Journey in the Development of Biologics Through End of Phase 3
Our Goals
To better understand the FDA’s CMC requirements and expectations for biologic manufacturing and product testing
To better visualize a cost-effective, risk-managed approach to manage these manufacturing processes and products through clinical development into market approval
To better appreciate the challenges involved with controlling safety, potency, and impurity profiles for these products
Process Development for Cell Therapy and Viral Gene TherapyMerck Life Sciences
Today’s viral vector manufacturing processes remain challenging. Process development is a critical enabler to bring safe, effective, sustainable products to market to address patient needs. When done properly, it can reduce the timeline of the project and the cost of producing the therapeutic product.
The webinar discusses our strategies for developing lentivirus and adeno associated virus (AAV) and the impact these early decisions can have on commercial readiness.
Watch the interactive webinar now: https://bit.ly/2VplwQq
Biosafety in Gene Therapy: Applying the latest regulatory guidance for RCL te...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/33WUiqE
Ensuring the safety and quality of your lentiviral vector is of the utmost importance. Attend this webinar to learn about testing strategies to monitor replication competent lentivirus. You will also hear about recent changes in regulatory guidance with regards to sample types and volumes tested.
The use of lentivirus vectors to produce groundbreaking gene therapies is on the rise. Ensuring the biosafety and quality of these vectors is achieved through a multi-tiered testing approach.
For lentivirus-based therapies, generation of replication competent particles is a potential risk. While improvements in design and manufacturing have decreased the probability of producing replication competent viruses, regulatory agencies provide guidelines to test for their presence at multiple stages in production. This webinar reviews the strategies for monitoring replication competent lentiviruses. We describe current methods and address: Sample types, testing volumes, and expected results.
In this webinar, you will learn about:
• The latest FDA regulatory guidelines on replication competent lentivirus (RCL) testing
• Methods used to monitor RCL
• Considerations on sample type and volume requirements
Risk Mitigation in Cell Line Development: Regulatory Considerations and Impac...Merck Life Sciences
In this webinar, you will learn about:
- Risk assessment approaches in upstream process development
- How early cell line development stage is linked to subsequent steps in the bioprocess to assure the quality of the final product
- Benefits of having a completely chemically defined cell line development process
Detailed description:
Chinese Hamster Ovary (CHO) cells are the preferred host for producing biotherapeutics where cell line development (CLD) is the foundation of the bioprocess. CLD processes are expected to be robust while meeting a myriad of regulatory requirements. The choice of production cell line, culture conditions, and having a chemically defined (CD) CLD process by using CD cloning media can impact the subsequent measures for the CMC (Chemistry, manufacturing, and controls).
In this presentation, we will discuss these choices and their impacts on subsequent bioprocess and CMC testing required by regulations and the benefits of incorporating CD cloning media into the CHOZN® expression platform.
Releasing Your AAV Therapy with Confidence: Regulatory Considerations and Key...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3icKkbZ
Ensuring the safety and quality of your AAV vector is of the utmost importance. Join this webinar for a high-level overview of the regulatory requirements for AAV testing throughout the manufacturing process, as well as a more detailed look at rcAAV and infectious titer assays.
Adeno-associated virus (AAV) vectors possess a number of advantages for use in human therapy including: high titer preparations, low immunogenicity, capacity to infect a wide range of cell types, and replication deficiency. Even with these advantages, there are biosafety concerns to consider when using AAV vectors.
This webinar will discuss key regulatory considerations across the manufacturing process, from the helper/packaging plasmids through to lot release testing. We will highlight critical assays that are required and delve into specifics on replication competent AAV testing and infectious titer determination by TCID50.
In this webinar, you will learn:
• Critical biosafety considerations for AAV vectors based on the latest regulatory guidance
• How replication competent AAV testing fits into your bulk and final release testing package
• The benefits of routine and platform assays over custom assay development
Presented by:
Steven McDade, Senior Technical Specialist, Field Technology Management
Alfonso Lavorgna, Ph.D., Operations Manager, Virology Services
An Integrated Approach to Ensure Viral Vector and Gene Therapy Commercial Rea...MilliporeSigma
Come learn more about our integrated approach to ensure viral vector and gene therapy commercial readiness. We will discuss topics relating to process development for viral vector manufacturing, biosafety testing and commercial readiness.
Significant progress has been made for the use of viral vectors for gene therapy. Promising clinical trial results as well as recent FDA approval for CAR-T cell therapy to treat certain children and young adults with B-cell lymphoblastic leukemia have signaled advancements in the field. This marks a historic action, providing opportunities for new viral vector technologies to transform medicine and the way patients are treated and even cured. The need for process development for viral vector manufacturing to improve yield to meet patient demand, biosafety testing for product characterization, potency and safety and commercial readiness to accelerate therapy to-market are critically important. Here, we emphasis an integrated approach that allows our customers solutions to ensure viral vector and gene therapy commercial readiness to meet the growing market need.
In this webinar, you will learn:
● Process development advances for production scale-up of viral vectors for gene therapy
● Methods specific for viral gene therapy product characterization, purity, potency, safety and release testing
● Commercial readiness through our US and UK Centers of Excellence for viral product manufacturing
Process development guidance for AAV and lentivirus manufacturing based on co...MilliporeSigma
Access the interactive recording here: https://bit.ly/37nl3Ex
Webinar summary:
An efficient production platform is essential for successful commercial implementation of gene therapy programs. AAV and Lentivirus manufacturing process are often developed with compressed timelines, reduced process optimization and low product yields which can have significant effect on costs.
In this webinar, you will learn:
* How manufacturing costs are examined for adeno-associated virus and lentivirus production with several different for each vector
* That key process characteristics like production titer, production of empty viral particles, downstream product recovery, and the batching strategy can effect the overall manufacturing cost
* How holistic evaluation is an important tool during process development to help prioritize different approaches to improve viral vector production processes
Abstract:
An efficient production platform is essential for successful commercial implementation of gene therapy programs. Viral vector manufacturing processes are often developed under timelines which are considerably shorter than those for more mature biopharmaceuticals. Consequently, the level of process optimization is reduced and challenges related to low product yields are common. These factors, as well as the small batch sizes common for these processes, can have significant effect on manufacturing costs.
Latest Updates in Biosafety Testing for Gene TherapyMilliporeSigma
The field of Gene Therapy is moving at a fast pace providing promise of lifesaving medicines to previously unmet clinical needs. Of significant importance in the development of these novel therapies is the ability to demonstrate their safety including freedom from adventitious agents originating from raw materials or introduced during the manufacturing process.
It can be challenging, in such a fast moving field, to identify and navigate the relevant regulatory requirements and expectations for biosafety testing of such therapies. So too it can be difficult to select the optimal test methods in light of limited product availability and shelf life. Encompassing current biosafety testing approaches for bacteria, fungi, mycoplasma and viruses on starting materials to drug product, this webinar will provide you with the fundamentals to design your own Gene Therapy testing strategy.
In this webinar, you will learn:
• The most up to date regulatory expectations for Gene Therapies
• How to design a testing strategy to meet US FDA and EMA requirements
• How selecting the right biosafety test can overcome some of the unique challenges with Gene Therapies
Process Development for Cell Therapy and Viral Gene TherapyMerck Life Sciences
Today’s viral vector manufacturing processes remain challenging. Process development is a critical enabler to bring safe, effective, sustainable products to market to address patient needs. When done properly, it can reduce the timeline of the project and the cost of producing the therapeutic product.
The webinar discusses our strategies for developing lentivirus and adeno associated virus (AAV) and the impact these early decisions can have on commercial readiness.
Watch the interactive webinar now: https://bit.ly/2VplwQq
Biosafety in Gene Therapy: Applying the latest regulatory guidance for RCL te...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/33WUiqE
Ensuring the safety and quality of your lentiviral vector is of the utmost importance. Attend this webinar to learn about testing strategies to monitor replication competent lentivirus. You will also hear about recent changes in regulatory guidance with regards to sample types and volumes tested.
The use of lentivirus vectors to produce groundbreaking gene therapies is on the rise. Ensuring the biosafety and quality of these vectors is achieved through a multi-tiered testing approach.
For lentivirus-based therapies, generation of replication competent particles is a potential risk. While improvements in design and manufacturing have decreased the probability of producing replication competent viruses, regulatory agencies provide guidelines to test for their presence at multiple stages in production. This webinar reviews the strategies for monitoring replication competent lentiviruses. We describe current methods and address: Sample types, testing volumes, and expected results.
In this webinar, you will learn about:
• The latest FDA regulatory guidelines on replication competent lentivirus (RCL) testing
• Methods used to monitor RCL
• Considerations on sample type and volume requirements
Risk Mitigation in Cell Line Development: Regulatory Considerations and Impac...Merck Life Sciences
In this webinar, you will learn about:
- Risk assessment approaches in upstream process development
- How early cell line development stage is linked to subsequent steps in the bioprocess to assure the quality of the final product
- Benefits of having a completely chemically defined cell line development process
Detailed description:
Chinese Hamster Ovary (CHO) cells are the preferred host for producing biotherapeutics where cell line development (CLD) is the foundation of the bioprocess. CLD processes are expected to be robust while meeting a myriad of regulatory requirements. The choice of production cell line, culture conditions, and having a chemically defined (CD) CLD process by using CD cloning media can impact the subsequent measures for the CMC (Chemistry, manufacturing, and controls).
In this presentation, we will discuss these choices and their impacts on subsequent bioprocess and CMC testing required by regulations and the benefits of incorporating CD cloning media into the CHOZN® expression platform.
Releasing Your AAV Therapy with Confidence: Regulatory Considerations and Key...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3icKkbZ
Ensuring the safety and quality of your AAV vector is of the utmost importance. Join this webinar for a high-level overview of the regulatory requirements for AAV testing throughout the manufacturing process, as well as a more detailed look at rcAAV and infectious titer assays.
Adeno-associated virus (AAV) vectors possess a number of advantages for use in human therapy including: high titer preparations, low immunogenicity, capacity to infect a wide range of cell types, and replication deficiency. Even with these advantages, there are biosafety concerns to consider when using AAV vectors.
This webinar will discuss key regulatory considerations across the manufacturing process, from the helper/packaging plasmids through to lot release testing. We will highlight critical assays that are required and delve into specifics on replication competent AAV testing and infectious titer determination by TCID50.
In this webinar, you will learn:
• Critical biosafety considerations for AAV vectors based on the latest regulatory guidance
• How replication competent AAV testing fits into your bulk and final release testing package
• The benefits of routine and platform assays over custom assay development
Presented by:
Steven McDade, Senior Technical Specialist, Field Technology Management
Alfonso Lavorgna, Ph.D., Operations Manager, Virology Services
An Integrated Approach to Ensure Viral Vector and Gene Therapy Commercial Rea...MilliporeSigma
Come learn more about our integrated approach to ensure viral vector and gene therapy commercial readiness. We will discuss topics relating to process development for viral vector manufacturing, biosafety testing and commercial readiness.
Significant progress has been made for the use of viral vectors for gene therapy. Promising clinical trial results as well as recent FDA approval for CAR-T cell therapy to treat certain children and young adults with B-cell lymphoblastic leukemia have signaled advancements in the field. This marks a historic action, providing opportunities for new viral vector technologies to transform medicine and the way patients are treated and even cured. The need for process development for viral vector manufacturing to improve yield to meet patient demand, biosafety testing for product characterization, potency and safety and commercial readiness to accelerate therapy to-market are critically important. Here, we emphasis an integrated approach that allows our customers solutions to ensure viral vector and gene therapy commercial readiness to meet the growing market need.
In this webinar, you will learn:
● Process development advances for production scale-up of viral vectors for gene therapy
● Methods specific for viral gene therapy product characterization, purity, potency, safety and release testing
● Commercial readiness through our US and UK Centers of Excellence for viral product manufacturing
Process development guidance for AAV and lentivirus manufacturing based on co...MilliporeSigma
Access the interactive recording here: https://bit.ly/37nl3Ex
Webinar summary:
An efficient production platform is essential for successful commercial implementation of gene therapy programs. AAV and Lentivirus manufacturing process are often developed with compressed timelines, reduced process optimization and low product yields which can have significant effect on costs.
In this webinar, you will learn:
* How manufacturing costs are examined for adeno-associated virus and lentivirus production with several different for each vector
* That key process characteristics like production titer, production of empty viral particles, downstream product recovery, and the batching strategy can effect the overall manufacturing cost
* How holistic evaluation is an important tool during process development to help prioritize different approaches to improve viral vector production processes
Abstract:
An efficient production platform is essential for successful commercial implementation of gene therapy programs. Viral vector manufacturing processes are often developed under timelines which are considerably shorter than those for more mature biopharmaceuticals. Consequently, the level of process optimization is reduced and challenges related to low product yields are common. These factors, as well as the small batch sizes common for these processes, can have significant effect on manufacturing costs.
Latest Updates in Biosafety Testing for Gene TherapyMilliporeSigma
The field of Gene Therapy is moving at a fast pace providing promise of lifesaving medicines to previously unmet clinical needs. Of significant importance in the development of these novel therapies is the ability to demonstrate their safety including freedom from adventitious agents originating from raw materials or introduced during the manufacturing process.
It can be challenging, in such a fast moving field, to identify and navigate the relevant regulatory requirements and expectations for biosafety testing of such therapies. So too it can be difficult to select the optimal test methods in light of limited product availability and shelf life. Encompassing current biosafety testing approaches for bacteria, fungi, mycoplasma and viruses on starting materials to drug product, this webinar will provide you with the fundamentals to design your own Gene Therapy testing strategy.
In this webinar, you will learn:
• The most up to date regulatory expectations for Gene Therapies
• How to design a testing strategy to meet US FDA and EMA requirements
• How selecting the right biosafety test can overcome some of the unique challenges with Gene Therapies
USFDA Approval Process For Drug Products & Biological Product i.e NDA Vs. BLA
Comparison of NDA and BLA application process in USA. IND, NDA, ANDA & BLA dossier submission procedure.
Process Development for Cell Therapy and Viral Gene TherapyMilliporeSigma
Today’s viral vector manufacturing processes remain challenging. Process development is a critical enabler to bring safe, effective, sustainable products to market to address patient needs. When done properly, it can reduce the timeline of the project and the cost of producing the therapeutic product.
The webinar discusses our strategies for developing lentivirus and adeno associated virus (AAV) and the impact these early decisions can have on commercial readiness.
Watch the interactive webinar now: https://bit.ly/2VplwQq
The Role of Process Characterization in Process ValidationDavid Goodrich
Process characterization is an activity used to identify and quantify significant process factors and sources of variation. It defines the relationship between process inputs and outputs, and establishes process limits for the significant process parameters. Process characterization is perhaps the most important activity to assure a robust process and a successful process validation. The presentation will discuss requirements and deliverables for a process characterization and will use case studies to provide characterization study examples.
Presented at the 2016 Cowtown Quality Roundup (Greater Fort Worth ASQ Section)
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
Vaccine Cell Bank and Virus Seed CharacterizationMilliporeSigma
In this webinar, you will learn:
- about the importance of characterising cell banks and virus seed stocks in order to meet worldwide regulatory requirements.
- the difference between guidance documents from different organizations worldwide
- new technologies for determining the identity of cell substrates and virus seed stocks
- detecting adventitious agent contamination
Releasing Your AAV Therapy with Confidence: Regulatory Considerations and Key...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3icKkbZ
Ensuring the safety and quality of your AAV vector is of the utmost importance. Join this webinar for a high-level overview of the regulatory requirements for AAV testing throughout the manufacturing process, as well as a more detailed look at rcAAV and infectious titer assays.
Adeno-associated virus (AAV) vectors possess a number of advantages for use in human therapy including: high titer preparations, low immunogenicity, capacity to infect a wide range of cell types, and replication deficiency. Even with these advantages, there are biosafety concerns to consider when using AAV vectors.
This webinar will discuss key regulatory considerations across the manufacturing process, from the helper/packaging plasmids through to lot release testing. We will highlight critical assays that are required and delve into specifics on replication competent AAV testing and infectious titer determination by TCID50.
In this webinar, you will learn:
• Critical biosafety considerations for AAV vectors based on the latest regulatory guidance
• How replication competent AAV testing fits into your bulk and final release testing package
• The benefits of routine and platform assays over custom assay development
Presented by:
Steven McDade, Senior Technical Specialist, Field Technology Management
Alfonso Lavorgna, Ph.D., Operations Manager, Virology Services
This presentation gives an idea about extractable and leachables, Analytical techniques used for conducting studies. importance of conducting E&L studies.
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...Merck Life Sciences
Register for the interactive, on-demand webinar now: https://bit.ly/USP665
Single-use plastic systems are being utilized more frequently especially for COVID-19 vaccine manufacturing. However, there are issues regarding standardization of quality information that limits implementation efficiencies. One of the challenges is the evaluation of leachables derived from a variety of different plastic components in a timely manner.
Since the USP <665> highlights a risk assessment approach with no typical pass/fail limit, approaches to decision-making based on the extractables data package will be reviewed. In addition, we will highlight legacy testing requirements which may not be necessary once USP <665> is implemented.
In this webinar, we will discuss:
- Regulatory expectations of extractables and leachables assessment today and tomorrow
- The right criteria that need to be assessed to select the type and quality of plastic materials for use in biopharmaceutical manufacturing
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
Learn how Quality By Design (QBD) principles can be applied to understand the critical processing and feed parameters affecting virus retention, allowing the development of a streamlined validation approach and robust process control strategy for virus clearance via filtration.
In this webinar, you will learn:
•How to simplify validation study design
•Identify critical process and feed parameters affecting virus retention
•How to compile a robust regulatory filing package
Abstract:
ICH Q8 defines Quality by Design (QbD) as “…a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on quality risk management.” Within the context of virus clearance for bioprocesses, QbD principles can be applied to understand the critical processing and feed parameters affecting virus retention, guiding the development of a streamlined validation approach and robust process control strategy for virus clearance unit operations. We will explore how QbD principles can be applied to downstream virus filtration of mAbs and recombinants, the application of these principles within the framework of the Viresolve® Pro Device (parvovirus retentive filter), the benefits through simplifying the validation strategy and increasing the robustness of your regulatory filing package.
This presentation from IVT Network's Method Validation Conference covers required and suggested regulations and guidances for biological process specifications. It also covers dosage form considerations and specifications for other components.
By choosing Covance as a single, centralized CMC analytical laboratory, you can obtain higher quality analytical data more efficiently and at lower cost/fewer resources than by working with multiple providers/CMOs. This analytical data is the key to knowledge and quality risk management throughout the product lifecycle.
USFDA Approval Process For Drug Products & Biological Product i.e NDA Vs. BLA
Comparison of NDA and BLA application process in USA. IND, NDA, ANDA & BLA dossier submission procedure.
Process Development for Cell Therapy and Viral Gene TherapyMilliporeSigma
Today’s viral vector manufacturing processes remain challenging. Process development is a critical enabler to bring safe, effective, sustainable products to market to address patient needs. When done properly, it can reduce the timeline of the project and the cost of producing the therapeutic product.
The webinar discusses our strategies for developing lentivirus and adeno associated virus (AAV) and the impact these early decisions can have on commercial readiness.
Watch the interactive webinar now: https://bit.ly/2VplwQq
The Role of Process Characterization in Process ValidationDavid Goodrich
Process characterization is an activity used to identify and quantify significant process factors and sources of variation. It defines the relationship between process inputs and outputs, and establishes process limits for the significant process parameters. Process characterization is perhaps the most important activity to assure a robust process and a successful process validation. The presentation will discuss requirements and deliverables for a process characterization and will use case studies to provide characterization study examples.
Presented at the 2016 Cowtown Quality Roundup (Greater Fort Worth ASQ Section)
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
Vaccine Cell Bank and Virus Seed CharacterizationMilliporeSigma
In this webinar, you will learn:
- about the importance of characterising cell banks and virus seed stocks in order to meet worldwide regulatory requirements.
- the difference between guidance documents from different organizations worldwide
- new technologies for determining the identity of cell substrates and virus seed stocks
- detecting adventitious agent contamination
Releasing Your AAV Therapy with Confidence: Regulatory Considerations and Key...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3icKkbZ
Ensuring the safety and quality of your AAV vector is of the utmost importance. Join this webinar for a high-level overview of the regulatory requirements for AAV testing throughout the manufacturing process, as well as a more detailed look at rcAAV and infectious titer assays.
Adeno-associated virus (AAV) vectors possess a number of advantages for use in human therapy including: high titer preparations, low immunogenicity, capacity to infect a wide range of cell types, and replication deficiency. Even with these advantages, there are biosafety concerns to consider when using AAV vectors.
This webinar will discuss key regulatory considerations across the manufacturing process, from the helper/packaging plasmids through to lot release testing. We will highlight critical assays that are required and delve into specifics on replication competent AAV testing and infectious titer determination by TCID50.
In this webinar, you will learn:
• Critical biosafety considerations for AAV vectors based on the latest regulatory guidance
• How replication competent AAV testing fits into your bulk and final release testing package
• The benefits of routine and platform assays over custom assay development
Presented by:
Steven McDade, Senior Technical Specialist, Field Technology Management
Alfonso Lavorgna, Ph.D., Operations Manager, Virology Services
This presentation gives an idea about extractable and leachables, Analytical techniques used for conducting studies. importance of conducting E&L studies.
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...Merck Life Sciences
Register for the interactive, on-demand webinar now: https://bit.ly/USP665
Single-use plastic systems are being utilized more frequently especially for COVID-19 vaccine manufacturing. However, there are issues regarding standardization of quality information that limits implementation efficiencies. One of the challenges is the evaluation of leachables derived from a variety of different plastic components in a timely manner.
Since the USP <665> highlights a risk assessment approach with no typical pass/fail limit, approaches to decision-making based on the extractables data package will be reviewed. In addition, we will highlight legacy testing requirements which may not be necessary once USP <665> is implemented.
In this webinar, we will discuss:
- Regulatory expectations of extractables and leachables assessment today and tomorrow
- The right criteria that need to be assessed to select the type and quality of plastic materials for use in biopharmaceutical manufacturing
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
Learn how Quality By Design (QBD) principles can be applied to understand the critical processing and feed parameters affecting virus retention, allowing the development of a streamlined validation approach and robust process control strategy for virus clearance via filtration.
In this webinar, you will learn:
•How to simplify validation study design
•Identify critical process and feed parameters affecting virus retention
•How to compile a robust regulatory filing package
Abstract:
ICH Q8 defines Quality by Design (QbD) as “…a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on quality risk management.” Within the context of virus clearance for bioprocesses, QbD principles can be applied to understand the critical processing and feed parameters affecting virus retention, guiding the development of a streamlined validation approach and robust process control strategy for virus clearance unit operations. We will explore how QbD principles can be applied to downstream virus filtration of mAbs and recombinants, the application of these principles within the framework of the Viresolve® Pro Device (parvovirus retentive filter), the benefits through simplifying the validation strategy and increasing the robustness of your regulatory filing package.
This presentation from IVT Network's Method Validation Conference covers required and suggested regulations and guidances for biological process specifications. It also covers dosage form considerations and specifications for other components.
By choosing Covance as a single, centralized CMC analytical laboratory, you can obtain higher quality analytical data more efficiently and at lower cost/fewer resources than by working with multiple providers/CMOs. This analytical data is the key to knowledge and quality risk management throughout the product lifecycle.
The successful development of a biosimilar presents unique challenges compared to that of an innovator biologic. In particular, one must prove the biosimilar candidate's structural and functional differences do not have a meaningful impact on the clinical safety and efficacy profile already established for the innovator. Comprehensive and rigorous analytical testing to assess biosimilarity is thus the foundation upon which the successful development of a biosimilar begins.
The successful development of a biosimilar presents unique challenges compared to that of an innovator biologic. In particular, one must prove the biosimilar candidate's structural and functional differences do not have a meaningful impact on the clinical safety and efficacy profile already established for the innovator. Comprehensive and rigorous analytical testing to assess biosimilarity is thus the foundation upon which the successful development of a biosimilar begins.
Biosimilar CMC Analytical Master Files & Development SolutionsCovance
The successful development of a biosimilar presents unique challenges compared to that of an innovator biologic. In particular, one must prove the biosimilar candidate's structural and functional differences do not have a meaningful impact on the clinical safety and efficacy profile already established for the innovator. Comprehensive and rigorous analytical testing to assess biosimilarity is thus the foundation upon which the successful development of a biosimilar begins.
Similar to The CMC Journey in the Regulation of Biologics (20)
The Team Member and Guest Experience - Lead and Take Care of your restaurant team. They are the people closest to and delivering Hospitality to your paying Guests!
Make the call, and we can assist you.
408-784-7371
Foodservice Consulting + Design
Integrity in leadership builds trust by ensuring consistency between words an...Ram V Chary
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Public Speaking Tips to Help You Be A Strong Leader.pdfPinta Partners
In the realm of effective leadership, a multitude of skills come into play, but one stands out as both crucial and challenging: public speaking.
Public speaking transcends mere eloquence; it serves as the medium through which leaders articulate their vision, inspire action, and foster engagement. For leaders, refining public speaking skills is essential, elevating their ability to influence, persuade, and lead with resolute conviction. Here are some key tips to consider: https://joellandau.com/the-public-speaking-tips-to-help-you-be-a-stronger-leader/
The case study discusses the potential of drone delivery and the challenges that need to be addressed before it becomes widespread.
Key takeaways:
Drone delivery is in its early stages: Amazon's trial in the UK demonstrates the potential for faster deliveries, but it's still limited by regulations and technology.
Regulations are a major hurdle: Safety concerns around drone collisions with airplanes and people have led to restrictions on flight height and location.
Other challenges exist: Who will use drone delivery the most? Is it cost-effective compared to traditional delivery trucks?
Discussion questions:
Managerial challenges: Integrating drones requires planning for new infrastructure, training staff, and navigating regulations. There are also marketing and recruitment considerations specific to this technology.
External forces vary by country: Regulations, consumer acceptance, and infrastructure all differ between countries.
Demographics matter: Younger generations might be more receptive to drone delivery, while older populations might have concerns.
Stakeholders for Amazon: Customers, regulators, aviation authorities, and competitors are all stakeholders. Regulators likely hold the greatest influence as they determine the feasibility of drone delivery.
Employment PracticesRegulation and Multinational CorporationsRoopaTemkar
Employment PracticesRegulation and Multinational Corporations
Strategic decision making within MNCs constrained or determined by the implementation of laws and codes of practice and by pressure from political actors. Managers in MNCs have to make choices that are shaped by gvmt. intervention and the local economy.
Specific ServPoints should be tailored for restaurants in all food service segments. Your ServPoints should be the centerpiece of brand delivery training (guest service) and align with your brand position and marketing initiatives, especially in high-labor-cost conditions.
408-784-7371
Foodservice Consulting + Design
Org Design is a core skill to be mastered by management for any successful org change.
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Senior Project and Engineering Leader Jim Smith.pdfJim Smith
I am a Project and Engineering Leader with extensive experience as a Business Operations Leader, Technical Project Manager, Engineering Manager and Operations Experience for Domestic and International companies such as Electrolux, Carrier, and Deutz. I have developed new products using Stage Gate development/MS Project/JIRA, for the pro-duction of Medical Equipment, Large Commercial Refrigeration Systems, Appliances, HVAC, and Diesel engines.
My experience includes:
Managed customized engineered refrigeration system projects with high voltage power panels from quote to ship, coordinating actions between electrical engineering, mechanical design and application engineering, purchasing, production, test, quality assurance and field installation. Managed projects $25k to $1M per project; 4-8 per month. (Hussmann refrigeration)
Successfully developed the $15-20M yearly corporate capital strategy for manufacturing, with the Executive Team and key stakeholders. Created project scope and specifications, business case, ROI, managed project plans with key personnel for nine consumer product manufacturing and distribution sites; to support the company’s strategic sales plan.
Over 15 years of experience managing and developing cost improvement projects with key Stakeholders, site Manufacturing Engineers, Mechanical Engineers, Maintenance, and facility support personnel to optimize pro-duction operations, safety, EHS, and new product development. (BioLab, Deutz, Caire)
Experience working as a Technical Manager developing new products with chemical engineers and packaging engineers to enhance and reduce the cost of retail products. I have led the activities of multiple engineering groups with diverse backgrounds.
Great experience managing the product development of products which utilize complex electrical controls, high voltage power panels, product testing, and commissioning.
Created project scope, business case, ROI for multiple capital projects to support electrotechnical assembly and CPG goods. Identified project cost, risk, success criteria, and performed equipment qualifications. (Carrier, Electrolux, Biolab, Price, Hussmann)
Created detailed projects plans using MS Project, Gant charts in excel, and updated new product development in Jira for stakeholders and project team members including critical path.
Great knowledge of ISO9001, NFPA, OSHA regulations.
User level knowledge of MRP/SAP, MS Project, Powerpoint, Visio, Mastercontrol, JIRA, Power BI and Tableau.
I appreciate your consideration, and look forward to discussing this role with you, and how I can lead your company’s growth and profitability. I can be contacted via LinkedIn via phone or E Mail.
Jim Smith
678-993-7195
jimsmith30024@gmail.com
Senior Project and Engineering Leader Jim Smith.pdf
The CMC Journey in the Regulation of Biologics
1. Edward Narke
Regulatory Managing Director
DS InPharmatics
Journey in the Development of Biologics
Through End of Phase 3
The CMC Pathway
2. The CMC Journey in the
Regulation of Biologics
Our Goals
• To better understand the FDA’s CMC requirements and
expectations for biologic manufacturing and product
testing
• To better visualize a cost-effective, risk-managed
approach to manage these manufacturing processes and
products through clinical development into market
approval
• To better appreciate the challenges involved with
controlling safety, potency, and impurity profiles for these
products
3. Process Overview of Biologics
Virus inactivation
Virus removal
Harvest
FiltrationFiltration
Chromatography
column (Size Exclusion) Chromatography column
(Ion Exchange)
Chromatography
column (HIC)
WCB
Bioreactor (fermentation)
Filtration
Sterile fill
lyophylization
5. A Big Picture Approach is Desirable
Pre-clinical
Phase 1
Phase 2
Phase 3
Phase Development
Not So Obvious
How much test method
validation, product
characterization, stability? How
tight should specs be? Do I need
a bioassay?
Unambiguous Requirements
Validated Test Methods
Complete Product Characterization
Final Specifications
Expiry Date Assigned
Bioassay Related to Function
Full Change Control Program
6. Question?
• What are some critical items to open an
IND and most common reasons why
INDs get placed on Clinical Hold, and
how to avoid this.
7. Product Characterization?
• Inadequate characterization data provided
– Identity*, heterogeneity/variants (size, charge, hydrophobicity,
glycosylation), aggregates, etc.
– Process-related impurities (HCPs, DNA, antibiotics, chemicals)
• Specifications inadequate to control quality
– Inadequate spectrum of release tests
– Acceptance criteria too wide
• What to do?
– Evaluate product as much as feasible before starting
nonclinical and clinical studies
9. BioActivity Assays?
• Absence of bioactivity/or Potency assay
specification
– Critical quality attribute for proteins
– Proteins inactivated by various conditions
– Potency assay required to evaluate and control product
quality
– Inability to assure consistent dosing of product between
lots; safe dose
• What to do?
– Develop and implement a relevant & quantitative
bioactivity and or potency assay and set a
meaningful specification
10. Viral Safety?
– Cell banks or animal-derived raw materials
not appropriately tested for endogenous or
adventitious agents (mostly viruses,
retroviruses)
– Manufacturing scheme not validated for its
ability to remove or inactivate retroviruses
• Transmission of infectious viruses to humans
• No information on country of origin of ruminant
derived materials used in manufacturing
– Concern over TSEs; BSE
11. Viral Safety?
– What to do?
Retroviruses
• Estimate retrovirus particle load in cells &
unpurified bulk; potential particles/product dose
• Document ability of process to adequately remove
retroviruses
Exogenous viruses
• Evaluate potential presence of viruses
• Include 2 robust, orthogonal viral reduction steps
12. Pharmaceutical Process-Related
Impurities Major Safety Concern for
the FDA!
The FDA can place your clinical study in
‘clinical hold’ for the following CMC reason:
MAPP 6030.1 – “if there are any reasons to
believe the manufacturing or controls for the
clinical trial product present unreasonable health
risks to the subjects … such as a product with
an impurity profile indicative of a potential health
hazard or an impurity profile insufficiently
defined to assess a potential health hazard”
13. Impurity Safety Assessment For
Biologics Product-Related Impurities
Protein Aggregation
Known immunogenecity
Amino Acid Changes
Immunogenecity (e.g., oxidation of methionine)
Glycosylation Changes
immunogenecity
14. FDA Guidance For Industry CMC IND
Content For Phase 2 and 3 1999
“Impurities should be identified, qualified, and
quantified, as appropriate. Suitable limits
based on manufacturing experience should
be established.”
“For peptides and proteins,
characterization should include data on the
amino acid sequence, peptide map, post-
transitional modifications (e.g., glycosylation,
gamma carboxylation), and secondary and
tertiary structure information, if known.”
15. Design of the Manufacturing
Process!
“The extent of purification of recombinant DNA products
should be consistent with the intended use of the product.
Drugs and biologics which are to be administered
repeatedly or at high concentrations should be adequately
pure to prevent the development of undesired immune or
toxic reaction to contaminants.
The purification process should be designed to specifically
eliminate detectable viruses, microbial and nucleic acid
contamination and undesirable antigenic materials.”
1985 FDA Guidance: Production and Testing
of Recombinant DNA-derived Products
16. List All Actual/Potential Impurities!
• Process-related impurities
Cell-substrate (DNA, HCP, proteases, endotoxins)
Cell-culture (cell-substrate [DNA, HCP, protease];
endotoxin; media components – antibiotics [tetracycline,
gentamicin], hormones [insulin, IGF-1, transferrin],
serum)
Purification (enzymes [DNase/RNase]; resin leachates;
surfactants; residual cleaning agents]
Product-related impurities
FDA Guidance for Review Staff and Sponsors: Gene Therapy 2004
17. Identify the “Critical Impurities”!
‘Critical Impurity’: That which must be
controlled to a defined level to assure
appropriate quality and/or safety!
Impurity that impacts patient safety risk
Impurity that is difficult to consistently remove
Impurity that varies from batch-to-batch or
changes with time
(case by case)
18. Risk Management of Impurities
Goal: Determine how you will demonstrate to
regulatory agencies adequate control of the specified
impurities!
Impurity Control Mechanisms
Process validation
In-process action limit monitoring
End product specification release/stability testing
Combination of above
19. Determine Acceptance Limits
What to Base Acceptance Limits On
• Known toxicity information
• Required regulatory targets/specs
• Levels consistent with clinical materials
• Company-specific requirements
20. Specifications: Early
Development
• Acceptance Criteria Generally Broad (Focus on
Safety/Efficacy)
– Define safety limits, where possible, with regulatory
guidance
– Example: LAL ≤5 EU/kg/dose
– Tighten specifications as manufacturing experience
increases
• Employ Quantitative Methods Where Feasible
• Push the Envelope With Toxicity Studies to
Underwrite Safety
• Understand the Impact of Process Changes on
Product Quality
21. Specifications Through
Development
• Specifications Are Expected to Change
– Changes to Analytical Methods
– Evaluation of Stability Data
– Changes to Formulation
– Process Changes and Process Capability
– Enhanced Understanding (Characterization)
– Increased Manufacturing Experience
– Process Validation and Clearance Studies
22. Specifications Through
Development
While acceptance criteria generally get tighter with
increased manufacturing experience, there may be
some cases where widening the criteria may be
acceptable.
• Analytical Testing May Decrease for Late Phase
Products
– May remove tests following process validation/clearance
• Examples: Viral Testing and DNA
– May remove tests based on process consistency
• Examples may include monitoring of oxidation/acidic variants
23. Specifications: Late
Development
• In General, Expect to Tighten Specifications
– Methods Are Fully Validated and Locked Down
– Extensive Manufacturing Experience
– Link Between Product Quality & Clinical Outcome
– Statistically Relevant Pool of Data
– Enhanced Understanding of Product Stability
• Internal Targets
– Reflect Process Capability
– Product quality may still be high outside of internal targets
• Make Specifications Relevant
24. Designing Relevant
Specifications
• The Good
– Supported by appropriate, well designed analytical methods
– Address all the quality attributes that impact safety and efficacy
– Underwrite safety and efficacy through end of shelf life
– Reflect a thorough understanding of the molecule and the process
• The Bad
– Analytical methods inappropriate, poorly validated, lacking specificity
– Contain tests that are irrelevant to product quality–Lack tests for
critical quality attributes due to poor characterization
– Lack relevance to clinical experience
– Driven by analytical or process capability
– Contain tests performed “because we can”
25. The Perfect Process
Early Phase Development
• Phase 1 Study with Pilot-Scale Material: Process Not Optimized
• Acceptance Criteria for Clips/Truncations Very Wide
• Process May Not Optimized for Removal of Aggregates
• No Assay for Acidic Species or Oxidation
• Clinical Data Shows Good Safety and Efficacy
Later Phase Development
• Methods Optimized: More Sensitive and Quantitative
• Clinical Samples Re-evaluated With Optimized, Quantitative Methods
• More Results Define Further Knowledge
• Specifications Based on Process Capabilities and Relevant Clinical
Experience
• Targets Set on Patient Safety Considerations and Process Capabilities
– Plan Ahead –Understanding of process capability will increase over time as you
gain experience.
26. A Few Key Questions
• What are some of the major challenges
that are faced in meeting CMC filing
requirements?
• What are the some strategies that are
applied to address the major challenges?
27. Assay Methods for Product
Release?
• Assay methods not suitable for intended
purpose
Examples:
– SEC for aggregates: Sample treated to
reduce aggregates before running column
– SDS-PAGE gels under-loaded
– Potency assay: “what is active”
28. COMPARISON OF NONCLINICAL
& CLINICAL LOTS?
– Product used in animal toxicology studies not
comparable to product intended for clinical
• Can’t rely on Tox studies establishing safety
(special emphasis on impurities, degradants,
aggregates)
– What to do?
• Do key Tox studies on appropriate material;
• Do side-by-side comparisons of non-clinical and
clinical lots
• Evaluate potential safety impact of differences
between Tox and clinical lots
29. Stability Testing?
– No stability data or testing plan
• Product stable throughout nonclinical studies
• Product will be stable for duration of clinical studies
– Stable under conditions of use (diluted, etc.)
• Product changes that would result in safety risk
– e.g., release of untargeted toxin
– e.g., release of radiolabel
– e.g., aggregation
– e.g., loss of sterility
30. Insufficient Information
Submitted?
– Clinical trial material not yet manufactured
• No release or characterization data on the actual
product to be administered to patients
• Uncertain that product suitable for clinical use
– Problem exacerbated by limited set of
specifications and wide acceptance criteria;
limited understanding of critical product
characteristics
– What to do?
• Manufacture clinical lots, provide release data
before submitting IND
31. Collecting the Data as the
Journey Continues
Key question: How and when to invest to really get to know the
manufacturing process and its outcome
Marginal conditions: Seek out regulatory authority advice. It’s all about
involving the agency as a partner
Milestones: A reality check for your CMC regulatory approach at any
transition
32. What Is ‘Potency’?
‘Potency’ = the assessment of
‘biological activity’
Impacted by both molecular
conformation and by molecular variants!
33. Potency is Invaluable in Biologic
Manufacturing!
• Parameter of product quality release testing
(‘active content’)
• Tool for assessing lot-by-lot manufacturing
consistency during normal manufacturing
operations
• Tool for assessing product stability
• Tool for demonstrating product comparability
after a manufacturing process change
34. BioAssays/Potency: Required
Measurement for Biologics
• 21 CFR 610.10
“Tests for potency shall consist of either in vitro or in vivo
tests, or both, which have been specifically designed for
each product so as to indicate its potency in a manner
adequate to satisfy the interpretation of potency given by
the definition in 600.3(s)”
21 CFR 600.3(s)
“The word potency is interpreted to mean the specific ability
or capability of the product, as indicated by appropriate
laboratory tests or by adequately controlled clinical data
obtained through the administration of the product in a
manner intended, to effect a given result”
35. Regulatory Expectations For the
Choice of Bioassay/Potency
“ A correlation between the expected clinical
response and the activity in the biological assay
should be established in pharmacodynamic
or clinical studies.”
ICH Q6B Specifications for Biologics
36. When Must a
Biologic/Biopharmaceutical Have a
Potency Bioassay?
“Potency assay (i.e., ability to induce immune
response such as proliferation of responder
cells, cytotoxicity or any other correlation with
biological activity) is to be in place at Phase
1/2, and established at Phase 3”
Regulatory Expectations During Product Development for
Tumor Vaccines, Raj Puri, FDA
37. What About Setting Potency
Specifications?
Regulatory guidance on setting potency
specs
- limited! (as with other specifications)
“The permissible range of values in potency assays that reflects
adequate biological activity of a product should be based on
experience……”
FDA PTC MAbs 1997
38. Development Phases
Controlling Quality
and Basis for QTPP?
• Do I have a reliable process that
is reproducible?
• Do I have a reliable, specific and
sensitive analytical method?
• What are the physical chemical
properties? Can it be readily
formulated-delivered and
maintain stability?
Pre-IND
Initiating Phase 1
Early Clin Dev
Transition Ph2 to
Ph3
POC to Registration
Continuous Improve
Key Questions
Conditions/Features
Basis/Considerations
Milestone/Result -
Further Actions
39. Development Phases
Basis for QTPP?
• How do I want to (need to)
deliver the drug?
• What, if any, are the key
properties of the drug that could
confound clinical results?
• Can I produce a compliant and
convincing CMC package?
Pre-IND
Initiating Phase 1
Early Clin Dev
Transition Ph2 to
Ph3
POC to Registration
Continuous Improve
Key Questions
Conditions/Features
Basis/Considerations
Milestone/Result -
Further Actions
42. Refusal to File BLA for
Protein Product?
• Facility not ready for inspection during the
time frame of the review clock
• Lack of process validation
• No stability data on product intended for
commercial use
43. Summary?
• Implications of Regulations?
• Principles for selecting effective
development and regulatory CMC
strategies in an evolving regulatory
environment?
• How Much Information?
• What is the best way to use opportunities
to consult with the Agency?
44. What you don’t know can
hurt you….
• “…there are known
knowns; there are
things we know we
know. We also know
there are known
unknowns; that is to
say, we know there
are some things we
do not know. But
there are also
unknown unknowns –
the ones we don’t
know we don’t know.”
Based on recent experiences, a discussion around observations, and the common features/obstacles for smaller companies facing the Regulatory process will take place. Arm yourself with the tools to write or assemble CMC sections of regulatory submissions, to prepare for CMC meetings with FDA, and avoid future non-compliance situations.
You are an emerging Pharma company, have just in-licensed a product and received funding. Now the fun starts as you sort through what development has been done, how to cope with taking over various contractors who have parts of the project and get a clinical trial started or keep one going all this while trying to cope with coming up with a concise CMC development and Regulatory strategy and plan as well as a budget for your Board of Directors through Launch. As you dig in and get going you realize that the company wants to keep spending to a minimum until certain clinical milestones are met. So what you would like to get accomplished and what will be funded are not the same thing. So how do you handle the product development, what drives the decision to do or to delay, what risks are associated, how do you mitigate those or lobby for support, when do you approach the regulatory agencies and how do you do it with the best package possible?
The Process May Include:–InoculumTrain (Cell Culture and Expansion)–Affinity Chromatography–One or More Ion Exchange Chromatography Steps–Filtration–Concentration–Neutralization–Centrifugation–Formulation–Lyophilization/Ultimately, all process steps have the potential to impact product quality….
Expression Construct
Genetic component that contains the coding sequence of the recombinant protein and the elements necessary for its expression (vector+gene)
Master Cell Bank (MCB)
An aliquot of a single pool of cells which generally has been prepared from the selected cell clone under defined conditions, dispensed into multiple containers and stored under defined conditions (host+vector+gene)(clonal)
Working Cell Bank (WCB)
An aliquot of a homogeneous suspension of cells obtained from culturing the MCB under defined culture conditions (expansion of MCB cells)
Where in the Manufacturing Process Does GMP’s Start? (ICH Q7A - Maintenance of Cell Bank)
Living SOURCES are used for the production of biologics and biopharmaceutical
Biologic/biopharmaceutical MOLECULES are complex structures, containing multiple molecular variants
The manufacturing PROCESS can significantly impact the produced biopharmaceutical or biologic
Living sources are used: Potential for physiological and genetic changes with cell age!
Bio molecules are complex structure: Potential for heterogeneity –
Manufacturing Process can significantly impact the produced bio product
Supplemental Testing & Specifications - Enhancing Our Understanding Through Characterization
Examples of Tests That Might be Performed for Comparability - Molecular Characterization,
Physiocochemical Analyses, Bioactivity, Impurities & Product-related Substances
The Good, the Bad and the Ugly.
Multiple bad elements make a specification both bad and ugly