Removing Rabbits from Irritation Testing: Current status of regulatory acceptance of ISO 10993-23

A discussion of the most recent revisions to ISO 10993-1 and the current and future states of alternative testing. For the past three to four decades, biocompatibility testing remained relativity unchanged, with basically a few simple steps to be followed: 1) look at your device 2) compare it to a chart 3) do the suggested testing. With the recent publication of ISO 10993-23, animal-free irritation testing is now being performed side by side with its animal counterpart. Current revisions to 10993-1 are emphasizing less animal testing and more alternative approaches. This talk will discuss this topic, in particular, the following: • The proposed changes to 10993-1 • The general response of regulators regarding alternative testing approaches • The outlook of 10993-1 for the future Attendees will walk away with a clearer picture of the alternatives to animal testing and what the alternatives might be next year and, in the years, to

Understanding the Power of the FDA Pre-Sub: Tips for a Successful Meeting

The submission process to the FDA can be a stressful and uncertain time for a medical device company. Delays in getting your device to market can cost millions of dollars in revenue. Changes to standards, new guidance documents, and review variability all add to the stress of a submission. The FDA pre-submission process can help reduce the stress and answer questions related to your specific device. In this webinar, we will cover what the pre-submission process is, how to initiate a meeting, and how to prepare and run the meeting to gain the best results. We will highlight tips we have used to make partnering with the FDA a rewarding experience. Join Thor Rollins and Matthew Jorgensen; PhD, DABT, as they cover: What is a pre-submission meeting (Q-sub) with the FDA? How do you set a Q-Sub? How do you deliver your plan during a Q-Sub? What is the meeting flow? Can I challenge the FDA? How do I get the most from the Q-Sub?

Animal Testing

Animals are traditionally used as test subjects during drug development studies in order to reliably detect the toxic properties of chemicals. Eliminating the use of animals in toxicology testing, is a difficult challenge. The purpose of this paper is to discuss the evolving methods to test toxicology in ways that minimize the negative impact on animals as much as possible.

The Use and Utility of General Chemistry Data in Extractables Assessment

This White Paper describes how General Chemistry Data obtained in controlled extraction studies, such as pH, UV absorbance and total organic carbon (TOC), is reported, used and discussed as part of a rigorous extractables assessment.

Use of Exaggerated Surface Area to Solution Volume Ratios in Extractables Studies; Equilibrium Case

The goal of this whitepaper is to provide guidance and justify appropriate practices about the proper use of exaggerated test article surface area to extraction solution volume ratios in exaggerated extractables st

Why Extractables and Leachables Matter

Medicines and other healthcare products rely for their value, integrity and commercial longevity on a delicate balance between quality, safety and efficacy. When that balance is disturbed by issues such as product adulteration, the damage to patients, revenues and corporate reputation can be substantial. That is why the pharmaceutical and medtech industries, along with their associated regulators, are paying increasing attention to testing requirements for extractables and leachables (E&L). Recent trends in product development and manufacturing have multiplied the risks of unintended chemical changes that could compromise product integrity either during the manufacturing process or on the shelf. Extractables and leachables are organic or inorganic chemical compounds, such as antioxidants, lubricants, polymers and dyes, with potential to migrate into finished products from the container, container closure, delivery system, primary, secondary and tertiary packaging, or various manufacturing components.

Cytotoxic Reactivity Understanding the Cause and the Path Forward

All medical devices intended to contact the patient are required to undergo a biological evaluation to demonstrate their safety. The overarching guidance document for biocompatibility assessments is ISO 10993-1 that provides a framework for this evaluation and defines the relevant endpoints needing assessment based on the contact type and duration that the specific device has. Regardless of the contact however, cytotoxicity as an endpoint is required for evaluation for all devices that fall under the scope of ISO 10993-1. Cytotoxicity, due to its high sensitivity, as well as quick turnaround time and low cost is commonly used by the medical device industry to screen devices for their potential to have any reactivity to the body. At the same time, this high sensitivity can also lead to elevated reactivity which needs to be followed with an investigation to understand whether the observed results are a concern when the device is used on a patient. This webinar will cover the basics of cytotoxicity testing and will provide some examples on how to perform an investigation and risk assessment on devices that demonstrate cytotoxic reactivity.

Face Masks and Respirators

This Nelson Lab's webinar is designed to help you understand the difference between medical face masks and N95/N99 respirators. We’ll discuss some of the physical differences, the testing that is required for each, and how to properly use them. We will also touch on how to protect yourself from respiratory type illnesses, and recommendations from the CDC and WHO. During this webinar you will learn: What is a face mask? What is a respirator? What testing is required for these items? How are they regulated? How can I tell if a mask has been tested?

ICH Stability Testing and Method Development

Stability testing is a vital part of product development and is conducted throughout a product’s life cycle. Stability is part of a biotherapeutic’s quality target product profile, and results help analysts understand how critical quality attributes (CQAs) of both drug substances and products are influenced under specific conditions of temperature, relative humidity (RH), light, storage, pH, and other factors. These studies are required to be conducted in a planned way following the guidelines issued by ICH, WHO and or other agencies. This presentation will provide a brief overview of the ICH guidelines for Stability testing, as well as aspects of analytical method development.

Mass Extraction Container Closure "CCIT" for Rigid Containers

Mass extraction is a relatively new container closure integrity test which is included on the USP 1207 list of approved deterministic CCIT test methods. This webinar explains the basic methodology behind a mass extraction test, the advantages of mass extraction testing over other CCI methods, and how the test is performed. By the end of this webinar you should know: 1. Why CCIT tests are preformed? 2. What kinds of samples are suitable for mass extraction testing? 3. How a mass extraction test is performed? 4. How to interpret mass extraction results?

MPO Packaging Validations – A Look at Current and Future State Testing

This webinar will touch on some of the changes implemented with the release of the MDR’s in the European Union and the impact to the packaging requirements. Specifically these new regulations prompted the changes to the packaging industry resulting in the newly published ISO 11607. A discussion on 3 key points regarding packaging will be discussed and how the ISO 11607 directs device manufacturers to meet these changes. Additionally, a brief discussion on the life cycle approach to packaging validations including an in-depth look at a couple specific tests and finally a high-level look at sample size considerations as part of the establishing a validation testing plan.

Packaging Validations - A look at Current and Future State Testing

This Nelson Lab's webinar will touch on some of the changes implemented with the release of the MDR’s in the European Union and the impact to the packaging requirements. Specifically these new regulations prompted the changes to the packaging industry resulting in the newly published ISO 11607. A discussion on 3 key points regarding packaging will be discussed and how the ISO 11607 directs device manufacturers to meet these changes. Additionally a brief discussion on the life cycle approach to packaging validations including an in-depth look at a couple specific tests and finally a high level look at sample size considerations as part of the establishing a validation testing plan.

The New FDA Draft Guidance for Biocompatibility of Certain Devices in Contact with Intact Skin: The Naughty and Nice list

In October of 2020, the FDA released a new draft biocompatibility guidance document. This new draft focuses on the biological evaluation of devices in contact with intact skin. This document signifies another step from the FDA toward their 3R animal initiative (reduce, refine, and replace animal use in testing when feasible). In this webinar, we will go into detail on this new FDA draft document. We will give flavor on why the FDA released this guidance and what it means for skin-contacting medical devices. We will look at the list of materials that fall into the guidance (the nice list) and then the ones that are excluded (the naughty list). We will also cover what should be included in your submission of these materials to make sure you have success with your FDA submission.

Biocompatibility and the New MDR

This presentation will include an overview of biocompatibility in compliance with the new MDR. The key focus will be on highlighting differences on previous approaches for CE marketing and the requirements in the MDR. Guidance will be provided to establish a roadmap to compliance.

An Introduction to large volume parenterals (LVPs) as a pharmaceutical dosage form

 Pharmaceutical dosage forms are differentiated primarily by their route of administration and secondarily by other dosing parameters. Parenteral dosage forms are those dosage forms that are injected through the skin or other external boundary tissue, or implanted within the body, to allow the direct administration of the active drug substance(s) into blood vessels, organs, tissues, or lesions. Large-volume parenteral drug products (LVPs) are liquid parenterals that are packaged in unit doses of greater than 100 ml. LVPs are typically packaged in flexible (i.e. plastic) packaging, opening the possibility of substances that leach from the packaging and become drug product impurities. Due to their large volume and sometimes complex composition, LVPs can be difficult to test (screen) for unspecified leachables. This presentation introduces LVP’s as a pharmaceutical dosage form and introduces the concept of the AET Challenge.

The Essence Of The EU MDR and its Key Consequences

The enhanced focus of the EU-MDR on biocompatibility and toxicity will be placed in perspective of the overall changes in details and concept of the European expectations. This presentation will provide some insight in the motivations to enhance the effective regulatory burden in a way that will help understand what focus should be taken for regulatory compliance.

MDR/IVDR – How MedPharmPlast is Helping Overcoming the Potential Challenges

MDR/IVDR makes it essential for OEMs to understand what substances are in their devices. This pattern is repeated in impending USP regulations to use so-called ‘well-characterized materials’. Faced with these questions, and a growing list of ‘substances of concern’, how will you be in compliance ? The usual approach of ask my suppliers ‘Does it contain XYZ?’ is likely to result in some surprising answers! Maybe you feel you don’t have a necessary depth of plastics materials knowledge? Does this mean I need to test for everything? A good ‘risk management’ strategy is first to understand what information is possible to have and what not. In this presentation we look at the practical challenges you will face to get the answers you will need. Also how MedPharmPlast Europe and its ‘vertical expertise’ can help overcome these challenges and tap into the 100’s of years of combined plastics and regulatory know how.

Upcoming Changes to Cleaning Validations for Reusable Medical Devices

AAMI TIR30 has been one of the primary documents used to provide guidance on the recommendations for the cleaning validations of reusable medical devices for the last ten years. During this time, the industry has changed due to the advancement of reusable medical devices and the test methods used to evaluate the effectiveness of the cleaning procedures. To ensure that the recommendations for cleaning validations are current with the industry changes, AAMI TIR30 is being revised to become a standard, AAMI ST98. Additionally, this standard will to provide clear guidance on how to perform cleaning validations as such a standard does not currently exist. This presentation will cover the upcoming changes to the requirements for the cleaning validations of reusable medical devices that will be found in AAMI ST98.

Changes in the Packaging Environment Relating to Regulations and Test Methods

The world today is complex and ever changing. Packaging is no exception, and the current pandemic has brought a new set of challenges related to supply issues. This presentation will review upcoming changes to packaging standards, packaging trends for the near future, ideas for mitigating packaging supply disruptions, and packaging validation considerations for changes. Originally presented at MDM West 2022.

Updates to Med Device E & L What about Chemistry on Limited Contact Devices

Recent feedback from global regulatory bodies have been requesting extractables and leachables (E&L) chemistry testing for all devices, even those with limited contact duration. This presentation will highlight recent regulatory feedback we have received and provides guidance on how to avoid the Limited Device E&L Trap. Originally presented at MDM West 2022.

EPA Regulatory and Testing Guidelines for Residual Efficacy

With the recent implementation of the EPA guidance for residual efficacy claims for antimicrobial products, there is a lot to unpack and understand when looking to make a claim for a residual sanitizing test substance. The goal of this webinar is to provide a top-down summary of what each of these methods is intended to accomplish and which may be the best fit for your test substance. Specifically, the webinar aims to provide insight into how the results of a residual efficacy evaluation for submission to the EPA will be gathered, interpreted, and best presented for the sponsor’s submission.

Selecting & Justifying Sample Sizes: Where to Begin?

Within our industry, we have seen several approaches to selecting samples sizes, this whitepaper will not cover all of the approaches, but it is a guide to give medical device manufacturers and pharmaceutical companies a good starting point for determining their own ideal sample size.

COVID-19, what we learned from the race to supply the market with respirators, masks, and other PPE

During these unprecedented times, medical device companies needed to be quick on their feet. These past few months, manufacturers were challenged by emergency authorization orders from FDA, an industry shortage of PPE, and limited testing capabilities. This session will cover the quick collaborations between regulators, laboratories, and medical device sponsors to meet the need. We will also discuss the learning that developed during this crisis and how you can apply this learning going forward to make our industry stronger. Key points in this webinar: What you need during the pandemic to get vital devices in the hands of the users? What considerations is FDA asking for? How did we show these devices were safe to the users—not just effective? How can we apply these learnings post pandemic?

Packaging Design Validation Testing

Manufacturers of medical devices need to ensure their terminally sterilized products are contained in validated packaging. Attendees of this webinar will learn about packaging design considerations and various package testing including shelf-life, distribution, strength, integrity, and microbial barrier.

The Production Process and Qualification of a Pharmaceutical Film

What is needed to qualify primary packaging materials for Large Volume Parenterals? And what to consider when selecting the right material? Dr Bianca Schweiger and Christian Kunz from PolyCine, a pharmaceutical film manufacturer, give insights on the requirements for IV-solution primary packaging materials. They will discuss how these materials are produced and the regulatory requirements that apply to these materials during their presentation regarding Production and qualification process for pharmaceutical films.

Hunt for N-nitrosamines in Medicinal Products

In the EMA newsletter published in September 2019, the pharma industry was given a wake-up call regarding the request to evaluate the risk of the presence of nitrosamine impurities in human medicinal products containing chemically synthesised active pharmaceutical ingredients. This presentation will look at case studies of analytical testing in the three-step request to review the risk for presence of nitrosamines in medicinal products process issued by EMA/FDA.

E&L Testing of Single-Use Systems for Production

2022 NELSON LABS VIRTUAL SYMPOSIUM: Leachables in pharmaceutical products could originate from manufacturing items (filters, bioreactors, etc.) used in the pro duction process. With the increasing use of disposables in the pharma industry, the concern in E&L has also developed considerably. Biopharma industry groups (BPSA, BPOG) have published recommendations when and how to perform E&L studies for these materials. Moreover, the USP has released chapter <665> and <1665>, which ad dress E&L for production materials in the (bio) pharmaceutical industry. The different steps in the assessment of the E&L impact of a production line will be outlined in this presentation. In addition, the recommendations of BPOG and USP for these materials will be discussed.

The Biocomp Trail A Challenging hike towards Animal Free Testing

The main purpose of ISO 10993-1 is to focus on a risk-based approach for evaluating biocompatibility of medical devices and to ensure patient safety. A second goal of the document is to ensure animal welfare and to minimize the number and exposure of animal tests. The introduction of the requirement for a biological evaluation plan in ISO10993-1 in 2018 and the need to rely on chemical and physical information to evaluate the necessity of in-vivo testing is an important step towards a reduction of the use of lab animals. This presentation will focus on the road towards an animal free testing environment to evaluate the biological safety of Medical Devices and present the current status for animal free test methods.

Guidance on Combining Biocompatibility and Cleaning Validation Testing

Testing all the biocompatibility endpoints at first-time use and then agian after multiple reprocessing cycles can be costly and time consuming. There are also many factors that can affect the biocompatibility of a device over time such as number of uses and reporcessing. This whitepaper discusses the different factors and approaches to be considered for both the reprocessing and biocompatibility of reusable devices.

Chemical Disinfection Validations for Reusable Device

During this 45-minutes webinar, Dr. Lise Vanderkelen will take you on a journey to address some of the key aspects of what is required for disinfection validation studies. This is the second step in the processing cycle of reusable devices and the second installment of our three-part webinar series on cleaning, disinfection and sterilization validations of reusable devices.

Design Control for the Contract Research Organization

Design Control is a requirement from the FDA as laid out in 21 CFR.820. It is the basis for how medical device companies in the United States (or those planning on market in the United States) set up a quality system surrounding the designing and development of their medical devices. We will review what design control is, using examples to better have an understanding, and then see how Nelson Labs can support sponsors with design control requirements.

Transportation and Distribution Testing for Medical Devices

An important, but sometimes overlooked component of a packaging shelf life validation is transportation and distribution testing. This testing is required for all commerce and is an important early step in total package design. This webinar will introduce you to the basics of transportation and distribution testing by explaining why it is important and what a typical distribution test sequence looks like. By the end of this webinar you should know: 

Reprocessing Validations of Reusable Medical Devices

Reprocessing validations of reusable medical devices have been overlooked for quite some time and the importance of these validations for medical device manufacturers has taken a back seat until recently. The upcoming MDR requirements and added US FDA scrutiny over reusable medical devices has shed a light on the importance and significance of validations. The presentation will highlight some of the key aspects of what is required for validation studies for reusable medical devices and how to perform these validations. It will give a perspective of what is needed to include in these validations and where in the design phase these validations make their presence. Alpa Patel explains the importance of cleaning and disinfection validations as well as sterilization validations.

The Necessity of Extractable and Leachable Qualifications for Lyophilized Drug Products: Some Fallacies Addressed

Lyophilized drug product containers and administration devices consist of the primary packaging (typically a glass vial and a rubber stopper), the reconstitution solution container (typically a vial or a prefilled syringe system), and the drug administration set (such as a disposable syringe, an intravenous bag, or a pump system with administration tubing) as shown in the Whitepaper.

The New FDA Draft Guidance for Biocompatibility of Certain Devices in Contact with Intact Skin: The Naughty and Nice list

In October 2020 FDA released a new draft biocompatibility guidance document which focuses on the biological evaluation of devices in contact with intact skin. As a draft document, it is therefore open for comments and possible changes. Release of this guidance signifies another step from FDA toward their 3R animal initiative (reduce, refine, and replace animal use in testing when feasible).

The Testing and Risk Management Impacts of Changing a Medical Device

A medical device and its support system may undergo hundreds of changes throughout its product life cycle. We are constantly dealing with the impact of change. Knowing how to properly evaluate and manage all areas that are impacted by a change is a critically important process for manufacturers to master. Learn how to evaluate possible safety impacts following any change that is made and how to effectively mitigate biocompatibility risks.

Benefits of Premarket and Postmarket Particulate Testing of Cardiovascular Devices

Device manufacturers that incorporate particulate testing into their product-development plans early are better equipped to navigate the regulatory clearance process and potentially reduce time to market. Particulate testing of cardiovascular medical devices is an important and valuable step on the road to regulatory clearance, market success, and patient safety. Device manufacturers that incorporate particulate testing into their product-development plans early are better equipped to navigate the regulatory clearance process and potentially reduce time to market. After premarket regulatory clearance is achieved, and the cardiovascular device is on the market in clinical use, post market lot release particulate testing and monitoring can help ensure product quality and safety going forward.

Biocompatibility for Medical Devices 101 – Prepare for Clinical Trial

This is a crash course overview of medical device biocompatibility. We will provide an overview of the guidance provided in ISO 10993-1 and FDA expectations for demonstration of biocompatibility leading up to a medical device clinical trial or 510(k) submission. Biocompatibility is discussed from the perspective of systemic vs non-systemic biological endpoints, with emphasis on test selection, sample preparation, chemistry testing, and toxicological evaluation. The “big 3” tests (cytotoxicity, sensitization, and irritation) are summarized followed by the fundamentals of medical device extractables testing and toxicological assessment.

Biocompatibility of Raw Materials for Medical Devices

Starting with a biocompatible material is important for medical device manufacturers. However, regulation is pushing the manufacturer to ask for more information and more support from their suppliers. Biocompatibility on materials is critical to stay competitive and provide your clients with the needed information. Webinar topics include: • An overview of ISO 10993-1 • MDR regulation regarding carcinogens, mutagens, and reproductive toxins (CMRs) for raw materials • Where is the line in responsibility for material supplier and device manufacturer? • What information and testing on raw material is useful for the biocompatibility of a final device?

Assessing the Safety of Extractables and Leachables for Drug Products: When and How?

In this webinar Kevin Breesch of Nelson Labs will speak about the challenges of toxicological-safety assessments for parenteral packaging systems. Typical toxicological challenges for extractables and leachables (E&L) are presented, such as difficulties in daily exposure evaluations for a selection of compounds to be evaluated, based on an appropriate selected threshold. Subsequently, typical burden in hazard and risk evaluation relate to data-poor substances often related to rubber closure systems. Within this context, E&L examples are selected for which the critical toxicological endpoints are discussed and evaluated by means of various methods, in terms of deriving appropriate safety limits. Key Learning Objectives: -To know how to select the right threshold for E&L screening methodologies. - To know how to determine a reasonable exposure of compounds to the patient. -To understand the toxicological-safety hurdles and how to overcome them.

Best Practices When Validating Reusable Devices

The advancement of reusable medical devices has changed the industry over the years and the requirements for validating reprocessing instructions have changed with it. It can be difficult to navigate these changes and ensure that the reprocessing validations meet the current industry standards and expectations. An understanding of the best practices when validating reusable medical devices will aid in navigating medical device manufacturers through these changes and challenges. The presentation will cover some of the best practices when validating the reprocessing instructions for reusable medical devices. Key Learning Objectives: Understanding which documents would play a key role in your reprocessing validation How to best design a reprocessing validation to avoid regulatory scrutiny Understanding new regulations regarding validations strategies for reusable medical devices.

How to Address Regulatory Change in Your Current Biocompatibility Program

In this course you will learn what changes are occurring in regulatory standards, including ISO 10993, Medical Device Regulations, and FDA guidance. Then based on these changes you will learn how to keep your biocompatibility program current. Recent regulatory changes and those in the pipeline need to be evaluated within the context of an existing biocompatibility program. You will learn how to evaluate your biocompatibility information and determine what the gaps are and your options in addressing them.

The Design and Qualification Process for a LVP Packaging System from a User Perspective

To meet the increasing patient need for LVP, more complex packaging systems are required to be designed and further qualified to house different solutions. The high maximum daily dose of the multi-components of the packaging system present challenges when evaluating extractables and leachables (E&L). Controlling E&L levels in LVP is vital for the safety, quality, and efficacy of the finished product. Leveraging existing regulations (Pharmacopeial and food compliance) and effective collaboration with the suppliers of the raw materials will provide the required knowledge to design accurate E&L assessments. E&L testing of LVP dictates a low detection limit due to the long LVP treatment duration and high volumes. Thus, impurities with ppb levels such as Nitrosamines trigger great analytical challenges. Approaching LVP based on E&L risk assessment at an early stage of the product’s life cycle, namely material selection, will allow the E&L strategy to succeed in ensuring patient safety and product compliance.

Satisfying ISO 18562 and FDA Biocompatibility Regulatory Requirements for Breathing Gas Pathways in Health Care Application

In March of 2017, the new ISO 18562 standard series was released. This four part standard covers the general principles regarding biocompatibility assessment of medical device materials which comprise the gas pathway. Some of the additional concerns will be addressed through the assessment of volatile organic compounds (VOCs), particulates, and leachable in condensate. The US FDA has recently recognized ISO 18562 parts 2 and 3 completely and portions of part 1 and 4. This series is meant to run as a perpendicular standard to the ISO 10993 standard suite providing supplemental testing and considerations for your overall Biological Safety Evaluation which should include a 3-step process: 1) Initial risk assessment – introduction of device, materials, processing, patient contact, areas of risk and mitigation steps 2) Testing and risk assessments 3) Summary report concluding that the device is biocompatible.

Packaging Validation 101

Have you wondered how to set up a packaging validation according to ISO 11607? Come join us for a Packaging Validation 101 webinar to learn the basics including: - Determining an appropriate sample size for testing - Writing the validation protocol - Developing the test plan - Selecting appropriate tests - Family grouping and worst-case considerations and creating the appropriate samples. ISO 11607 Part 2 covers packaging process validation. We will be discussing: - Basic validation concepts - Defining the validation process - Seal acceptance criteria and qualifications – along with routine process monitoring.

A Stepwise Approach to Deal with In Vitro Cytotoxicity Failures

Manufacturers are required to perform a biological evaluation of any medical device as outlined in ISO 10993-1. One particular endpoint that has to be evaluated for every medical device is cytotoxicity. Due to the highly sensitive nature of the cytotoxicity test combined with its low cost and short turnaround time, this endpoint is most often expected to be evaluated through testing. An in vitro cell culture is used to evaluate the potential cytotoxic effects of the final finished form of a medical device. It is known that in vitro cytotoxicity testing is a sensitive assay that can often result in failures. A failing result often causes panic. This is understandable given a compromised medical device will not be approved for commercialization. ISO 10993-5 provides a statement on the assessment of in vitro cytotoxicity results: Any cytotoxic effect can be of concern. However, it is primarily an indication of potential for in vivo cytotoxicity and the device cannot necessarily be determined unsuitable based solely on cytotoxicity data. Any in vitro cytotoxicity failure is a source of concern that should be investigated to identify whether there is a risk for in vivo cytotoxicity. This does not automatically mean a medical device is not biocompatible, provided proper risk assessment is performed, there are several alternatives to defend such a result and move toward a successful submission. This document aims at providing the reader a guide on how to investigate and assess in vitro cytotoxicity failures in order to determine the appropriate way forward.

Single Use & Newly Manufactured Device Cleaning Validations

Performing a cleaning validation during the initial phase of a device’s lifecycle aids manufacturers in complying with current good manufacturing practices (CGMP) and quality system (QS) regulation as set forth by FDA for medical device manufacturers. The data gathered during cleaning validations helps manufacturers have confidence in the quality of their finished medical devices during on-site audits performed by both customers and regulators. Find out more on: The importance of a cleaning validation Considerations for the initial validation Residual sources of contamination Analytical test methods.

Successful Medical Device Cleaning Validations: What You Need to Know

Validating cleaning instructions for a tray of reusable orthopedic devices is an important milestone on the path to obtaining FDA clearance for those devices. Although the process of validation can seem daunting at first, medical device manufacturers seeking to successfully navigate this process can do so confidently and efficiently if they are armed with knowledge, education, and guidance. This white paper provides detailed information on successful medical-device cleaning validations.

After E&L Updates to the Standard for Toxicological Risk Assessment 10993-17

Use of extractables and leachables (E&L) chemistry testing has become commonplace (and often essential) in medical device biocompatibility evaluations. The details of how E&L is conducted have received a lot of attention in the industry; however it must be remembered that this testing is conducted to serve a toxicological risk assessment (TRA) and it is the demands of proper toxicology that has put constraints on E&L in the first place. The ISO standard for TRAs, ISO 10993-17 is undergoing a long overdue update. This presentation will discuss updates present in the current draft of the new standard and how those will impact future TRAs, chemistry for toxicology, and biocompatibility at large. Key takeaways: Fundamental principles of TRA for medical devices will be reviewed Updates to 10993-17 focus include rational exposure estimates The Threshold of Toxicological Concern (TTC) vs the Analytical Evaluation Threshold (AET)

Applying a Risk Based Approach to Biological Evaluation of Medical Devices Based on the ISO 10993-1:2018

All medical devices that are intended to contact patients or medical personnel (directly or indirectly) require an evaluation of their biocompatibility prior to regulatory submission and market release. The umbrella document for this evaluation is the international standard ISO 10993-1 which includes the framework and thought process for the biological evaluation of medical devices. The potential risks that medical devices carry depend highly on its intended contact type and cumulative duration of use. However, before jumping into testing for the specified biological endpoints identified by Table A.1 in ISO 10993-1, one should consider available information that could provide evidence in support of biological safety and reduce the need for testing. This so-called “risk-based approach” is the heart of the standard and should be applied to any medical device (either being newly submitted for market release or undergoing changes). This presentation will provide an overview of the thought process and flow of medical device biological evaluations (often called a biological evaluation plan or BEP) with an emphasis on the proper application of a risk-based approach.

Becoming Compliant with the MDRs, A Real Life Case Study

The new Medical Device Regulations (MDRs) become enforceable May 2022. After that, all new devices set for market in the European market will have to demonstrate compliance with ISO 10993, even if the device has been on the market for years. This presentation will walk through a real life example of bringing a device that has been on the market in Europe into compliance with the ISO 10993 and the new MDRs.

Evaluating the biocompatibility of reusable medical devices during their whole life cycle

In the past, the focus for reusable devices has been on validating the reprocessing efficacy with regards to infection control. Recently however, and especially with the advent of the new era of MDR, the focus has expanded to include the aspect of biocompatibility, e.g. how the numerous reprocessing cycles could impact the device and whether it continues to be safe for the patient throughout its life cycle. It is also stated in ISO 10993-1. The theory sounds simple, but in reality, it poses extra challenges for reusable devices as they are reused and reprocessed over and over again. With that, questions, including what is happing to the materials over the lifetime of the reusable devices as these materials are attacked with detergents, disinfectants and are exposed to high temperatures, need to be answered and explored. This presentation will give more insights on: The design of a biological evaluation plan for reusable medical devices Current expectations of regulatory agencies Consideration from the biocompatibility perspective for first-time use, in-use, as well as end-of-life cycle for a reusable medical device.

Extractables and leachables testing of a combination device: testing in between regulations for pharmaceutical products and medical devices

Extractables and Leachables testing of combination devices requires a specific study set-up which differentiates from a typical chemical characterization study according to ISO10993-18. In this presentation, we will explain how a chemical characterization study of a combination device should be performed, based on a case study of an insulin device. Furthermore, we will clarify how to integrate in the study set-up the requirement for Carcinogenic, Mutagenic and Reprotoxic Compounds (CMRs) as specified in section 10.4 in Annex I of the MDR. This requirement is especially important for products falling under article 117.Finally, drug-device compatibility should not be neglected or forgotten in an overall biocompatibility evaluation.

Guidance for Cleaning, Disinfection and Sterilization of Reusable Medical Devices

All reusable devices should contain specific instructions for cleaning, disinfecting and/or sterilization of the device. In order to be compliant with global regulations, manufactures should have their instructions for use (IFU) validated to ensure patient safety and mitigating cross contamination. It is recommended to validate at least one method for each applicable stage of reprocessing of the medical device. During this webinar you will learn more about: The full processing cycle (What is reprocessing and what devices should be considered for this type of testing) How to comply with the new EU MDR The validation of a cleaning procedure (To what extend the device design can impact the validation protocol) Methods for disinfection or sterilization instructions The importance of cytotoxicity testing after a reprocessing cycle

Biocompatibility: Applying the New ISO 10993 Standards

A new updated ISO 10993-1 standard came out in Aug of 2018 that drastically changed how we access medical devices for biocompatibility. We also are dealing with the impact of the Medical Device Regulations in Europe. The timing of these two documents has greatly disrupted the medical device industry. In this webinar we will discuss the changes and efficient approaches to navigate through the troubles. From this webinar you will learn: Overview of the new ISO 10993-1 Performing a Biological Evaluation Plan Overview of the “Big Three” including new in vitro alternatives What is needed in a Biological Evaluation Report for FDA?

Design Change Impact on Biocompatibility and Documentation

Change Management, especially related to a medical device’s design, is one of the most commonly-cited issues in FDA 483s and Warning Letters. Unfortunately, change is constant in the medical device industry, so it’s imperative to learn how to effectively evaluate change and incorporate findings into biocompatibility testing and documentation. In this webinar, industry experts from Nelson Labs and Greenlight Guru will teach you how to: Accurately identify change Evaluate change’s impact on biocompatibility and testing Effectively and proactively document changes Remain compliant when changes inevitably occur.

Ethylene Oxide Sterilization, Revision of Annex E, Single Batch Release

ANSI/AAMI/ISO 11135:2014 Annex E recently underwent revision expanding on the requirements for the release of product from a single batch Ethylene Oxide (EO) sterilization process. This addendum builds on the current allowances and requirements for the release of product from a single lot sterilization batch to demonstrate that the process delivered the desired Sterility Assurance Level (SAL) to the exposed product. This presentation takes a comprehensive look at the single lot release approach, the factors that determine what testing is necessary, and how the requirements in Annex E of ANSI/AAMI/ISO 11135 have changed. This presentation will help the manufacturer navigate through some of the considerations for execution of a single batch release process. The training will assist in the development of a test plan, including sample size requirements, for performing a single batch sterilization process. Attendees will learn: Regulatory background and industry expectation for single batch release from EO processes Pre-evaluation of product design, packaging design, and loading configurations Establishing a compliant test plan for single batch release from EO processes Proper assessment of process and test results, including required documentation to support single batch release from EO processes.

The New ISO 10993 – 18 Standard and its Impact on Chemical Characterization of Medical Devices

To meet the heightened focus on chemical characterization in ISO 10993-1:2018, a major revision of ISO 10993-18 “Chemical characterization of medical device materials within a risk management process” was undertaken. The revised document published in January 2020. In this presentation, Dr Ted Heise focuses on key parts of the new document, bringing in experience and lessons learned from multi-stakeholder development of the final standard.

Reusable Advices For Reusable Medical Devices

Ensuring that reusable devices can be properly cleaned, disinfected and/or sterilized is imperative to ensure patient safety and to minimize healthcare-acquired infections, corrective actions, and recalls. Regulatory agencies and healthcare facilities are increasingly concerned about the spread of diseases. The COVID-19 pandemic has increased that concern even further. Therefore, having proper cleaning, disinfection and/or sterilization instructions in place that have been validated to ensure compliance with current regulatory standards is paramount. In order to assist our customers with the development and validation of reprocessing instructions in an ever-changing regulatory landscape, Nelson Labs has a dedicated team of experts actively serving on relevant ISO and AAMI committees capable of helping with every step of the way. We offer full-range services starting from writing an appropriate Instructions for Use documents, selecting worst-case devices that should be validated, and performing the actual validations in ISO17025 and GLP accredited laboratories. When performing intake conversations with our clients, it is clear that deciding which regulatory aspects are applicable to a specific and individual medical device can be challenging. In our series of advices, we have therefore attempted to summarize the regulatory guidance that is offered and how it can be applied to a specific medical device. This list is by no means exhaustive, nor does it cover all aspects related to reprocessing validations. Instead, it covers a selection of frequently asked questions, with Nelson Labs experts available at your disposal to answer any questions.

Disinfectant Efficacy Testing for Submission to the US Environmental Protection Agency

When developing a disinfectant or sanitizer (herein referred to as disinfectant) for use on environmental surfaces, the Sponsor must first develop and support a label claim based upon guidelines set forth by the United States Environmental Protection Agency (EPA). In order to substantiate the claim the Sponsor is planning to make on their label, they must perform one, or more, evaluations as dictated by the EPA.

Considerations for Sterilization and Biocompatibility of 3D-Printed Orthopedic Devices

This whitepaper to learn about the various biocompatibility and sterilization considerations surrounding 3D-printed orthopedic devices. 3D-printed orthopedic medical devices are gaining attention and popularity due to their potential for enhanced biocompatibility, customizability, and cost-effectiveness. As of late 2015, FDA had cleared more than 85 total 3D-printed medical devices, with more regulatory clearances on the horizon.

Designing an End-to-End Sterility Assurance Program

Sterility assurance for a pharmaceutical product is critical and includes many aspects outside of the actual sterilization cycle or aseptic process. There is some recent movement in the health care industry regarding the term End-to-End Sterility Assurance, along with a document being written through AAMI to provide guidance on the topic. Effective sterility assurance includes extensive collaboration with parties across the product life cycle. In the webinar we will address the various aspects of sterility assurance and provide guidance on establishing a complete program.

Microbiological Control in a Pharmaceutical Manufacturing Environment

This webinar will address the evaluation of microbiological, environmental monitoring data as well as what would be considered significant differences in data. We will review microbiological trending and how it can assist in understanding what is significant in each particular situation. We discuss how the analysis of this trended data enables a company to establish alert and action levels as well as methods for determining these levels. We will review cleaning validation protocols, methods, and procedures to evaluate and define a robust program to protect your products, personnel, and equipment. We will discuss correlating disinfectant validations with the trending of routine-environmental monitoring data to establish a compliant program in a clean room environment. Finally, water is perhaps the most extensively used raw material in pharmaceutical manufacturing. Its use as an inactive ingredient, active pharmaceutical ingredient (API), analytical reagent, and even as a solvent in cleaning processes, leads to potential product and environmental contamination from residual water impurities. This presentation addresses the removal and control of microbiological and chemical impurities in a quality water system.

DISINFECTION VALIDATION: How to Classify and Validate Your Medical Device Disinfection Process

Medical device reprocessing, and the scientific validation of reprocessing instructions, are critical steps to ensuring devices are safe and effective for patient use. The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, as well as past infection outbreaks, have prompted increased concern over disinfection and sterilization of reusable medical devices.

N-Nitrosamines in Primary Packaging for SVP’s

2022 NELSON LABS VIRTUAL SYMPOSIUM: Because of recent product recalls due to the unexpected presence of N-Nitrosamines, it is important to look at the formation of these amines on materials prominently used in the primary packaging of drug products. The unanswered question is: do we know everything about the materials of construction of a container closure system and their ability to generate N-Nitrosamines? It is commonly known that secondary amines (and potentially tertiary amines) are a precursor to N-Nitrosamine formation and that these need to be taken into consideration when evaluating the extraction pro file of materials of construction. The question however remains should this raise a “red flag” in an N-Nitrosamine risk mitigation strategy.

Big Changes to ISO 10993-1: What is happening to the main biocompatibility standard now?

In 2018, TC194, the ISO committee for biocompatibility, released a new version of 10993-1. This new version focused more on a risk-based approach and made significant changes. We are now making more significant changes to the main biocompatibility standard. In this talk we will go over the areas of the standard that is being changed, the reasoning behind the change, and the initial acceptance of these changes around the globe.

Slimy Biofilms A Brief Overview

A biofilm is a community of microorganisms embedded in a slimy matrix which can attach to various surfaces. A great diversity of species has been found in biofilms, including bacteria, viruses, and fungi. Biofilms can exist on inert surfaces such as glass, plastic, and metal, but can also use plant and animal tissues as a substrate. The slimy extracellular matrix provides protection for the microorganisms within the biofilm, resulting in an increased resistance to disinfectants, antibiotics, and a host’s immune system. Biofilms can create major problems in the health care, food, and manufacturing industries, including infections from implantable medical devices, contamination of food/food-contact surfaces, and corrosion or other damage to industrial equipment. This presentation will introduce the formation of biofilms, current standardized test methods to evaluate antibiofilm agents, and regulatory considerations.

Understanding Container Closure Integrity Test Failures

Does a container closure integrity test (CCIT) failure always mean a defective closure? In this webinar we will explore failure modes that can occur on a perfectly sealed container and discuss how to determine if a CCIT failure is a true container leak or something else. Additionally, we will discuss the value of product specific method qualifications to ensure the test method and fixturing are suitable for your product as using a less than ideal test set up can lead to false failures.

Parenteral Drug Development Exploring the Potential Benefits of Terminal Sterilization

In this webinar, originally part of Pharmapack Europe 2022, S. Ross Tsakas, Pharmaceutical Segment Leader, Sterigenics discusses parenteral drug development. Parenteral drugs and the drug development lifecycle represent complexities across the multi-year, multi-million pledges made. With over 90 years of experience supporting the pharmaceutical, biotech, and medical device industries, we have identified 5 key hurdles: sterility, quality control, compliance, regulatory affairs, and routine manufacturing, we will delve into each challenge in a systematic, concise, yet compelling manner. As sterilization becomes a top-of-mind priority for clients along the entire supply chain, we stand poised to facilitate bolstering global health through strategic support initiatives that expedite products to market and help ensure their safety.

Establishing the Proper Alcohol/Water Proportion for Simulating Solvents Used in Controlled Extraction Studies

The purpose of this whitepaper is to provide guidance on determining the proper alcohol/water proportion for simulating solvents used in controlled extraction studies relevant to drug products that are packaged in plastic container systems, administered via plastic devices or manufactured using systems that consist of plastic components. This whitepaper provides scientific guidance as well as a case study on the effect of solvent polarity (Ethanol/water proportion) on the levels of Extractables.

Use of Accelerated Conditions in Extractables and/or Leachables Studies

The purpose of this whitepaper is to consider the scientific basis for accelerated contact conditions (via the proper combination of contact temperature and duration) for studies which involve the migration of substances (either extractables or leachables) from plastics and into contact solution (such as extraction solvent or drug products). Considering this scientific basis, recommendations concerning proper acceleration strategies are provided.

Irritation Testing is Becoming Less Irritating

Medical devices around the world are required to be assessed for biocompatibility to determine how the materials and manufacturing processes affect the patient based on contact type and duration. There are three basic tests in this analysis that are applicable for every medical device: cytotoxicity, sensitization, and irritation. We call these the “Big Three.” While these tests provide valuable information and protect patients, they also come at a cost in animal lives. Until recently, only cytotoxicity was performed in vitro, meaning “in glass” or not using animals; while sensitization and irritation testing still require the use of animals. Earlier in 2018 a series of articles was published in Toxicology In Vitro reporting data from an international Round Robin study to determine the reliability and predictivity of an in vitro irritation method for assessing medical devices. This data is driving change in irritation testing impacting international testing standards (ISO 10993-10) and seeking regulatory acceptance in the US. In this webinar, we will discuss the history of irritation testing, the innovations that have led to this change, the incorporation of the method into international acceptance, and where the method is in all of this process.

Packaging Trends Leading to Increased 483’s

This presentation will take a look at some of the recent Packaging trends that are outlined by increased 483 letters to medical device manufacturers. Using data from the FDA website I will highlight cited issues with packaging manufacturing including issues with design, processing and validation testing. Additionally, an examination into how to prevent these common trends from occurring within your company by following validated standard test methods specifically called out in the reviewed data.

Recent FDA biocompatibility feedback from 510k submissions

Submitting for an approval for a medical device through the FDA can be a stressful and anxious time. It is important to understand the most recent recommendations from the agency. Too often these recommendations are given through feedback from the submission process itself, making a proactive approach difficult. In this presentation we will review recent FDA suggestions from real 510k submissions. These suggestions will touch on all aspects of the ISO 10993 standard series from cytotoxicity, sample preparation, E&L, toxicology, and more.

The Necessity of Extractable and Leachable Qualifications for Lyophilized Drug Products: Some Fallacies Addressed

When selecting and qualifying the primary packaging for lyophilized drug products, an obvious question is: How deep should one go into the extractables and leachables qualification process of a lyophilization container? As the drug product is in a solid state, it is expected that the interaction between the lyophilized drug product and the components of a lyo-container will be low. This is also reflected in the USP <1664> Monograph on Leachables and the EMA Guideline on “Plastic Immediate Packaging Materials” (2005). However, the mechanism of interaction between the lyo-cake and the rubber stopper of a lyo vial is not always fully understood. The interaction mechanism is based upon outgassingof the rubber stopper, where the lyo cake acts as an adsorbent. Not only can this lead to substantial accumulation of the volatile and semi-volatile leachable compounds onto the lyophilized drug product, it may also induce chemical reactions between the leachables and the drug product, (i.e. when the adsorbed leachables show electrophilic properties). The webcast will explain the outgassing mechanism of the lyo-stoppers, which may lead to further accumulation of leachables adsorbed onto the lyo-cake. In addition, an experimental testing strategy will be explained that covers both the discovery, identification, and quantification of those leachables, as well as the formation of secondary leachables through chemical reactions between these reactive leachables and the drug product and its ingredients.

Bioburden Alert and Action Levels – Low Hanging Fruit for a FDA Citation

Most standards regarding bioburden and environmental testing refer to establishing alert and action levels. These standards sometimes include guidance, however, to allow for a flexibility do not provide detailed direction. This webinar will cover common practices in the medical device industry for setting levels, and the different types. It is important to understand the different approaches as some are more appropriate for a given application than others. This presentation will provide a foundation for setting alert and action levels including some common suggestions for bioburden excursion actions.

The Big Three: Cytotoxicity, Sensitization & Irritation Testing

Of all the tests manufacturers need to be prepared to conduct on their medical devices, none are more important than the Big Three—Cytotoxicity, Sensitization, and Irritation tests. Manufacturers need to understand these three tests because they must be conducted on every device before they can be submitted to the Food and Drug Administration (FDA). There is no way you can get around these tests without strong and accurate justification. Understanding the Big Three, manufacturers can be better prepared for submission to the FDA and better prepared to write justifications when the tests indicate a failure. This talk will review the current status of these big three tests, what the future holds, and how to problem-solve. By attending this webinar, attendees will learn: An overview of the Big Three tests Discussion regarding the updated 10993-1 2018 and the possibility of a big Five Current regulatory trends for these tests and what the standard committees are working.

Cleaning Validations for Reusable Devices A Road Trip to the EU and US Market

Reprocessing validations of reusable medical devices have been overlooked for quite some time. With the upcoming MDR requirements and US FDA Scrutiny over reusable medical devices has shed a light to their importance and significance. The presentation will highlight some of the key aspects of what is required for cleaning validation studies, the first step in the reprocessing cycle.

Container Closure Integrity and Stability Testing for Rigid Containers

Are you wondering how to set up a stability test plan for your vial product? Are you confused at all the options for Container Closure Integrity Testing and wondering how to decide which one to choose for your product? Then join us for a webinar on Stability and CCI testing. We will outline the basics for setting up a stability test plan for rigid containers including aging conditions and testing frequency. We will look at how probabilistic methods differ from deterministic methods and will discuss each of the common CCI test options outlined in USP 1207. We will conclude with CCI method validation basics.

Shifting Requirements Within the FDA: Expectations in Chemistry Study Design

Expectations of the FDA regarding the design of chemistry studies in support of medical device toxicology has been shifting rapidly. New expectations have primarily been communicated to laboratories through submission feedback, and pre-submission meetings, as the FDA has not yet released guidance on application of ISO 10993-18. This presentation focuses on how chemistry study design has changed over the last 12 months in response to FDA received from the FDA.

LVP Polyolefin Solutions Addressing Different Packaging and Regulatory Requirements

LVP can be packed in different packaging formats made from polyolefins: pouches, bottles produced in blow-fill-seal process or Injection stretch blow molding. The different packaging options drive the need for different raw materials and depending on the material, different key regulatory requirements. This presentation will look at the different packaging formats, the materials that can be used, and their specific regulatory requirements; as well as the regulatory support available for regulated “Medical Grade Plastics.” A short overview will be given on sustainable materials to be used in such applications.

An Outline of Current Medical Face Mask Performance Requirements and Testing

Medical face masks and respirators have taken the spotlight during the current pandemic. With the increased emphasis on wearing of face coverings an understanding of the testing required for approval of these products is imperative. An understanding of the difference between these two products and the test methods used to prove compliance is important for choosing the appropriate product to ensure the right mask is used for each purpose. Test methods can range from simple air differential tests to complicated bacterial filtration efficiency tests; each of these tests gives important information about the functionality of the product. Medical face masks are manufactured and tested with the patient in mind, and testing demonstrates this. Testing for these products is directed toward expected conditions in a medical environment, and includes bacterial filtration efficiency testing, flammability testing, and synthetic blood penetration testing. NIOSH approved respirators are generally used in industrial settings and are meant to protect the user. Testing for these products focuses more on expected conditions when protection is needed from small particulates.

Packaging Design for Sterilization

When bringing a medical device from conception to market an often-overlooked key step is packaging design and engineering. Not only does one need to take into account the look, feel, and protective qualities of the packaging but design should also be considered when determining the sterilization method for the medical device. While the product will determine the optimal sterilization method, the packaging system must support the method chosen. Each of the different sterilization methods, EO, Steam, Gamma and so on, have unique qualities which must be taken into account during the design process. In this webinar we will discuss the various methods of sterilization, how to design around them, and where to look when solving difficult or unique problems. Careful consideration of the many factors present allows for a reduction in material cost, optimization of performance, minimization of risk, decrease in cycle or dose times, and overall improved functionality.

Challenges and Considerations for Complex LVP Drug Products

The technical challenges associated executing a strategy to address the toxicological risk associated with patient exposure to leachables vary depending on the unique characteristics of the dosage form. For Metered Dose Inhalers (MDIs), widely regarded as the highest risk dosage form from an E&L perspective, often contain leachables at levels that require a strategy to be put in place to control leachables in commercial batches of the drug product after approval. Topical drugs have complex formulations that present unique analytical challenges to analyze the topical drug product and/or justify an appropriate surrogate solvent system to generate extracts of the container closure system. Large Volume Parenteral (LVP) drug products are similar to Small Volume Parenteral (SVP) drug products in the sense that most are aqueous based, however the increased daily dosage volume present analytical challenges that are pushing the boundaries of science and the capabilities of the state of the art analytical instruments that are available today. The talk discusses some of the complexity associated with deriving the Maximum Daily Dosage (MDDs) of LVP drug products and how this can impact the AET. Furthermore, the challenges associated with detecting and identifying extractables/leachables in line with evolving Safety Concern Thresholds (SCTs) is discussed along with when it is appropriate to consider the value of incorporating risk based concepts into a leachable study to ensure the level of effort (i.e. extent of testing) is commensurate with the level of risk.

Risk Assessment for Potential Elemental Impurities on Drug Products and Medical Devices

When Drug Products were submitted for approval, Regulatory authorities ask the question, “Are you submitting your Risk Assessment for the Potential Elemental Impurities as well?”. This webinar will address how to deal with “Risk Assessment for Potential Elemental Impurities” on Drug Products and Medical Devices. The USP, in parallel with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), has published standards for measuring inorganic impurities in pharmaceuticals and their ingredients. The USP General Chapters USP 232 (Elemental Impurities – Limits) and 233 (Elemental Impurities – Procedures) were implemented as of January 2018. The equivalent ICH method was defined in the Guideline for Elemental Impurities (Q3D) and Revision 1 was adopted on March, 2019. The ICH Q3D and USP 232 chapters include catalyst elements, and other inorganic contaminants that may enter a drug product from raw materials, the manufacturing process, the environment, packaging and container closure systems (CCS). The maximum exposure limits are defined according to each impurity's toxicity and route of exposure. What you will learn in this webinar: • Learn the concept of risk assessment for potential elemental impurities • How Potential Elemental Impurities on Drug Products/Medical Devices are regulated. • Get expert insights on how to develop methodologies regarding Elemental Impurities on Drug Products/Medical Devices via ICP-MS.

Primary and Secondary Packaging Materials as Potential Source of Nitrosamines

Recently there have been a number of drug product recalls due to the unexpected presence of N-Nitrosamines. While in most of those cases, N-Nitrosamine formation occurred at the level of the drug substance synthesis and stability, it is well known and documented that some materials, used in primary packaging can also be a source for N-Nitrosamine contamination of the packaged drug product (e.g. older grade elastomers and nitrocellulose laminated blister foils).

Cytotoxicity Failure What Now

Cytotoxicity endpoint is marked for all medical devices that contact the patient/user, regardless of type or duration of contact. A cytotoxicity test is an in vitro cell culture assay where the medical-device extract is placed in contact with mammalian fibroblast monolayer and their viability is measured either qualitatively or quantitatively. Cytotoxicity testing is widely used in the medical industry for screening purposes when there are changes occurring in either materials or processing or when evaluating the impact of device aging.

Cleaning Validations for Newly Manufactured Medical Devices

With the implementation of 19227:2018 Implants for surgery – Cleanliness of orthopedic implants – General requirements, evaluation of residual levels after the final manufacturing process has become a regular expectation from both OEM customers and regulatory bodies. However, determining a test strategy based on the device use remains a challenge for many. Learn about cleaning validations for newly manufactured devices and considerations for devices outside the scope of ISO 19227. This webinar will focus on the cleaning validation plan from identification of potential contaminants, to test strategy, and evaluations of results.

Preservative Effectiveness Testing - Calling Attention to Burkholderia SPP

Require more attention when it comes to a robust preservative system – Considerations for both the pharmaceutical and personal care industries. Controlling the growth of microbes within non-sterile formulations is critical to providing a safe effective product as well as meeting regulatory expectations. Rising concerns over persistent opportunistic pathogens is calling attention to the Burkholderia cepacia Complex (BCC). The BCC has proven to be a significant health risk to patients who are immune compromised, using ventilators, or suffering from underlying illnesses. This Gram-negative, rod-shaped bacterium is an opportunistic pathogen that can establish itself in water systems and manufacturing equipment surfaces. Assuring an effective preservative system for Burkholderia sp. is not just for drug manufactures, but also for cosmetics and personal care products. The FDA has issued several product recalls which have included oral liquid drugs, liquid dietary supplements, saline solutions, and hand sanitizers, all associated with persistent opportunistic pathogens. This presentation will provide a general overview of the antimicrobial preservative effectiveness test and its use to further mitigate risk and questions related to the preservative systems effectiveness on other opportunistic organisms of concern.

What is Changing in the Realm of Validations Regarding Reusable Devices?

Over the past decade there has been a great deal of movement in requirements from regulatory agencies regarding reprocessing validations for reusable medical devices, and whether to classify them as invasive or non-invasive (critical/non-critical). The expectation to specify a category for these validations has encouraged the scientific community to come together and collaborate on standards which provide more information to manufacturers regarding validation requirements and considerations. The continuous addition of regulations and scrutiny surrounding reprocessing validations is inevitable. In this presentation you will learn about the challenges related to reusable medical device reprocessing validations and how to overcome them. Originally presented at MDM West 2022.

Virucidal Efficacy Testing for Submission to Regulatory Agencies

Virucidal efficacy testing is a type of testing that is used to determine effect of disinfectants or antiseptic products on viruses. The anti-viral testing describes methodologies applied to study antiviral drugs. Virucidal products are aimed at reducing or eliminating viruses from inanimate surfaces (disinfectants, antimicrobial coated surfaces) and human skin (antiseptics). Anti-viral drugs target viral diseases of humans or animals. The goal of this presentation is to provide a general overview of virucidal efficacy testing methodologies recognized by different regulatory agencies and used for virucidal label claims. This presentation will include details on critical testing requirements and acceptance criteria of current standardized and modified methodologies applied by Virology Laboratory at Nelson Laboratories Bozeman.

Understanding the EU Medical Device Regulation for Device Companies

The new European Union (EU) Medical Device Regulation (MDR) will impact medical device manufacturers’ product-development timelines. All companies intending to sell their devices in Europe must understand the new MDR and how it differs from the previous directives, especially in terms of new biocompatibility standard requirements. The regulation, which goes into effect in May 2020, mandates CE marking for some products that did not previously require it. The new regulation will require adherence to ISO 10993-1:2018, which has also been updated to have stricter guidelines in certain areas. This will make more testing necessary, that could take a significant amount of time to perform. Device companies need to account for this extra time and expense to avoid delays in EU product approvals.

Coronavirus & Barrier Material Tests

According to the CDC and OSHA, when there is possible contact with the corona virus, the minimum recommended protection is an N95 disposable respirator. N-series filters are evaluated using a sub-micron 0.3µm Sodium Chloride aerosol applied at a flow rate of 85 L/min. Nelson Labs can pre-qualify your product for certification by NIOSH and perform routine testing following certification to verify manufacturers maintain quality levels as required by NIOSH. The required tests for pre-qualification are: 1) filtration efficiency, 2) inhalation resistance, 3) exhalation resistance, and 4) exhalation valve leak (when applicable). There are additional respiratory protective standards required in other countries, including CSA Z94.4-01 in Canada, HSE 282/28 in the United Kingdom, AS/NZS 1715:1994 in Australia and EN529:2005 in Europe.

Considerations for Third Party Reprocessing of Single-Use Medical Devices

Reusing single-use devices that have been safely reprocessed by a third-party reprocessor can enable healthcare providers to maintain high-quality patient care while saving on costs and reducing medical waste. Validated functionality testing must be paired with validated cleaning, disinfection, and sterilization processes to ensure safety and compliance of regulatory requirements. This webinar training session is appropriate for design teams, quality assurance and regulatory personnel, and anybody interested in learning more about single-use device reprocessing. The knowledge gained form this presentation will aid in the safe and effective reprocessing of single-use devices.

Decontamination, Sterile Processing, and Performance Testing of Personal Protective Equipment (PPE)

During the COVID-19 pandemic personal protective equipment, especially medical face masks and respirators, were in short supply. Many new suppliers entered the market hoping to fill the need however were unaware of the testing requirements needed for, the FDA issued emergency use authorizations (EUA) for face mask approval. Laboratories and hospitals all over the world came up with novel solutions for providing personal protective equipment for their employees, including techniques for decontamination of N95 respirators which were in short supply. Decontamination techniques were utilized to render previously single use respirators safe for re-use. These techniques were evaluated and emergency approvals for use of these techniques were issued. Testing laboratories scrambled to keep up with increasing demand from new and existing suppliers, and to aid in the efforts to determine new and better ways to render these products safe for re-use. This webinar will give some history of the changes that have ensued due to the pandemic and teach you about the differences between medical face masks and respirators. We will discuss the testing that is required for approval of each of these products, and re-processing techniques for extending the useful life of some products.

FDA Feedback Reguarding Chemistry for Toxicological Risk Assessment - How to Make Sure FDA will Accept Your Protocol

We share trends in feedback received from the FDA regarding extractables chemistry testing, including the level of detail expected in identifications, compound reporting, and descriptions of methods. What you’ll learn: Level of identification expected, and how this should be reported Level of quantification expected, and what evidence might support that Amount of detail recommended in chemistry reports.

Method Development for Decontamination and Sterile Processing of Personal Protective Equipment (PPE)

Throughout the COVID-19 crisis there has been a huge emphasis on bringing critical products to the healthcare market in a timely fashion. This webinar will feature our collective learnings on required novel approaches to decontamination/sterile processing of items such as PPE. Manufacturers, regulators and end users have been pressed to develop new processing methods in a very accelerated fashion. It is important to understand when developing new methods that while accelerated or abbreviated test methods may be required, that does not obviate the need for holistic view ensuring all critical parameters are tested.

Testing Disinfectant Agents for Antimicrobial Action on Hard Surfaces

Disinfectants must be qualified on the surfaces in a pharmacopeial manufacturing environment prior to use in the facility. Building a study with robust parameters and avoiding common pitfalls is critical to avoid negative responses from regulatory agencies. Spending more time on study design and development upfront will save valuable resources in the long run.

Good Identification Practices For Organic Extractables & Leachables Via Mass Spectrometry

This series of white papers focus on the aspect of identification and, more specifically, the process by which mass spectral data and other supporting evidence are used to secure, judge, and justify complete and correct identities for all relevant extractables or leachables. • Part one of the four-part series thoroughly explains the identification Classes, Process & Practices for mass spectrometry. • Part two of this whitepaper series addresses the process of securing a compound’s identity via mass spectral matching. • In part three of this whitepaper series the identification strategy of Mass Spectral Interpretation is explored. • The final part four, presents various means of “augmenting” identities to be considered, and additional evidence supporting higher-level identifications are explored.

Get the Facts on Microbial Reduction in Food Ingredients

There’s a lot of urban legend when it comes to using gamma radiation to reduce pathogens in food ingredients. One of these statements is fact; one of these statements is fiction. Do you know which is which? -No one will know whether my food products are irradiated or not. -Governments allow irradiated food ingredients into their countries. Learn fact from fiction when you download this fast-read Sterigenics eBook.

Key Elements of a Sterility Assurance Program

This Webinar will cover various aspects of a sterility assurance program for a pharmaceutical product. Sterility assurance begins at the early stages of product development and follows through the entire product lifecycle. The concepts will be discussed in the context of a product lifecycle including examples of how they might be applied. Topics that are addressed include: Product and packaging Manufacturing process design Evaluation and selection of materials Microbiological process controls and testing Sterility assurance validation and maintenance Change control.

Future Trends To Control Risks From Extractables and Leachables

Prior to 2018, ophthalmic drug products (ODPs) and parenteral drug products (PDPs) were both treated the same way when undergoing Extractables and Leachables (E&L) testing. However, ODPs differ significantly from PDPs in terms of route of administration, toxicological endpoints and the nature of their container closure system. Hence, it is needless to say that E&L testing for ODPs requires a specific study design compared to other dosage forms. For example, low-density polyethylene containers allow for volatile and semi-volatile compounds to migrate through the material into the ophthalmic solution and, as such, compromise the product’s safety. This implies that secondary packaging components and even tertiary packaging components should be included in the E&L risk evaluation. Furthermore, until now no consensus has been reached regarding the toxicological limits to be applied during the safety assessment of leachables in ODPs. Given that the scientific knowledge on E&L testing is continuously evolving, as are the expectations of the agencies, the industry is faced with an increasing uncertainty concerning what would be an adequate approach for qualifying their packaging systems. In this webinar, best practices and challenges related to the design of an E&L study for ODPs will be addressed.

Setting up Extractables & Leachables Studies for Small Volume Parenteral Applications

2022 NELSON LABS VIRTUAL SYMPOSIUM: In this presentation, general extractables and leachables principles will be explained for small volume parenteral (SVP) applications including vials, cartridges, and pre-filled syringes—as these are the main container closure systems used in SVP applications.

Material Consideration Radiation Processing

Each polymer reacts differently to ionizing radiation. Thus, it is important to verify that the maximum administered dose will not have a detrimental effect on the product’s function or the patient’s safety over the product’s intended shelf life. This whitepaper reviews typical tests of physical properties and serves as a general guide to radiation stability of materials.

Chemical Disinfection Validations for Reusable Device

During this 45-minutes webinar, Dr. Lise Vanderkelen will take you on a journey to address some of the key aspects of what is required for disinfection validation studies. This is the second step in the processing cycle of reusable devices and the second installment of our three-part webinar series on cleaning, disinfection and sterilization validations of reusable devices.

Design Control for the Contract Research Organization

Design Control is a requirement from the FDA as laid out in 21 CFR.820. It is the basis for how medical device companies in the United States (or those planning on market in the United States) set up a quality system surrounding the designing and development of their medical devices. We will review what design control is, using examples to better have an understanding, and then see how Nelson Labs can support sponsors with design control requirements.

Transportation and Distribution Testing for Medical Devices

An important, but sometimes overlooked component of a packaging shelf life validation is transportation and distribution testing. This testing is required for all commerce and is an important early step in total package design. This webinar will introduce you to the basics of transportation and distribution testing by explaining why it is important and what a typical distribution test sequence looks like. By the end of this webinar you should know: 

How to Evaluate a New Product Against an Existing Product in a Validated EO Process

As defined in Section 12 of ISO 11135:2014, a new or modified (“candidate”) product can be added to a validated Ethylene Oxide (EO) sterilization process if an evaluation shows that the candidate product is either equivalent to or a lesser challenge than an “existing” product or Internal Process Challenge Device (IPCD). Such an outcome could save considerable time and money. By reading this White Paper, Quality Assurance, Project Management, Sterility Assurance and Validation personnel within the medical device, pharmaceutical, commercial and food industries learn the necessary steps to evaluate a candidate product.

Reprocessing Validations of Reusable Medical Devices

Reprocessing validations of reusable medical devices have been overlooked for quite some time and the importance of these validations for medical device manufacturers has taken a back seat until recently. The upcoming MDR requirements and added US FDA scrutiny over reusable medical devices has shed a light on the importance and significance of validations. The presentation will highlight some of the key aspects of what is required for validation studies for reusable medical devices and how to perform these validations. It will give a perspective of what is needed to include in these validations and where in the design phase these validations make their presence. Alpa Patel explains the importance of cleaning and disinfection validations as well as sterilization validations.

The Necessity of Extractable and Leachable Qualifications for Lyophilized Drug Products: Some Fallacies Addressed

Lyophilized drug product containers and administration devices consist of the primary packaging (typically a glass vial and a rubber stopper), the reconstitution solution container (typically a vial or a prefilled syringe system), and the drug administration set (such as a disposable syringe, an intravenous bag, or a pump system with administration tubing) as shown in the Whitepaper.

The New FDA Draft Guidance for Biocompatibility of Certain Devices in Contact with Intact Skin: The Naughty and Nice list

In October 2020 FDA released a new draft biocompatibility guidance document which focuses on the biological evaluation of devices in contact with intact skin. As a draft document, it is therefore open for comments and possible changes. Release of this guidance signifies another step from FDA toward their 3R animal initiative (reduce, refine, and replace animal use in testing when feasible).

The Testing and Risk Management Impacts of Changing a Medical Device

A medical device and its support system may undergo hundreds of changes throughout its product life cycle. We are constantly dealing with the impact of change. Knowing how to properly evaluate and manage all areas that are impacted by a change is a critically important process for manufacturers to master. Learn how to evaluate possible safety impacts following any change that is made and how to effectively mitigate biocompatibility risks.

Benefits of Premarket and Postmarket Particulate Testing of Cardiovascular Devices

Device manufacturers that incorporate particulate testing into their product-development plans early are better equipped to navigate the regulatory clearance process and potentially reduce time to market. Particulate testing of cardiovascular medical devices is an important and valuable step on the road to regulatory clearance, market success, and patient safety. Device manufacturers that incorporate particulate testing into their product-development plans early are better equipped to navigate the regulatory clearance process and potentially reduce time to market. After premarket regulatory clearance is achieved, and the cardiovascular device is on the market in clinical use, post market lot release particulate testing and monitoring can help ensure product quality and safety going forward.

Biocompatibility for Medical Devices 101 – Prepare for Clinical Trial

This is a crash course overview of medical device biocompatibility. We will provide an overview of the guidance provided in ISO 10993-1 and FDA expectations for demonstration of biocompatibility leading up to a medical device clinical trial or 510(k) submission. Biocompatibility is discussed from the perspective of systemic vs non-systemic biological endpoints, with emphasis on test selection, sample preparation, chemistry testing, and toxicological evaluation. The “big 3” tests (cytotoxicity, sensitization, and irritation) are summarized followed by the fundamentals of medical device extractables testing and toxicological assessment.

Biocompatibility of Raw Materials for Medical Devices

Starting with a biocompatible material is important for medical device manufacturers. However, regulation is pushing the manufacturer to ask for more information and more support from their suppliers. Biocompatibility on materials is critical to stay competitive and provide your clients with the needed information. Webinar topics include: • An overview of ISO 10993-1 • MDR regulation regarding carcinogens, mutagens, and reproductive toxins (CMRs) for raw materials • Where is the line in responsibility for material supplier and device manufacturer? • What information and testing on raw material is useful for the biocompatibility of a final device?

Assessing the Safety of Extractables and Leachables for Drug Products: When and How?

In this webinar Kevin Breesch of Nelson Labs will speak about the challenges of toxicological-safety assessments for parenteral packaging systems. Typical toxicological challenges for extractables and leachables (E&L) are presented, such as difficulties in daily exposure evaluations for a selection of compounds to be evaluated, based on an appropriate selected threshold. Subsequently, typical burden in hazard and risk evaluation relate to data-poor substances often related to rubber closure systems. Within this context, E&L examples are selected for which the critical toxicological endpoints are discussed and evaluated by means of various methods, in terms of deriving appropriate safety limits. Key Learning Objectives: -To know how to select the right threshold for E&L screening methodologies. - To know how to determine a reasonable exposure of compounds to the patient. -To understand the toxicological-safety hurdles and how to overcome them.

Best Practices When Validating Reusable Devices

The advancement of reusable medical devices has changed the industry over the years and the requirements for validating reprocessing instructions have changed with it. It can be difficult to navigate these changes and ensure that the reprocessing validations meet the current industry standards and expectations. An understanding of the best practices when validating reusable medical devices will aid in navigating medical device manufacturers through these changes and challenges. The presentation will cover some of the best practices when validating the reprocessing instructions for reusable medical devices. Key Learning Objectives: Understanding which documents would play a key role in your reprocessing validation How to best design a reprocessing validation to avoid regulatory scrutiny Understanding new regulations regarding validations strategies for reusable medical devices.

Satisfying ISO 18562 and FDA Biocompatibility Regulatory Requirements for Breathing Gas Pathways in Health Care Application

In March of 2017, the new ISO 18562 standard series was released. This four part standard covers the general principles regarding biocompatibility assessment of medical device materials which comprise the gas pathway. Some of the additional concerns will be addressed through the assessment of volatile organic compounds (VOCs), particulates, and leachable in condensate. The US FDA has recently recognized ISO 18562 parts 2 and 3 completely and portions of part 1 and 4. This series is meant to run as a perpendicular standard to the ISO 10993 standard suite providing supplemental testing and considerations for your overall Biological Safety Evaluation which should include a 3-step process: 1) Initial risk assessment – introduction of device, materials, processing, patient contact, areas of risk and mitigation steps 2) Testing and risk assessments 3) Summary report concluding that the device is biocompatible.

Product Safety Future State of Sterility Assurance and the Role of Terminal Sterilization

Sterilization is a pivotal step in the pharmaceutical drug development process to help ensure overall safety is maintained. Regulation is clear that, whenever possible, products intended to be sterile should be terminally sterilized in their final container. Only if terminal sterilization is not possible, filtration or aseptic assembly should be applied. This webinar will focus on trends in the concept of sterility assurance including the revision of USP <71> and elements to evaluate prior to selecting aseptic assembly for the manufacturing of sterile drug products. What you will get from this webinar: • A deeper understanding of terminal sterilization and aseptic processing of drug products through a regulatory lens as well as that of a manufacturer • Mitigation strategies for the use of terminal sterilization with radiation, ethylene oxide and novel modalities • Trends in the concept of sterility assurance.

Polymer-based, Pre-filled Syringes designed to Minimize the Aggregation Risk of Sensitive Biodrugs

2022 NELSON LABS VIRTUAL SYMPOSIUM: Biopharmaceutical drugs offer new therapeutic solutions to numerous human diseases and conditions. However, with this comes the risk of efficacy loss due to protein interactions potentially leading to immunogenicity impacting the patient’s safety and therapeutic outcome. Terumo’s PLAJEX™ pre-fillable syringes (PFS) are designed to meet the needs of a wide variety of types of drugs including those requiring low reactive containers. In this presentation, we will highlight some of the main values our PLAJEX™ PFS offer as well as the experience we have built over two decades with processing our primary containers on our own fill-and-finish lines in Japan.

Combination Products and Parenteral Packaging a US Perspective

2022 NELSON LABS VIRTUAL SYMPOSIUM: This presentation will include a short summary of the types of Drug Delivery Combination products codified by US FDA regulation, and the types of other drug delivery products where the combination must be addressed. It will detail the current technical expectations for development, incorporating Design Verification approaches, including FDA Essential Performance Requirements (EPRs), recently updated ISO 11608 series, and FDA and IEC requirements for addressing Human factors; and GMP/System requirements required under FDA 21 CFR Part 4 regulations. Among other areas, the presentation will touch on requirements for clinical requirements and unique challenges for generic products.

Primary Packaging Considerations from a Biologics Product Development Perspective

2022 NELSON LABS VIRTUAL SYMPOSIUM: In this presentation, Dr. Mahler will give an overview of biologics product development, with a specific emphasis on how primary packaging for parenteral biologics drug products are being chosen and appropriately qualified.

Packaging Validation 101

Have you wondered how to set up a packaging validation according to ISO 11607? Come join us for a Packaging Validation 101 webinar to learn the basics including: - Determining an appropriate sample size for testing - Writing the validation protocol - Developing the test plan - Selecting appropriate tests - Family grouping and worst-case considerations and creating the appropriate samples. ISO 11607 Part 2 covers packaging process validation. We will be discussing: - Basic validation concepts - Defining the validation process - Seal acceptance criteria and qualifications – along with routine process monitoring.

2022 State of the Medical Device Industry Quality, Biocompatibility, and Changing Regulations

Another year is here with regulatory changes, updated mandates, and the continued effects of the COVID-19 pandemic. Join leaders from Nelson Labs and Greenlight Guru to discuss the current state of the industry and forecast for 2022. For each of the following three areas, we will discuss what the impending changes are, when these changes may take affect and how medical device manufacturers should prepare: • Increasing importance of quality • Changes to ISO 10993-1 • The end of the EUA

FDA Medical Device Inspections in the Post Pandemic World

The FDA is ramping up its inspections of medical device manufacturing facilities. Will you be ready? Since March 2020, the agency has focused on mission-critical inspections, but that’s about to change. As Omicron cases go down, the agency is expected to transition back to its normal inspection schedule, and it has a great deal of catching up to do. Make no mistake: “normal operations” does not mean normal inspection methods. The FDA developed novel approaches to conducting inspections during the pandemic, including remote record reviews and other virtual activities. And it will undoubtedly continue using the most effective of these going forward, even post pandemic.

IVDR Regulation for Medical Device Directive in EU: Impact Assessment of Revision of the Regulatory Framework for MDD in EU

The existing regulatory framework has been in place for 20 years; recently coming under harsh criticism in the media and the political arena, in particular after findings of the French health authorities that a French manufacturer (Poly Implant Protese, PIP) over several years used industrial silicone instead of medical grade silicone for manufacture of breast implants. Several weaknesses undermined the main objectives of the three medical device directives, i.e., safety of medical devices and their free circulation within the internal market were identified in public consultation held by Commission in 2008, and again in 2010. This revision aims at overcoming the flaws and gaps while maintaining the overall objectives of the legal framework.

Get the Facts on Bioburden Control and Sterilization for Food & Beverage Packaging

This eBook, Get the Facts on Bioburden Control and Sterilization for Food & Beverage Packaging, answers the most common questions that food and beverage manufacturers ask our Industry Subject Matter Experts about the use of Gamma irradiation to keep molds, fungi and other micro-organisms out of packaging.

Regulatory Landscape for EO Residue Levels in Medical Devices

The global regulatory landscape around Ethylene Oxide (EO) residues is a topic of increasing interest. This webinar will provide an overview of EO sterilization and the status of ISO standard 10993-7:2008, which serves as an international authoritative document for medical device manufacturers in order to know how to set your company up for the future. The following topics will be covered: - Testing according to product category and product use - Concomitant EO exposure - Topical contact - Special situations (e.g., intra ocular lenses, cardiopulmonary bypass devices …) - Test method and validation - ISO 10993-7 revision for products intended for neonates and children /recommendation by ANSM – French Regulator - Fugitive EO emission from EO treated products, which must be monitored throughout the supply chain to safeguard worker exposure - Legislation regarding EO emissions in the supply chain.

Single Use & Newly Manufactured Device Cleaning Validations

Performing a cleaning validation during the initial phase of a device’s lifecycle aids manufacturers in complying with current good manufacturing practices (CGMP) and quality system (QS) regulation as set forth by FDA for medical device manufacturers. The data gathered during cleaning validations helps manufacturers have confidence in the quality of their finished medical devices during on-site audits performed by both customers and regulators. Find out more on: The importance of a cleaning validation Considerations for the initial validation Residual sources of contamination Analytical test methods.

Successful Medical Device Cleaning Validations: What You Need to Know

Validating cleaning instructions for a tray of reusable orthopedic devices is an important milestone on the path to obtaining FDA clearance for those devices. Although the process of validation can seem daunting at first, medical device manufacturers seeking to successfully navigate this process can do so confidently and efficiently if they are armed with knowledge, education, and guidance. This white paper provides detailed information on successful medical-device cleaning validations.

After E&L Updates to the Standard for Toxicological Risk Assessment 10993-17

Use of extractables and leachables (E&L) chemistry testing has become commonplace (and often essential) in medical device biocompatibility evaluations. The details of how E&L is conducted have received a lot of attention in the industry; however it must be remembered that this testing is conducted to serve a toxicological risk assessment (TRA) and it is the demands of proper toxicology that has put constraints on E&L in the first place. The ISO standard for TRAs, ISO 10993-17 is undergoing a long overdue update. This presentation will discuss updates present in the current draft of the new standard and how those will impact future TRAs, chemistry for toxicology, and biocompatibility at large. Key takeaways: Fundamental principles of TRA for medical devices will be reviewed Updates to 10993-17 focus include rational exposure estimates The Threshold of Toxicological Concern (TTC) vs the Analytical Evaluation Threshold (AET)

Applying a Risk Based Approach to Biological Evaluation of Medical Devices Based on the ISO 10993-1:2018

All medical devices that are intended to contact patients or medical personnel (directly or indirectly) require an evaluation of their biocompatibility prior to regulatory submission and market release. The umbrella document for this evaluation is the international standard ISO 10993-1 which includes the framework and thought process for the biological evaluation of medical devices. The potential risks that medical devices carry depend highly on its intended contact type and cumulative duration of use. However, before jumping into testing for the specified biological endpoints identified by Table A.1 in ISO 10993-1, one should consider available information that could provide evidence in support of biological safety and reduce the need for testing. This so-called “risk-based approach” is the heart of the standard and should be applied to any medical device (either being newly submitted for market release or undergoing changes). This presentation will provide an overview of the thought process and flow of medical device biological evaluations (often called a biological evaluation plan or BEP) with an emphasis on the proper application of a risk-based approach.

Becoming Compliant with the MDRs, A Real Life Case Study

The new Medical Device Regulations (MDRs) become enforceable May 2022. After that, all new devices set for market in the European market will have to demonstrate compliance with ISO 10993, even if the device has been on the market for years. This presentation will walk through a real life example of bringing a device that has been on the market in Europe into compliance with the ISO 10993 and the new MDRs.

Evaluating the biocompatibility of reusable medical devices during their whole life cycle

In the past, the focus for reusable devices has been on validating the reprocessing efficacy with regards to infection control. Recently however, and especially with the advent of the new era of MDR, the focus has expanded to include the aspect of biocompatibility, e.g. how the numerous reprocessing cycles could impact the device and whether it continues to be safe for the patient throughout its life cycle. It is also stated in ISO 10993-1. The theory sounds simple, but in reality, it poses extra challenges for reusable devices as they are reused and reprocessed over and over again. With that, questions, including what is happing to the materials over the lifetime of the reusable devices as these materials are attacked with detergents, disinfectants and are exposed to high temperatures, need to be answered and explored. This presentation will give more insights on: The design of a biological evaluation plan for reusable medical devices Current expectations of regulatory agencies Consideration from the biocompatibility perspective for first-time use, in-use, as well as end-of-life cycle for a reusable medical device.

Extractables and leachables testing of a combination device: testing in between regulations for pharmaceutical products and medical devices

Extractables and Leachables testing of combination devices requires a specific study set-up which differentiates from a typical chemical characterization study according to ISO10993-18. In this presentation, we will explain how a chemical characterization study of a combination device should be performed, based on a case study of an insulin device. Furthermore, we will clarify how to integrate in the study set-up the requirement for Carcinogenic, Mutagenic and Reprotoxic Compounds (CMRs) as specified in section 10.4 in Annex I of the MDR. This requirement is especially important for products falling under article 117.Finally, drug-device compatibility should not be neglected or forgotten in an overall biocompatibility evaluation.

Guidance for Cleaning, Disinfection and Sterilization of Reusable Medical Devices

All reusable devices should contain specific instructions for cleaning, disinfecting and/or sterilization of the device. In order to be compliant with global regulations, manufactures should have their instructions for use (IFU) validated to ensure patient safety and mitigating cross contamination. It is recommended to validate at least one method for each applicable stage of reprocessing of the medical device. During this webinar you will learn more about: The full processing cycle (What is reprocessing and what devices should be considered for this type of testing) How to comply with the new EU MDR The validation of a cleaning procedure (To what extend the device design can impact the validation protocol) Methods for disinfection or sterilization instructions The importance of cytotoxicity testing after a reprocessing cycle

Biocompatibility: Applying the New ISO 10993 Standards

A new updated ISO 10993-1 standard came out in Aug of 2018 that drastically changed how we access medical devices for biocompatibility. We also are dealing with the impact of the Medical Device Regulations in Europe. The timing of these two documents has greatly disrupted the medical device industry. In this webinar we will discuss the changes and efficient approaches to navigate through the troubles. From this webinar you will learn: Overview of the new ISO 10993-1 Performing a Biological Evaluation Plan Overview of the “Big Three” including new in vitro alternatives What is needed in a Biological Evaluation Report for FDA?

Cobalt-60: The Heart of Radiation Sterilization

For more than 50 years, Cobalt-60 has been used as a source of gamma radiation for a wide variety of applications, and has grown to become one of the most prevalent modalities for sterilization of single use medical devices. Medical device manufacturers typically do not have good visibility of the Cobalt-60 supply chain and resulting supply/demand dynamics, given that many of them are one step removed through the use of contract sterilization providers. This can lead to lack of clarity around current and future gamma capacity, important for making sterilization modality selection decisions. This webinar will provide insight into the workings of the global Cobalt-60 supply chain, and explain the impact of recent events on both supply and demand. The presentation will also touch on Nordion’s long-term strategies for maintaining and growing Cobalt supply, and highlight some key supply initiatives.

Design Change Impact on Biocompatibility and Documentation

Change Management, especially related to a medical device’s design, is one of the most commonly-cited issues in FDA 483s and Warning Letters. Unfortunately, change is constant in the medical device industry, so it’s imperative to learn how to effectively evaluate change and incorporate findings into biocompatibility testing and documentation. In this webinar, industry experts from Nelson Labs and Greenlight Guru will teach you how to: Accurately identify change Evaluate change’s impact on biocompatibility and testing Effectively and proactively document changes Remain compliant when changes inevitably occur.

The New ISO 10993 – 18 Standard and its Impact on Chemical Characterization of Medical Devices

To meet the heightened focus on chemical characterization in ISO 10993-1:2018, a major revision of ISO 10993-18 “Chemical characterization of medical device materials within a risk management process” was undertaken. The revised document published in January 2020. In this presentation, Dr Ted Heise focuses on key parts of the new document, bringing in experience and lessons learned from multi-stakeholder development of the final standard.

Radiation Sterilization of SVPP: RTU and fill/finished. Do not default to 25 kGy – 40 kGy.

2022 NELSON LABS VIRTUAL SYMPOSIUM: Examples will be presented for radiation sterilization of RTU SVPP as well as terminal sterilization of fill/finished items. A critical aspect in validation of the irradiation processes is the Process Definition step, where there is considerable benefit to not default to a specification of 25 kGy to 40 kGy. Methods and practices for widening the specification will be discussed.

Combination Products and Parenteral Packaging: A Notified Body (EU) Perspective

2022 NELSON LABS VIRTUAL SYMPOSIUM: This presentation will provide an overview of considerations regarding biological risks from primary packaging materials for CE marking of combination products. Furthermore, combination products falling under the Art 117 MDR requiring a NBOp (regulatory background and common pitfalls) will be discussed.

Disinfectant Efficacy Testing for Submission to the US Environmental Protection Agency

When developing a disinfectant or sanitizer (herein referred to as disinfectant) for use on environmental surfaces, the Sponsor must first develop and support a label claim based upon guidelines set forth by the United States Environmental Protection Agency (EPA). In order to substantiate the claim the Sponsor is planning to make on their label, they must perform one, or more, evaluations as dictated by the EPA.

Challenges in Design Development - Why Design Control Makes Sense

The time and investment needed to bring an idea for a new medical product all the way to commercial realization can be daunting. In developing new drugs, the costs and timing required to conduct multiple stages of clinical studies, even under the best of circumstances, can be a “non-starter” if the projected long-term revenue and profit potential is not sufficient to justify the cost and risk associated with development. Similarly, the development of software-driven instrumentation products is complex in the extent of interactions among components and the number of areas where a seemingly small problem with one mechanical component, or a mistake in one line of software coding, can lead to catastrophic product system failure. Even the development of “simple” single-use medical devices can involve years of development and millions of dollars in capital investment.

Considerations for Sterilization and Biocompatibility of 3D-Printed Orthopedic Devices

This whitepaper to learn about the various biocompatibility and sterilization considerations surrounding 3D-printed orthopedic devices. 3D-printed orthopedic medical devices are gaining attention and popularity due to their potential for enhanced biocompatibility, customizability, and cost-effectiveness. As of late 2015, FDA had cleared more than 85 total 3D-printed medical devices, with more regulatory clearances on the horizon.

Microbiological Control in a Pharmaceutical Manufacturing Environment

This webinar will address the evaluation of microbiological, environmental monitoring data as well as what would be considered significant differences in data. We will review microbiological trending and how it can assist in understanding what is significant in each particular situation. We discuss how the analysis of this trended data enables a company to establish alert and action levels as well as methods for determining these levels. We will review cleaning validation protocols, methods, and procedures to evaluate and define a robust program to protect your products, personnel, and equipment. We will discuss correlating disinfectant validations with the trending of routine-environmental monitoring data to establish a compliant program in a clean room environment. Finally, water is perhaps the most extensively used raw material in pharmaceutical manufacturing. Its use as an inactive ingredient, active pharmaceutical ingredient (API), analytical reagent, and even as a solvent in cleaning processes, leads to potential product and environmental contamination from residual water impurities. This presentation addresses the removal and control of microbiological and chemical impurities in a quality water system.

DISINFECTION VALIDATION: How to Classify and Validate Your Medical Device Disinfection Process

Medical device reprocessing, and the scientific validation of reprocessing instructions, are critical steps to ensuring devices are safe and effective for patient use. The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, as well as past infection outbreaks, have prompted increased concern over disinfection and sterilization of reusable medical devices.

N-Nitrosamines in Primary Packaging for SVP’s

2022 NELSON LABS VIRTUAL SYMPOSIUM: Because of recent product recalls due to the unexpected presence of N-Nitrosamines, it is important to look at the formation of these amines on materials prominently used in the primary packaging of drug products. The unanswered question is: do we know everything about the materials of construction of a container closure system and their ability to generate N-Nitrosamines? It is commonly known that secondary amines (and potentially tertiary amines) are a precursor to N-Nitrosamine formation and that these need to be taken into consideration when evaluating the extraction pro file of materials of construction. The question however remains should this raise a “red flag” in an N-Nitrosamine risk mitigation strategy.

US Food and Drug Administration Regulatory Pathways

There has been an explosion of new and innovative medical device products launched in the US and global markets over the last 5 years. The medical device industry is now capable of using 3D printers to produce everything from prosthetic parts to artificial knees to surgical tools. In addition to the use of 3D printers, the advancement of mobile health (mHealth) applications for smart phones and other electronic communication devices has seen an upsurge in usage and availability. Medical device users, consumers, and patients expect medical device manufacturers to consistently develop and launch contemporary, state-of-the-art products and technologies that are cheaper, easier to use, and achieve greater benefits for the patient that ultimately result in more effective and efficient patient care and outcomes. To ensure these products are safe and effective, the FDA and other global Regulatory Authorities place a heavy burden on the medical device industry to demonstrate that such products are designed, developed, tested, and manufactured according to Current Good Manufacturing Practices and other applicable Standards and Guidance. Obtaining regulatory clearance or approval for new medical device products and technologies has historically been a complex and challenging process for many manufacturers. However, in recent years the FDA has taken a more proactive approach to collaborate with industry and streamline the evaluation process of these innovative medical devices to bring safe, effective, and novel products to market faster for the ultimate goal of advancing of public health.

Big Changes to ISO 10993-1: What is happening to the main biocompatibility standard now?

In 2018, TC194, the ISO committee for biocompatibility, released a new version of 10993-1. This new version focused more on a risk-based approach and made significant changes. We are now making more significant changes to the main biocompatibility standard. In this talk we will go over the areas of the standard that is being changed, the reasoning behind the change, and the initial acceptance of these changes around the globe.

Slimy Biofilms A Brief Overview

A biofilm is a community of microorganisms embedded in a slimy matrix which can attach to various surfaces. A great diversity of species has been found in biofilms, including bacteria, viruses, and fungi. Biofilms can exist on inert surfaces such as glass, plastic, and metal, but can also use plant and animal tissues as a substrate. The slimy extracellular matrix provides protection for the microorganisms within the biofilm, resulting in an increased resistance to disinfectants, antibiotics, and a host’s immune system. Biofilms can create major problems in the health care, food, and manufacturing industries, including infections from implantable medical devices, contamination of food/food-contact surfaces, and corrosion or other damage to industrial equipment. This presentation will introduce the formation of biofilms, current standardized test methods to evaluate antibiofilm agents, and regulatory considerations.

Understanding Container Closure Integrity Test Failures

Does a container closure integrity test (CCIT) failure always mean a defective closure? In this webinar we will explore failure modes that can occur on a perfectly sealed container and discuss how to determine if a CCIT failure is a true container leak or something else. Additionally, we will discuss the value of product specific method qualifications to ensure the test method and fixturing are suitable for your product as using a less than ideal test set up can lead to false failures.

Parenteral Drug Development Exploring the Potential Benefits of Terminal Sterilization

In this webinar, originally part of Pharmapack Europe 2022, S. Ross Tsakas, Pharmaceutical Segment Leader, Sterigenics discusses parenteral drug development. Parenteral drugs and the drug development lifecycle represent complexities across the multi-year, multi-million pledges made. With over 90 years of experience supporting the pharmaceutical, biotech, and medical device industries, we have identified 5 key hurdles: sterility, quality control, compliance, regulatory affairs, and routine manufacturing, we will delve into each challenge in a systematic, concise, yet compelling manner. As sterilization becomes a top-of-mind priority for clients along the entire supply chain, we stand poised to facilitate bolstering global health through strategic support initiatives that expedite products to market and help ensure their safety.

Sterilization Dose Audits – The “Why” and the “How”

In the medical device industry, sterilization processing is performed to obtain a Sterility Assurance Level (SAL) as required by regulatory authorities to designate the treated product as “sterile”. When SAL is established using Method 1, Method 2 or Method VDmax, a periodic sterilization dose audit is required by ANSI/AAMI/ISO 11137-1. The purpose of such audits is to demonstrate the continued effectiveness of the established sterilization dose. By reading this Whitepaper, Quality Assurance, Sterility Assurance and Validation personnel will learn how to perform sterilization dose audits.

Understanding the EU Medical Device Regulation for Device Companies

The new European Union (EU) Medical Device Regulation (MDR) will impact medical device manufacturers’ product-development timelines. All companies intending to sell their devices in Europe must understand the new MDR and how it differs from the previous directives, especially in terms of new biocompatibility standard requirements. The regulation, which goes into effect in May 2020, mandates CE marking for some products that did not previously require it. The new regulation will require adherence to ISO 10993-1:2018, which has also been updated to have stricter guidelines in certain areas. This will make more testing necessary, that could take a significant amount of time to perform. Device companies need to account for this extra time and expense to avoid delays in EU product approvals.

Outsource Quality and Regulatory Agencies Right-Sizing Need and Cost

Small or emerging life science organizations often put off hiring Quality and Regulatory executives, exposing the company to risk or worse. Other organizations add full time leaders before they have full time needs, resulting in over-spending. This whitepaper suggests another model: variable outsourcing of Quality and Regulatory leadership to best match needs and spending.

Disinfectant Efficacy Testing Coupon/Carrier Method

Disinfectants must be qualified on the surfaces in a pharmocipeial manufacturing environment prior to use in the facility. Building a study with robust parameters and avoiding common pitfalls is critical to avoid negative responses from regulatory agencies. Spending more time on study design and development upfront will save valuable resources in the long run. The goal of this presentation is to provide a general overview of disinfectant efficacy testing and to provide a detailed methodology to assist in designing coupon studies that accurately represent facility procedures. As we attempt to bridge the gap between laboratory conditions and environmental conditions, test method acceptance criteria and interpretation of coupon study results will also be discussed. Specifically, we aim to provide insight into how the results of a coupon study can be utilized to improve cleaning procedures. Webinar Attendees will learn: • Study Design – how to choose parameters that are representative of your facility while meeting regulatory expectations • Indications that initial or subsequent disinfectant efficacy testing needs to be performed • Interpretation of results – translating microorganism log reductions into useful information on the efficacy of facility cleaning procedures and disinfectants.

Testing and Risk Management Impacts Changing Medical Device

Change Management, especially related to a medical device’s design, is one of the most commonly cited issues in FDA 483s and Warning Letters. Unfortunately, change is constant in the medical device industry, so it’s imperative to learn how to effectively evaluate change and incorporate findings into biocompatibility testing and documentation. In this webinar, industry experts from Nelson Labs will teach you how to: • Accurately identify change • Evaluate change’s impact on biocompatibility and testing • Effectively and proactively predict and document rational of changes • Remain compliant when changes inevitably occur.

EO Sterilization: Considerations for Neonate Products and Medical Devices and ISO 10993-7

EO sterilized items are life-saving and critical devices that are sterilized in highly regulated environment, under strict normative rules and with the greatest care. This webinar will review important considerations for EO Sterilization of neonate products and medical devices. Aspects of EO sterilization will be covered, including the consideration for EO residues that takes into account the amendment of the governing standard, ISO 10993-7. The use of risk assessment, risk/benefit evaluation, validation and application of the right method to define the most suitable limits will also be discussed during this webinar.

Why is the Sterility of your Drug Product much more than just a Test of Sterility?

A lack of sterility and sterility assurance continue to be a significant reason for drug recalls and regulatory citations and can pose a very real risk to patient safety and public health. Sterilization is a pivotal step in the pharmaceutical drug development process to help ensure overall safety is maintained. In this presentation we will:- Examine the goal and science of sterility assurance including the revision of AAMI ST67- Introduce and contrast Terminal Sterilization and Aseptic Processing of drug products through a regulatory lens as well as that of a manufacturer - Discuss modification strategies to consider in order to use Terminal Sterilization This information is meant to provide manufacturers with a better understanding of sterility to help them make the best decisions in regards to their specific drug product and relative patient safety.

Do's and Don't in setting up Extractables and Leachable Studies, taking into account Existing Standards Guidelines and Recommendations

2022 NELSON LABS VIRTUAL SYMPOSIUM: During their production, storage/distribution and administration, small volume parenteral drug products leach chemicals from their manufacturing, packaging, and delivery systems. These foreign impurities (leachables) can potentially have a significant effect on the quality of the SVPs and may affect the efficiency with which the SVP is produced. To establish the effects of these impurities, drug products are profiled for leachables and manufacturing, packaging, and delivery systems are tested for extractables (as probable leachables). In this presentation, the scientific and practical aspects and principles of the chemical characterization of SVPs and their related systems will be introduced; including a review of the relevant regulatory guidance, standards and best demonstrated practice recommendations. The presentation will provide suggested best practices (dos and don’ts) for the design, implementation, interpretation, and submission of E&L studies.

FDA Regulation of Hand Sanitizers - What Testing Should be conducted to Market a new Hand Sanitizer?

All hand sanitizers, whether used by consumers or healthcare professionals, are considered over-the-counter (OTC) drugs that are regulated by the FDA. As with any new human use product entering the market, the FDA requires Good Manufacturing Practices, safety data, and in vitro and in vivo efficacy data before the product is marketed to the public. This presentation will discuss the required in vitro and clinical safety & efficacy testing to conduct and important study design considerations. Key Learning Objectives: • FDA monograph and current requirements • What is required for Safety Testing • What are the Applicable screening tests and basic methodologies • Overview of clinical evaluations for hand sanitizers

Good Identification Practices for Organic Extractables and Leachables Via Mass Spectrometry

The function of a pharmaceutical drug product or a medical device is to provide the patient with a desired therapeutic benefit. If the drug product or the medical device were pure (meaning without impurities), ideally the therapeutic benefit would be largely realized with minimal adverse patient effects. However, since the practical reality is that drug products and medical devices contain impurities, a patient is exposed to these impurities during treatment and these impurities could potentially trigger an increase of adverse patient effects.

FAQs for Pet Treats Manufacturers: Get the Facts on Pathogen Reduction in Pet and Animal Nutrition

If you’re a manufacturer, you want to reduce bacteria in the pet treats and animal feed that you sell to businesses and consumers. If you have questions about using Gamma radiation for pathogen reduction in your pet treats and animal nutrition, this eBook is for you. Get answers to your commonly asked questions when you download this informative and fast-read Sterigenics eBook.

3D Printed Medical Devices and Biocompatibility Whitepaper

The use of three-dimensional (3D) printing techniques to address challenging fabrication problems has become mainstream over the past decade. While this rich resource has extended fabrication of personalized medical devices to the limit of our imagination, the myriad materials and morphologies available present a unique concern from a toxicological perspective. A range of standalone 3D printers are commercially available with compatible materials ranging from plastics to oxides and metals. Raw materials used in the fabrication process often have highly customized properties, achieved through the use of proprietary additives and specific microscale morphologies which can affect the overall biocompatibility of the finished device. Therefore, 3D printed medical devices require versatile approaches to the assessment of their biocompatibility that consider several factors which will be addressed in this document: Possible additives to raw materials which enhance workability Details of the material curing process Post-printing finishing and rinsing processes Time allowed for aeration between device manufacture and use.

Choosing Colorants for Medical Devices

Colorants are often added to the substrates and material components of medical devices with the primary intent of improving the usability of the devices. For instance, color coding can assist users in matching devices or sizes together when multiple options are available. Colorants can also be used to brand medical devices from a particular manufacturer, thereby ensuring that only compatible components and accessories are used with the company’s products. And in some cases, colorants can be used to improve the user appeal of a device, meeting the expectations of users and helping manufacturers to build and maintain customer loyalty.

A Delay in MDR? Where are we now?

With the COVID-19 crisis, the Medical Device Regulations (MDR) have been pushed back one year, this delay has given a respite for those companies that were not quite ready for the increase regulations. In this talk we will be discussing the current status of the medical device industry regarding MDR and what are others doing to get read This webinar will provide information on: What additional requirements are in the MDR? Where is the industry currently at and how many companies feel ready for their first submission? What have we learned from the first submissions under MDR? What are others doing now, to save time and money?

If Something Looks Clean, Is It Really Clean? Cleaning Validations for Reusable Devices

Reprocessing validations of reusable medical devices have been overlooked for quite some time. But the upcoming MDR requirements and US FDA Scrutiny over reusable medical devices has shed a light to their importance and significance. The presentation will highlight some of the key aspects of what is required for validation studies for these types of devices and how to perform these validations. During her presentation, Lise Vanderkelen mainly focuses on cleaning validation for reusable devices.

MDR Effects on Cleaning and Sterilization Validations

The new Medical Devices Regulation (2017/745/EU) (MDR) brings EU legislation into line with technical advances, chang­es in medical science, and progress in law making. There are many updates that effect reusable medical device manufacturers. This presentation will outline all of the testing and documentation that needs to occur prior to the MDR deadline.

The Biological Evaluation Plan (BEP): A crucial first step in the Biocompatibility evaluation of a Medical Device

In the evaluation of medical devices for biocompatibility, the assessment of patient safety should be made based on risk rather than on a check-box approach. In this aspect, we will see how to construct a Biological Evaluation Plan as per ISO 10993-1 (2018). The presentation will especially show how understanding patient contact and gathering information is the key in defining an adequate biocompatibility testing program.

Identifying and Mitigating Errors in Organic Extractables and Leachables Screening

The discipline of Organic Chromatographic “Screening” to discover, identify and (semi-)quantify organic compounds in an extract (from a pharmaceutical container closure system or from a medical device) or in a drug product is a relatively new concept to both the Pharmaceutical and Medical Device Industries. Typically, a combination of chromatographic techniques is used to cover a broad range of organic compounds with a wide variety of physicochemical properties and chemical functionalities. A combination of Headspace G/MS (Volatile Organic Compounds), GC/MS (Semi-Volatile Organic Compounds) and LC/MS (Non-Volatile Organic Compounds) is applied in Screening processes. While the Chromatographic Screening process is the best solution to cover the three functions is should serve (discovery, identification and quantification), each function of the screening process is prone to errors that are inherent to the screening methodology.

Changing Regulatory Requirements for Extractables & Leachables Testing on Pharmaceutical Packaging Systems

In the past decades, there has been a change in the scrutiny of the way EMEA or FDA regulators looked at E&L data. They have gradually increased the requirements, not backed up with any official document (Guidance, guideline…) which left the Pharmaceutical Industry in the dark, second guessing of what the current position and requirements are of regulators to support a submission. In this presentation, the key factors of success of any given E&L project will be highlighted. Crucial is to understand what regulators really want and to align the design space of an E&L study to their expectations. Facing the reality of the ever-evolving regulatory landscape, analytical testing labs need to be on the forefront with expertise in the field of extractables and leachables testing and state-of –the art technology. Meeting the development needs and requirements, of the pharmaceutical and biopharmaceutical industries, also raises the bar for material suppliers. Only through successful partnering between drug product vendors, material suppliers and the CRO performing the test, a true mitigation of the risk related to packing can be established.

Changes to ISO10993-1 and relationship to Medical Device Regulation

The 2018 revision of ISO 10993-1 goes hand-in-hand with the MDR to give clear and more detailed guidance on what is required. This presentation will highlight the increased focus on the chemical and physical nature of the product. The presentation was recorded at our Open House Event in Leuven on 4 March. At that time there was no question that the date for the entry into force of the MDR might be postponed.

The Necessity of Extractables and Leachables Qualifications for Lyophilized Drug Products: Some Fallacies Addressed.

2022 NELSON LABS VIRTUAL SYMPOSIUM: When selecting and qualifying the primary packaging for lyophilized drug products (LDPs), one of the obvious questions is How far should you go into the E&L-qualification process? As the drug product is in a solid state, you would expect that the interaction between the LDP and the components of its container would be low. But is this really the case? The presentation will provide a view on the current status of regulatory requirements and will address some of the fallacies that exist in E&L qualifications for lyophilized drug products.

On the Origin of Extractable Species

The Universe of Extractables is extremely diverse; there are many different types of materials being used in the construct of a Container/Closure system or medical devices. All with a different formulation, polymerization, processing, and manufacturing. The impurities profile of a material is typically composed of compounds that were intentionally added to a material to protect the material during production or during its life cycle or to increase performance or functionality. In this case, we are talking about polymer additives, such as antioxidants, slip agents, acid scavengers, clarifying/nucleating agents, colorants, UV stabilizers, adhesives, etc. However, there is even a longer list of compounds that are present in a material that were not intentionally added. These compounds have typically been introduced during the production process of the material or component, or they are the result of ageing of the material. Typical examples are solvent residues, cleaning residues, catalyst residues, oxidation/degradation compounds of the polymer, oxidation/degradation compounds of the polymer additives, polymer oligomers, etc. The presentation will give an overview of the most common materials used in container/closure systems or medical devices and the main classes of compounds that are often detected in extractable studies. The presentation will explain why they are there, what their functions are or how they have been formed. Understanding the composition of a material and what the impact is on the extractables profile is an important and necessary first step in performing a proper evaluation of data and for a subsequent risk assessment.

Testing of Packaging Systems for Large-Volume Parenteral Drugs: Extractables Study Design and Challenges

Flexible bag systems for LVPs are subject to high levels of regulatory oversight for extractables and leachables testing given the potential for high dose exposure. For such applications, AETs are quite low and the analytical and toxicological workload is high. To allow for efficient identification of problematic product components, extractables studies for flexible bag systems should include all components of the packaging system, including components with minimal product contact (ports, secondary packaging, overwrap, etc.). A three-step approach is recommended, with a materials assessment consisting of a controlled, worstcase extraction study of individual components; a packaging assessment consisting of a real-world simulation study of the entire flexible bag system; and a product assessment consisting of a leachables study using the potential leachables set identified in the packaging assessment.

Clinical Evaluation Requirements for Medical Device – Meeting Medical Device Clinical Evidence Requirements – CE Marking

Clinical Evaluations are required by the Medical Device Directive (MDD) to ensure the safety of devices marketed in the European Union. The requirements are clearly outlined. However, many manufacturers are challenged by the process and rejections by the reviewers are not uncommon. In this whitepaper Industry expert, Chris Henza, shares her insights on compiling Clinical Evaluations, including tips from a recent submission which was approved in just 22 hours.

EO Residue Levels in Medical Devices: Best Practices for Demonstrating Compliance with ISO 10993-7

Sterilizing medical devices via ethylene oxide gas is an effective and common practice within the industry. EO gas is active at a relatively low temperature compared to other methods, such as steam, and it is compatible with plastics, polymers, and many products that are not compatible with other sterilization techniques, such as radiation. However, because of the potentially harmful effects of exposure to EO residue to patients, it is crucial to ensure the levels of EO residue meet the standards defined by ISO 10993-7:2008 by using validated testing methods. This paper will provide an overview of best practices for demonstrating compliance with that standard, and for demonstrating products sterilized via EO gas are safe for use.

New Guidance on Product Family Adoption for Radiation Sterilization: TIR 35:2016

Product family grouping is discussed in Clause 4 of ANSI/AAMI/ISO 11137-2:2013 entitled ‘Sterilization of health care products – Radiation – Part 2: Establishing the sterilization dose’. This document is designed to provide general requirements and guidance for establishing a product family for radiation sterilization. Family grouping is commonly used in the industry so that not every product type manufactured needs to be tested. AAMI’s Technical Information Report (TIR) 35 originally addressed alternative sampling plans for radiation sterilization using Method 1 and Method 2. When it was due for revision, the AAMI committee decided it would be an opportunity to provide additional guidance to the industry regarding different approaches that could be used for product family adoption. In 2016, AAMI TIR35 was published and entitled ‘Sterilization of health care products— Radiation sterilization— Product adoption and alternative sampling plans for verification dose experiments and sterilization dose audits. This TIR contains additional information on how to adopt a product into an existing family. This webinar will discuss the concepts found in this document and provide examples of how the guidance might be applied.

Considerations for Third-Party Reprocessing of Single-Use Medical Devices

Reusing single-use devices that have been safely reprocessed by a third-party re-processor can enable health care providers to maintain high-quality patient care while saving on costs and reducing medical waste. Validated functionality testing must be paired with validated cleaning, disinfection, and sterilization processes to ensure safety and compliance of regulatory requirements. This whitepaper is appropriate for design teams, quality assurance and regulatory personnel, and anybody interested in learning more about single-use device reprocessing. The knowledge gained from this presentation will aid in the safe and effective reprocessing of single-use devices.

When Drug Meets Device

When a medicinal product (drug or biologic) meets a medical device, a combined product is created. Incompatibility between the components can present a danger to the patient, but how can one demonstrate the fit between a medicinal product and a device? This paper describes the relevant definitions, the existing regulatory framework for combined products (or better the lack thereof) and focuses on stability testing to assess drug or biological-device compatibility.

Cleaning, Disinfection and Sterilization of Medical Devices: Updates to Reprocessing Guidance Documents AAMI TIR 12 and TIR30 (ST98)

In the last few years reusable medical devices have gained the spotlight in the medical device industry and regulatory landscape. This attention has forced the standards that govern reusable device validations to update with more clear concise guidelines. The guidance found in AAMI TIR 30 on cleaning validation steps is in the process of being replaced by a new standard AAMI ST98. AAMI TIR12, which offers guidance on which processes are appropriate, was updated at the end of 2020. This webinar will discuss the updates to TIR 12 and the upcoming new standard ST98, and how those changes apply to cleaning, disinfection, and sterilization validations of medical devices.

When Drug meets Device: How to assess compatibility?

The frequent contact of patients with combined products, a concept that describes the joint use of drugs and devices, makes the assessment of the compatibility of a device with certain drugs a very important topic. In this webinar, Dr. Lise Vanderkelen and Dr. Ruth Verplaetse talk passionately about the necessity of a good relationship between the drug and the device for the benefit of the patient. Determining the compatibility of combined products includes many different aspects. All these aspects need to be in balance to establish a healthy relationship within the combined products and to avoid any danger that may harm a patient. This webinar will particularly focus on drug stability, chemical compatibility and biocompatibility.

Thermal Disinfection & Steam Sterilization Validation for Reusable Devices

This webinar hosted by Jason Pope and Lise Vanderkelen will address some of the key aspects of what is required for thermal disinfection validation studies and steam sterilization validations. These are two different, but important, steps in the processing cycle of reusable devices. This session should give you a deeper understanding of: Why a validation of the thermal disinfection procedure is crucial to demonstrate the effectiveness of the disinfection. The 3 different steps that you need to include to obtain a successful steam sterilization (sterility assurance level, dry time validation & thermocoupling) The different requirements for EU and US registrations.

ISO 10993-18 in the MDR: understanding the restrictions and risk assessment for compounds which are carcinogenic, mutagenic, toxic to reproduction (CMR) or have endocrine-disrupting (ED) properties (section 10.4)

This presentation explains to what extent a chemical characterization study (ISO 10993-18) can assist in meeting the requirements of section 10.4 of the MDR. A workflow for both the labeling obligation as well as the risk assessment is proposed. This requires a clear understanding of the difference between a targeted and screening analytical approach and the corresponding level of quantification.

MDR with Brexit_ How the Combination is Impacting the European Medical Device Industry

With the COVID-19 crisis, the Medical Device Regulations (MDR) have been pushed back one year, this delay has given a respite for those companies that were not quite ready for the increased regulations. This delay put the new MDR requirements in the same time period as the impact of Brexit. In this presentation we will be discussing the status of the medical device industry regarding MDR and Brexit, and what are others doing to get ready. Attendees will learn: What additional requirements are in the MDR? How is Brexit impacting submissions to the UK? Where is the industry currently at and how many companies feel ready for their first submission? What have we learned from the first submissions under MDR? What are others doing now, to save time and money?

Navigating Packaging Changes in Light of New Regulatory Requirements

We will look at the new updates to the MDR’s that have driven the ISO 11607 Packaging changes and what that means with the deadline for implementation fast approaching.

Medical Device Extractable and Leachables Testing in 2020

The world of physics has a foundation built on beautiful universal constants, which work their way steadfastly into the equations governing electrodynamics, and then further extend themselves into our very hands in the design of smart interconnected electrical devices that are commonplace to modern life. Ironically, universal constants form the founda­tion of life for which it is popularly said that the only constant is change. This constancy of change is also very well proven in the world of medical device regulation, perhaps especially with respect to biocompatibility and how chemical information fits into that puzzle. Over the past 5 years, the medical device community has swung from nearly full ignorance of the poten­tial power of chemistry testing, to full adoration and acceptance, and now back – in a sense – to a state of scrutiny and skepticism. Regulators, in response to an influx of medical device submissions centered on supporting chemistry data, have increased their knowledge and finesse with the science and have been asking tough questions. Widely circulated studies have been critical of chemistry testing for toxicological evaluation of medical devices. Therefore, in response to this feedback, as medical device chemistry for toxicology (ChemTox) has matured, the overall strategy has changed dramatically on some points.

Chemical Interactions between Leachables and Biopharmaceuticals

Leachable compounds are currently only evaluated on the toxicological risk they pose to the patient. The effects that leachable compounds have on the quality and safety of pharmaceutical drug products, especially protein drug products, is often overlooked. Interactions of reactive leachable compounds with protein drug products can lead to a loss of efficiency, decrease of stability and increased immunogenicity in the patient population at risk. This webinar describes reactive leachable compounds, the scientific basis to predict leachable-protein interactions and a proof of concept.

Pharma Packaging Considerations for Radiation Processing using Gamma and Electron Beam and Discussion on the New Container Closure Integrity Testing

This webinar is designed to build your foundational knowledge of pharma packaging. The type and method of packaging is an important consideration for radiation processing using gamma and electron beam. This webinar discusses how product packaging and presentation (density, weight and product orientation) can affect routine processing. Examples will be presented how certain considerations are taken into account when developing the product packaging to ensure an effective radiation process. The webinar will also cover mass extraction a relatively new container closure integrity test which is included on the USP 1207 list of approved deterministic CCIT test methods. You will learn the basic methodology behind a mass extraction test, the advantages of mass extraction testing over other CCI methods, and how the test is performed.

Manufacturing an SVP Drug Containment Solution: Quality by Design

2022 NELSON LABS VIRTUAL SYMPOSIUM: Considerations that need to be taken into account when choosing, designing, and manufacturing an SVP drug container solution. The drug product, route of administration, and life cycle management play an important role in the selection of the primary container, the manufacturing process, and the components chosen to safeguard the drug and the patients. An insight into the different manufacturing capabilities and controls to manufacture the required container.

Rubber Manufacturing and Composition of Pharma Rubbers

2022 NELSON LABS VIRTUAL SYMPOSIUM: Rubber closures are often used in the primary packaging system of small volume parenterals. This presentation aims to provide more insight into the manufacturing process and basic composition of rubber compounds used for pharma applications. Additionally, it will discuss how the properties of rubber can be adjusted to match specific requirements and how to ensure that the rubber meets all the relevant criteria for safe use in the final application.

The Road to Market Authorization for Sterile Medical Devices within the European Union

Sterile Medical Devices must follow the regulations and standards for CE marking that went into effect May 2021. Medical devices being sold in Europe require a CE mark, even if the product is imported from outside the Economic European Area (EEA). CE marking certifies that a medical device complies with regulatory requirements under European Regulation (MDR 2017/745 and IVDR 2017/746). Upon receipt of the certification /CE mark the product can be freely marked, sold and marketed anywhere in the Economic European Area (EEA). In this webinar, the strategic process of obtaining a CE mark, the defined product use and classification, as well as conformity assessment and review will be covered. Additionally, the interaction and experiences with contract sterilizers regarding MDR will be reviewed, including key validation information required for obtaining a CE mark for a sterile product.

Risk Assessment for Single Use Systems: USP 665 vs. BPOG

Disposable plastic components of biopharmaceutical drug manufacturing systems are becoming more popular due to their cost and low contamination benefits. The risk of using these components needs to be evaluated to determine impact to the final product. Historically each manufacture will determine their risk using understood risk assessment processes, these include established procedures like BPOG to frame a risk assessment. Currently USP has a draft section, 665 and 1665, that will give additional guidance to this risk process, including recommendations for testing. In this presentation, we will explore the principles behind these options and give insights on how to perform a single use component(s) risk assessment. We will also include real life examples of risk assessments and regulatory outcomes.

Life Science Due Diligence Beyond the Obvious: Managing Business Risks During Life Science M and A Due Diligence

In the business press, discussions of mergers or acquisitions (M&A) invariably include percentages of deals that did not realize their expected value creation. Failure numbers, ranging from 60-80 percent, are surprisingly high. Clearly, many companies move forward on medical device or pharma deals without a clear picture of their risks. A due diligence process that’s too high-level or superficial is often to blame. For example, when a life sciences company considers a merger or acquisition, the due diligence team typically looks for 483s, Warning Letters, notified body findings, and product recalls – any signs of potential problems with the FDA. But when a deal does not deliver value, the real causes are often strategic, cultural, or technical.

Best Practice Implementation of Parametric Release for EO Sterilization

This webinar reviews the benefits of parametric release and how best to establish a compliant, capable process design and ISO 11135: 2014 standards. The following questions will be addressed: - What is parametric release and how can it benefit the manufacturer? - What are the current requirements as stated in the ISO 11135: 2014 Standard? - What are some of the best practices in setting and challenging parametric limits?

Gamma: The Heart of Radiation Sterilization Past, Present and Future

The Covid-19 global pandemic of 2020 has brought into sharp focus the critical role that the medical device supply chain plays in the terms of bringing safe, effective healthcare to the world’s population. A key part of this supply chain is the sterilization of these devices, historically accomplished primarily through the use of ethylene oxide and gamma irradiation, using Cobalt-60. This whitepaper “Gamma: The heart of radiation sterilization past, present and future” provides a brief overview of the importance and contribution of gamma irradiation as a sterilization modality, with a focus on why it has grown to hold a significant position in the 50 years it has been in use. It will also provide clarity on the current and future state of Cobalt-60 supply, and demonstrate to stakeholders that there is no compelling reason to consider switching from a modality that continues to deliver efficacy, reliability and cost effectiveness.

PQ dose mapping and routine irradiation of products with non-uniform density distribution

Operational Qualification dose mapping of gamma irradiators is performed using homogeneous materials. Product sent for irradiation may deviate substantially from this model, which introduces complexity into Performance Qualification dose mapping as well as control of the irradiation process. This webinar examines Performance Qualification dose mapping and routine irradiation and provides a set of examples about how product with non-uniform density distribution within or between irradiation containers could be handled in practice.

Validating, Optimizing and Monitoring EO Sterilization Processes - Part 2

Establishing an EO sterilization process can be a complicated path as multiple factors play a role in the design of a successful validation: adequate product characterization to determine an appropriate monitor device, definition of process parameters that are adequate for the product and sterilization load, and the definition of the validation activities to verify adequacy. Selecting the right validation approach would reduce the need for future cycle optimization to address things like the reduction of EO usage, reduction in product residuals, reduction in cycle times or the development of an appropriate process for parametric release. The validation approach selected can also facilitate (or complicate) annual validation and process review and/or requalification. During the two-part webinar attendees will learn: - A 101 approach to cycle validation and ancillary activities - An expanded view of BIO/Bioburden and Cycle Calculation validation approaches - A definition of annual review activities - The first steps to cycle optimization.

Product Adoption for Ethylene Oxide Sterilization

Changes to the design of an existing product and adoption of a new product into a device family requires a product change assessment to the existing EO sterilization cycle that has been previously validated. This webinar provides guidance for a product change assessment per ISO 11135:2014 to help limit the extent and costs of validation work, while at the same time, helping to ensure the safety of products and compliance to regulatory requirements. Medical device manufacturers developing new products or improving the design, packaging and/or load configurations of existing products will gain a greater understanding of the: - Requirements of ISO 11135 for product adoption and change assessment - Conduct of adoption studies for changes of new products - Benefits of product adoption.

Fundamentals of EBeam Sterilization

Since the 1950’s the irradiation of medical devices using electron beam (e-beam) sterilization has been a common practice. Decades later, as medical devices and packaging configurations have become more complex, so has the demand for higher power e-beam accelerators. This webinar will cover the fundamentals of e-beam sterilization and review the processing capabilities of today’s modern equipment. We will review comparisons of e-beam and photon-based sterilization modalities, covering topics specific to product qualification, transitions between modalities, and ideal products to consider for e-beam irradiation.

Critical First Steps of an Ethylene Oxide (EO) Validation - Process Definition The Critical First Steps in the Validation of an EO Sterilization Process

In this webinar, you will learn about the importance of process definition (fractional) work as a part of an Ethylene Oxide (EO) validation and why it is not only important but required. The following topics are covered: - Relative resistance for Internal PCDs - Confirming BI appropriateness - Evaluating an appropriate External PCD - Calculating a D-Value to help determine an appropriate gas dwell time for the half cycle and full cycles.

The Road to Parametric Release for EO Sterilization

Parametric release can be invaluable to companies by accelerating their sterile product’s release-to-market. It is based upon a documented review of processing records rather than the testing of biological indicators (BIs) or process challenge devices (PCDs). This webinar defines parametric release, reviews the advantages that merit its consideration, and provides a practical way to implement the process. It will provide you with a better understanding of the approach, which is widely accepted in the industry and recognized within ANSI/AAMI/ISO 11135:2014, and its potential to address urgent demand and market fluctuations.

FAQs for Pet Treats Manufacturers: Get the Facts on Pathogen Reduction in Pet and Animal Nutrition

If you’re a manufacturer, you want to reduce bacteria in the pet treats and animal feed that you sell to businesses and consumers. If you have questions about using Gamma radiation for pathogen reduction in your pet treats and animal nutrition, this eBook is for you. Get answers to your commonly asked questions when you download this informative and fast-read Sterigenics eBook.

Materials Qualification of Healthcare Products to Radiation Sterilization

New products that are biological in nature or made of materials that are sensitive to standard forms of terminal sterilization are requiring more developed tools to bring together the expertise needed to solve common problems in the sterilization industry. This webinar provides guidance for healthcare product manufacturers in qualifying the material used in products being sterilized with radiation. You will learn: - How to select the ideal polymer candidate - How to identify effective ways of using radiation sterilization on various healthcare products - How to determine sterilization processing conditions. Consideration of these requirements in the R&D phase or early design stage is critical to ensuring that they’re integrated in the qualification process. Ultimately, evaluating radiation sterilization on materials will help lead to a safe, functional product that meets end-user needs.

Get the Facts on Microbial Reduction in Food Ingredients

There’s a lot of urban legend when it comes to using gamma radiation to reduce pathogens in food ingredients. One of these statements is fact; one of these statements is fiction. Do you know which is which? -No one will know whether my food products are irradiated or not. -Governments allow irradiated food ingredients into their countries. Learn fact from fiction when you download this fast-read Sterigenics eBook.

Performance Qualification for Gamma Irradiators

Sterilization validation is a critical phase in the life cycle of your sterile product. This webinar will focus on the Performance Qualification (PQ) methods for Gamma irradiators which are the final step before moving into routine sterilization. This webinar will review the purpose of PQ along with the reference standards used in the industry. You will learn how to develop a PQ strategy that is both efficient and capable of consistently meeting your product specification. Using a real-life example, you will increase your knowledge of the inputs/outputs of PQ and how to maintain effectiveness of this critical process.

What is a Sterilization Dose Audit and How are they Performed?

The performance of periodic sterilization dose audits is required, where a sterilization dose has been established using Method 1, Method 2, or Method VDmax. This webinar will focus on the purpose and activities associated with such audits to demonstrate the continued effectiveness of the established sterilization dose. This webinar will provide a greater understanding of why the sterilization dose audit is needed and how to complete a dose audit for a wide variety of medical devices that have been validated using the ANSI/AAMI/ISO 11137.

Tools of the Trade Ways to make EO Processing More Efficient

Ethylene Oxide (EO) sterilization is the most complex of the common sterilization methods, and there are many approaches to executing the EO process. There are a variety of tools that can make the EO process more efficient and can assist personnel in understanding the situation when things do not go as planned. This webinar describes some of the tools used in validation, routine processing, and maintenance as well as how the tools can be used as part of the investigation of processing failures. These tools document the process, help conduct statistical / predictive analysis and show the data in clear ways that can assist with quality and operational decision making.

The 3Rs of EO Sterilization - Sustaining the Continued Safe Use of EO

Expectations of the FDA regarding the design of chemistry studies in support of medical device toxicology has been shifting rapidly. New expectations have primarily been communicated to laboratories through submission feedback, and pre-submission meetings, as the FDA has not yet released guidance on application of ISO 10993-18. This presentation focuses on how chemistry study design has changed over the last 12 months in response to FDA received from the FDA. Originally presented at MDM West 2022.

An Introduction to Radiation Dosimetry and the Mathmatical Model

An overview of radiation dosimetry will be provided with emphasis on dosimetry principles and calibration methods in order to maintain measurement traceability. The importance of estimating measurement uncertainty is discussed, including how uncertainty can be applied to the radiation process, and to assess new product process capability for new products. An introduction to the mathematical model is given with emphasis on how it can be used to complement radiation dosimetry and assist with the validation of an irradiator change.

Validating, Optimizing and Monitoring EO Sterilization Processes - Part 1

Establishing an EO sterilization process can be a complicated path as multiple factors play a role in the design of a successful validation: adequate product characterization to determine an appropriate monitor device, definition of process parameters that are adequate for the product and sterilization load, and the definition of the validation activities to verify adequacy. Selecting the right validation approach would reduce the need for future cycle optimization to address things like the reduction of EO usage, reduction in product residuals, reduction in cycle times or the development of an appropriate process for parametric release. The validation approach selected can also facilitate (or complicate) annual validation and process review and/or requalification. During the two part webinar attendees will learn: - A 101 approach to cycle validation and ancillary activities - An expanded view of BIO/Bioburden and Cycle Calculation validation approaches - A definition of annual review activities - The first steps to cycle optimization.

Pharma Packaging Considerations for Radiation Processing using Gamma and Electron Beam and Discussion on the New Container Closure Integrity Testing

This webinar is designed to build your foundational knowledge of pharma packaging. The type and method of packaging is an important consideration for radiation processing using gamma and electron beam. This webinar discusses how product packaging and presentation (density, weight and product orientation) can affect routine processing. Examples will be presented how certain considerations are taken into account when developing the product packaging to ensure an effective radiation process. The webinar will also cover mass extraction a relatively new container closure integrity test which is included on the USP 1207 list of approved deterministic CCIT test methods. You will learn the basic methodology behind a mass extraction test, the advantages of mass extraction testing over other CCI methods, and how the test is performed.

Successfully Execute a Nitrogen Dioxide Sterilization Validation for a Drug in a Pre Filled Syringe

Biotech drugs are the fastest growing segment of pharmaceutical and biotech pipelines. About 60-70% of these drugs are delivered in a pre-filled syringe or similar delivery device. Biotech drugs are often highly sensitive to temperature, vacuum and sterilant ingress. Nitrogen dioxide sterilization offers an alternative sterilization method with many advantages important for these drug-device combination products: sterilizes at 10 °C-30 °C, a gas sterilization process that can reach complex geometries, surface sterilant with no to low ingress into the syringe, and vacuum can range from 20 Torr – 500 Torr – ideal for pressure-sensitive delivery devices. Nitrogen Dioxide is a recent addition to the sterilization options a company can consider for their product. Nitrogen Dioxide was selected by the FDA for Innovation Challenge 1 – Alternative Sterilization Methods (to ethylene oxide) in November 2019. This webinar is intended to walk the participants through assessment of the pre-filled syringe, identify things that should be considered prior to validation, the appropriate ISO and TIR guidelines, a recent case study of a sterilization validation of a pre-filled syringe.

Material Consideration Radiation Processing

Each polymer reacts differently to ionizing radiation. Thus, it is important to verify that the maximum administered dose will not have a detrimental effect on the product’s function or the patient’s safety over the product’s intended shelf life. This whitepaper reviews typical tests of physical properties and serves as a general guide to radiation stability of materials.

How to Evaluate a New Product Against an Existing Product in a Validated EO Process

As defined in Section 12 of ISO 11135:2014, a new or modified (“candidate”) product can be added to a validated Ethylene Oxide (EO) sterilization process if an evaluation shows that the candidate product is either equivalent to or a lesser challenge than an “existing” product or Internal Process Challenge Device (IPCD). Such an outcome could save considerable time and money. By reading this White Paper, Quality Assurance, Project Management, Sterility Assurance and Validation personnel within the medical device, pharmaceutical, commercial and food industries learn the necessary steps to evaluate a candidate product.

The Design and Qualification Process for a LVP Packaging System from a User Perspective

To meet the increasing patient need for LVP, more complex packaging systems are required to be designed and further qualified to house different solutions. The high maximum daily dose of the multi-components of the packaging system present challenges when evaluating extractables and leachables (E&L). Controlling E&L levels in LVP is vital for the safety, quality, and efficacy of the finished product. Leveraging existing regulations (Pharmacopeial and food compliance) and effective collaboration with the suppliers of the raw materials will provide the required knowledge to design accurate E&L assessments. E&L testing of LVP dictates a low detection limit due to the long LVP treatment duration and high volumes. Thus, impurities with ppb levels such as Nitrosamines trigger great analytical challenges. Approaching LVP based on E&L risk assessment at an early stage of the product’s life cycle, namely material selection, will allow the E&L strategy to succeed in ensuring patient safety and product compliance.

Product Safety Future State of Sterility Assurance and the Role of Terminal Sterilization

Sterilization is a pivotal step in the pharmaceutical drug development process to help ensure overall safety is maintained. Regulation is clear that, whenever possible, products intended to be sterile should be terminally sterilized in their final container. Only if terminal sterilization is not possible, filtration or aseptic assembly should be applied. This webinar will focus on trends in the concept of sterility assurance including the revision of USP <71> and elements to evaluate prior to selecting aseptic assembly for the manufacturing of sterile drug products. What you will get from this webinar: • A deeper understanding of terminal sterilization and aseptic processing of drug products through a regulatory lens as well as that of a manufacturer • Mitigation strategies for the use of terminal sterilization with radiation, ethylene oxide and novel modalities • Trends in the concept of sterility assurance.

Medical Packaging and the Impact of NO2 Sterilization

Novel sterilization modalities are becoming more common in the healthcare industry. When determining the sterilization modality that is best for your product and organization, many factors apply. In this presentation, you will learn about NO2 sterilization technology, how it works, where it’s currently being used and how medical device manufacturers are incorporating it into their processes. In addition, the presenters will share technical data on common medical packaging materials to ensure appropriate considerations are made during material selection. Originally presented at MDM West 2022.

Radiation Sterilization Strategies for Improved Processing Options and Timing

Supply and material constraints are a part of our world and with the increased popularity of radiation sterilization, demand has outpaced supply. Creative strategies are necessary to ensure sterilization capacity, minimization of testing, and remaining compliant. This presentation will cover dose optimization for improved irradiator options and processing times, family grouping to reduce validations and testing, as well as max dose to provide flexibility and ensure compliance with the standards. Originally presented at MDM West 2022.

Pros Cons and Considerations of Using a Developmental Chamber During Ethylene Oxide Validation

A developmental chamber is usually smaller than a production chamber and used to perform studies to support Ethylene Oxide validation. This white paper discusses use of a developmental chamber for Process Definition performed as part of a validation, in adherence with ISO 11135:2014, using the Overkill Approach. Project Management and Quality Assurance personnel within the medical device, pharmaceutical, commercial and food industries will learn what to consider when contemplating either a developmental or production chamber, as well as advantages and disadvantages of using a developmental chamber. As an example, one advantage of using a developmental chamber is that smaller sample sizes in the smaller developmental chamber will oen mean lower laboratory testing costs.

Get the Facts on Bioburden Control and Sterilization for Food & Beverage Packaging

This eBook, Get the Facts on Bioburden Control and Sterilization for Food & Beverage Packaging, answers the most common questions that food and beverage manufacturers ask our Industry Subject Matter Experts about the use of Gamma irradiation to keep molds, fungi and other micro-organisms out of packaging.

A Review of Ionizing Radiation Sterilization Modalities

The use of high-energy ionizing radiation for sterilization purposes is an established and proven method for the inactivation of microorganisms on healthcare, food, and general industrial products. Several ionizing radiation modality options are available including Gamma, Electron Beam, and X Ray technologies. What modality is the appropriate and most efficient option for the sterilization your product? This webinar will focus on a comparison of Gamma, Electron Beam, and X-Ray technologies to guide a manufacturer through this critical decision. Each option has advantages, disadvantages, and limitations that a manufacturer should take into account during the design and development phase of the product lifecycle. The selection of the proper modality will help ensure a safe, efficient, and capable process to consistently meet your product specification.

Establishing Maximum Acceptable Dose in Radiation Sterilization

Manufacturers utilizing ionizing radiation (gamma, electron beam, or X-ray) for sterilization purposes need to establish the maximum acceptable dose for the specified product. Compliance to the ISO11137 standard requires an experimental program that demonstrates that a product treated with the maximum acceptable dose meets its specified functional requirements throughout its defined lifetime. This webinar will focus on radiation interaction with materials and the proper design of experiments to establish a product’s maximum acceptable dose. It examines why manufacturers should be cognizant of the possible impact of radiation to the product’s mechanical properties and how this may influence performance following sterilization.

Regulatory Landscape for EO Residue Levels in Medical Devices

The global regulatory landscape around Ethylene Oxide (EO) residues is a topic of increasing interest. This webinar will provide an overview of EO sterilization and the status of ISO standard 10993-7:2008, which serves as an international authoritative document for medical device manufacturers in order to know how to set your company up for the future. The following topics will be covered: - Testing according to product category and product use - Concomitant EO exposure - Topical contact - Special situations (e.g., intra ocular lenses, cardiopulmonary bypass devices …) - Test method and validation - ISO 10993-7 revision for products intended for neonates and children /recommendation by ANSM – French Regulator - Fugitive EO emission from EO treated products, which must be monitored throughout the supply chain to safeguard worker exposure - Legislation regarding EO emissions in the supply chain.

Cobalt-60: The Heart of Radiation Sterilization

For more than 50 years, Cobalt-60 has been used as a source of gamma radiation for a wide variety of applications, and has grown to become one of the most prevalent modalities for sterilization of single use medical devices. Medical device manufacturers typically do not have good visibility of the Cobalt-60 supply chain and resulting supply/demand dynamics, given that many of them are one step removed through the use of contract sterilization providers. This can lead to lack of clarity around current and future gamma capacity, important for making sterilization modality selection decisions. This webinar will provide insight into the workings of the global Cobalt-60 supply chain, and explain the impact of recent events on both supply and demand. The presentation will also touch on Nordion’s long-term strategies for maintaining and growing Cobalt supply, and highlight some key supply initiatives.

Ethylene Oxide Sterilization, Revision of Annex E, Single Batch Release

ANSI/AAMI/ISO 11135:2014 Annex E recently underwent revision expanding on the requirements for the release of product from a single batch Ethylene Oxide (EO) sterilization process. This addendum builds on the current allowances and requirements for the release of product from a single lot sterilization batch to demonstrate that the process delivered the desired Sterility Assurance Level (SAL) to the exposed product. This presentation takes a comprehensive look at the single lot release approach, the factors that determine what testing is necessary, and how the requirements in Annex E of ANSI/AAMI/ISO 11135 have changed. This presentation will help the manufacturer navigate through some of the considerations for execution of a single batch release process. The training will assist in the development of a test plan, including sample size requirements, for performing a single batch sterilization process. Attendees will learn: Regulatory background and industry expectation for single batch release from EO processes Pre-evaluation of product design, packaging design, and loading configurations Establishing a compliant test plan for single batch release from EO processes Proper assessment of process and test results, including required documentation to support single batch release from EO processes.

Radiation Sterilization of SVPP: RTU and fill/finished. Do not default to 25 kGy – 40 kGy.

2022 NELSON LABS VIRTUAL SYMPOSIUM: Examples will be presented for radiation sterilization of RTU SVPP as well as terminal sterilization of fill/finished items. A critical aspect in validation of the irradiation processes is the Process Definition step, where there is considerable benefit to not default to a specification of 25 kGy to 40 kGy. Methods and practices for widening the specification will be discussed.

Establishing Maximum Acceptable Dose for Medical Devices in Radiation Sterilization

Medical device manufacturers using ionizing radiation (gamma, electron beam or X-Ray) for sterilization purposes should establish the maximum acceptable dose for the specified product. Manufacturers must comply with the ISO 11137 standard, which requires an experimental program to demonstrate that, when treated with the maximum acceptable dose, the product meets its specified functional requirements throughout its defined lifetime. Quality Assurance, Project Management, R&D, Sterility Assurance, Engineering and Validation personnel will benefit from this whitepaper that includes a “Sample Use Case”.

Three Methods to Establish the Sterilization Dose of a Medical Device

In the medical device industry, sterilization processing is performed to obtain a Sterility Assurance Level (SAL) as required by regulatory authorities to designate the treated product as “sterile”. There are several approaches—the sterilization dose setting methods 1 and 2, and the substantiation method VDmax SD—that may be used to establish the minimum dose that results in the required degree of sterility assurance. By reading this Whitepaper, Quality Assurance, Sterility Assurance and other interested professionals will learn about the different aspects of each method that have to be considered in order to make the best decision for a specific product.

Sterility, Manufacturing and Regulatory Challenges in a Constantly Changing World of Biopharmaceuticals

The Biopharmaceutical sector has been changing very rapidly from monoclonal antibodies to Cell and Gene Therapy and RNA-based Therapeutics. The growing healthcare needs demand cost effective and rapid manufacturing technologies. The approval of biosimilars and continuous manufacturing has joined hands with manufacturers to meet these demands. This shift from fixed stainless steel to single use systems (SUS) has revolutionized the therapeutic market. The rapid market growth for SUS, composed primarily of plastic components that are sealed and sterilized using irradiation, is expected to continue. This webinar will focus on product development, including sterilization and lab testing strategies, to help ensure there is no contamination in the development and manufacturing of SUS to promote end-user safety.

Designing an End-to-End Sterility Assurance Program

Sterility assurance for a pharmaceutical product is critical and includes many aspects outside of the actual sterilization cycle or aseptic process. There is some recent movement in the health care industry regarding the term End-to-End Sterility Assurance, along with a document being written through AAMI to provide guidance on the topic. Effective sterility assurance includes extensive collaboration with parties across the product life cycle. In the webinar we will address the various aspects of sterility assurance and provide guidance on establishing a complete program.

Sterilization Dose Audits – The “Why” and the “How”

In the medical device industry, sterilization processing is performed to obtain a Sterility Assurance Level (SAL) as required by regulatory authorities to designate the treated product as “sterile”. When SAL is established using Method 1, Method 2 or Method VDmax, a periodic sterilization dose audit is required by ANSI/AAMI/ISO 11137-1. The purpose of such audits is to demonstrate the continued effectiveness of the established sterilization dose. By reading this Whitepaper, Quality Assurance, Sterility Assurance and Validation personnel will learn how to perform sterilization dose audits.

EO Sterilization: Considerations for Neonate Products and Medical Devices and ISO 10993-7

EO sterilized items are life-saving and critical devices that are sterilized in highly regulated environment, under strict normative rules and with the greatest care. This webinar will review important considerations for EO Sterilization of neonate products and medical devices. Aspects of EO sterilization will be covered, including the consideration for EO residues that takes into account the amendment of the governing standard, ISO 10993-7. The use of risk assessment, risk/benefit evaluation, validation and application of the right method to define the most suitable limits will also be discussed during this webinar.

The Impact of Radiation Sterilization Modalities on Flexible Sterile Barrier Packaging

When determining the sterilization technology that is best for your product and organization, many factors apply. In this webinar, you will learn about radiation sterilization technologies (Gamma, Electron beam and X-Ray), how they work and how medical device and pharma manufacturers are incorporating it into their processes. In addition, Sterigenics, Segment Leader, Accelerator Modalities, Chad Rhodes, an industry leader with over 25 years of radiation and sterilization expertise, and Oliver Healthcare Packaging’s Senior Principal Engineer, Jeremy Elwell, a medical packaging expert with over 16 years' experience in the medical device industry will share technical data on common medical packaging materials to ensure appropriate considerations are made during material selection.

EO Residue Levels in Medical Devices: Best Practices for Demonstrating Compliance with ISO 10993-7

Sterilizing medical devices via ethylene oxide gas is an effective and common practice within the industry. EO gas is active at a relatively low temperature compared to other methods, such as steam, and it is compatible with plastics, polymers, and many products that are not compatible with other sterilization techniques, such as radiation. However, because of the potentially harmful effects of exposure to EO residue to patients, it is crucial to ensure the levels of EO residue meet the standards defined by ISO 10993-7:2008 by using validated testing methods. This paper will provide an overview of best practices for demonstrating compliance with that standard, and for demonstrating products sterilized via EO gas are safe for use.

New Guidance on Product Family Adoption for Radiation Sterilization: TIR 35:2016

Product family grouping is discussed in Clause 4 of ANSI/AAMI/ISO 11137-2:2013 entitled ‘Sterilization of health care products – Radiation – Part 2: Establishing the sterilization dose’. This document is designed to provide general requirements and guidance for establishing a product family for radiation sterilization. Family grouping is commonly used in the industry so that not every product type manufactured needs to be tested. AAMI’s Technical Information Report (TIR) 35 originally addressed alternative sampling plans for radiation sterilization using Method 1 and Method 2. When it was due for revision, the AAMI committee decided it would be an opportunity to provide additional guidance to the industry regarding different approaches that could be used for product family adoption. In 2016, AAMI TIR35 was published and entitled ‘Sterilization of health care products— Radiation sterilization— Product adoption and alternative sampling plans for verification dose experiments and sterilization dose audits. This TIR contains additional information on how to adopt a product into an existing family. This webinar will discuss the concepts found in this document and provide examples of how the guidance might be applied.

Lessons from the Lab

This eBook addresses common challenges and best practices for medical-device manufacturers with questions about testing their products. This publication was created in partnership with Medical Products Outsourcing Magazine. Topics and articles include: EO Optimization and Potential Effects on Sterile-Barrier Packaging, Patient-Specific Implants Often Require More Testing, Extractable Chemical Characterization and Risk Assessment: What is the Worst Case? Understanding Biological Evaluation Plans, What Cleaning Procedure Should You Have in Place for Your Reusable Device, Four Important Things to Know About Particulate Testing and Medical Devices.