The document discusses testing done to qualify the use of x-ray sterilization for a Lynx S2S connector. Physical, chemical, and biological tests were performed on connectors that underwent either x-ray or gamma sterilization. Test results showed comparable extractable levels, thermal properties, and chromatographic profiles between the two sterilization methods. This provides evidence that x-ray sterilization is a suitable alternative to gamma sterilization for this connector.
Potential Impact of Draft Annex 1 on Sterilizing FiltrationMilliporeSigma
Access the interactive recording here: https://bit.ly/2mvFxs7
Abstract:
The support for EMA GMPs related to sterile medicinal products is Annex 1. EMA, PICS and WHO have collaborated on the largest and most comprehensive revision of Annex 1 since it was first written in 1997.
There are a number of proposed changes to the sections in Annex 1 dealing with filtration, integrity testing and single-use.
This presentation will compare the current version with the proposed changes and highlight areas of specific interest to companies who either manufacture in or export to EMA countries, PICS member countries, and WHO compliant countries.
USP <665> draft standard : A rational risk-based approach to characterization...Merck Life Sciences
This webinar will cover risk-based characterization of filters and single-use systems used in biopharmaceutical manufacturing according to USP <665>.
Novel innovative biomanufacturing systems such as single-use assemblies often comprise of polymeric materials. There is a lack of standards for characterization of these polymeric systems. USP <665> draft standard is the first standard in development addressing this topic. This chapter recommends risk assessment with respect to patient safety, risk level assignment and risk level appropriate characterization of components.
In this webinar we will discuss:
● Risk assessment to assign a risk level
● Risk level based testing
● Our approach for compliance
● Emprove™ Dossiers for Filters and Single-use systems
Viral safety of biologics: What's changing with the ICH Q5A revision?Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3t7X9tg
How does the ICH Q5A revision impact viral safety strategies for biologics?
Biologics continue to grow at a fast pace. Manufactured using cell lines of human or animal origin, these are at risk of viral contamination making safety strategies critical. A comprehensive risk mitigation strategy using multiple orthogonal measures is a regulatory expectation. ICH Q5A, the globally-harmonized guideline outlines the expectations. ICH Q5A is currently being revised to address recent scientific advancements including novel therapeutic modalities, new manufacturing paradigms, updates in viral clearance applications, and alternate detection technologies. We’ll discuss the expected changes and potential impact on viral safety strategies with case studies and examples.
In this webinar, you will learn about:
• The Importance of virus testing in biologics products
• Regulatory landscape, expectations for the Q5A revision
• What's new and changing
• Examples of alternate testing schedules, impact on viral clearance
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Alison Armstrong, PhD, Sr. Director, Technical and Scientific Solutions
Restriction of Hazardous Substances(RoHS) and REACHAmit Ghai
A historical perspective, current revisions and guidelines for RoHS and REACH compliance. Includes typical case studies, challenges and ways to overcome them
Potential Impact of Draft Annex 1 on Sterilizing FiltrationMilliporeSigma
Access the interactive recording here: https://bit.ly/2mvFxs7
Abstract:
The support for EMA GMPs related to sterile medicinal products is Annex 1. EMA, PICS and WHO have collaborated on the largest and most comprehensive revision of Annex 1 since it was first written in 1997.
There are a number of proposed changes to the sections in Annex 1 dealing with filtration, integrity testing and single-use.
This presentation will compare the current version with the proposed changes and highlight areas of specific interest to companies who either manufacture in or export to EMA countries, PICS member countries, and WHO compliant countries.
USP <665> draft standard : A rational risk-based approach to characterization...Merck Life Sciences
This webinar will cover risk-based characterization of filters and single-use systems used in biopharmaceutical manufacturing according to USP <665>.
Novel innovative biomanufacturing systems such as single-use assemblies often comprise of polymeric materials. There is a lack of standards for characterization of these polymeric systems. USP <665> draft standard is the first standard in development addressing this topic. This chapter recommends risk assessment with respect to patient safety, risk level assignment and risk level appropriate characterization of components.
In this webinar we will discuss:
● Risk assessment to assign a risk level
● Risk level based testing
● Our approach for compliance
● Emprove™ Dossiers for Filters and Single-use systems
Viral safety of biologics: What's changing with the ICH Q5A revision?Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3t7X9tg
How does the ICH Q5A revision impact viral safety strategies for biologics?
Biologics continue to grow at a fast pace. Manufactured using cell lines of human or animal origin, these are at risk of viral contamination making safety strategies critical. A comprehensive risk mitigation strategy using multiple orthogonal measures is a regulatory expectation. ICH Q5A, the globally-harmonized guideline outlines the expectations. ICH Q5A is currently being revised to address recent scientific advancements including novel therapeutic modalities, new manufacturing paradigms, updates in viral clearance applications, and alternate detection technologies. We’ll discuss the expected changes and potential impact on viral safety strategies with case studies and examples.
In this webinar, you will learn about:
• The Importance of virus testing in biologics products
• Regulatory landscape, expectations for the Q5A revision
• What's new and changing
• Examples of alternate testing schedules, impact on viral clearance
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Alison Armstrong, PhD, Sr. Director, Technical and Scientific Solutions
Restriction of Hazardous Substances(RoHS) and REACHAmit Ghai
A historical perspective, current revisions and guidelines for RoHS and REACH compliance. Includes typical case studies, challenges and ways to overcome them
A presentation about NFPA diamonds and MSDSs. Highly modified off of one I found on the internet here -- http://www.nisd.net/communicationsarts/pages/chem/ppt/safety_pres.ppt
Equipment risk management - a quality systems approachPalash Das
Refer before performing risk assessment for pharmaceutical equipment. Can be considered before preparation of User Requirement Specification. in case of existing equipment can be prepare as a part of annual risk review.
Watch the presentation of this webinar here: https://bit.ly/3tDy8Ei
Recent PDA/BioPhorum publications outline risks for PUPSIT in sterilizing filtration. This webinar will summarize the key points and best practices for implementing PUPSIT.
PDA and BioPhorum have partnered to form a task force whose goal was to provide the industry and regulators with scientific data and analysis on the potential risks and benefits of implementing PUPSIT to improve sterility assurance. This webinar will describe the data generated by the task force studies and discuss considerations and best practices when implementing PUPSIT.
In this webinar, you will learn:
• How changing industry perspectives help overcome regulatory concerns and may influence regulatory perspective
• How improved process understanding affects risk assessment
• How improved final fill assembly design simplifies PUPSIT
EU GMP Annex 1 Draft: Implications on Sterilizing Grade Filter ValidationMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3kk0Qs1
In this webinar, you will learn:
- About the GMP Annex 1 draft regulatory overview
- How to incorporate the integrity testing & PUPSIT in the filtration systems validation
- How to design a bacterial retention test in terms of organism selection and single vs multiple use validation
Detailed description:
In this webinar we will discuss the implications of the EU GMP Annex 1 draft on the filtration of medicinal products and how this impacts the validation studies.
Bacterial Retention Testing is a critical part of the manufacturing validation process and is required by all regulatory bodies worldwide. Using case studies, our experts will explain how the Annex 1 draft is incorporated into the filtration systems validation exercise, specifically for integrity testing & PUPSIT (Pre-Use Post Sterilization Integrity Testing), the selection and justification of the appropriate test organism, and validation implications of single versus multiple use.
The two most commonly used within microbiology are
HACCP (which originated in the food industry) and FMEA
(developed for engineering). This article explores these two
approaches, first with a description of HACCP, followed by a
description and case study of FMEA in sterility testing.
Labelling & packaging of hazardous chemicalsAnaPavi2
Here's my presentation on labelling and packaging of hazardous chemicals. In it you'll find the most important information and recommendations regarding the labelling and packaging of hazardous chemicals.
ISO 9001, 14001, 45001 (IMS) basics training materialRanganathanR9
This training material contains Basics of integrated management system on ISO 9001:2015, ISO 14001:2015 & ISO 45001:2018.
This training material will benefit the beginners who wants to learn about integrated management system & it benefits.
Also it will be useful to understand the benefit of integrate all 3 system in one.
Eu actions to regulate Per- and Polyfluoroalkyl SubstancesOECD Environment
On Tuesday 25 February 2020, Eeva Leinala of the OECD Environment Directorate and Valentina Bertato of the DG Environment, European Commission presented the European Union's actions to regulate PFASs. It covered recent actions for restricting PFASs compounds and a strategy moving forward. This webinar is part of a series aiming to share information on issues related to PFASs and support a global transition towards safer alternatives.
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-Use Sys...Merck Life Sciences
Biopharmaceutical manufacturing capacities have expanded dramatically which has resulted in an increased demand for single-use systems (SUS) as they have their own advantages. Although SUS are well established in the biopharmaceutical industry there is limited guidance on regulatory expectations. Please attend the webinar to learn more!
“Pharmaceutical Processing is the process of drug manufacturing and can be broken down into a range of unit operations such as blending, granulation, milling, coating, tablet pressing, filling and others.
Waste conversion of the future, operating facility in FranceSandy Gutner
This innovative technology accepts mixed municipal solid waste, recovers recyclable materials, and refuse derived fuel (RDF), and produces a marketable soil amendment. The presentation provides photos of newly operational facility.
A presentation about NFPA diamonds and MSDSs. Highly modified off of one I found on the internet here -- http://www.nisd.net/communicationsarts/pages/chem/ppt/safety_pres.ppt
Equipment risk management - a quality systems approachPalash Das
Refer before performing risk assessment for pharmaceutical equipment. Can be considered before preparation of User Requirement Specification. in case of existing equipment can be prepare as a part of annual risk review.
Watch the presentation of this webinar here: https://bit.ly/3tDy8Ei
Recent PDA/BioPhorum publications outline risks for PUPSIT in sterilizing filtration. This webinar will summarize the key points and best practices for implementing PUPSIT.
PDA and BioPhorum have partnered to form a task force whose goal was to provide the industry and regulators with scientific data and analysis on the potential risks and benefits of implementing PUPSIT to improve sterility assurance. This webinar will describe the data generated by the task force studies and discuss considerations and best practices when implementing PUPSIT.
In this webinar, you will learn:
• How changing industry perspectives help overcome regulatory concerns and may influence regulatory perspective
• How improved process understanding affects risk assessment
• How improved final fill assembly design simplifies PUPSIT
EU GMP Annex 1 Draft: Implications on Sterilizing Grade Filter ValidationMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3kk0Qs1
In this webinar, you will learn:
- About the GMP Annex 1 draft regulatory overview
- How to incorporate the integrity testing & PUPSIT in the filtration systems validation
- How to design a bacterial retention test in terms of organism selection and single vs multiple use validation
Detailed description:
In this webinar we will discuss the implications of the EU GMP Annex 1 draft on the filtration of medicinal products and how this impacts the validation studies.
Bacterial Retention Testing is a critical part of the manufacturing validation process and is required by all regulatory bodies worldwide. Using case studies, our experts will explain how the Annex 1 draft is incorporated into the filtration systems validation exercise, specifically for integrity testing & PUPSIT (Pre-Use Post Sterilization Integrity Testing), the selection and justification of the appropriate test organism, and validation implications of single versus multiple use.
The two most commonly used within microbiology are
HACCP (which originated in the food industry) and FMEA
(developed for engineering). This article explores these two
approaches, first with a description of HACCP, followed by a
description and case study of FMEA in sterility testing.
Labelling & packaging of hazardous chemicalsAnaPavi2
Here's my presentation on labelling and packaging of hazardous chemicals. In it you'll find the most important information and recommendations regarding the labelling and packaging of hazardous chemicals.
ISO 9001, 14001, 45001 (IMS) basics training materialRanganathanR9
This training material contains Basics of integrated management system on ISO 9001:2015, ISO 14001:2015 & ISO 45001:2018.
This training material will benefit the beginners who wants to learn about integrated management system & it benefits.
Also it will be useful to understand the benefit of integrate all 3 system in one.
Eu actions to regulate Per- and Polyfluoroalkyl SubstancesOECD Environment
On Tuesday 25 February 2020, Eeva Leinala of the OECD Environment Directorate and Valentina Bertato of the DG Environment, European Commission presented the European Union's actions to regulate PFASs. It covered recent actions for restricting PFASs compounds and a strategy moving forward. This webinar is part of a series aiming to share information on issues related to PFASs and support a global transition towards safer alternatives.
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-Use Sys...Merck Life Sciences
Biopharmaceutical manufacturing capacities have expanded dramatically which has resulted in an increased demand for single-use systems (SUS) as they have their own advantages. Although SUS are well established in the biopharmaceutical industry there is limited guidance on regulatory expectations. Please attend the webinar to learn more!
“Pharmaceutical Processing is the process of drug manufacturing and can be broken down into a range of unit operations such as blending, granulation, milling, coating, tablet pressing, filling and others.
Waste conversion of the future, operating facility in FranceSandy Gutner
This innovative technology accepts mixed municipal solid waste, recovers recyclable materials, and refuse derived fuel (RDF), and produces a marketable soil amendment. The presentation provides photos of newly operational facility.
Michael G. Szarka, Director, Commercial Development, GreenCentre Canada, spoke at the CEC Chemicals Management Forum in San Antonio, Texas, on May 16, 2012. More information at: http://www.cec.org/chemicals2012
Monica becker turi cont ed - session c green materials for turi websitezevoush
2012 presentation on Innovative Business / University Partnership: The Safer Plasticizer Assessment Project - Project for the Green Chemistry & Commerce Council (GC3)
Brokerage session: expertise
Title: LEITAIT: offering expertise in treatment, reutilization, valorization and sanitation
Presented by Joan Roig, LEITAT
Open Innovation Challenge Winner: Vivek NairPaulaEsp1
Vivek Nair is an Indian engineer that participated in and won the open innovation challenge organized by ennomotive and Codelco Tech. The goal of this challenge was to identify applications for a new copper/graphene nanocomposite.
Solutions that Integrate – BioCompatic: A Robust USP Class VI Silicone Altern...NorthwireCable
This White Paper from cable engineering company Northwire, Inc. and precision cable connector leader LEMO, discusses BioCompatic - their new, durable USP Class VI alternative to the silicone jacketed cable. Ideal for use in medical applications and beyond, BioCompatic highlights R&D advancements and next-generation technology offered by LEMO and Northwire in their pursuit of 100% reliability, extended life cycle, and safety in cables and connectors.
The global demand for achieving the net zero emission target by 2050 has pushed governments all over to adapt and adopt advanced carbon removal technologies to go carbon negative.
It is, indeed, an important topic of discussion, because a carbon free environment is the need of the hour to save our planet. And, therefore, BIS Research is glad to announce its upcoming webinar on this particular subject.
Agenda:
The main agenda of this webinar is to understand and explore the following:
• Primary sources of carbon emissions and associated environmental issues
• Carbon dioxide removal – key technology and adoption scenario
• Carbon dioxide removal (CDR): trends and key market developments
• Carbon dioxide removal as a credible solution
• Conclusion and future outlook
In 2019, Yole Développement has released this Discrete Power Device Packaging: Material Market and Technology Trends report to complement our year-long Power Module Packaging report edition.
This report’s main objectives are as follows:
Provide an overview of the main applications for discrete power devices, along with their drivers and future trends
Discuss the impact of application trends on package design and packaging materials
Furnish an analysis of each packaging component, along with forecasts and future technology development
Give an overview of the discrete power device supply chain
(devices and packaging components)
Analyze the shifting of business models, synergies with other industries, and opportunities for newcomers in discrete power devices
Better by Design workshop, Wilton Centre, 26th Nov 2013BenPeace
Sustainable Business and Chemical Engineering.
Run by C-Tech Innovation, in collaboration with Chemistry Innovation and Environmental Sustainability Knowledge Transfer Networks, and the IChemE.
Discrete Power Device Packaging: Materials Market and Technology Trends 2019 ...Yole Developpement
Despite the transition to SiP, SoC, and power modules, discrete device packaging still represents a big opportunity especially for materials suppliers.
More information on https://www.i-micronews.com/products/discrete-power-device-packaging-materials-market-and-technology-trends-2019/
The Viscosity Reduction Platform: Viscosity-reducing excipients for improveme...Merck Life Sciences
Protein viscosity is a major challenge in preparing highly concentrated protein formulations suitable for subcutaneous injection. Recently, the Viscosity Reduction Platform (VRP) was introduced and its technical key features and benefits for formulations were discussed. However, highly viscous solutions do not only pose a challenge when administering a drug to a patient, they can also impose technical limitations in the manufacturing process.
This white paper evaluates the effect of the excipients in the Viscosity Reduction Platform on ultrafiltration processes used to produce a highly concentrated formulation of a monoclonal antibody (mAb). Two filtration methods are demonstrated in this work.
Find more information about the Viscosity Reduction Platform on our website: https://www.sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Use of Excipients in Downstream Processing to Improve Protein PurificationMerck Life Sciences
Excipients are used to improve the stability of protein-based therapeutics by protecting the protein against a range of stress conditions such as temperature changes, pH changes, or agitation. Similar stresses are applied to proteins during downstream purification. Shifts in pH during Protein A chromatography, subsequent incubations at low pH for virus inactivation, and changes in conductivity in ion exchange chromatography can lead to aggregation, fragmentation, or other chemical modifications of the therapeutic protein. Given the potential impact on the protein’s structural integrity, there is a need for approaches to reduce the risk presented by the conditions during downstream processing. For example, integration of a solution to prevent aggregation of proteins would be a more efficient strategy than implementing steps to remove multimeric forms.
This white paper highlights the results from a recent paper by Stange et. al., in which protein stabilizing excipients such as polyols, sugars, and polyethylene glycol (PEG4000) were used as buffer system additives. Effect of the excipients on elution patterns, stabilization of the monomer antibody, host-cell protein removal, virus inactivation rates and binding capacity of cation exchange chromatography were explored.
Exploring the protein stabilizing capability of surfactants against agitation...Merck Life Sciences
Agitation of therapeutic protein solutions during manufacturing, shipping and handling is one of the major initiators for protein aggregation and particle formation during the life history of a protein drug. Adsorption of protein molecules to liquid-air interfaces leads to the formation of highly concentrated protein surface films. The rupture of these protein films due to various mechanical processes can then result in the appearance of protein aggregates and particles in the bulk solution phase.
One technique to stabilize proteins against stress induced by liquid-air interfaces is the use of non-ionic surfactants. About 91% of antibody formulations commercially available in 2021 contained a surfactant. Polysorbate 20 and 80, composed of a hydrophilic polyoxyethylene sorbitan and hydrophobic fatty acid esters, made up the largest part being employed in 87% of said formulations.
Despite their frequent use in parenteral drug products, concerns have been raised for decades about the application of polysorbates as surfactants in biopharmaceutical formulations. Autoxidation of polysorbate, caused by residual peroxides in polysorbates, can damage the proteins and can further drive the oxidative degradation of polysorbate. Chemical and enzymatic hydrolysis of polysorbate may lead to the formation of free fatty acid particles, which may become visible; and both mechanisms eventually lead to the reduction in polysorbate concentration. Therefore, the purpose of the current study was to compare various molecules for their capabilities to reduced agitation-induced protein aggregation and particle formation; and furthermore, investigate their underlying protein stabilizing mechanisms.
The Viscosity Reduction Platform: Viscosity Reducing Excipients for Protein F...Merck Life Sciences
Protein viscosity is one of the major obstacles in preparing highly concentrated protein formulations suitable for subcutaneous injection.
This whitepaper examines how combining an amino acid with a second viscosity-reducing excipient circumvents adverse effects on protein stability and improves viscosity-reducing capacity.
To find more information about the Viscosity Reduction Platform, please visit our website: https://sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Characterization of monoclonal antibodies and Antibody drug conjugates by Sur...Merck Life Sciences
Watch the presentation of this webinar: https://bit.ly/3Pjpjvr
Highlights of this webinar:
- Surface plasmon resonance as a powerful tool for biologic characterization including mAbs and ADCs.
- SPR allows rapid binding analysis in real time without using labels for SARS-CoV-2 receptor binding domain mutations.
- Kinetic data is indicative of possible neutralizing activity allowed assessment of neutralizing ability of therapeutic monoclonal antibodies.
- The application can provide preliminarily efficacy information and facilitated mAbs/ACDs candidate selection process
Detailed description:
Characterization of therapeutic monoclonal antibodies (mAbs) or Antibody drug conjugates (ADCs) is challenging due to their ability to bind to a variety of proteins via their Fc and Fab domains, giving rise to diverse biological functions associated with each domain. The Fc domain of mAbs interacts with Fc receptors with varying affinities, which can influence biological processes such as Complement-dependent cytotoxicity (CDC) and Antibody-dependent cellular cytotoxicity (ADCC), transcytosis, phagocytosis, and/or serum half-life.
An important characteristic of an antibody is its Fc effector function. Antibodies can be engineered to obtain desired binding of the Fc region to Fc receptors expressed on effector cells. Hence, it is crucial to evaluate the binding interaction of mAbs/ADC with Fc receptors in the early phase of drug development to understand the potential biological activity of the product in vivo.
Surface Plasmon Resonance (SPR) is a powerful technique to establish binding kinetics in real-time, label free, and high sensitivity with low sample consumption. Along with target antigen binding, it is crucial to evaluate the binding interaction of antibodies and ADCs with Fc receptors. Our SPR case studies investigated the impact on binding kinetics of ADCs with different linkers and the binding interactions of SARS-CoV-2 spike protein variants and evaluated the neutralizing ability of therapeutic mAbs. SPR characterisation can be facilitated in all stages of the product life cycle to ensure the quality and safety of mAbs and ADCs.
The Role of BioPhorum Extractables Data in the Effective Adoption of Single-U...Merck Life Sciences
Regulatory expectation does require patient safety evaluations with supporting data for manufacturing components that directly come into contact with drug manufacturing process streams. Readily available extractables data can help manufacturers using singleuse technology to accelerate product qualifications, risk assessments and process optimization
This white paper guides you on how to save time and resources with supplier-provided single-use system extractables data and gives you an overview about the overall strategy for Extractables & Leachables. At the end you will find a case study.
Find more information about filters and single-use components on our website: https://www.sigmaaldrich.com/DE/en/services/product-services/emprove-program/emprove-filter-and-single-use-component-portfolio
Watch the recording of this presentation here: https://bit.ly/3zTOpe4
Detailed description:
SARS-CoV-2 showed us that technology supports us during our inspection activity even if on-site visits are not possible. Travel restrictions of various kinds will remain a risk in the future. The use of new technologies has shown that inspections and audits can be carried out despite these restrictions. We will focus on what possibilities the new technologies offer and take a look at the future of inspections and audits.
In this webinar, you will learn:
• Regulatory overview of remote audits
• The technologies needed to support the audit process
• What types of inspections are possible with the use of these technologies
• How audits may look in the future
Presented by:
Daniel Buescher, Product Manager - Digital Solutions
Moving your Gene Therapy from R&D to IND: How to navigate the Regulatory Land...Merck Life Sciences
Watch the recording of this presentation here: https://bit.ly/3SqOsoP
Novel therapies, including cell and gene therapies, continue to be central to innovation in healthcare and represent the fastest growing area of therapeutic medicine. As a consequence, the number of gene therapies undergoing clinical trials has increased significantly in the last five years.
Manufacturing processes for these novel therapeutics are very complex with a high risk of contamination. Regulatory agencies world-wide have responded by issuing guidance to outline their expectations for development and manufacture of cell and gene therapies. Currently, regulatory guidance is not harmonized globally and can often lead to confusion within industry and increased risk of non-compliance.
In this webinar, we'll answer:
• Which regulatory guidelines do you need to comply for your INDs?
• When do you start implementing GMPs and validated assays?
• How do you get your QC testing strategy ‘right the first time’?
• How do you ensure testing is not your rate limiting step for the IND submission?
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Dr. Alison Armstrong, Sr. Director, Technical and Scientific Solutions
Identity testing by NGS as a means of risk mitigation for viral gene therapiesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3RijkHC
Detailed description:
Imagine you’ve just completed a manufacturing run for your viral vector. Identity testing is performed to confirm the vector sequence. But when the results come back the data reveals unexpected sequence variants! With an appropriate risk mitigation testing strategy, this situation can be prevented.
The situation described above is not hypothetical, and happens more that you think, costing valuable time and resources.
Investigatory testing has shown that sequence variants present in starting materials (e.g. plasmids) are likely to make their way to the final product. Adequate identification of low-level variants with an appropriately sensitive method is critical in ensuring the quality of the final product. A risk-based testing strategy, in the context of identity, for viral vector manufacturing will be presented, focusing on key testing points. NGS assays for identity and variant detection will be highlighted due to their extremely sensitive nature compared to traditional approaches.
In this webinar, we'll explore:
• Regulatory requirements for identity testing
• NGS applications for identity testing as compared to traditional methods
• A case study on the impact of not establishing a proper risk-based testing strategy
Presented by: Bradley Hasson, Director of Lab Operations for NGS Services
Latest advancements of melt based 3D printing technologies for oral drug deli...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3A2WcH4
The application of polymer excipients in 3D printing manufacturing is usually limited due to the concerns of filament strength, high processing temperature and large scale manufacturing.
Latest technology developments are targeting a direct melt deposition to simplify the process and enable a constant and efficient process. Two different processing approaches will be presented:
The advanced melt drop deposition, where individual three dimensional geometries can be created by depostition of polymer droplets and the MED® 3D printing technology which allows by precise layer-by-layer deposition to produce objects with well-designed geometric structures.
In this webinar, you will learn:
• Latest advancements of melt based 3D printing approaches
• Application examples for the individual technologies
• Deep dive in the MED® 3D printing technology to design dedicated drug release profiles
Presented by:
Dr. Thomas Kipping, Head of Drug Carriers
Dr. Xianghao Zuo, Deputy Director of R&D, Triastek
CAR-T Manufacturing Innovations that Work - Automating Low Volume Processes a...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3NDNIKe
Automated, fit-for-purpose tools are essential in CAR-T processing to support sustainable manufacturing of clinical and market-approved cell therapy products. This webinar will discuss how the ekko™ Acoustic Cell Processing System uses acoustic technology as a touchless approach to manipulate cells, enabling a modular tool across the CAR-T manufacturing workflow. Typical performance of templated ekko™ System processes for DMSO washout of leukapheresis material, low volume and high cell concentrate for electroporation preparation, and harvest of expanded T cells will be reviewed.
This webinar will also give an early glimpse at the ekko™ Select System for unmatched T cell selection.
In this webinar, you will:
• Uncover how the ekko™ System supports the broad industrialization of cell therapy, with particular focus on how to achieve low volume, high concentrate cell product for critical transduction and transfection steps
• Discover how ekko™ System for wash and concentrate processes throughout the cell therapy workflow achieve high cell recovery, viability, and effective residual removal
• Preview to ekko™ Select, our cell therapy selection platform, to achieve unmatched ease-of-use with direct processing from leukopaks reducing the need for preparation steps
Presented by:
Benjamin Ross-Johnsrud, Acoustic Technology Expert
Robert Scott, Mechanical Engineer III
Improve Operational Efficiency by Over 30% with Product, Process, & Systems A...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3adaxWh
When implementing new automation systems, organizations must consider things like deployment time, user adoption, and costs.
They must also consider the cost of doing nothing – that is, what competitive advantage is lost in standing still? What time and quality is lost in repetitive, manual tasks rather than an automated, digital workflow? What operational efficiencies are lost?
In this webinar we examine how a product, process, and system agnostic automation platform can be deployed faster than traditional system specific software while bringing greater operational efficiencies (in many cases over 30% improvement).
To remain competitive in the market, biopharma manufacturers must adopt automation and digital technologies, but most plants still have island of automation consisting of independently functioning, standalone unit operations. This results in operational inefficiency, regulatory concerns, and a poor understanding of the process and product life cycle.
Taking the first, right step must include considering risks, costs, timelines, and technology alternatives. Traditional automation approaches tied to specific systems, processes, and products are, by their nature, limited; while an agnostic platform will address current biomanufacturing business challenges and ensure future readiness. With the right platform, a phased automation implementation can yield operational efficiency gains of up to 30% and improved product quality and regulatory compliance.
In this webinar, let's explore:
• Challenges of automation and digital technology adoption
• What a product, process, and system agnostic platform entails
• Applications and benefits of a process orchestration platform
• Ensuring future readiness with process orchestration
Presented by:
Braj Nandan Thakur, Global Product Manager - Automation
Insights from a Global Collaboration Accelerating Vaccine Development with an...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3Nbb5ug
Get insights and best practices from a multinational team establishing a platform for vaccine production. See how a long-term collaboration on a bench-scale process used to produce a Virus Like Particle (VLP) vaccine for SARS-CoV-2 was successfully converted to a robust GMP-compatible, scalable process.
The COVID-19 pandemic further emphasized the need for collaboration in the development of urgently needed vaccines and therapeutics. In this webinar, we take you behind the scenes of our collaboration with Technovax and Innovative Biotech in which a scalable VLP vaccine platform was optimized for use in a production facility in Nigeria in response to the need for local production of SARS-CoV-2 vaccines. The flexibility and robustness of the platform will enable its rapid deployment to support the West African pandemic readiness program. Initial development of the VLP process began in late 2019 and by March 2020, was already adapted for production of a SARS-CoV-2 vaccine.
In this webinar, you will learn:
• About building a priceless collaborative network with integrated solutions
• Virus-Like Particle Vaccines
• Process Development Overview and Challenges
• Pre-clinical Results and Next Steps
Presented by:
Jose M. Galarza, PhD,
President and Founder of TechnoVax
Naomi Baer,
Business development consultant, Emerging Biotech, BioProcess division
Youssef Gaabouri, Eng. ,
Associate Director, Head of Sales Middle East & Africa, BioProcess division
Rapid replication competent adenovirus (rRCA) detection: Accelerate your lot ...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3MJ4u9V
Testing for presence of replication competent adenovirus (RCA) is a key component to ensure patient safety and a requirement for all biologicals manufactured using adenoviral vectors. For many adenoviral-based products, the RCA assay is a rate-limiting assay for lot release.
Join this webinar to learn about a rapid RCA detection assay currently in development, which combines a 7-day culture assay with a highly sensitive molecular endpoint specific for RCA. The method can detect presence of as little as 1 RCA in adenoviral vector material at an approximate concentration of 5x107 - 2x108 vector particles (VP)/mL, making it a suitable method to meet regulatory requirements while accelerating your lot release timelines.
In this webinar, you will learn about:
• Regulatory framework for adenoviral vector products
• Considerations for lot release testing of adenoviral-based therapies
• Advantages of a rapid method for RCA testing on production lot material
Presented by:
Axel Fun, Ph.D.,
Principal Scientist
Alberto Santana, MBA,
Product Manager, Biologics Biosafety Testing
The High Intensity Sweeteners Neotame and Sucralose: 2 Ways to ace the Patien...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3vQyN7K
Bitter medicines are an important issue, especially for pediatric applications. As several APIs have bitter tasting components, high intensity sweeteners for taste optimization are of great interest. Join our webinar to discover our new sweetener toolbox enabling safe and stable formulations.
Mask bitter aftertaste for a sweeter pill to swallow! Patients’ compliance and the therapeutic benefit are supported by a pleasant taste of pharmaceutical formulations. With the high intensity sweeteners Neotame and Sucralose, you have efficient tools at hand which are superior to other sweeteners in many aspects:
• excellent sugar-like taste profile
• outstanding sweetness factors
• use effectiveness
• enhanced stability
We will present our new toolbox of two high performance sweeteners and focus on aspects of stability, safety, the application in various dosage forms, and market perception.
In this webinar, you will learn:
• How to optimize the patients' taste experience of your pharmaceuticals
• How sweeteners can be differentiated by their sensory profiles and features
• How our new product offering Neotame can be effectively used in your targeted formulations
Presented by:
Almut von der Brelie,
Senior Manager Strategic Marketing
Excipients for Solid Applications
The Developability Classification System (DCS): Enabling an Optimized Approac...Merck Life Sciences
This whitepaper by Dr. Daniel Joseph Price outlines how poorly soluble drug formulations can be designed using the developability classification system (DCS).
The DCS identifies the root cause of low solubility and enables lean, cost-effective and effective formulations to be developed.
#solubility #pharmaceuticalmanufacturing #oralsoliddosage #drugdevelopment
In this webinar, you will learn about:
The advantages of using advanced intermediates to develop ADC therapies
How to increase ADC solubility and efficiency
Fast, small-scale ADC library generation
Seamless supply chain with reduced complexity and regulatory support
The ADCore product line offers versatile intermediates that simplify the synthesis of common ADC payloads (dolastatins, maytansinoids, and PBDs) by greatly reducing the number of synthetic steps. This translates to savings in development and manufacturing costs and shorter timelines to the clinic. To address the poor solubility of many ADC payloads, ChetoSensar™ was developed to significantly increase the hydrophilicity of the drug linker, which has been shown to also substantially increase the efficacy of ADCs and broaden the therapeutic window.
Lastly, the ADC Express™ service leverages conjugation chemistry and analytical expertise to help design and quickly synthesize sets of potential ADC therapies suitable for screening to simplify candidate selection and get ADC therapies to market faster.
Regulatory Considerations for Excipients used in Lipid NanoparticlesMerck Life Sciences
Lipid excipients and delivery systems such as lipid nanoparticles (LNPs) are essential for a wide variety of therapeutics including mRNA vaccines and therapeutics and gene therapy.
The purity and safety of novel, synthetic lipid excipients must be demonstrated due to their central role in the function of the drug product, distinct physicochemical properties, and the potential for interaction with other ingredients or the physicochemical environment. These excipients must comply with challenging and complex regulatory requirements, similar to those expected of the active pharmaceutical ingredient itself.
This whitepaper provides an overview of the regulatory classification of lipid nanoparticles, liposomes and novel excipients. Specific requirements outlined in guidance documents are shared along with strategies to stay ahead of emerging regulatory challenges.
To find more information about synthetic lipids for pharmaceutical applications and gene therapy, please visit our website:
https://www.sigmaaldrich.com/DE/en/products/pharma-and-biopharma-manufacturing/formulation/synthetic-lipids
https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/formulation/synthetic-lipids
Introducing our novel Sf9 rhabdovirus-negative (Sf-RVN®) Platform.pdfMerck Life Sciences
The Baculovirus Expression Vector System (BEVS) is a powerful eucaryotic vector system and Spodoptera frugiperda (Sf) cell lines are widely used as hosts for BEVS. However, the majority of Sf9 and Sf21 cell lines contain a Sf-rhabdovirus which is considered a process contaminant and must be eliminated during the process. To improve the safety profile of the BEVS production method, we offer a Sf9 rhabdovirus-negative (Sf-RVN®) cell line with companion chemically defined medium. Combined, they form the Sf-RVN® Platform which provides a performant rhabdovirus-free BEVS alternative to produce recombinant protein, VLP and AAV and enhances risk mitigation.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
Medical Technology Tackles New Health Care Demand - Research Report - March 2...pchutichetpong
M Capital Group (“MCG”) predicts that with, against, despite, and even without the global pandemic, the medical technology (MedTech) industry shows signs of continuous healthy growth, driven by smaller, faster, and cheaper devices, growing demand for home-based applications, technological innovation, strategic acquisitions, investments, and SPAC listings. MCG predicts that this should reflects itself in annual growth of over 6%, well beyond 2028.
According to Chris Mouchabhani, Managing Partner at M Capital Group, “Despite all economic scenarios that one may consider, beyond overall economic shocks, medical technology should remain one of the most promising and robust sectors over the short to medium term and well beyond 2028.”
There is a movement towards home-based care for the elderly, next generation scanning and MRI devices, wearable technology, artificial intelligence incorporation, and online connectivity. Experts also see a focus on predictive, preventive, personalized, participatory, and precision medicine, with rising levels of integration of home care and technological innovation.
The average cost of treatment has been rising across the board, creating additional financial burdens to governments, healthcare providers and insurance companies. According to MCG, cost-per-inpatient-stay in the United States alone rose on average annually by over 13% between 2014 to 2021, leading MedTech to focus research efforts on optimized medical equipment at lower price points, whilst emphasizing portability and ease of use. Namely, 46% of the 1,008 medical technology companies in the 2021 MedTech Innovator (“MTI”) database are focusing on prevention, wellness, detection, or diagnosis, signaling a clear push for preventive care to also tackle costs.
In addition, there has also been a lasting impact on consumer and medical demand for home care, supported by the pandemic. Lockdowns, closure of care facilities, and healthcare systems subjected to capacity pressure, accelerated demand away from traditional inpatient care. Now, outpatient care solutions are driving industry production, with nearly 70% of recent diagnostics start-up companies producing products in areas such as ambulatory clinics, at-home care, and self-administered diagnostics.
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
QA Paediatric dentistry department, Hospital Melaka 2020Azreen Aj
QA study - To improve the 6th monthly recall rate post-comprehensive dental treatment under general anaesthesia in paediatric dentistry department, Hospital Melaka
Welcome to Secret Tantric, London’s finest VIP Massage agency. Since we first opened our doors, we have provided the ultimate erotic massage experience to innumerable clients, each one searching for the very best sensual massage in London. We come by this reputation honestly with a dynamic team of the city’s most beautiful masseuses.
Risk-Based Qualification of X-Ray Sterilization for Single-Use Systems
1. The life science business of Merck KGaA,
Darmstadt, Germany operates as
MilliporeSigma in the U.S. and Canada.
Risk-Based Qualification of
X-ray Sterilization for Single
Use & Integrated Systems
Monica Cardona and Paul Kilian
May 05, 2022
2. The life science business
of Merck KGaA, Darmstadt,
Germany operates as
MilliporeSigma in the U.S.
and Canada
5. Rationale & Benefits for X-Ray Implementation
X-Ray Sterilization Overview | May 2022
5
Rationale Details
Capacity • Capacity concerns in a growing market for Irradiation
services
• Some providers starting they will not build Gamma
capacity
• COVID19 – increases short to mid term capacity concerns
Cobalt Supply • Supply chain under scrutiny
Benefit Details
Business Continuity • Access to use alternative sterilization modalities
7. Fundamentals of Irradiation Sterilization Modalities
Ionization Radiation Sterilization Modalities
X-Ray Sterilization Overview | May 2022
7
Selecting Optimal Irradiation Sterilization Technology
Definition: Ionization Sterilization
Radiation, traveling as a particle or electromagnetic wave, that carries sufficient energy to
detach electrons from atoms or molecules, thereby ionizing an atom or a molecule.
Ionization
Radiation
Gamma
Rays
X-Rays
E-beam
Photon
electromagnetic
energy
Electron
particle
Accelerated electrons
typically produced by an
electron accelerator
Electricity is the source
of energy
Photons emitted by the decay
of a radioactive material
typically 60CO
Electricity is the source
of energy
Accelerated electrons
impinge on high density
surface and transform into
photons (Bremsstrahlung)
Source: Accelerator-driven Medical Sterilization to Replace Co-60 Sources; A study submitted to NNSA performed by
Fermi National Accelerator Laboratory (2017)
Radioactive isotopes are
the source of energy
8. Biochemical interaction of matter with ionization radiation
leads to inactivation of cells and microorganisms
Fundamentals of Irradiation Sterilization Modalities
Interactions with Matter
X-Ray Sterilization Overview | May 2022
8
Source:
https://sites.duke.edu/missiontomars/the-
mission/cancer/what-is-cancer/
Biochemical Interaction → Influence on Cells and Microorganisms
• Radiolysis of water / formation of Peroxide
• Modification of amino acids / enzymes
• Damage of DNA
Physio-chemical Interactions → Materials
• Chemical radicals
• Gaseous radiolysis products
• Oxidation of products
Modification of material properties, typically undesired site effects in our industry.
Effects of irradiation on the product must be evaluated
9. Selecting Optimal Irradiation Sterilization Technology
X-Ray Sterilization Overview | May 2022
Resistance to
irradiation?
Penetration
needs
E-beam X-ray
Yes
Homogeneous
Sensitive
products?
X-ray or Gamma
Start
High
Low
No
High
Low
Are products
homogeneous in their
packaging?
What is the product
resistance to
radiation (dose max)?
Is high penetration
required to penetrate
product or packaging?
1
2
3
Are products fragile or
sensitive to irradiation
(coloration, oxidation)?
4
Yes No
9
10. Ionizing Radiation Sterilization Technology Comparison
E-Beam X-Ray Gamma
Processing Format Boxes Pallets Pallets/Totes
Labor Requirements High Low Low/High
Source Energy Electricity Electricity Cobalt 60
Electron Beam Photons in the same direction Isotropic Photons
Energy Efficiency Excellent Good Low
Stop Irradiation Source Yes Yes No
Product Penetration Low Very High High
Dose Uniformity Ratio Average Excellent Good/Excellent
Tolerance for Non-
homogeneity
Low Very Good Good
Dose Rate Very High Medium Low
Treatment Time Seconds Hours More Hours
Processing Time <8 hours <24 hours <24 hours
Cost Efficiency Excellent Good Good
Temperature Max 50 C 35-40 C 45 -50 C
Oxidation Sensitivity Small Comparable to E-beam > E-beam & X-Ray
Regulation ISO 11137 ISO 11137 ISO 11137
IBA. Review of Radiation Sterilization Technologies for Medical Devices.
Steris Fundamentals of X-Ray Sterilization Webinar September 9, 2020
X-Ray Sterilization Overview | May 2022
10
11. Technology Transfer Photons to Photons
Using a Risk Based Approach
X-Ray vs Gamma Risk
Sterilization /Min Dose Equivalent No
Dose Rate Higher Low
Temperature Lower Low
Exposure Time Less Low
Penetration
(Dose Uniformity Ratio, DUR)
Better No
Product Handing Equivalent No
Source: Steris Teck Talk Fundamentals of X-Ray Irradiation Processing Webinar September 2020
Watch out – Activation of metal components
X-Ray Sterilization Overview | May 2022
11
12. • 70% of global supply is from an unstable region
• Supply chain under scrutiny
• Conflict mineral concerns
• Apple, Google, Dell, Microsoft and Tesla have been named as
defendants in a lawsuit filed in Washington DC by human rights
firm International Rights Advocates on behalf of 14 parents and
children from the Democratic Republic of the Congo (DRC).
• Capacity concerns
• The highest consumption of cobalt is for the battery & cell
phone industries unless these industries make significant strides
with alternate materials and/or recycling; demand will eventually
out pace supply
• McKinsey Global Institute estimates sufficient supply until 2025,
even though the pace at which additional cobalt mine capacity
reaches the market will be crucial to keep up with rising demand
Cobalt Supply Concerns
X-Ray Sterilization Overview | May 2022
12
https://blog.sourceintelligence.com/blog/cobalt-new-conflict-mineral
https://www.theguardian.com/global-development/2019/dec/16/apple-and-google-named-in-us-lawsuit-over-congolese-child-cobalt-mining-deaths
https://www.globalfleet.com/fr/safety-safety-environment-technology-and-innovation/global/features/fact-or-fiction-shortage-lithium
13. Cobalt 60
production 3-year
Lead Time
One major global
supplier /
distributor of
Cobalt 60
Most contract
sterilizing service
providers
purchase Cobalt
60 from one
source
Cobalt 60 Supply Chain – Highly Consolidated
Nuclear Reactor
Cobalt 60
X-Ray Sterilization Overview | May 2022
13
15. Risk Assessment & Test Protocol for Representative
Components
15
Full Team Review
Common Risks & Test Consensus
• Sterilization process compatibility
• Material Color & Visual Inspection
• Shelf Life
• Particulates
• Biological Reactivity
• Extractables
• Resin & Material Compliances
Quality Test
Matrices
BPSA Technical Assessment Workstream October 2020
BPSA Single Use Manufacturing Component Quality Test Matrices 2015
15
X-Ray Sterilization Overview | May 2022
16. Connectors Film Filters
Pressure Burst Test
X
X
Fastener Test X
Elongation X
O2 and CO2 Permeability X
Water Vapor Transmission
Rate
X
Tensile Strength (ASTM
D882)
X
Material Color
Yellowness Index (ASTM
D1925)
X X X
Glass Transition
Temperature by DSC
X X
X
Thermogravimetric
analysis (TGA)
X X X
Material by FTIR-ATR X X X
Physical Tests
Internal Components
X-Ray Sterilization Overview | May 2022
16 DSC- Differential scanning calorimetry
17. Functional Tests
Internal Components
X-Ray Sterilization Overview | May 2022
17
Connectors Film Filters
Water Flow
Pressure Drop
X
Accelerated Aging
(Shelf Life) X
In an assembly
X
In an assembly
X
Particulates
(USP 788) X X X
Integrity Test
X X
X
Bacterial Retention
X
Bacterial Challenge/
Soiling Test
X
18. Chemical Tests
Internal Components
X-Ray Sterilization Overview | May 2022
18
Connectors Film Filters
Extractables
Water
50% Ethanol
X X X
Physicochemical Test
USP <661>
X
X X
Conductivity Test
USP <645>
X
pH Shift Test
USP <791>
X
TOC Test
USP <643>
X
19. Other Tests
Internal Components
X-Ray Sterilization Overview | May 2022
19
Biological Connectors Film Filters
Endotoxins
USP <85> X X X
Biological Reactivity USP
<87>
X
X X
Sterilization Connectors Film Filters
Sterilization validation
ISO 11137-2 X X X
20. Supplier Validation Strategy
X-ray Sterilization
X-Ray Sterilization Overview | May 2022
20
v
Supplier A
•Supplier is active
in the BPSA X-ray
subgroup
•Clear
understanding
which components
are being tested
and when
•Test strategy is
deemed sufficient
Supplier B
•Supplier is part of
the BPSA
subgroup
•Clear
understanding
which components
are being tested
and when
•Test strategy is
deemed
insufficient
Supplier C
•Supplier is not
active in any
industry groups
investigating X-
ray
•Clear line of
communication is
in place the
supplier agreed to
do X-ray testing in
house
Supplier D
•Supplier is not
active in any
industry groups
investigating X-
ray
•Supplier will not
test their
materials post X-
ray irradiation
Supplier E
•Supplier is not
active in any
industry groups
investigating X-
ray
•Supplier is unclear
on timeline for X-
ray testing
No further actions
required
Risk analysis and
testing based on
materials of
construction
Additional tests are
being conducted
internally
No further actions
required
Supplier components
pushed out for Phase
III implementation
21. Minimal Requirement
Test plan for 3rd party components
External Components
X-Ray Sterilization Overview | May 2022
21
Chemical Tests Tubing Non-Fluid Contact Layer
Components
Fluid Contact Layer
Components
Extractables
Water
50% Ethanol
X X
Off-gassing studies X
Sterilization Tubing Non-Fluid Contact Layer
Components
Fluid Contact Layer
Components
Sterilization validation ISO
11137-2 X X X
Risk Assessment on material compatibility of X-ray. If applicable supplier data, internal data
and/or AAMI TIR17:2017 Annex A relative radiation compatibility data is used for evaluation
Extended requirements if applicable:
28. 1. A Female and a Male Lynx S2S® Connector were
connected. One end of the device was sealed with Teflon
tape (fluid contacting) and aluminum foil (vapor barrier),
and then secured with a piece of ½” tubing.
2. Model solvent was added to each of the connected device
to full capacity (12 mL). The other opening was then
sealed in a similar fashion described above.
3. Two model solvents were used for extraction: Milli-Q
Water and 50% Ethanol.
4. A solvent blank was prepared in a PFA jar for each model
solvent.
5. The samples were placed in an incubator on an orbital
shaker at 50 rpm and at 40°C for 24 hours.
Lynx S2S® Connector – Extraction Procedure
X-Ray Sterilization Overview | May 2022
28
29. All results in µg C/ Device
Model
Solvent
Gamma Irradiated X-Ray Irradiated
Lot 1 Lot 2 Average Lot 1 Lot 2 Average
Milli-Q Water 33.5 32.1 32.8 30.5 28.2 29.4
Reporting Limit = 0.6 µg C/ Device
Lynx S2S® Connector – Extraction TOC Results
X-Ray Sterilization Overview | May 2022
29
30. Lynx S2S® Connector – HPLC Chromatograms
214
nm
Absorbance
[AU]
-0.02
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
0.18
0.20
Time (minutes)
0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00
X-Ray Lot 2
X-Ray Lot 1
Gamma Lot 2
Gamma Lot 1
Water Blank
214
nm
Absorbance
[AU]
-0.02
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
0.18
0.20
Time (minutes)
0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00
X-Ray Lot 2
X-Ray Lot 1
Gamma Lot 2
Gamma Lot 1
50% EtOH Blank
Water Extracts
50% Ethanol Extracts
X-Ray Sterilization Overview | May 2022
30
34. Lynx S2S® Connector – Summary
1. No differences were observed in appearance, TGA, DSC, or FTIR for the X-ray irradiated Lynx S2S®
Connectors compared to the gamma irradiated Lynx connectors.
2. TOC results of X-ray irradiated Lynx S2S® Connectors were at comparable concentrations to the
gamma irradiated connectors.
3. Water from a Milli-Q® system was used as the extraction solvent. HPLC chromatograms water extracts
and 50% Ethanol extracts were comparable. No new compounds were generated by X-ray irradiation.
The concentration of compounds observed were comparable.
4. Water from a Milli-Q® system was used as the extraction solvent. GCMS-HS chromatograms water
extracts and 50% ethanol extracts were comparable. No new Volatile Organic Compounds (VOCs)
were generated by X-ray irradiation. All concentrations were comparable.
5. Water from a Milli-Q® system was used as the extraction solvent. GCMS-DI chromatograms water
extracts and 50% ethanol extracts were comparable. No new Semi-volatile Organic Compounds
(SVOCs) were generated by X-ray irradiation. All concentrations were comparable.
X-Ray Sterilization Overview | May 2022
34
36. PureflexTM Plus Film – Appearance Comparison
36
X-Ray Irradiated Gamma Irradiated
X-Ray Sterilization Overview | May 2022
37. PureflexTM Plus Film – TGA and DSC Comparison
37
TGA Overlays
DSC Melting Thermograms
EVA
melting
peak
PE layers
melting
peak
Tie-layers
melting
peak
EVOH
Meltingm peak
X-Ray Sterilization Overview | May 2022
38. PureflexTM Plus Film – FTIR Comparison
38 X-Ray Sterilization Overview | May 2022
39. 1. The test stands were modified to have a 0.33 cm
gap, providing a 6:1 surface area to volume
extraction ratio.
2. To each bag was added a predetermined amount
of model solvent from the opening. The openings
were sealed with a Male Luer lock and a Press-in
Plug with PTFE tape to minimize evaporation.
3. The samples were extracted in two model
solvents: (i) Milli-Q® Water and (ii) 50% Ethanol
4. Sample extraction were performed in duplicate.
5. Controls of each solvent were prepared in PFA
jars.
6. Extracts were placed in an incubator at 40°C for
24 hours on an orbital shaker at 50 rpm.
PureflexTM Plus Film – Extraction Procedure
39 X-Ray Sterilization Overview | May 2022
X-Ray Sterilization Overview | May 2022
40. PureflexTM Plus Film – TOC Results
40
All results in µg C/cm²
Sample Reporting Limit = 0.01 µg C/cm2
Model
Solvent
Gamma Irradiated X-Ray Irradiated
Rep 1 Rep 2 Average Rep 1 Rep 2 Average
Milli-Q Water 1.0 0.9 1.0 0.8 1.0 0.9
X-Ray Sterilization Overview | May 2022
X-Ray Sterilization Overview | May 2022
41. 214
nm
Absorbance
[AU]
0.0000
0.0096
0.0192
0.0288
0.0384
0.0480
0.0576
0.0672
0.0768
0.0864
0.0960
Time (minutes)
0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00
PureflexTM Plus Film – HPLC Chromatograms
41
X-Ray PureFlex Plus Rep-2
X-Ray PureFlex Plus Rep-1
Gamma PureFlex Plus Rep-2
Gamma PureFlex Plus Rep-1
Water Control
214
nm
Absorbance
[AU]
-0.025
0.000
0.025
0.050
0.075
0.100
0.125
0.150
0.175
0.200
0.225
0.250
Time (minutes)
0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00
X-Ray PureFlex Plus Rep-2
X-Ray PureFlex Plus Rep-1
Gamma PureFlex Plus Rep-2
Gamma PureFlex Plus Rep-1
50% Ethanol Control
Water Extracts
50% Ethanol Extracts
41 X-Ray Sterilization Overview | May 2022
X-Ray Sterilization Overview | May 2022
42. Water Extracts
50% Ethanol Extracts
Volatile Organic Compounds
PureflexTM Plus Film – GCMS-HS Chromatograms
42 X-Ray Sterilization Overview | May 2022
42 X-Ray Sterilization Overview | May 2022
43. Water Extracts
50% Ethanol Extracts
Semi-Volatile Organic Compounds
PureflexTM Plus Film – GCMS-DI Chromatograms
43 X-Ray Sterilization Overview | May 2022
43 X-Ray Sterilization Overview | May 2022
44. µS/cm
0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
8.00
9.00
10.00
Minutes
0.00 2.00 4.00 6.00 8.00 10.00 12.00 14.00 16.00 18.00 20.00 22.00 24.00 26.00 28.00 30.00 32.00 34.00 36.00 38.00 40.00
X-Ray PureFlex Plus Rep-2
X-Ray PureFlex Plus Rep-1
Gamma PureFlex Plus Rep-2
Gamma PureFlex Plus Rep-1
Water Control
7,6 7,0 7,0
0,0
2,0
4,0
6,0
8,0
10,0
12,0
14,0
Control Gamma X-ray
pH Results
Water Extracts
Water Extracts
44 X-Ray Sterilization Overview | May 2022
PureflexTM Plus Film – Ion Chromatography and pH
44 X-Ray Sterilization Overview | May 2022
45. PureflexTM Plus Film – Results
45 X-Ray Sterilization Overview | May 2022
45 X-Ray Sterilization Overview | May 2022
46. • No differences were observed in appearance, TGA, DSC, or FTIR between the X-ray irradiated Lynx
connectors and the gamma irradiated Lynx® connectors.
• TOC results showed comparable results for the PureFlex™ Plus bags irradiated by X-ray and gamma.
• HPLC chromatograms were comparable for both the water extracts and the 50% ethanol extracts. No
new compounds were generated by X-ray irradiation. All compounds observed had similar
concentrations.
• GCMS-HS chromatograms were comparable for both the water extracts and the 50% ethanol extracts.
Both irradiation techniques generated the same compounds (small alkanes and oxygenated alkanes) at
similar concentrations.
• GCMS-DI chromatograms were comparable for both the water extracts and the 50% ethanol extracts.
Both irradiation techniques generated the same compounds (antioxidant breakdown products) at
comparable concentrations.
PureflexTM Plus Film – Summary
46 46 X-Ray Sterilization Overview | May 2022
X-Ray Sterilization Overview | May 2022
47. • IC chromatograms were comparable for the water extracts. Both irradiation techniques
generated the same compounds (small organic acids) at similar concentrations.
• pH values showed comparable results for the PureFlex™ Plus bags irradiated by X-ray and
gamma. Both extracts had a small shift (0.6 pH units) to lower pH compared to the water
control.
PureflexTM Plus Film – Summary (cont)
47 47 X-Ray Sterilization Overview | May 2022
X-Ray Sterilization Overview | May 2022
49. Conclusion
49 49 X-Ray Sterilization Overview | May 2022
Extractable studies have shown comparable results. No new extractable compounds are
being formed due to X-ray irradiation. All concentrations of compounds generated by X-ray
irradiation are comparable to concentrations observed from gamma irradiation.
Testing to-date has demonstrated that X-ray Irradiation is equivalent to Gamma Irradiation.
Components continue to meet the requirements of standards (e.g. USP) or our validation
guides.
Our strategy is to qualify our components, which includes Physical, Chemical, Biological,
Functional, and Sterility Testing.
Due to supply constraints of Cobalt-60 there is a need to qualify X-ray Irradiation.
X-Ray Sterilization Overview | May 2022