosamines
Perfluorinated Carboxylic acids, -Amides, -Sulfonamides by LC-MS/MS
NMR- Technology, IR and others
22. 22
Identification Categories
Establish a classification scheme that characterizes the significance of peak
identification data (tentative, confident, confirmed and unknown)
Best identification means the comparison of both the retention index and the
mass spectrum of an extracted component with its authentic reference
standard
Identificatio
n category
Identification Data
A Interpretation of mass spectrometric
fragmentation behavior or component could be
grouped to a series
B Confirmation of molecular weight
C Confirmation of elemental composition (not
conducted in this study)
D Mass spectrum matches automated library or
literature spectrum
E Chromatographic retention index match
authentic specimen
F Mass spectrum and chromatographic retention
index match authentic specimen
X No characterization possible
Attribute Description
Confirmed A Confirmed identification means that identification
categories A, B (or C), and D (or E or F) have been
fulfilled
Confident A Confident identification means that sufficient data to
preclude all but the most closely related structures
have been obtained, Library match factor ≥ 90
Tentative A Tentative identification means that data have been
obtained that are consistent with a class of molecule
only
unknown No sufficient information’s could be obtained
WHAT IS A TRUSTABLE IDENTIFICATION?
23. 23
WHAT INFLUENCES A
MATERIAL’S CHEMICAL PROFILE?
Some major processing impacts (to be considered in assessment)
Defects and changes can be caused by incompatible resistance due
to:
Short and long term exposure to:
Chemicals
Irradiation such as UV, e-Beam and Gamma
Ozone, Oxygen, Ethylene oxide (ISO 10993-7)
Moisture
Biological (see ISO 10993 framework)
Temperature
24. 24
INFLUENCES ON MATERIAL CHEMICAL PROFILE –
EXAMPLE RADIATION RESISTANCE
Gamma Radiation
Sterility means that a product is free from microorganisms capable of
reproduction
EN ISO 11137 regulates the sterilization of health care products by
radiation: the manufacture and sterilization of a medical product labeled as
‘sterile’ has to take place under appropriate conditions
Both the manufacturing process and the subsequent sterilization process
have to be validated (biodurden)
No validation regarding changes in polymer structure and chemical profile is
considered by EN ISO 11137.
25. 25
INFLUENCES ON MATERIAL CHEMICAL PROFILE –
EXAMPLE RADIATION RESISTANCE
Acrylonitrile butadiene styrene (ABS),
Literature: “Radiation Chemistry of Polymers”, V.S. Ivanov, VSP 1992; “Radiation resistance of polymer materials”, Atomic Energy, Vol. 76, No. 5, pp. 422–428, May, 1994; “A
review of radiation resistance for plastic and elastomeric materials”, Radiation Physics and Chemistry (1977), Volume 24, Issues 5-6, 1984, Pages 503-510
26. 26
INFLUENCES ON MATERIAL CHEMICAL PROFILE –
EXAMPLE RADIATION RESISTANCE
Carbonic acids: C1, C2, C3 etc.
C2 – C5 -Aldehydes
Ketones
BHT derived from Irganox 1010,
1076
2,5-di-tert-butyl benzene and
2,5-di-tert- butyl phenol from
Irgafos 168
Gamma 20-
25/45 kGy
BHT: 3,5-di-tert-butyl-4-hydroxytoluol
Oxidation of free radicals:
The energy-rich beta or gamma rays trigger chemical reactions in the plastics
which result in networking or ‘cross-linking’ of the polymer molecules.
Demertzis, P.G.; Franz, R.; Welle, F.; „The Effects of Gamma-Irradiation on Compositional Changes in Plastic Packaging Films”, Packaging
Technology and Science 12 (1999), S.119-130.
27. 27
INFLUENCES ON MATERIAL CHEMICAL PROFILE –
EXAMPLE RADIATION RESISTANCE
Validation of radiation regarding impact on extraction level was missed!
Dose: approx. 32 kGy
Extraction of Pt cured silicone tube at 50 °C for 24 h with WFI
Analyte Blank µg/mL µg/cm2 Compared to Blank
(LOQ) an increase by
factor of
Formaldehyde < LOQ1 21 7 233
Formiate < LOQ2 106 34 25
Acetate < LOQ2 18 14 9
1 0.03 µg/cm2
2 1.6 µg/cm2
28. 28
PHYSICOCHEMICAL, MECHANICAL, MORPHOLOGICAL AND
TOPOGRAPHICAL CHARACTERIZATION OF MATERIALS –
ISO 109993-19
Parameters to be Analyzed are depend on the clinical exposure/application
of the device:
Porosity
Morphology: crystallinity of polymer, amorphous, transition phases, hardness
Surface energy / charge: protein absorption/repulsion, cell attachment etc.
Abrasion resistance, stability of treated surface
Topography: surface chemical mapping, roughness
Particles and release of it: Size, shape, distribution
29. 29
FACTORS INFLUENCING BIOCOMPATIBILITY –
WETTING OF SURFACES
Wetting is an important phenomenon in many industrial processes, it
has a strong influence on cell growth around implants
Wetting is dependent on both chemical composition and morphology of
the surface
Wetability can be studied by measuring the contact angle of the
substrate with the given liquid
Surface roughness measurements, see ISO 25178 and related normative frame work.
31. 31
Application: Surface characterization of medical stents
Problem: Determination of Surface Elemental composition ,100 nm layer depth
Method: AES (Auger Electron Spectroscopy)
Result: The stent is made from alloyed steel with a layer thickness of 22 nm
AES-Tiefenprofil, Stent D1
0
20
40
60
80
100
4 6 8 10 12 14
Sputterzeit [min]
Atomkonzentration[%]
C
O
Fe
Cr
Ni
Mo
Removal of surface
contamination by sputtering.
SURFACE CHARACTERIZATION OF MEDICAL
PRODUCT
32. 32
Product failures are most costly at the pharmaceutical end-user side
Materials safety and robustness should be considered in any risk assessment
Product failures causes:
Recalls or delays in drug product registration
Warranty claims
Costs for independent failure analysis
Brand damage
The best strategy is to avoid failures:
Qualify your supplier and starter materials quality
Start to qualify your process at the early stage of product development
Generally problems do not solve themselves – usually the situation gets worse
Identify ways to improve or avoid failure in current and future parts
Advance the knowledge related to materials, design, production methods,
installation techniques, and testing methods
FAILURE ANALYSIS – WHY IS A FAILURE
ANALYSIS IMPORTANT?
33. 33
MATERIAL ANALYSIS - DO YOU KNOW ALL OF
THESE TECHNIQUES?
Materialography, Light Microscopy
Electron Microscopy (REM, SEM)
Atomic-force microscopy (AFM)
X-ray diffraction (XRD; XRT)
Electron Probe Microanalyzer (ESMA)
Photoelectron Spectrometry (XPS)
Auger Electron Spectroscopy (AES)
Spreading Resistance Profiling (SRP)
Secondary Ion Mass spectrometry (SIMS)
Infrared Spectroscopy (IR),
Thermoanalysis (DTA, DSC)
Liquid Chromatography (HPLC, IC)
Gas Chromatography (GC-MS, HID, TEA, FID, ECD
Particle analysisD-SIMS Cameca ims 7f
XPS Quantum 2000
ICS 3000
34. 34
STEPS FOR PERFORMING FAILURE ANALYSIS
(PLASTICS)
Obtain Part History
Macroscopic Examination
Microscopic Examination
• Stereomicroscopy
•Scanning Electron Microscopy
•Cross Section
Material Analysis
Composition
•FT-IR
•Energy Dispersive X-ray
•Thermo Gravimetric Analysis
Molecular Structure
•Differential Scanning Calorimetry
•Molecular Weight Evaluation
Physicochemical Analysis
•Dynamic Mechanical Analysis
•Mechanical testing
•Hardness
Determine Failure Mode and
Cause
Determine Contribution
Factors
35. 35
Embedded
Bubbles
The needle was inadequately glued in Luer-lock connector.
There is a high risk for leakage and particle formation.
The glue does not fill the whole space between
connector and needle.
Cracking
FAILURE ANALYSIS – SYRINGE NEEDLE
36. 36
Observation of Calcium phosphate crystals in finished drug:
Route cause: Ca2+ ions are leached out from Rubber stopper
forming Calcium phosphate precipitation due to incompatibility to
drug formula.
Calcium/Octa phosphate Ca3(PO4)2 / Ca4(PO4)3 3·H2O pKsp 28.9
/ 46.9**
Calcium phosphate are less soluble in neutral and alkaline
conditions and dissolve in acid.
*see: Institute of Validation Technology, published on IVT Network; Alan M. Mancini , Joanne Wong Paul L. Pluta, Ph.D., Compliance Case Study #11 ;
„Glass Fragments in a Parenteral Product , Aug 29, 2014.
** S. Kubo, T. Takahashi, H. Morinaga, and H. Ueki, “Inhibition of Calcium Phosphate Scale on Heat Exchanger: The Relation between Laboratory Test Results
and Tests on Heat Transfer Surfaces”, Corrosion’79, Paper No. 220, Atlanta (1979)
ROUTE CAUSE ANALYSIS – RUBBER
INCOMPATIBILITY TO DRUG FORMULA*