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!
What is likely to go into the revised Annex 1, including:
Terminal sterilisation vs aseptic processing
WFI produced by reverse osmosis
Guidance for media simulation trials
This remains speculative
The two most commonly used within microbiology are
HACCP (which originated in the food industry) and FMEA
(developed for engineering). This article explores these two
approaches, first with a description of HACCP, followed by a
description and case study of FMEA in sterility testing.
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).
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.
What is likely to go into the revised Annex 1, including:
Terminal sterilisation vs aseptic processing
WFI produced by reverse osmosis
Guidance for media simulation trials
This remains speculative
The two most commonly used within microbiology are
HACCP (which originated in the food industry) and FMEA
(developed for engineering). This article explores these two
approaches, first with a description of HACCP, followed by a
description and case study of FMEA in sterility testing.
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).
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.
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.
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.
Previously certain classes of active substances were required to be manufactured in dedicated or segregated self-contained facilities Certain antibiotics, Certain hormones, Certain cytotoxic ,Certain highly active drugs .This was due to the perceived risk of these active substances.
Pharmaceuticals not covered under these criteria were addressed by a cleaning validation process This involved reduction of the concentration of residual active substance to a level where the maximum carryover from the total equipment train would result in no greater than 1/1000th of the lowest clinical dose of the contaminating substance in the maximum daily dosage of the next product to be manufactured.
This criterion was applied concurrently with a maximum permitted contamination of 10 ppm of the previous active substance in the next product manufactured. Whichever of these criteria resulted in the lowest carryover, constituted the limit applied for cleaning validation. However, these limits did not take account of the available pharmacological and toxicological data They may have been too restrictive or not restrictive enough. EMA therefore felt for a more scientific case by case approach for all classes of pharmaceutical substances.
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.
The subject of cleaning validation in active pharmaceutical ingredient manufacturing plants has continued to receive a large amount of attention from regulators, companies and customers alike.
The integration of Cleaning Validation within an effective Quality System supported by Quality Risk Management Processes should give assurance that API Manufacturing Operations are performed in such a way that Risks to patients related to cleaning validation are understood, assessed for impact and are mitigated as necessary.
It is important that the requirements for the finished manufacturing companies are not transferred back in the process to active pharmaceutical ingredient manufacturers without consideration for the different processes that take place at this stage.
This presentation covers the requirements of Cleaning Validation for a Multipurpose API Manufactuirng Plant
Aseptic / sterile- “ A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbiological contamination of the exposed sterile product”
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
Good Manufacturing PracticeFor LVP,SVP, ophthalmic veterinary medicine, bulk chemicals & invitro diagnostic
For Good business Practice
A control process gives reproducibility & product consistency with in known limits
Provides license to do business.
Watch the presentation of this webinar here: https://bit.ly/3tDy8Ei
Recent PDA/BioPhorum publications outline risks for PUPSIT in sterilizing filtration. This webinar will summarize the key points and best practices for implementing PUPSIT.
PDA and BioPhorum have partnered to form a task force whose goal was to provide the industry and regulators with scientific data and analysis on the potential risks and benefits of implementing PUPSIT to improve sterility assurance. This webinar will describe the data generated by the task force studies and discuss considerations and best practices when implementing PUPSIT.
In this webinar, you will learn:
• How changing industry perspectives help overcome regulatory concerns and may influence regulatory perspective
• How improved process understanding affects risk assessment
• How improved final fill assembly design simplifies PUPSIT
EU GMP Annex 1 Draft: Implications on Sterilizing Grade Filter ValidationMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3kk0Qs1
In this webinar, you will learn:
- About the GMP Annex 1 draft regulatory overview
- How to incorporate the integrity testing & PUPSIT in the filtration systems validation
- How to design a bacterial retention test in terms of organism selection and single vs multiple use validation
Detailed description:
In this webinar we will discuss the implications of the EU GMP Annex 1 draft on the filtration of medicinal products and how this impacts the validation studies.
Bacterial Retention Testing is a critical part of the manufacturing validation process and is required by all regulatory bodies worldwide. Using case studies, our experts will explain how the Annex 1 draft is incorporated into the filtration systems validation exercise, specifically for integrity testing & PUPSIT (Pre-Use Post Sterilization Integrity Testing), the selection and justification of the appropriate test organism, and validation implications of single versus multiple use.
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.
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
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.
Problem formulation for environmental risk assessment in the context of EC Re...OECD Environment
The seminar on Problem Formulation for the Risk Assessment of Biopesticides stemmed from a previous CRP-sponsored event on Innovating Microbial Pesticide Testing that identified the need for an overarching guidance document to determine when in vivo tests are necessary. Problem Formulation, a common practice in pesticide risk assessment, was highlighted as a useful approach for addressing uncertainties in data requirements for biopesticides.
The seminar featured presentations from various perspectives, including industry, regulatory bodies, and academia. Topics included the history and principles of Problem Formulation, industry perspectives on Problem Formulation and how it is applied internally for microbial pesticides, regulatory approaches, and specific case studies. The seminar provided an overview of the challenges, considerations, and potential solutions in harmonising Problem Formulation for biopesticide risk assessment. It emphasised the need for collaboration and discussion to develop Problem Formulation guidance for biopesticides.
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.
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.
Previously certain classes of active substances were required to be manufactured in dedicated or segregated self-contained facilities Certain antibiotics, Certain hormones, Certain cytotoxic ,Certain highly active drugs .This was due to the perceived risk of these active substances.
Pharmaceuticals not covered under these criteria were addressed by a cleaning validation process This involved reduction of the concentration of residual active substance to a level where the maximum carryover from the total equipment train would result in no greater than 1/1000th of the lowest clinical dose of the contaminating substance in the maximum daily dosage of the next product to be manufactured.
This criterion was applied concurrently with a maximum permitted contamination of 10 ppm of the previous active substance in the next product manufactured. Whichever of these criteria resulted in the lowest carryover, constituted the limit applied for cleaning validation. However, these limits did not take account of the available pharmacological and toxicological data They may have been too restrictive or not restrictive enough. EMA therefore felt for a more scientific case by case approach for all classes of pharmaceutical substances.
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.
The subject of cleaning validation in active pharmaceutical ingredient manufacturing plants has continued to receive a large amount of attention from regulators, companies and customers alike.
The integration of Cleaning Validation within an effective Quality System supported by Quality Risk Management Processes should give assurance that API Manufacturing Operations are performed in such a way that Risks to patients related to cleaning validation are understood, assessed for impact and are mitigated as necessary.
It is important that the requirements for the finished manufacturing companies are not transferred back in the process to active pharmaceutical ingredient manufacturers without consideration for the different processes that take place at this stage.
This presentation covers the requirements of Cleaning Validation for a Multipurpose API Manufactuirng Plant
Aseptic / sterile- “ A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbiological contamination of the exposed sterile product”
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
Good Manufacturing PracticeFor LVP,SVP, ophthalmic veterinary medicine, bulk chemicals & invitro diagnostic
For Good business Practice
A control process gives reproducibility & product consistency with in known limits
Provides license to do business.
Watch the presentation of this webinar here: https://bit.ly/3tDy8Ei
Recent PDA/BioPhorum publications outline risks for PUPSIT in sterilizing filtration. This webinar will summarize the key points and best practices for implementing PUPSIT.
PDA and BioPhorum have partnered to form a task force whose goal was to provide the industry and regulators with scientific data and analysis on the potential risks and benefits of implementing PUPSIT to improve sterility assurance. This webinar will describe the data generated by the task force studies and discuss considerations and best practices when implementing PUPSIT.
In this webinar, you will learn:
• How changing industry perspectives help overcome regulatory concerns and may influence regulatory perspective
• How improved process understanding affects risk assessment
• How improved final fill assembly design simplifies PUPSIT
EU GMP Annex 1 Draft: Implications on Sterilizing Grade Filter ValidationMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3kk0Qs1
In this webinar, you will learn:
- About the GMP Annex 1 draft regulatory overview
- How to incorporate the integrity testing & PUPSIT in the filtration systems validation
- How to design a bacterial retention test in terms of organism selection and single vs multiple use validation
Detailed description:
In this webinar we will discuss the implications of the EU GMP Annex 1 draft on the filtration of medicinal products and how this impacts the validation studies.
Bacterial Retention Testing is a critical part of the manufacturing validation process and is required by all regulatory bodies worldwide. Using case studies, our experts will explain how the Annex 1 draft is incorporated into the filtration systems validation exercise, specifically for integrity testing & PUPSIT (Pre-Use Post Sterilization Integrity Testing), the selection and justification of the appropriate test organism, and validation implications of single versus multiple use.
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.
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
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.
Problem formulation for environmental risk assessment in the context of EC Re...OECD Environment
The seminar on Problem Formulation for the Risk Assessment of Biopesticides stemmed from a previous CRP-sponsored event on Innovating Microbial Pesticide Testing that identified the need for an overarching guidance document to determine when in vivo tests are necessary. Problem Formulation, a common practice in pesticide risk assessment, was highlighted as a useful approach for addressing uncertainties in data requirements for biopesticides.
The seminar featured presentations from various perspectives, including industry, regulatory bodies, and academia. Topics included the history and principles of Problem Formulation, industry perspectives on Problem Formulation and how it is applied internally for microbial pesticides, regulatory approaches, and specific case studies. The seminar provided an overview of the challenges, considerations, and potential solutions in harmonising Problem Formulation for biopesticide risk assessment. It emphasised the need for collaboration and discussion to develop Problem Formulation guidance for biopesticides.
Phụ lục 1 tiêu chuẩn GMP EU về sản xuất thuốc vô trùng trong đó có các tiêu chuẩn về:
1. Hệ thống chất lượng thuốc vô trùng.
2. Nhân sự trong nhà máy thuốc vô trùng.
3. Nhà xưởng, trang thiết bị nhà máy thuốc vô trùng.
4. Hệ thống phụ trợ nhà máy thuốc vô trùng.
5. Công nghệ sản xuất.
6. Hệ thống giám sát, quản lý môi trường sản xuất và quá trình vận hành.
7. Kiểm soát chất lượng thành phẩm đầu ra
In this webinar, you will learn:
Sources of endotoxin contamination
Contamination control strategy
Endotoxin removal strategies
Detailed description:
Endotoxin, a lipopolysaccharide (LPS), is a type of pyrogen and is a component of the exterior cell wall of Gram-negative bacteria. To ensure safety on patient’s endotoxin content in the drug should always be controlled. In a biological processing it may emanate from facility, utility, raw materials, process, and personnel. In this webinar we discuss the regulatory norms, strategies for prevention & removal of endotoxin to ensure that the final drug product is safe.
Endotoxin Control and Clearance in BiomanufacturingMilliporeSigma
In this webinar, you will learn:
Sources of endotoxin contamination
Contamination control strategy
Endotoxin removal strategies
Detailed description:
Endotoxin, a lipopolysaccharide (LPS), is a type of pyrogen and is a component of the exterior cell wall of Gram-negative bacteria. To ensure safety on patient’s endotoxin content in the drug should always be controlled. In a biological processing it may emanate from facility, utility, raw materials, process, and personnel. In this webinar we discuss the regulatory norms, strategies for prevention & removal of endotoxin to ensure that the final drug product is safe.
Jukka Malm: European Regulatory Framework for Chemicals - Protecting Citizens...THL
Jukka Malm, Deputy Executive Director, European Chemicals Agency (ECHA), at Europe That Protects - Safeguarding Our Planet, Safeguarding Our Health EU side event, 3-4 Dec 2019, THL, Helsinki
Emerging research agenda in pesticide scienceDevakumar Jain
I request the users to cite the source while using any material from this presentation. Once this slide deck is used in my publication, it can be freely used.
Phụ lục 3 tiêu chuẩn GMP EU về sản xuất thuốc phóng xạ bao gồm:
1. Hệ thống chất lượng.
2. Nhân sự trong nhà máy thuốc phóng xạ.
3. Nhà xưởng, trang thiết bị nhà máy thuốc phóng xạ.
4. Hệ thống phụ trợ nhà máy thuốc phóng xạ.
5. Công nghệ sản xuất.
6. Hệ thống giám sát, quản lý môi trường sản xuất và quá trình vận hành.
7. Kiểm soát chất lượng thành phẩm đầu ra
Webinar on Best Environmental Practices (BEP) for Textiles (per- and polyfluo...OECD Environment
On 12 September 2018, Eeva Leinala of the OECD Environment Directorate and Kai Schubert from the Chemours Company presented Best Environmental Practices in the textile industry.
How to tackle chemicals of high concern in products – The construction Sector as a case study. Stylianos Kephalopoulos, Leader of Competence Group Exposure, European Commission – Joint Research Centre
Similar to EU GMP Annex 1 Draft - Closed System Design Consideration with Single-Use Systems (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.
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
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
Empowering ACOs: Leveraging Quality Management Tools for MIPS and BeyondHealth Catalyst
Join us as we delve into the crucial realm of quality reporting for MSSP (Medicare Shared Savings Program) Accountable Care Organizations (ACOs).
In this session, we will explore how a robust quality management solution can empower your organization to meet regulatory requirements and improve processes for MIPS reporting and internal quality programs. Learn how our MeasureAble application enables compliance and fosters continuous improvement.
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
The Importance of Community Nursing Care.pdfAD Healthcare
NDIS and Community 24/7 Nursing Care is a specific type of support that may be provided under the NDIS for individuals with complex medical needs who require ongoing nursing care in a community setting, such as their home or a supported accommodation facility.
Explore our infographic on 'Essential Metrics for Palliative Care Management' which highlights key performance indicators crucial for enhancing the quality and efficiency of palliative care services.
This visual guide breaks down important metrics across four categories: Patient-Centered Metrics, Care Efficiency Metrics, Quality of Life Metrics, and Staff Metrics. Each section is designed to help healthcare professionals monitor and improve care delivery for patients facing serious illnesses. Understand how to implement these metrics in your palliative care practices for better outcomes and higher satisfaction levels.
Medical Technology Tackles New Health Care Demand - Research Report - March 2...pchutichetpong
M Capital Group (“MCG”) predicts that with, against, despite, and even without the global pandemic, the medical technology (MedTech) industry shows signs of continuous healthy growth, driven by smaller, faster, and cheaper devices, growing demand for home-based applications, technological innovation, strategic acquisitions, investments, and SPAC listings. MCG predicts that this should reflects itself in annual growth of over 6%, well beyond 2028.
According to Chris Mouchabhani, Managing Partner at M Capital Group, “Despite all economic scenarios that one may consider, beyond overall economic shocks, medical technology should remain one of the most promising and robust sectors over the short to medium term and well beyond 2028.”
There is a movement towards home-based care for the elderly, next generation scanning and MRI devices, wearable technology, artificial intelligence incorporation, and online connectivity. Experts also see a focus on predictive, preventive, personalized, participatory, and precision medicine, with rising levels of integration of home care and technological innovation.
The average cost of treatment has been rising across the board, creating additional financial burdens to governments, healthcare providers and insurance companies. According to MCG, cost-per-inpatient-stay in the United States alone rose on average annually by over 13% between 2014 to 2021, leading MedTech to focus research efforts on optimized medical equipment at lower price points, whilst emphasizing portability and ease of use. Namely, 46% of the 1,008 medical technology companies in the 2021 MedTech Innovator (“MTI”) database are focusing on prevention, wellness, detection, or diagnosis, signaling a clear push for preventive care to also tackle costs.
In addition, there has also been a lasting impact on consumer and medical demand for home care, supported by the pandemic. Lockdowns, closure of care facilities, and healthcare systems subjected to capacity pressure, accelerated demand away from traditional inpatient care. Now, outpatient care solutions are driving industry production, with nearly 70% of recent diagnostics start-up companies producing products in areas such as ambulatory clinics, at-home care, and self-administered diagnostics.
Deep Leg Vein Thrombosis (DVT): Meaning, Causes, Symptoms, Treatment, and Mor...The Lifesciences Magazine
Deep Leg Vein Thrombosis occurs when a blood clot forms in one or more of the deep veins in the legs. These clots can impede blood flow, leading to severe complications.
ICH Guidelines for Pharmacovigilance.pdfNEHA GUPTA
The "ICH Guidelines for Pharmacovigilance" PDF provides a comprehensive overview of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines related to pharmacovigilance. These guidelines aim to ensure that drugs are safe and effective for patients by monitoring and assessing adverse effects, ensuring proper reporting systems, and improving risk management practices. The document is essential for professionals in the pharmaceutical industry, regulatory authorities, and healthcare providers, offering detailed procedures and standards for pharmacovigilance activities to enhance drug safety and protect public health.
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-Use Systems
1. The life science business of Merck operates
as MilliporeSigma in the U.S. and Canada.
Closed System Design Consideration with Single-Use
Systems
Somasundaram (Som), Senior Technical Consultant, Asia Pacific
Dr. Simone Biel, Senior Regulatory Consultant
EU GMP
Annex 1 Draft
4. “Closed system. Where a drug substance or product is not exposed to
the immediate room environment during manufacture.” (1)
“Live organisms and spores are prevented from entering non-related areas or
equipment by addressing all potential routes of cross-contamination and
utilizing single use components and engineering measures such as
closed systems.” (1)
“Closed or contained equipment should be used whenever
appropriate.” (2)
“Concurrent production of two different ATMPs/batches in the same area is not
acceptable. However, closed and contained systems may be used to
separate activities…” (3)
The use of closed systems [i.e. single use systems] can reduce the risk of
extraneous contamination such as microbial, particulate and chemical from
the adjacent environment (4)
(1) EudraLex Vol 4, Annex 2: Manufacture of Biological active substances and Medicinal Products for Human Use
(2) EudraLex Vol 4, Part II: Basic Requirements for Active Substances used as Starting Materials
(3) EudraLex Vol 4, Part IV: GMP Guiedelines specific to Advanced Therapy Medicinal Products
(4) EudraLex Vol 4, Annex 1 draft (2020): Manufacture of Sterile Products
Single-Use Systems to Reduce Cross-Contamination
Closed System – Some Quotes
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
5. Contamination Risks Throughout the Process
Manufacturing process can affect patient outcomes
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
6. Closed Systems – Benefits of Single-Use Technology
Compared to stainless-steel manufacturing
Benefits of single-use technologies
Speed to
market
Ease of use
Increased
productivity
• Plug and play
• Sterile connections
• Reduced room
classification stringency
• Decreased risk of
product cross-
contamination
• Elimination of SIP/CIP
and decontamination
process steps
• Reduced capital
investment in facility
and equipment
• Reduced time to get
facility up and running
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
7. Who is doing what?
Regulatory and Industry Expectations
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
Law
Country specific drug law
Regulatory Agencies
Provide regulations and recommendations
Market authorization
Surveillance
Compendia - Reference for quality control of
medicines
Ph. Eur is legally binding
USP standards are legally recognized
Harmonization effort
Through consensus organizations
Industry expectations
Interpretation and elaboration on regulatory
expectations
8. Ongoing consultation of new draft – global approach
EU GMP, Annex 1: Manufacture of Sterile Products
1971 → ensure sterility of medicinal
products
− Since then several updates
2017 → full review of Annex 1
− 140 companies provided more than
6200 comments
2020 → targeted stakeholder
consultation
− 16 organisations
− WHO and PIC/S to maintain
global alignment
PIC/S, The Pharmaceutical Inspection Co-
operation Scheme
non-binding, informal co-operative
arrangement between Regulatory
Authorities in the field of Good
Manufacturing Practice (GMP) of medicinal
products
54 participating authorities from Europe,
Africa, America, Asia and Australia
Mission:
lead the international development,
implementation and maintenance of
harmonised GMP standards and quality
systems of inspectorates in the field of
medicinal products.
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
9. Prevent any contamination in the final product
EU GMP Annex 1 draft – Scope
Scope
“…to provide guidance for the manufacture of sterile
products. However, some of the principles and guidance,
such as contamination control strategy, design of
premises, cleanroom classification, qualification,
monitoring and personnel gowning, may be used to
support the manufacture of other products that are not
intended to be sterile such as certain liquids, creams,
ointments and low bioburden biological intermediates but
where the control and reduction of microbial, particulate and
pyrogen contamination is considered important.”
Annex 1 draft, 2020
https://ec.europa.eu/health/sites/health/files/files/gmp/2020_annex1ps_sterile_medicinal_products_en.pdf
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
11. • Why & What is Contamination Control Strategy
• Understand the impact of bioburden excursions
• Recognize the sources of bioburden
• Develop strategies to mitigate risk
Contamination control strategy (CCS)
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
12. CCS – Definition & Regulatory Drivers
“A planned set of controls for microorganisms, pyrogens and particulates, derived from current product and process
understanding that assures process performance and product quality”.
The controls can include parameters and attributes related to active substance, excipient and drug product materials and
components, facility and equipment operating conditions, in-process controls, finished product specifications, and the
associated methods and frequency of monitoring and control.
EU GMP Annex 1 Draft 2020:
‘A contamination control strategy should be implemented across the facility in order to assess the effectiveness of all the
control and monitoring measures employed’
CCS is mentioned 44 times in the update
PIC/S GMP Part I, 2021:
‘Cross-contamination should be prevented for all products by appropriate design and operation of manufacturing facilities.
The measures to prevent cross contamination should be commensurate with the risks. Quality Risk Management
principles should be used to assess and control the risks’
‘5.10 At every stage of processing, materials and products should be protected from
microbial and other contamination’
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
13. Contamination Control Strategy: Holistic program
that encompasses concepts within the context of the
entire manufacturing facility and process
Facility Design: Designed according to GMP Regulations
/ Guidelines, Best practice and process requirements
Personnel: Gowning regime with personnel monitoring
program, suitable limits and action plan, training and
culture
Cleaning and Disinfection/Sterilisation: Consistent
removal of soiling and microbial load deactivation
Environmental Monitoring: Monitor viable and non-
viable, suitable limits and action plan
Process Simulation: End to end testing including
intervention assessment and worse case stressing
Process Design: Process controls including GMP and
GEP to ensure product is microbial/pyrogen, chemical,
non-viable and cross-contamination free.
What is a Contamination Control Strategy
Process
Design
Process
Simulation
Environmental
Monitoring
Cleaning &
Disinfection/Sterlisation
Personnel
Facility Design
Contamination
Control Strategy
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
15. 30
Percent
1- 6
Months
1-14
Million Euro
Percent of process deviations
caused by contamination*
Length of time to complete
an investigation
Operations cost
*Sources Langer 2013, Wiebe 2014
Biologics in-process contamination
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
16. 30
Percent
1- 6
Months
1-14
Million Euro
*Sources Langer 2013, Wiebe 2014
Biologics in-process contamination
Impact
Productivity losses
Material replacement costs
Batch loss
Interruption of product supply
Delay in clinical development
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
18. Facility & Environment
Equipment
Processes
Materials
Utilities
Personnel
Each source
contributes
to the
process
bioburden
profile
Sources of bioburden
Staphylococcus
Bacillus
Non-fermenting
Gram Negative
rods
Aspergillus
Source: Public domain CDC/
Robert Simmons
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
19. • Many routes for microbial ingress
• Bioburden excursions are often the result of
− Improper cleaning, storage, or sanitization
− Suboptimal system design
− Aseptic connections
− Sampling
− Lapses in aseptic technique
Intensive risk assessments can prevent many of these contaminations or excursions
Key Points
Sources of bioburden
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
20. Downstream
Risk profile & control strategies differ throughout the process
Secondary
Clarification
Chromatography
Protein A
Final Filling
Final Sterile
Filtration
Concentration
& Formulation
Bulk Storage
and Transport
Viral
Inactivation
Chromatography
CEX
Virus Filtration
Clearance
Ultrafiltration /
Diafiltration
Bioreactor
Primary
Clarification
MCB WCB Seed Train
Raw Materials
Filtration Bioburden
Reduction
Bioburden
Reduction
Chromatography
AEX
Bioburden
Reduction
Bioburden
Reduction
Final Fill
Risk Areas
Upstream
Downstream
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
21. The risk profile varies from upstream to final fill
Risk Hammock
Upstream Downstream Finish and Fill
Operations
Risk
High
Low
Aseptic Aseptic
Bioburden Controlled
“The level of effort, formality and
documentation of the quality risk
management process should align
with the level of risk”
(ICH Q9A)
Shifting “the QRM focus from
reactive to proactive will enable
continual improvement to become a
key aspect of the PQS. Revision of
ICH Q9 is of strategic importance.
ICH Q(R1) Concept Paper, 2020
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
23. Assess Risks
Key Points
▪ Characterize the microbial profile of the process
▪ Utilize a combination of assessment tools
▪ A cross-functional team is crucial to the process
▪ Your Bioburden risk mitigation strategy should
address
▪ Patient safety
▪ Drug supply
▪ Business risk
0
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
24. Prevent Contamination by Containment (Risk Mitigation)
Implement Single Use Systems and Closed Sampling
Eliminate
bioburden
contribution
Prevent
microbial
ingress
Minimize
process
validation
Mitigate
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
25. Downstream Monitoring
What do I test for? Where? Why?
Chromatography
Protein A
Bulk Storage
and Transport
Viral
Inactivation
Chromatography
CEX
Virus Filtration
Clearance
Ultrafiltration /
Diafiltration
Bioburden
Reduction
Bioburden
Reduction
Chromatography
AEX
Bioburden
Reduction
Bioburden
Reduction
Bioburden
Virus
Mycoplasma
Endotoxin
V
M
B
E
B
E
B
E
B
E
V
E
V
E
B
E
B
E
M
Monitor
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
27. Case Study
Bioburden/Endotoxin excursions in the Protein A Pool
Chrom
Protein A
Bulk
Storage and
Transport
Viral
Inactivation
Chrom
CEX
Virus
Filtration
Clearance
Ultrafiltration
Diafiltration
Bioburden
Reduction
Bioburden
Reduction
Chrom
AEX
Bioburden
Reduction
Bioburden
Reduction
Situation
• Spore-forming bioburden alert-level excursions in the
Protein A pool over several campaigns
Root Cause
• Failure to recognize a trend in the pattern of excursions
• Sanitization solution was not sporicidal
• Sub-optimal sanitization process
Corrective and Preventative Actions
• Scale down studies with a new sanitizer and
optimization of sanitization conditions
• Process scale verification
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
28. Case Study
Bioburden action-level excursions of in the UF/DF step
Chrom
Protein A
Bulk
Storage and
Transport
Viral
Inactivation
Chrom
CEX
Virus
Filtration
Clearance
Ultrafiltration
Diafiltration
Bioburden
Reduction
Bioburden
Reduction
Chrom
AEX
Bioburden
Reduction
Bioburden
Reduction
Situation
• Bioburden and endotoxin exceeded action levels in
multiple batches
• Intensive investigation of the process and support areas
Root Cause
• Bioburden formation in the TFF cassettes due to inadequate
cleaning and storage processes
Corrective and Preventative Actions
• Improve cleaning and storage processes
• Sterilization or sanitization of buffer tanks
• Assessment of the water for injection (WFI) system and
transfer lines
• Introduction of bioburden reducing filters
• Validation of hold times and storage conditions
• Revision of bioburden limits based on process capability
Buffer, Sanitizer, and
Storage Solutions
Operations
WFI
Operation
Suvarna K. et. al. “Case Studies of Microbial Contamination in Biologic Product”,
American Pharmaceutical Review 14(1) January/February 2011.
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
29. Case Study
Sporadic bioburden action-level excursions
Chrom
Protein A
Bulk
Storage and
Transport
Viral
Inactivation
Chrom
CEX
Virus
Filtration
Clearance
Ultrafiltration
Diafiltration
Bioburden
Reduction
Bioburden
Reduction
Chrom
AEX
Bioburden
Reduction
Bioburden
Reduction
Situation
• Sporadic mixed bioburden excursions at multiple
points in the downstream process
Root Cause
• Aseptic connections of equipment and sampling devices
Corrective and Preventative Actions
• Short term:
• Retrained operators in aseptic techniques
• Long term:
• Reduced the number of aseptic connections
• Implemented sterile to sterile connectors and steam
to sterile connectors.
• Introduced a facility-wide sterile sampling system
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
30. Case study
Bulk solution contamination with Bacillus species
Chrom
Protein A
Bulk
Storage and
Transport
Viral
Inactivation
Chrom
CEX
Virus
Filtration
Clearance
Ultrafiltration
Diafiltration
Bioburden
Reduction
Bioburden
Reduction
Chrom
AEX
Bioburden
Reduction
Bioburden
Reduction
Situation
• Prefiltration bioburden load was 20 x the
specification
• Bacillus species suggested a steam-in-place issue
Root Cause
• Equipment design: improper pipe slope resulted in cold
spots that were insufficiently sterilized
Corrective and Preventative Actions
• Discard (scrap) the batch
• Redesign piping
• Requalify SIP (steam-in-place) cycle
• New processes will use single-use storage systems
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
32. Formulation Filtration Filling
Connect Connect
Closed processing (maintaining sterility)
Entire process can be designed with single-use assemblies
Focus: Sterile Production
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
33. Lots of components, connections, assemblies
Your Single-Use System Process
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
34. Critical steps are transferred from end-user to supplier
SUT in Manufacturing – Considerations
EU GMP Annex 1 draft (Feb 2020)
“specific risks associated with SUS” → contamination control
strategy
− Interaction with DP and SUS surface
− Integrity (“fragile”, “risk of holes and leakage”, “complexity”
− Risk of particulate contamination
Some guidance
− Supplier qualification, including sterilization verification
− Evaluation of adsorption and reactivity of product
− Verification of integrity throughout the process
− Establish acceptance criteria and incoming control procedure
− Operator training
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
35. A Collaboration between Supplier and End User
Integrity Assurance
Components
Bag and
assembly
manufacture
Packaging
and shipping
Receipt and
unpacking
Pre-use
stage
Post-use
stage
Tear resistant
and superior
bond strength
bag film
Sterile connector
integrity test
Quality by
design
Automated bag
bonding
Visual inspection
Integrity/leak
test
Define packaging
instructions
Shelf life
validation
Shipping
validation
Best handling
practices
Visual inspection
to confirm the
design
Best practices
for installation
Point of use
integrity/leak
test
Visual
verification
Supplier
End-user
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
36. Do you know what your supplier does?
Manufacturing and Control
Bag manufacturing
Automation
Validated process
In-process leak test
Assembly
Standard operating
procedures
Operator training
In-process controls
Release testing
Visual inspection
Final product leak testing
Fluid path water extract
testing (particles, endotoxin)
Leak/integrity testing
Various methods depending
on application and sensitivity
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
37. Leak Test Integrity Test Helium Integrity Test
Leak Test vs Integrity Test
Release Test
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
Detects defects of a known size that have a correlation to a known
parameter using a specific test methodology such as aerosolized or
liquid bacterial ingress.
Detects gross leaks in a system
Decreasing Defect Detection Size Limit
Increasing Level of Risk-Reduction
System Volume
Approximate
Detection Limit
Tubing Assemblies 50 µm
1 – 9 L 150 µm
10 – 999 L 1000 µm
>1,000 L 2000 µm
System Volume
Validated
Detection Limit
Tubing Assemblies 20 µm
Up to 50 L 20 µm
System Volume
Validated
Detection Limit
Tubing Assemblies 2 µm
Up to 50L 2 µm
38. Aerosol Challenge Test
Bags with known defect sizes (filled with TSB)
Microbial aerosol concentration 106 cfu/ml
60 mins
Correlation between leak size and bacterial ingress
Single-Use System Integrity Test
Incubation
30-35 °C
14 days
Result
Growth present in bags with
defects 12.65 µm or greater
BPSA Technical Guide, Design, Control, and Monitoring of Single-use Systems for Integrity Assurance, 2017
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
39. ISO 11137, Sterilization of Health Care Products — Radiation
Sterilization Validation
Irradiation Process
− Development, validation, and routine control of
sterilization process (VDmax)
− Establishing sterilization dose with SAL <10-6
− Guidance on dosimetric measurement of
radiation
Quarterly dose audits to substantiate the
sterilization dose on an on-going basis.
− Demonstrate clean environment by testing
bioburden of reference assemblies pre-gamma
− Sterility test after low irradiation dose
Review of historical data over the last decade
− verifies robustness of sterility validation
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
40. Ensure integrity during shipment
Packaging Design
Protect rigid components
Qualified packaging
material (shelf life, low
particle load, outgassing)
Ensure that easy unpacking
is possible
Vacuum in packaging bags
to avoid movement of
components
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
41. Ensure Integrity during shipment
Transport Validation
Manufacturing
Visual inspection
Leak test (assembly)
assembly packaged
and boxed per
packaging SOP
Gamma irradiation
(25-40kGy)
ISTA 2A treatment
1st Vibration Test
Impact Test (drop
Test)
2nd Vibration Test
Bubble Emission
testing of vacuum
sealed packaging
bags
Visual inspection
Leak test (assembly)
ISTA 2A
Reference
Assembly
Irradiation Testing
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
42. Proper installation of SUS is key to keep integrity
New Handling Procedures for End-User
Outside
Isolator
Inside
Isolator
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
43. Combined filtration and filling set
Dosing pump inside isolator
Dosing pump
outside isolator
Sterile connection
device required
There is no common or standard approach
Final Filling Single-Use Set - Examples
Grade C Grade A
Bulk
Product
Peristaltic
Pump
Sterile
Filter
Header
Bag
Peristaltic
Pump
Filling
Needle
Grade C Grade A
Bulk
Product
Peristaltic
Pump
Sterile
Filter
Header
Bag
Peristaltic
Pump
Filling
Needle
Sterile filtration
inside isolator
Transfer of entire
SUS via Getinge
DPTE® Beta Bag
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
44. 8.118 It is critical to ensure the sterility of all product contact surfaces of
closed systems used for aseptic processing. The design and selection of any
closed system used for aseptic processing should ensure maintenance of
sterility. Connection of sterile equipment (e.g. tubing / pipework) to
the sterilized product pathway after the final sterilizing filter should
be designed to be connected aseptically (e.g. by intrinsic aseptic
connectors or fusion systems).
8.119 Appropriate measures should be in place to ensure the integrity
of components used in aseptic connections. The means by which this is
achieved should be determined and captured in the CCS. Appropriate
system integrity tests should be considered when there is a risk of
compromising product sterility. Supplier assessment should include the
collation of data in relation to potential failure modes that may lead to a loss
of system sterility.
8.120 The background in which closed systems are located should be based on
their design and the processes undertaken. For aseptic processing and where
there are any risks that system integrity may be compromised, the system
should be located in a Grade A zone. If the system can be shown to
remain integral at every usage (e.g. via pressure testing and/or
monitoring) then a lower classified area may be used.
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
“Determined and captured in the Cross-Contamination Strategy”
Annex 1 Draft and Closed Systems
45. Reduce complexity and keep flexibility of the SUS
Sterile Connection Device
Handling
Quick and easy
Avoid operator mistakes
Design
Robust and consistent
performance
100% air-integrity tested in
manufacturing
Validation
Aerosolized microbial challenge test
Media fill
Brevundimonas diminuta aerosol
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
46. SUS enable your process closed!
Microbial & Particulate contamination present
a real & underappreciated risk
Testing is just one aspect of integrity
assurance
Include your SUS supplier in your
cross-contamination/contamination
control strategy
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-use Systems
Reduce complexity with the right SUS design
to enable easy operator handling
Impact of Microbial contamination/excursions
can be highly significant