As single-use technologies continue to expand in pharmaceutical manufacturing processes, the risk assessment for extractables and leachables becomes increasingly complex. Join this webinar to obtain guidance on how to perform risk evaluation on a process with multiple single-use components.
A Single-Use System (SUS) is typically designed for a specific process step. In many cases, single-use components are chosen based on their functionality. The challenge arises when there are multiple processing steps-- as the different applications and product matrices are evaluated, the complexity of the risk assessment increases. Complexity includes component evaluation, process conditions, and model solvents streams which ultimately relates to the patient safety risk.
This webinar will evaluate the different single-use components with respect to compatibility and extractables and leachables. A case study will be used to demonstrate the complexity and potential concerns when performing a risk evaluation on the manufacturing process.
In this webinar, you will learn:
- Risk assessment of extractables
- Single-use component evaluation
- Complexity when evaluating multiple assemblies
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...MilliporeSigma
What are the major drivers for the new Annex 1? Join us to know more about implications for Filters & Single Use.
In this webinar, you will learn:
• Closed Processing and Single Use Technology implementation
• Points to consider using Single Use Technology
• Sterile Filtration
The Annex 1 “Manufacture of sterile medicinal products” of the EU GMP Guide is currently being revised. A first draft of the revised version was published in 2017 and released for public comment. The second draft as of February 2020 was open for targeted consultation via stakeholder from selected industry organisations. The current Annex 1 draft emphasises Contamination Control Strategy (CCS) multiple times and as a key consideration.
Aseptic Process Sampling to address Risk of Contamination & Containment in co...MilliporeSigma
Watch this webinar here: bit.ly/asepticwebinar2020
In this webinar, you will learn:
- The challenges tied to contamination control within a biopharmaceutical environment.
- What closed processing is, and how sampling solutions are an integral component towards that end.
- Advantages of sterile sampling from both a technical and economical viewpoint; with the review of a technical study confirming contamination risk reduction and total cost of ownership.
- Recommendations and requirements stated by these major regulatory authorities around the monitoring of the manufacturing process with the execution of sampling.
Detailed description:
Biopharmaceutical manufacturers are required to ensure drug product quality attributes for patient safety. Strong contamination control strategies should be considered early in process design, and have direct influence on the production environment and equipment selection.
Sampling at each step is a critical component in maintaining a contamination control strategy. Regulators are critical in the sampling process, as it predicts the state of the product or process, and needs to be Representative. A case study will be presented that demonstrates a closed, robust sampling solution capable of maintaining a sterile flow path when challenged with Brevundimonas diminuta. The sampling option you select can help support your goal in achieving a closed process, improving your risk mitigation strategy and product safety.
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...Merck Life Sciences
What are the major drivers for the new Annex 1? Join us to know more about implications for Filters & Single Use.
In this webinar, you will learn:
• Closed Processing and Single Use Technology implementation
• Points to consider using Single Use Technology
• Sterile Filtration
The Annex 1 “Manufacture of sterile medicinal products” of the EU GMP Guide is currently being revised. A first draft of the revised version was published in 2017 and released for public comment. The second draft as of February 2020 was open for targeted consultation via stakeholder from selected industry organisations. The current Annex 1 draft emphasises Contamination Control Strategy (CCS) multiple times and as a key consideration.
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...Merck Life Sciences
Register for the interactive, on-demand webinar now: https://bit.ly/USP665
Single-use plastic systems are being utilized more frequently especially for COVID-19 vaccine manufacturing. However, there are issues regarding standardization of quality information that limits implementation efficiencies. One of the challenges is the evaluation of leachables derived from a variety of different plastic components in a timely manner.
Since the USP <665> highlights a risk assessment approach with no typical pass/fail limit, approaches to decision-making based on the extractables data package will be reviewed. In addition, we will highlight legacy testing requirements which may not be necessary once USP <665> is implemented.
In this webinar, we will discuss:
- Regulatory expectations of extractables and leachables assessment today and tomorrow
- The right criteria that need to be assessed to select the type and quality of plastic materials for use in biopharmaceutical manufacturing
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!
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
WHO has recently issued draft document titled "Guidelines on Validation". These guidelines (i.e., the main text included in this working document) cover the general principles of validation and qualification.
These guidelines focus mainly on the overall concept of validation and are not intended to be prescriptive in specific validation requirements. This document serves as general guidance only and the principles may be considered useful in its application in the manufacture and control of starting materials and finished pharmaceutical products (FPPs), as well as other areas. Validation of specific processes and systems, for example, in sterile product manufacture, requires much more consideration and a detailed approach that is beyond the scope of this document. The general text in this document may be applicable to validation and qualification of premises, equipment, utilities, systems, processes, and procedures.
The draft on the specific topics, the appendices to this main text, will follow. The following is an overview on the appendices that are intended to complement the text of this working document:
Appendix 1: Validation of heating, ventilation and air-conditioning systems - will be replaced by cross reference to WHO Guidelines on GMP for HVAC systems for considerations in qualification of HVAC systems (update - working document QAS/15.639/Rev. 1)
Appendix 2: Validation of water systems for pharmaceutical use - will be replaced by cross-reference to WHO Guidelines on water for pharmaceutical use for consideration in qualification of water purification systems
Appendix 3: Cleaning validation - consensus to retain
Appendix 4: Analytical method validation - update in process
Appendix 5: Validation of computerized systems - update in process
Appendix 6: Qualification of systems and equipment - update in process
Appendix 7: Non-sterile process validation - update already published as Annex 3, WHO Technical Report Series, No. 992, 2015
Comments on this draft document are due by July 12, 2016.
A presentation on this guidance is given below:
Presentation on New WHO Guidance on Validations
EU GMP Annex 1 Draft: Implications on Sterilizing Grade Filter ValidationMilliporeSigma
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.
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...MilliporeSigma
What are the major drivers for the new Annex 1? Join us to know more about implications for Filters & Single Use.
In this webinar, you will learn:
• Closed Processing and Single Use Technology implementation
• Points to consider using Single Use Technology
• Sterile Filtration
The Annex 1 “Manufacture of sterile medicinal products” of the EU GMP Guide is currently being revised. A first draft of the revised version was published in 2017 and released for public comment. The second draft as of February 2020 was open for targeted consultation via stakeholder from selected industry organisations. The current Annex 1 draft emphasises Contamination Control Strategy (CCS) multiple times and as a key consideration.
Aseptic Process Sampling to address Risk of Contamination & Containment in co...MilliporeSigma
Watch this webinar here: bit.ly/asepticwebinar2020
In this webinar, you will learn:
- The challenges tied to contamination control within a biopharmaceutical environment.
- What closed processing is, and how sampling solutions are an integral component towards that end.
- Advantages of sterile sampling from both a technical and economical viewpoint; with the review of a technical study confirming contamination risk reduction and total cost of ownership.
- Recommendations and requirements stated by these major regulatory authorities around the monitoring of the manufacturing process with the execution of sampling.
Detailed description:
Biopharmaceutical manufacturers are required to ensure drug product quality attributes for patient safety. Strong contamination control strategies should be considered early in process design, and have direct influence on the production environment and equipment selection.
Sampling at each step is a critical component in maintaining a contamination control strategy. Regulators are critical in the sampling process, as it predicts the state of the product or process, and needs to be Representative. A case study will be presented that demonstrates a closed, robust sampling solution capable of maintaining a sterile flow path when challenged with Brevundimonas diminuta. The sampling option you select can help support your goal in achieving a closed process, improving your risk mitigation strategy and product safety.
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...Merck Life Sciences
What are the major drivers for the new Annex 1? Join us to know more about implications for Filters & Single Use.
In this webinar, you will learn:
• Closed Processing and Single Use Technology implementation
• Points to consider using Single Use Technology
• Sterile Filtration
The Annex 1 “Manufacture of sterile medicinal products” of the EU GMP Guide is currently being revised. A first draft of the revised version was published in 2017 and released for public comment. The second draft as of February 2020 was open for targeted consultation via stakeholder from selected industry organisations. The current Annex 1 draft emphasises Contamination Control Strategy (CCS) multiple times and as a key consideration.
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...Merck Life Sciences
Register for the interactive, on-demand webinar now: https://bit.ly/USP665
Single-use plastic systems are being utilized more frequently especially for COVID-19 vaccine manufacturing. However, there are issues regarding standardization of quality information that limits implementation efficiencies. One of the challenges is the evaluation of leachables derived from a variety of different plastic components in a timely manner.
Since the USP <665> highlights a risk assessment approach with no typical pass/fail limit, approaches to decision-making based on the extractables data package will be reviewed. In addition, we will highlight legacy testing requirements which may not be necessary once USP <665> is implemented.
In this webinar, we will discuss:
- Regulatory expectations of extractables and leachables assessment today and tomorrow
- The right criteria that need to be assessed to select the type and quality of plastic materials for use in biopharmaceutical manufacturing
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!
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
WHO has recently issued draft document titled "Guidelines on Validation". These guidelines (i.e., the main text included in this working document) cover the general principles of validation and qualification.
These guidelines focus mainly on the overall concept of validation and are not intended to be prescriptive in specific validation requirements. This document serves as general guidance only and the principles may be considered useful in its application in the manufacture and control of starting materials and finished pharmaceutical products (FPPs), as well as other areas. Validation of specific processes and systems, for example, in sterile product manufacture, requires much more consideration and a detailed approach that is beyond the scope of this document. The general text in this document may be applicable to validation and qualification of premises, equipment, utilities, systems, processes, and procedures.
The draft on the specific topics, the appendices to this main text, will follow. The following is an overview on the appendices that are intended to complement the text of this working document:
Appendix 1: Validation of heating, ventilation and air-conditioning systems - will be replaced by cross reference to WHO Guidelines on GMP for HVAC systems for considerations in qualification of HVAC systems (update - working document QAS/15.639/Rev. 1)
Appendix 2: Validation of water systems for pharmaceutical use - will be replaced by cross-reference to WHO Guidelines on water for pharmaceutical use for consideration in qualification of water purification systems
Appendix 3: Cleaning validation - consensus to retain
Appendix 4: Analytical method validation - update in process
Appendix 5: Validation of computerized systems - update in process
Appendix 6: Qualification of systems and equipment - update in process
Appendix 7: Non-sterile process validation - update already published as Annex 3, WHO Technical Report Series, No. 992, 2015
Comments on this draft document are due by July 12, 2016.
A presentation on this guidance is given below:
Presentation on New WHO Guidance on Validations
EU GMP Annex 1 Draft: Implications on Sterilizing Grade Filter ValidationMilliporeSigma
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.
Process equipment characterization – how standardized extractables data suppo...Merck Life Sciences
View the recording here: https://bit.ly/35KIwBb
Biopharmaceutical Industry recently increased adoption of Single-Use systems and components in manufacturing process operations. Drug manufacturers are responsible for the characterization of SU components and systems used for the production to ensure patient safety. SUS Suppliers are encouraged by BPOG and BPSA to provide comprehensive extractables data package to support drug manufacturer’s E&L assessments.
This webinar will give an overview of the E&L evaluation workflow and practical study approaches from both supplier and end-user perspective, in accordance with the latest industry’s standards and upcoming USP <665> requirements. Case studies will be presented on how the data from suppliers are used to mitigate risk associated to SU materials, highlighting the key role of collaboration between the supplier and the drug manufacturer.
The presentation was an overview of the GMP regulations specific to cleaning validation for medicine manufacturers. New guidelines for Health Based Exposure Limits were discussed along with common GMP deficiencies observed during TGA inspections.
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...MilliporeSigma
Register for the interactive, on-demand webinar now: https://bit.ly/USP665
Single-use plastic systems are being utilized more frequently especially for COVID-19 vaccine manufacturing. However, there are issues regarding standardization of quality information that limits implementation efficiencies. One of the challenges is the evaluation of leachables derived from a variety of different plastic components in a timely manner.
Since the USP <665> highlights a risk assessment approach with no typical pass/fail limit, approaches to decision-making based on the extractables data package will be reviewed. In addition, we will highlight legacy testing requirements which may not be necessary once USP <665> is implemented.
In this webinar, we will discuss:
- Regulatory expectations of extractables and leachables assessment today and tomorrow
- The right criteria that need to be assessed to select the type and quality of plastic materials for use in biopharmaceutical manufacturing
In the last year or so the FDA and the EMA have issued new guidance/ draft guidance on "Process Validation".These align process validation activities with a product lifecycle concept and the International Conference on Harmonisation (ICH) guidances for industry, Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System. The earlier guidelines were developed before the elaboration of the new ICH guidelines.With these new guidelines, additional opportunities are available to verify the control of the process by alternative means to the manufacture of traditional process validation batches. The main objective of process validation remains that a process design yields a product meeting its pre-defined quality criteria. ICH Q8, Q9 and Q10 provide a structured way to define product critical quality attributes, design space, the manufacturing process and the control strategy. ICH Q8 refers to an ‘enhanced’ approach to pharmaceutical development which includes an alternative to the traditional process validation.
Continuous process verification [see definition in ICH Q8(R2) glossary] can be utilised in process validation protocols for the initial commercial production and for manufacturing process changes for the continual improvement throughout the remainder of the product lifecycle.
There is now a new paradigm in process validation. This presentation has been prepared from material available from FDA , EMA and ICH for beginners to have an overview of the new paradigm.
Considerations to Extractables and Leachables Testing SGS
How to organize Extractables Assessments? FDA continues to issue Warning Letters to companies that fail to properly complete Design Verification, Design Validation, and Process Validation, and recently to include failures of manufacturers in Risk Management. The evaluation of extractables and leachables has become an increasingly important aspect in the Quality by Design (QbD) initiative of the FDA in the area of drug product design, including materials used in the drug product production process and container and closure systems used for product packaging. This presentation provides general approaches and practical aspects in E&L testing.
USP <665> draft standard : A rational risk-based approach to characterization...MilliporeSigma
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
This presentation covers the manufacture and testing of all sterile drug products, including drugs that are sterilized by filtration or other means and aseptically processed, and drug products that are terminally sterilized. The type of products covered include sterile bulk drugs, ophthalmic drugs, otic dosage forms, small volume parenteral (SVS) products for small molecule and licensed biological
therapeutic drug products, large volume parenteral (LVP) products, and any other drug products required to be sterile or labeled as sterile. Center for Biologics Evaluation and Research (CBER) regulated products and veterinary drug products are excluded from coverage under this program.
The guidance information is tailored to sterile manufacturing operations and should be used in conjunction with the Compliance Program for Drug Manufacturing Inspections (CP 7356.002).
Implementing and Managing Pre-use Post-sterilization Integrity Testing (PUPSIT)Merck Life Sciences
This presentation explores best practices and case studies in aseptic processing, including how to implement and manage PUPSIT. You will learn:
• Integrity Testing – the background on IT itself, why it is important, and how it works
• Filtration setups and single-use technology
• The PUPSIT debate and how PUPSIT can be achieved with current technology, final filling, formulation, filtration
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/remotevisit
Using Single-use Technology to Overcome the Challenges of ADC ProcessingMerck Life Sciences
Participate in the interactive webinar: http://bit.ly/SU-ADCWebinar
Challenges of ADC manufacturing can be tackled by adopting single-use technology. Solutions will be presented about how to overcome concerns and implement a processing platform, supported through a strong vendor-manufacturer relationship.
Explore our webinar library: www.merckmillipore.com/webinars
The Role of BPOG Extractables Data in the Effective Adoption of Single-Use Sy...Merck Life Sciences
The successful adoption of single-use technologies in a biopharmaceutical process largely relies on confidently selecting the right components for use in the fluid path of a product, within a specific process. An important step in choosing such components requires generating an extractables profile, which can be done by carefully selecting the solvent streams and extraction conditions to model the product and process steps complemented with the right analytical strategy.
In this webinar, you will learn:
● An approach to adopt the BioPhorum Operations Group (BPOG) extractables protocol as a baseline testing strategy.
● How to apply extractables data to a specific process followed by a systematic, risk-based safety assessment approach used for comparing known safety concern thresholds.
● The important stages in the risk assessment process as demonstrated by case studies from typical drug manufacturing processes where single-use components were used.
Process equipment characterization – how standardized extractables data suppo...MilliporeSigma
View the recording here: https://bit.ly/35KIwBb
Biopharmaceutical Industry recently increased adoption of Single-Use systems and components in manufacturing process operations. Drug manufacturers are responsible for the characterization of SU components and systems used for the production to ensure patient safety. SUS Suppliers are encouraged by BPOG and BPSA to provide comprehensive extractables data package to support drug manufacturer’s E&L assessments.
This webinar will give an overview of the E&L evaluation workflow and practical study approaches from both supplier and end-user perspective, in accordance with the latest industry’s standards and upcoming USP <665> requirements. Case studies will be presented on how the data from suppliers are used to mitigate risk associated to SU materials, highlighting the key role of collaboration between the supplier and the drug manufacturer.
Process equipment characterization – how standardized extractables data suppo...Merck Life Sciences
View the recording here: https://bit.ly/35KIwBb
Biopharmaceutical Industry recently increased adoption of Single-Use systems and components in manufacturing process operations. Drug manufacturers are responsible for the characterization of SU components and systems used for the production to ensure patient safety. SUS Suppliers are encouraged by BPOG and BPSA to provide comprehensive extractables data package to support drug manufacturer’s E&L assessments.
This webinar will give an overview of the E&L evaluation workflow and practical study approaches from both supplier and end-user perspective, in accordance with the latest industry’s standards and upcoming USP <665> requirements. Case studies will be presented on how the data from suppliers are used to mitigate risk associated to SU materials, highlighting the key role of collaboration between the supplier and the drug manufacturer.
The presentation was an overview of the GMP regulations specific to cleaning validation for medicine manufacturers. New guidelines for Health Based Exposure Limits were discussed along with common GMP deficiencies observed during TGA inspections.
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...MilliporeSigma
Register for the interactive, on-demand webinar now: https://bit.ly/USP665
Single-use plastic systems are being utilized more frequently especially for COVID-19 vaccine manufacturing. However, there are issues regarding standardization of quality information that limits implementation efficiencies. One of the challenges is the evaluation of leachables derived from a variety of different plastic components in a timely manner.
Since the USP <665> highlights a risk assessment approach with no typical pass/fail limit, approaches to decision-making based on the extractables data package will be reviewed. In addition, we will highlight legacy testing requirements which may not be necessary once USP <665> is implemented.
In this webinar, we will discuss:
- Regulatory expectations of extractables and leachables assessment today and tomorrow
- The right criteria that need to be assessed to select the type and quality of plastic materials for use in biopharmaceutical manufacturing
In the last year or so the FDA and the EMA have issued new guidance/ draft guidance on "Process Validation".These align process validation activities with a product lifecycle concept and the International Conference on Harmonisation (ICH) guidances for industry, Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System. The earlier guidelines were developed before the elaboration of the new ICH guidelines.With these new guidelines, additional opportunities are available to verify the control of the process by alternative means to the manufacture of traditional process validation batches. The main objective of process validation remains that a process design yields a product meeting its pre-defined quality criteria. ICH Q8, Q9 and Q10 provide a structured way to define product critical quality attributes, design space, the manufacturing process and the control strategy. ICH Q8 refers to an ‘enhanced’ approach to pharmaceutical development which includes an alternative to the traditional process validation.
Continuous process verification [see definition in ICH Q8(R2) glossary] can be utilised in process validation protocols for the initial commercial production and for manufacturing process changes for the continual improvement throughout the remainder of the product lifecycle.
There is now a new paradigm in process validation. This presentation has been prepared from material available from FDA , EMA and ICH for beginners to have an overview of the new paradigm.
Considerations to Extractables and Leachables Testing SGS
How to organize Extractables Assessments? FDA continues to issue Warning Letters to companies that fail to properly complete Design Verification, Design Validation, and Process Validation, and recently to include failures of manufacturers in Risk Management. The evaluation of extractables and leachables has become an increasingly important aspect in the Quality by Design (QbD) initiative of the FDA in the area of drug product design, including materials used in the drug product production process and container and closure systems used for product packaging. This presentation provides general approaches and practical aspects in E&L testing.
USP <665> draft standard : A rational risk-based approach to characterization...MilliporeSigma
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
This presentation covers the manufacture and testing of all sterile drug products, including drugs that are sterilized by filtration or other means and aseptically processed, and drug products that are terminally sterilized. The type of products covered include sterile bulk drugs, ophthalmic drugs, otic dosage forms, small volume parenteral (SVS) products for small molecule and licensed biological
therapeutic drug products, large volume parenteral (LVP) products, and any other drug products required to be sterile or labeled as sterile. Center for Biologics Evaluation and Research (CBER) regulated products and veterinary drug products are excluded from coverage under this program.
The guidance information is tailored to sterile manufacturing operations and should be used in conjunction with the Compliance Program for Drug Manufacturing Inspections (CP 7356.002).
Implementing and Managing Pre-use Post-sterilization Integrity Testing (PUPSIT)Merck Life Sciences
This presentation explores best practices and case studies in aseptic processing, including how to implement and manage PUPSIT. You will learn:
• Integrity Testing – the background on IT itself, why it is important, and how it works
• Filtration setups and single-use technology
• The PUPSIT debate and how PUPSIT can be achieved with current technology, final filling, formulation, filtration
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/remotevisit
Using Single-use Technology to Overcome the Challenges of ADC ProcessingMerck Life Sciences
Participate in the interactive webinar: http://bit.ly/SU-ADCWebinar
Challenges of ADC manufacturing can be tackled by adopting single-use technology. Solutions will be presented about how to overcome concerns and implement a processing platform, supported through a strong vendor-manufacturer relationship.
Explore our webinar library: www.merckmillipore.com/webinars
The Role of BPOG Extractables Data in the Effective Adoption of Single-Use Sy...Merck Life Sciences
The successful adoption of single-use technologies in a biopharmaceutical process largely relies on confidently selecting the right components for use in the fluid path of a product, within a specific process. An important step in choosing such components requires generating an extractables profile, which can be done by carefully selecting the solvent streams and extraction conditions to model the product and process steps complemented with the right analytical strategy.
In this webinar, you will learn:
● An approach to adopt the BioPhorum Operations Group (BPOG) extractables protocol as a baseline testing strategy.
● How to apply extractables data to a specific process followed by a systematic, risk-based safety assessment approach used for comparing known safety concern thresholds.
● The important stages in the risk assessment process as demonstrated by case studies from typical drug manufacturing processes where single-use components were used.
Process equipment characterization – how standardized extractables data suppo...MilliporeSigma
View the recording here: https://bit.ly/35KIwBb
Biopharmaceutical Industry recently increased adoption of Single-Use systems and components in manufacturing process operations. Drug manufacturers are responsible for the characterization of SU components and systems used for the production to ensure patient safety. SUS Suppliers are encouraged by BPOG and BPSA to provide comprehensive extractables data package to support drug manufacturer’s E&L assessments.
This webinar will give an overview of the E&L evaluation workflow and practical study approaches from both supplier and end-user perspective, in accordance with the latest industry’s standards and upcoming USP <665> requirements. Case studies will be presented on how the data from suppliers are used to mitigate risk associated to SU materials, highlighting the key role of collaboration between the supplier and the drug manufacturer.
Manufacturing Investigational Medicinal Products - Legislative and GMP requir...TGA Australia
Presentation on Legislative requirements, specific risks for IMP manufacturing, manufacturing authorisations, PIC/S Guide to GMP PE009-13 and common issues
Aseptic Process Sampling to address Risk of Contamination & Containment in co...Merck Life Sciences
In this webinar, you will learn:
- The challenges tied to contamination control within a biopharmaceutical environment.
- What closed processing is, and how sampling solutions are an integral component towards that end.
- Advantages of sterile sampling from both a technical and economical viewpoint; with the review of a technical study confirming contamination risk reduction and total cost of ownership.
- Recommendations and requirements stated by these major regulatory authorities around the monitoring of the manufacturing process with the execution of sampling.
Detailed description:
Biopharmaceutical manufacturers are required to ensure drug product quality attributes for patient safety. Strong contamination control strategies should be considered early in process design, and have direct influence on the production environment and equipment selection.
Sampling at each step is a critical component in maintaining a contamination control strategy. Regulators are critical in the sampling process, as it predicts the state of the product or process, and needs to be Representative. A case study will be presented that demonstrates a closed, robust sampling solution capable of maintaining a sterile flow path when challenged with Brevundimonas diminuta. The sampling option you select can help support your goal in achieving a closed process, improving your risk mitigation strategy and product safety.
ISO 10993 Series Part 1: Evaluation and Testing In The Risk Management ProcessNAMSA
ISO 10993 Series Part 1: Evaluation and Testing In The Risk Management Process discusses what ISO 10993-1 addresses, as well as the general principles governing the biological evaluation of medical devices within a risk management process.
The International Society for Pharmaceutical Engineering (ISPE) would like to submit comments on the revision of Annex 1, on manufacturing of sterile medicinal products, of the Eudralex Volume 4.
pilot plant is a small system which is operated to find out about the behavior of a process before using it on a large industrial scale. so, this presentation tries to illustrate its objective and significance to understand the methodologies of various pharmaceutical dosage forms.
This presentation presents points to consider for building and using models in the regulated pharmaceutical industry and offers examples of how models can play a part in the Quality by Design (QbD) framework.
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productieplanning
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production planning
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Implementation of the Defined Approaches on Skin Sensitisation (OECD GL 497) ...OECD Environment
Humans and the environment are exposed every day to chemicals. How do we make sure that these chemicals are safe?
Industry is required to test these chemicals to understand how they may affect people and the environment. In the past, these tests were most commonly carried out on animals. As scientific methods and tools progress, the use of animals to test a product designed for humans are becoming obsolete, in addition to being unethical. With new methods being developed, it is possible to perform these tests on human and animal cell cultures with equally rigorous and robust results. Because the OECD is committed to chemical safety and animal welfare, a new ground-breaking Guideline on Defined Approaches for Skin Sensitisation (OECD GL 497: https://doi.org/10.1787/b92879a4-en) was released on 14 June 2021. It is the first ever Guideline that uses non-animal methods to predict whether a chemical can cause skin allergies.
The OECD organised a webinar on 18 October 2021 at 14:00 to discuss the implementation of the Defined Approaches on Skin Sensitisation for chemical safety in member countries. This webinar paved the way for companies and authorities to determine the environmental toxicity of chemicals without having to resort to animal testing.
Speakers:
Nicole Kleinestreuer: NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)
Silvia Casati: European Union Reference Laboratory for alternatives to animal testing (EURL ECVAM)
Anna Lowit: U.S. Environmental Protection's Office of Pesticide Programs (US EPA OPP)
Paul Brown: U.S. Food and Drug Administration (US FDA)
Laura Rossi: European Chemicals Agency (ECHA)
Andre Muller: National Institute for Public Health and the Environment (RIVM)
Access the video replay and more information about our work at: https://oe.cd/testing-assessment-webinars
Similar to Challenges using Multiple Single-use Systems: Functionality versus Extractables and Leachables (20)
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
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
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
Risk-Based Qualification of X-Ray Sterilization for Single-Use SystemsMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3vQf0qv
In the single-use bioprocess industry, X-ray irradiation warrants consideration as an alternate sterilization technology. Using a risk-based qualification testing strategy is important when evaluating and implementing equivalent ionizing irradiation sterilization methods.
The urgent need for life-saving therapies as a result of the global pandemic has reinforced the criticality of flexibility in pharmaceutical manufacturing, including sterilization. The single-use bioprocess industry traditionally has employed gamma irradiation sterilization. X-ray irradiation is being considered as an additional sterilization technology for business and supply continuity. We will share a risk-based qualification testing strategy including Extractables and data generated to support comparability of gamma irradiation and X-ray irradiation as equivalent ionizing irradiation sterilization methods.
In this webinar, you will learn about:
• The comparison of gamma and X-ray irradiation sterilization
• A risk-based qualification test strategy
• Data evaluation of gamma versus X-ray sterilized single-use components
Presented by:
Monica Cardona,
Global Senior Program Manager
Paul Killian, Ph.D.,
R&D Director, Analytical Technologies
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.
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
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
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
One of the most developed cities of India, the city of Chennai is the capital of Tamilnadu and many people from different parts of India come here to earn their bread and butter. Being a metropolitan, the city is filled with towering building and beaches but the sad part as with almost every Indian city
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/
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
Telehealth Psychology Building Trust with Clients.pptxThe Harvest Clinic
Telehealth psychology is a digital approach that offers psychological services and mental health care to clients remotely, using technologies like video conferencing, phone calls, text messaging, and mobile apps for communication.
We understand the unique challenges pickleball players face and are committed to helping you stay healthy and active. In this presentation, we’ll explore the three most common pickleball injuries and provide strategies for prevention and treatment.
Leading the Way in Nephrology: Dr. David Greene's Work with Stem Cells for Ki...Dr. David Greene Arizona
As we watch Dr. Greene's continued efforts and research in Arizona, it's clear that stem cell therapy holds a promising key to unlocking new doors in the treatment of kidney disease. With each study and trial, we step closer to a world where kidney disease is no longer a life sentence but a treatable condition, thanks to pioneers like Dr. David Greene.
Nursing Care of Client With Acute And Chronic Renal Failure.ppt
Challenges using Multiple Single-use Systems: Functionality versus Extractables and Leachables
1. The life science business of Merck KGaA, Darmstadt, Germany
operates as MilliporeSigma in the U.S. and Canada.
Challenges using
Multiple Single-use
Systems:
Functionality versus
Extractables and
Leachables
Jessica Shea
April 18, 2019
2. The life science business
of Merck KGaA, Darmstadt,
Germany operates as
MilliporeSigma in the U.S.
and Canada
5. Extractables and Leachables
Regulatory Requirements
FDA EU
European Commission, EUDRALEX Volume 4,
“Good Manufacturing Practices, Medicinal Products for
Human and Veterinary Use”, Chapter 3, “Premise and
Equipment”, 2003 “
Production equipment shall not present any hazard
to the product. The parts of the production
equipment that come into contact with the product
must not be reactive, additive or absorptive to
such an extent that it will affect the quality of the
product and thus present any hazard.”
FDA, Code of Federal Regulations,
Part 211, “Current Good Manufacturing
Practice for Finished Pharmaceuticals”,
Part 211.65, “Equipment Construction”, 2005
“Equipment shall be constructed so that surfaces
that contact components, in-process materials, or
drug products shall not be reactive, additive, or
absorptive so as to alter the safety, identity,
strength, quality, or purity of the drug
product beyond the official or other
established requirements.”
Challenges Using Multiple Single-Use Systems5
6. Regulatory expectation
Risk-based approach is recommended by
regulators
• CBER recommends a risk-based approach to evaluate extractables and leachables. Where you take
multiple aspects into account (e.g., indication, safety issues, product characteristics, dosage,
formulation, and stability profile).
• If there’s no relevant risk associated with the (materials in question), vendor data can be cross
referenced and a detailed justification for the application of these data and a justification for no
additional testing should be submitted.
• Where there is relevant risk, the drug sponsor may have to determine toxicity based on
maximum dosage of potential leachables based on extractables data.
• If the maximum dosage of potential leachables presents a safety risk, leachable evaluation and
testing may be necessary.
• Additionally, if product quality could be affected by potential leachable, studies may need to be
performed to assess the effect on product quality, including efficacy.
Destry M. Sillivan – Senior Regulatory Review Officer, CBER, FDA. IBC’s 7th International Single Use Application for Biopharmaceutical
Manufacturing Conference, la Jolla, CA, June 14, 2010
Challenges Using Multiple Single-Use Systems6
7. Why Worry?: FDA Warning Letters
“Please provide data from an extractables/leachables study conducted
on the vessel, tubing and filters used for drug product
manufacturing. Please ensure that the studies are conducted taking
into account the nature of the non-aqueous vehicle used in your
proposed drug product.”
“We recommend you to conduct a leachable study for the filtration
system with the drug solution to ensure the absence of leachable in
the drug product after filtration.”
Challenges Using Multiple Single-Use Systems7
8. Industrial References: PDA Technical Report 66
Application of Single-Use Systems in Pharmaceutical Manufacturing
2014: Implementation of SUS
1
2
Regulatory Environment For Filters And
Single Use Equipment
Compendial Standard: USP <665> Draft
Plastic Components and Systems Used in Pharmaceutical Manufacturing:
Focus on defining extractables standards
3 Regulations: EMA/CHMP/BWP/187338/2014
Guideline on process validation for the manufacture of biotechnology-derived
active substances and data to be provided in the regulatory submission
Defining requirements for single use equipment
Challenges Using Multiple Single-Use Systems8
9. Evolving Industry Guidance Expectations
PDA Technical Report 66, 20141
•“Supplier documentation may be sufficient for certain applications
where risk is low (such as, short term exposure, no contact with drug
product, or position in the process stream); but more detailed
studies may be required where significant risk (such as longer
term contact and extreme conditions) exists.”
•Extractables is essential step in the accurate prediction of leachables
•To check the impact of E&L by risk assessment on process, patient
safety and product quality
•If high, leachables data may be need
How to use
supplier’s data
Step wise
approach
Challenges Using Multiple Single-Use Systems9
Source: Parenteral Drug Association
10. 2 USP <665> Draft March 2019: Plastic Components and Systems Used in Pharmaceutical
Manufacturing
Emprove® Program For Filters and Single Use
Evolving Industry Guidance Expectations
• Addresses the qualification of plastic components used in the manufacture of both pharmaceutical and
biopharmaceutical active pharmaceutical ingredients (APIs) and drug products (DPs)
• Risk assessment based on dosage form (i.e., oral solid/liquid is low risk) and application
• Extraction requirements:
Solution Composition Tests Performed
Acid/salt buffer, pH 3 Organic extractables
Phosphate buffer, pH 10 Organic extractables
Ethanol and water (50:50) Organic extractables. Low risk tests
Challenges Using Multiple Single-Use Systems10
11. EMA/CHMP/BWP/187338/2014 (28 April 2016)
Guideline on process validation for the manufacture of biotechnology-derived
active substances and data to be provided in the regulatory submission
Chapter 6.1.3.: General issues related to single use equipment
▪ “…consideration should be given to leachables* and extractables.”
▪ “Information should be provided on the nature and amount of potential leachables*,…”
▪ “Besides data, this normally includes a risk assessment.”
▪ “Data do not necessarily need to be generated under actual process conditions, for example
supplier data or data generated under representative model conditions may be suitable.”
▪ “For verification studies, commercial scale equipment should be used.”
▪ “Various batches of disposable components should be used, as appropriate,…”
*leachables can be done only under process conditions, here we offer the Bioreliance services.
Emprove® Dossiers: Support Fulfilling Regulatory
Requirements
3
Challenges Using Multiple Single-Use Systems11
13. Biopharma Market
Trends
Market: $200 B, CAGR 15%
1. Greater focus on
manufacturing efficiency and
productivity improvements
2. Survey responses stated
the use of single-use and
disposable devices improved
the biomanufacturing
performance
Top Reasons for
Implementing
Single-Use
1. Reduce capital investment
with facility and equipment
2. Eliminate cleaning
requirements with associated
validation
3. Reduced time in getting
facility up and running
4. Decrease risk of product
cross contamination
Top Single-Use Product
Attributes
1. Reliable lead-time & faster
delivery
2. Extractables & leachables
data is the top reason for
restricting use.
3. Quality of product
4. Cost of product
Single-use Adoption Enables Desired Process Efficiency
Improvements in Biomanufacturing
Source: Bioplan 2016, 13th Annual report of Biopharmaceutical manufacturing capacity and production
Challenges Using Multiple Single-Use Systems13
14. Product & Process
Single-Use Assembly DrawingsTesting for E&L
Assembly Train Sequence
Flow Path on Drawing
Challenges Using Multiple Single-Use Systems
Evaluation Process
1
2
5
4
3
14
16. 16
Compatibility: Choosing the right material for the application
Compatibility
• Understand the materials of construction
and its compatibility with the process
stream
• Minimize temperature and duration with
more difficult process streams.
• Minimize the risk for patient safety and
potential leachables
USP <665> draft
• Components are characterized depending
on the level of risk associated with their
application in a particular manufacturing
operation
Quantity
and
Type
Material of Construction
Process
Stream
Process
Conditions
Temp and duration
Challenges Using Multiple Single-Use Systems16
17. Grouping SU
components
for
Extractables
Studies.
Components Extractables Test Strategy
Can we group components?
What
type of
MOC?
Which
Resin is
used?
Any
process-
ing
aids?
How are
they
manufac
-tured?
Who are
the
vendors?
Resin
Group
2
Resin
Group
n
Resin
Group
1
Challenges Using Multiple Single-Use Systems
17
18. ConnectorsBags
Challenges Using Multiple Single-Use Systems
Pureflex® Film
Pureflex Plus® Film
Pharma® 50, 60, 80
Tubing
APT® Tubing
Braided Tubing
C-Flex® Tubing
All other tubing
Lynx S2S® Connectors
Lynx ST® Connectors
Kleenpak® Connectors
Readymate®
Connectors
Aseptiquik®
Connectors
Steam Connectors
Needles with
Polycarbonate Over-
Mold
Tubing Needle
Components to Validate
18
20. Classes of E&L from Single-Use Systems
Stabilizer Irgafos® 168
Slip agents
Erucamide
Lubricants
Plasticizer
DEHP
Pigment
Degradation Products
BHT
OH
O
O
OH
O O
OH
O
O
OH
O
O
Irganox® 1010
Antioxidants
Monomers
Styrene
Extractables and Leachables
Challenges Using Multiple Single-Use Systems20
22. Most Unit Operations Consist of Polymeric Components
Monoclonal
Antibody
Typical monoclonal
antibody processes
can be multi-use or
single-use.
High Risk
ClearanceChallenges Using Multiple Single-Use Systems22
23. Cleaning Validation of the UF/DF Device
First Use and Re-use Qualification
Prior to implementation of a UF/DF step, the
process must be validated, including
validation of two cleaning procedures.
The first cleaning procedure is to remove
the preservative solution from the device.
The Re-use cleaning process between runs
to restore the membrane that was stored in
sanitizing solution
Removal during TFF Processing Step
Diafiltration is a conventional method used to
achieve high purification of macrosolutes
In the diafiltration mode the permeate is
sent to waste and a makeup buffer is
added to the reservoir to maintain the
volume.
This process also reduced leachables that
are present from previous processing steps
Challenges Using Multiple Single-Use Systems
Risk Reduction – 2 Ways
Tangential Flow Filtration
23
24. Challenges Using Multiple Single-Use Systems
Removal during TFF Processing Step
Tangential Flow Filtration
Ultrafiltration/ Diafiltration: Testing was performed in the diafiltration modes and recycle mode.
The study demonstrate a >3x log reduction of Bisphenol-A (BPA)
Removal of Leachables by Ultrafiltration and Diafiltration (2018). MilliporeSigma Technical Brief TB4663EN00
24
25. Conclusion
Studies demonstrated the ability of an TFF
membrane to remove leachables generated
upstream of the product stream.
The risk is reduced for steps prior to the UF/DF
step.
Basic information of the materials are sufficient
for steps prior to the UF/DF step due to the low
risk level.
Challenges Using Multiple Single-Use Systems
Removal during TFF Processing Step
Tangential Flow Filtration
Diafiltration Mode
An example of typical clearance for the seven potential E/L from single-use
technologies in Protein 4 and its associated buffer control run.
Magarian, N., Lee, K., Nagpal, K., Skidmore, K., & Mahajan, E. (2016). Clearance of Extractables and Leachables from Single-Use
Technologies via Ultrafiltration/Diafiltration Operations. Biotechnol. Prog., 32:718–724
25
26. Validation of the cleaning procedure includes:
Determine the flush volume necessary to remove the preserving
solution. The flush volume is typically determined using a Total
Organic Carbon (TOC) endpoint.
Fill the device with a sanitizer (e.g. alkali solution) and determine
how much contact time is needed to reduce the bioburden.
(Typically, companies have established minimal hold times)
Determine the volume required to remove the sanitizer. Sanitize
the TFF device with an alkaline solution. This second flush volume
is usually determined using conductivity.
Result
TFF unit operation is low risk and need not be subjected to
extractables studies when it can be restored to water for
injection (WFI) like conditions with specifications of < 500
ppb TOC.
Challenges Using Multiple Single-Use Systems
Cleaning Validation of the UF/DF Device
Tangential Flow Filtration
26
Agalloco,James, (1992). Points to Consider in the Validation of Equipment Cleaning Procedures. J. Parent. Sci. and
Technol., 46(5), 163-168
Bader, FG, A Bum, BD Garfinkle, D MacFarland, T Massa, and TL Copmann, (1992). Multiuse Manufacturing
Facilities for Biologicals. Biopharmaceuticals, 5(7), 34-42
FDA, Guide to Inspection of Validation of Cleaning Processes, US GPO, Wash. DC, July 1993
27. Challenges Using Multiple Single-Use Systems
Mitigating Factors - USP <1665> Draft
Post-contact processing step that clears extracted substances
Reduce the concentration of extractables by diluting them via
the process stream
mitigating factor = 1
Tangential Flow Filtration
27
Understood by Regulations
Risk Assessment
29. Risk Dimensions for Consideration
USP <1665> Draft
Plastic
component
Chemical nature of
process stream
Duration of contact
Temperature of
contact
Material of
construction
The risk evaluation matrix considers four dimensions that address the risk that a polymeric
component will be leached to such an extent that its extractables may be impactful. These
dimensions include:
29 Challenges Using Multiple Single-Use Systems
30. Challenges Using Multiple Single-Use Systems
Clinical Use Mitigating Factors - USP <1665> Draft
1 The dosage form is a solid or liquid oral
2 The duration of clinical use is <7 days
3 The daily dose volume is <10 mL
Lowering the Risk Level
30
31. Challenges Using Multiple Single-Use Systems
Other Mitigating factors
Clearance
(TFF)
Significant
Dilution
(pH adjustment)
Material
Consideration:
Flushing
31
32. Challenges Using Multiple Single-Use Systems
USP <665> Draft
Risk
Level
Biological Reactivity Chemical Assessment Extraction Solution Component Testing
Low None Partial 50% Ethanol
NVR, pH Differential, UV
absorbance
Medium
USP <87>,
Biological reactivity
in vitro
Limited
50% Ethanol
1. Low-risk tests
2. Organic extractables
profiling
High
1. USP <87>
Cytotoxicity tests
2.USP <88>
Systemic Injection
Test, Intracutaneous
Test
Full
1. 0.2M KCl, pH 3
2. 0.1M Phosphate
buffer, pH 10
3. 50% EtOH
1. Low risk tests
2. Standard
extractables protocol
3. Extractable elements
(as necessary and
appropriate)
32
34. Challenges Using Multiple Single-Use Systems
Final Filling – Single-use
Risk Assessment – Example
5’’ Express
PES Filter
10L Pureflex
plus Bag
34
35. • Water, 2% API, 0.02% PS80, 2% dextrose, pH 5
Drug Product
• 8 hours
Filter Contact Time
• 25 °C
Filtration Temperature
Typical Injectable Application
Challenges Using Multiple Single-Use Systems35
36. Challenges Using Multiple Single-Use Systems
Risk Matrix - USP <1665> Draft
If the process streams contain multiple solubilizers, e.g. protein and
surfactant, the risk is compounded.
organic
solvents (by
volume)
surfactants
(by weight)
blood/blood-derived
substances (by
weight)
lipids and
proteins
(by weight)
pH
Aqueous
Level 1
<5% <0.1% blood-derived <1% <1% ≥ 3 and ≤ 9
Somewhat
organic
Level 2
5-40% 0.1-0.5% blood-derived 1-25% 1-5%
Highly
organic
Level 3
>40% >0.5%
blood or blood-
derived >25%
>5% <3 or >9
Process
stream
36
37. Challenges Using Multiple Single-Use Systems
Risk Matrix - USP <1665> Draft
Additives (by weight)
Treatment for
sterilization
Processing
Inert
Level 1
<0.1%
Intermediate
Level 2
0.1-1%
chemical
adhesives/bonding of
component's
materials
Reactive
Level 3
>1%
irradiation/chemi
cal treatment
chemical
adhesives/bonding of
component's
materials
Material
Flushing/rinsing can be
used to reduce the
material reactivity
terms by one level,
37
38. Challenges Using Multiple Single-Use Systems
Risk Matrix - USP <1665> Draft
Temperature (°C) Duration
Level 1 Frozen (<-10) < 24 hrs
Level 2
refrigerated (2-8)
Ambient (15-25) 1-7 days
Level 3 Elevated (>30) > 7 days
Temperature duration
38
39. Challenges Using Multiple Single-Use Systems
Table A-2. Linking the Numerical Risk Sequence with a Level of Characterization
Risk Matrix - USP <1665> Draft
If... And... Then the Characterization Level is...
Four dimension scores are Level 3 There is no additional qualifier (3333) Level C (High Risk)
Three dimension scores are Level 3
The other dimension score is Level 2 (3332) Level C
The other dimension score is Level 1 (3331) Level C
Two dimension scores are Level 3
The other two dimension scores are both Level 2
(3322) Level C
One dimension score of Level 2 (3321)
Level B (Moderate Risk) or C (High
Risk)a,b
The other two dimension scores are Level 1 (3311) Level A or Bb,c
One dimension score is Level 3
All of the other dimension scores are Level 2
(3222) Level B
One of the other dimension scores is Level 1 (3221)Level B
Two of the other dimension scores are Level 1
(3211) Level A or Bb,c
All of the other dimension scores are Level 1
(3111) Level A
No dimension score is Level 3
All of the dimension scores are Level 2 (2222) Level B
Not all of the dimension scores are Level 2 Level A
a If the Level 2 score is in temperature, solvent, or duration dimensions, then Level C; otherwise, Level B.
b In these cases the temperature, solvent, or duration dimensions have a greater influence on risk than do material
considerations.
c If one of the Level 1 scores is in the material considerations dimension, then Level A; otherwise, Level B.
Flushing
39
41. Increased Contact Time and Formulation Change
Challenges Using Multiple Single-Use Systems41
• Water, 2% API, 0.1% PS80, 2% dextrose, pH 5
Drug Product
• 30 Days
Filter Contact Time
• 25 °C
Filtration Temperature
42. Challenges Using Multiple Single-Use Systems
Risk Matrix - USP <1665> Draft
If the process streams contain multiple solubilizers, e.g. protein and
surfactant, the risk is compounded.
organic
solvents (by
volume)
surfactants
(by weight)
blood/blood-derived
substances (by
weight)
lipids and
proteins
(by weight)
pH
Aqueous
Level 1
<5% <0.1% blood-derived <1% <1% ≥ 3 and ≤ 9
Somewhat
organic
Level 2
5-40% 0.1-0.5% blood-derived 1-25% 1-5%
Highly
organic
Level 3
>40% >0.5%
blood or blood-
derived >25%
>5% <3 or >9
Process
stream
42
43. Challenges Using Multiple Single-Use Systems
Risk Matrix - USP <1665> Draft
Additives (by weight)
Treatment for
sterilization
Processing
Inert
Level 1
<0.1%
Intermediate
Level 2
0.1-1%
chemical
adhesives/bonding of
component's
materials
Reactive
Level 3
>1%
irradiation/chemi
cal treatment
chemical
adhesives/bonding of
component's
materials
Material
Flushing/rinsing can be
used to reduce the
material reactivity
terms by one level,
43
44. Challenges Using Multiple Single-Use Systems
Risk Matrix - USP <1665> Draft
Temperature (°C) Duration
Level 1 Frozen (<-10) < 24 hrs
Level 2
refrigerated (2-8)
Ambient (15-25) 1-7 days
Level 3 Elevated (>30) > 7 days
Temperature duration
44
45. Challenges Using Multiple Single-Use Systems
Table A-2. Linking the Numerical Risk Sequence with a Level of Characterization
Risk Matrix - USP <1665> Draft
If... And... Then the Characterization Level is...
Four dimension scores are Level 3 There is no additional qualifier (3333) Level C (High Risk)
Three dimension scores are Level 3
The other dimension score is Level 2 (3332) Level C
The other dimension score is Level 1 (3331) Level C
Two dimension scores are Level 3
The other two dimension scores are both Level 2
(3322) Level C
One dimension score of Level 2 (3321)
Level B (Moderate Risk) or C (High
Risk)a,b
The other two dimension scores are Level 1 (3311) Level A or Bb,c
One dimension score is Level 3
All of the other dimension scores are Level 2
(3222) Level B
One of the other dimension scores is Level 1 (3221)Level B
Two of the other dimension scores are Level 1
(3211) Level A or Bb,c
All of the other dimension scores are Level 1
(3111) Level A
No dimension score is Level 3
All of the dimension scores are Level 2 (2222) Level B
Not all of the dimension scores are Level 2 Level A
a If the Level 2 score is in temperature, solvent, or duration dimensions, then Level C; otherwise, Level B.
b In these cases the temperature, solvent, or duration dimensions have a greater influence on risk than do material
considerations.
c If one of the Level 1 scores is in the material considerations dimension, then Level A; otherwise, Level B.
45
46. • Total quantity below the AET (Analytical Evaluation Threshold)
• Individual quantitation
• Scale data to surface area
• Sum the quantitation if present in more than one component
Extractables Identification
• Manufacturing process
• Posology
Exposure Assessment
• Evaluate based on the TTC (Threshold of toxicological concern)?
• Establish a PDE (Permitted daily exposure)?
Safety Evaluation
Single-Use Component Evaluation
Assessing the Risk
46 Challenges Using Multiple Single-Use Systems
47. Patient Safety
Evaluation of Organic Extractables
No
Yes
Quantity
above the
TTC/PDE?
Risk Mitigation
Leachables?
Dilution?
Material/ Process
Change?
Risk is acceptableQuantity of Each
Extractable
Challenges Using Multiple Single-Use Systems47
49. More than Extractables Data
Emprove® Program and BioReliance® Validation Services
49
Emprove® program offers…
• Support on material qualification, risk assessment
& process optimization efforts through three well-
organized Emprove® Dossiers:
− Material Qualification Dossier
− Quality Management Dossier
− Operational Excellence Dossier
• The Operational Excellence dossier aligns with
the BPOG standardized extractables testing
protocol & the USP 665 (draft chapter)
• Complete profile of extractables over a wide
scope of the filtration, chromatography and single
use portfolio
• Provides seamless access to most updated
documents anytime anywhere saving valuable
customer resources
Online 24/7 access through
Emprove® suite
Certificates & custom extractables
reports
Customer extractables and
leachables studies
Patient safety evaluation (risk
assessment)
Consultancy and risk mitigation
1
3
4
5
6
2
Operational Excellence dossier
(standard extractables report aligned
with BPOG & USP 665)
Challenges Using Multiple Single-Use Systems49
50. More than Extractables Data
Emprove® Program and BioReliance® Validation Services
50
BioReliance® Validation Services
offers…
Assistance in:
Analyzing data of the Operational Excellence
dossier and conducting risk assessment
Preparing product- and process-specific
extractables reports
Designing and executing custom extractables and
leachables studies
Determining if the resulting drug product presents
any toxicological risks
Recommending mitigation steps if necessary
Other services: complete Validation of sterilizing
filters & Mobius® Single use technology used in
critical process steps
Online 24/7 access through
Emprove® suite
Certificates & custom extractables
reports
Customer extractables and
leachables studies
Patient safety evaluation (risk
assessment)
Consultancy and risk mitigation
1
3
4
5
6
2
Operational Excellence dossier
(standard extractables report aligned
with BPOG & USP 665)
Challenges Using Multiple Single-Use Systems50
51. Challenges Using Multiple Single-Use Systems
Component Selection
Choose the appropriate materials for
the process
Ensure functionality and compatibility.
TFF processing Step
UF/DF provides clearance of
extractables and leachables from the
previous step
Reduces risk to the patient
51
52. Clinical Use
Short term use and low volume dosages
lower the risk.
Downstream Processing
Highest risk to the patient
No dilution of potential leachables
Consider flushing to reduce risk
Leachables and Patient Safety
Ensuring the quantity of leachables is below
the concern levels
Challenges Using Multiple Single-Use Systems
Risk Assessment
52