Name: Evolve Manufacturing Processes by Implementing Disruptive Technologies
Start: 2018-11-19T17:00:00Z
End: 2018-11-19T17:01:16.000Z
Location: BrightTALK
Rating: 4

BioPharma Webinars aims to keep its global audience abreast of all developments in the areas of Drug Development, Manufacturing, Quality Assurance, Outsourcing and Regulatory Affairs, with only the highest quality webinars, presented by the most respected people, working with companies in Pharmaceutical, Biopharmaceutical, Biologics and Biotech Industry.

This presentation will cover the current sustainability challenges for biopharma industry and how biopharma industry should prepare to solve for this looming sustainability challenges. This talk will also indicate on some aspects of future of manufacturing processes through technological evolution.

Finally, the audience will also hear on a case study which stresses on how a technology evolution and process development can enhance the sustainability issues of Biomanufacturing. 

The second presentation will cover guidance of adopting Phase appropriate orthogonal high-end tools in early-stage product development and Selection of analytical tools for expedited biopharmaceutical development. This talk will provide overview on Significance of High throughput and sensitive analytical tools from Clone to Formulation ranking. This talk will also cover the contemporary challenges in HCP by ELISA and approach to defeat these challenges by alternate approach.

Enhancing Sustainability in Biopharmaceutical Drug Development and Manufacturing

Andrey Sarafanov; PhD., Principal Investigator at U.S. FDA, Center for Biologics Evaluation and Research
Presenting: Analytical Assessment of Leachables in Biological Drug Products: FDA Approach in Reviewing Information

Sandi Schaible, Executive Director, Analytical Chemistry and Regulatory Toxicology at WuXi AppTec

James Hathcock, Sr. Director, Regulatory and Validation Strategy at Cytiva

Analytical Assessment of Leachables in Biological Drug Products: FDA Approach in Reviewing Information

Cell and gene therapy (CGT) is particularly well-suited for the application of big data analytics.  Although our understanding of these complex therapies remains limited, CGT manufacturing processes and analytical methods generate substantial datasets that can be analyzed using artificial intelligence and machine learning algorithms. These advanced computational tools are instrumental in identifying critical characteristics of novel CGT products, optimizing manufacturing and analytical methods, and defining predictive biomarkers, among other applications. This presentation will discuss the role of big data in the development and manufacturing of CGT products and will explore opportunities for crowdsourcing data in the precompetitive space.

Big Data Strategies for Cell Therapy Manufacturing

Continuous capture chromatography is a chromatographic technique promising higher efficiency through higher resin utilization, higher productivity and lower buffer consumption compared to batch chromatography capture processes.

Designing cSMB processes is more challenging than designing standard batch processes because each chromatographic phase is influenced by the previous phase. An iterative approach can be used to identify optimal conditions.

Our traditional process design approach was based on single column breakthrough curves and feeding the breakthrough data into a model. However, this concept leads to a sub-optimal process as it is based on a single loading flow rate during all phases, while effectively, flow rates and volumes in interconnected and parallel load phases should be different for an optimal process. In this webinar, I will present an approach where different flow rates and different breakthrough curves are used as model inputs together with pressure-flow dependencies for the resin of interest. Using the improved process design, significantly higher productivities were achieved compared to the standard procedure. The effect was confirmed for a given in-house model process with approximately 50% higher productivities which has been confirmed at laboratory scale. Finally, implications of the new cSMB design approach for large-scale manufacturing are discussed.

Optimisation of Continuous Capture Chromatography Processes

Presented by Yana Chervona, Drug Safety Team Lead in Drug Safety Research and Development at Pfizer

Read Across Assessment for Potential Leachables Without Toxicological Data

USP <86>, “Bacterial Endotoxins Test Using Recombinant Reagents” states, “Regulatory authorities may require supplemental data prior to acceptance…An example of supplemental data may include a comparative study of the material tested by techniques described in this chapter and those in 〈85〉.”  The term, “supplemental data” may refer to the use of a statistically robust analysis of test results obtained from a single sample containing assayable levels of endotoxins activity, using both the predicate assay (<85>) and the candidate recombinant assay (<86>) .

This webinar discusses the difference between 50-200% acceptance testing and statistical equivalence.  In addition, using data in the public domain as examples, the speakers will stress the importance of using a split sample containing assayable levels of contaminating or potentially contaminating endotoxins activity as the test article for these studies.

Beyond USP <86>:  Supplemental Testing

Full title: Advancing Cell & Gene Quality Control with GMP Next Generation Sequencing (NGS): Regulatory Insights and Industry Case Study

This webinar focuses on the established role of GMP-compliant Next Generation Sequencing (NGS) in quality control for cell and gene therapies. With evolving regulatory guidelines addressing advanced therapeutic products, NGS offers a robust and highly sensitive approach to ensure compliance and product safety.

Key topics include an overview of the regulatory landscape, insights into GMP standards for cell and gene therapy products, and a real-world industry case study demonstrating the practical application of NGS. The session will address common challenges, implementation strategies, and best practices for integrating NGS into quality control workflows.

Designed for professionals in quality control, regulatory affairs, and biopharma manufacturing, this session provides valuable guidance on leveraging NGS for enhanced safety in cell and gene therapies.

Advancing Cell & Gene Quality Control with GMP Next Generation Sequencing (NGS)

Using risk management to design aseptic process simulations:

Annex 1 states that “QRM (Quality Risk Management) applies to this document in its entirety”. Does this mean we can use QRM to justify non-compliance with Annex 1 requirements? The answer here is obvious: No.

So when and where can we use QRM? And for what purposes?

During this webinar we will go through several real and practical examples for using QRM to design Aseptic Process Simulations (media fills): 1) When using QRM is not allowed, 2) When it is permitted; and 3) When it is mandatory.

Using Risk Management to Design Aseptic Process Simulations

Establishing a personnel monitoring (PM) program requires a risk-based approach per the current EU Annex I. Presently, there is no specific industry or regulatory guidance on how to establish sample locations and sampling frequencies using Quality Risk Management (QRM) for personnel monitoring and the methodology behind a risk-based approach can vary greatly from site to site. Implementing a global risk-based methodology is desirable for consistency.  Takeda has developed a global personnel monitoring risk assessment tool that can be used across a range of production facilities.  This tool applies to both gowning qualification sample site determination and routine personnel monitoring associated with batch production.  Utilizing QRM principles, contamination hazards and sources were identified and assessed to inform risk scoring criteria.  The personnel monitoring assessment takes into consideration the process understanding of both gowning and manufacturing operations. A case study for the application of the risk-based tool will be presented.

Design of a Global Risk-Based Personnel Monitoring Assessment for a Multi-Production Operation Company

The principles for developing traditional biologics are well established, but do not always translate well to cell and gene therapy products.  Creative yet practical adaptations are necessary to advance gene therapy programs toward licensure.  During this presentation we will explore three key areas where practical adaptations are required:

Building toward the commercial process: change control and managing product evolution for non-traditional development pathways, comparability challenges, and regulatory expectations

Maturation of analytics – the level of product understanding expected as programs advance, method advancement from early to late phase, ensuring repeatability and robustness in method performance

Finding the right partners – finding the right match in terms complementary capabilities, technical performance, phase-appropriate GMP compliance and client service infrastructure

CMC Progression from Early to Late Phase – Practical Considerations for Gene Therapy

The toxicological risk assessment of E&L compounds is typically conducted on a compound-by-compound basis; however, for compounds that lack toxicity data, it may be useful to group compounds together that have similar structural and physical-chemical properties, as
well as a similar toxicological mechanism of action, to derive a class-specific Tolerable Intake (TI) or Permitted Daily Exposure (PDE) that is applicable for all compounds in that group. This talk explores ways to group compounds based on their structural and toxicological
similarity and how to use computational models to identify a proposed toxicological mechanism of action for compounds in a group. The presentation will also review methods to conduct a cumulative risk assessment of the
compounds in the assembled group. This approach of first assembling a group of compounds with a common toxicological mechanism, then conducting a risk toxicological assessment of the compounds in the group, has the potential to streamline the toxicological risk assessment
process when large numbers of extractable or leachable compounds are released from a polymeric material and provides a science-based method for setting TI/PDE values that is presumably less conservative than the use of Threshold of Toxicological Concern (TTC) values as default TI/PDE values for the individual compounds

Grouping Extractable and Leachable (E&L) Compounds with a Common Mechanism of Action for Toxicological Risk Assessment

Biologic manufacturing processes are vulnerable to microbial growth, requiring strong contamination controls and in-process bioburden monitoring.

Bioburden in-process limit excursions should be rare but when they occur, the impact from microbial impurities can be unclear. Filtration alone does not remove them and unlike endotoxin, there is no reliable way to detect the full range of microbial by-products, e.g. exotoxins, PAMPs, and proteases. From a patient safety and product quality perspective, the potential impact of microbial contamination must be assessed as part of the investigation.

The biologics industry has not harmonized on a method for conducting microbial impact assessments. This leads to inconsistency in how firms respond to in-process bioburden excursions, particularly when deciding whether to release or to discard the resulting batch.

This presentation will highlight the specific challenges and best practices for assessing the potential product quality impact of an in-process bioburden contamination, including two distinct approaches: a quantitative method built on extensive studies of Roche/Genentech, and a qualitative approach focused on process vulnerability from PDA TR. 90.

Microbial Impact Assessment of In-Process Bioburden Limit Excursions

The approval and widespread adoption of mRNA vaccines have revolutionized the field of immunization, offering rapid and scalable solutions to combat infectious diseases. This success has spurred significant research into using mRNA for other therapies, including cell therapies, protein production, genome editing and protein replacement. Ensuring the quality and safety of mRNAs in these therapies is crucial, requiring detailed impurity profiling and advanced analytical techniques. Incorporating mRNA into drug products presents significant manufacturing and analytical challenges, particularly in maintaining the integrity of mRNA drug substances and drug products. Rigorous release and stability testing are essential to ensuring these therapeutic products remain effective and safe throughout their lifecycle.

Impurity profiling is an essential part of analytical characterization for mRNA-based products. During production, both process and product impurities can arise, such as truncated mRNA fragments, double-stranded RNA (dsRNA), and residual DNA from the plasmid template. These impurities can potentially impact the drug’s performance or trigger unintended immune responses. This presentation explores the types of impurities commonly found in mRNA-based products and the advanced analytical methods used to analyze them. We will also discuss the challenges faced, potential solutions, and the importance of analytical methods in supporting development programs and meeting expanding regulatory requirements. Continuous improvements in these analytical methods are crucial to address the evolving challenges in mRNA-based drug production and to maintain high standards of safety and effectiveness.

Navigating the Complexities of mRNA Therapies Analysis: Challenges, Techniques, and Quality Assessment Strategies

Transfer of equipment and materials is identified as “one of the greatest potential sources of contamination” in cleanrooms as per EU Annex 1 (Aug 2022); therefore, effective material transfer processes within classified and critical areas play a key role in the safety and quality of products.

This presentation will describe one firm’s risk-based approach to material transfer validation. Key aspects of the approach include identifying and evaluating critical factors associated with the process of material transfer (such as impact on product contamination, impact on environmental contamination, cleanability, and materials/equipment size) and a roadmap to validation execution. Through a structured risk management framework, the critical factors are analyzed to determine their impact on contamination control, and the validation execution and maintenance ensures robust planning, testing, and lifecycle management. The result is a material transfer process integrated into the site’s contamination control strategy, supported by evidence-based validation.

Case Study: A Risk-Based Approach to Material Transfer Validation

This webinar will provide an in-depth exploration of a QbD-based method development approach for quantifying host cell DNA in gene therapy products, a critical quality attribute to ensure product safety and regulatory compliance. The session will begin by examining the measurement principles of two widely used techniques: qPCR and dPCR, while highlighting their respective advantages and limitations. A central focus will be on establishing a robust conversion factor for dPCR implementation. This factor is critical for accurately converting results from copies/μL, the standard dPCR output format, to ng/dose, as required by regulatory guidelines. The discussion will emphasize the importance of selecting an appropriate target gene and utilizing reliable reference materials to ensure precise reporting. Additionally, the webinar will address other essential aspects of method development, including sample dilution requirements, the primary sources of residual host cell DNA, and a summary of the method qualification results.

The Critical Role of Conversion Factor in Quantitative Determination of Host Cell DNA with dPCR

Empty full ratio of AAV particles in a gene therapy drug is an important critical quality attribute. Due to the complexity of biological production process specifically, viral vector production mechanisms, AAV particles are quite heterogeneous. Purification process can’t entirely separate empty, partial and full particles from the process and hence a significant amount of empty and partial particles gets retained in the final product, potentially compromising quality of the product and raising safety concerns. The complexity of the challenge is understandable as the as gene therapy drugs contain multimeric protein assembly enclosing a genetic material. Where the actual process of DNA packaging remains loosely understood. There are various analytical technologies available for the characterization of these particles but almost every technology has some limitations, either in terms of the sample requirement, quality of information, precision, affordability, complexity of the assay or for their suitability in the GMP environment. AUC maintains its central role in this process and remains as a gold standard but at the same time has limited applicability across various phases of drug development due to its limited throughput and high sample requirements. There are various alternative technologies coming into play, including DLS, CDMS and Mass spectrometry, mass photometry and others. In this webinar we will discuss opportunities and challenges in various analytical technologies in characterizing this critical quality attribute of AAV vector for gene therapy.

Deciphering Empty-Full Characterization: A Comparative Analysis of Available Analytical Methods

Presented by Therese Choquette, Head of Analytical and Translational Sciences at Tigen Pharma

This talk will focus on the analytical testing needed for the release of cell and gene therapy products. A lot of focus has been on improvements and automation of equipment used in manufacturing of cell therapies such as bioreactors. However, to improve and speed up the release testing, this needs to be done also on the analytical side.

Today, in most Quality Control labs, the instruments and methods that are used for in-process and release testing are high throughput (bigger sized instruments) and require experienced analysts for the execution of the test, for example in flow cytometry. The preparation of the sample involves manual manipulation, such as for the potency assay, sometimes very extensive and lengthy before ready to be tested. Once the test is performed, the data needs to be analyzed and calculated for the reportable results, it may for example be from an ELISA for cytokines or the genetic transduction by PCR. The entire procedure from the sample preparation to the data analysis for the results provides opportunities for errors, and the manipulation of the samples can have an impact on the cells. This may decrease the precision of the assay and potentially cause Out Of Specification and delay of product release.  

Depending on each specific product, different analytical tests and assays are required for the release of the product. However, safety tests for determination of absence of mycoplasma, endotoxin, and bacterial and fungal contamination are mandatory for all products. No matter the type of tests or assays, there is a need for faster and less hands-on technology.  Using automated instruments and methods with less manipulation of the sample and automated data analysis, offers opportunities to reduce time and costs for the release testing, as well as providing assays with improved performance and less prone for errors.

Leveraging Instrumentation to Accelerate Release Testing & Minimize Human Input

Jay Bolden, Senior Director, Eli Lilly and Company Global Quality Laboratories. Presenting:
An Overview of Recent USP Bacterial Endotoxins Standards Development

Dr David Roesti, PhD. Microbiologist/Facilitator QA/QC at Novartis Pharma AG. Presenting:
Overview and Future Plans of the USP Rapid Microbiological Methods Subcommittee

Veronika Wills, Manager, Technical Services at Associates of Cape Cod, Inc
Presenting: Early Implementation of Recombinant Cascade Reagent PyroSmart NextGen® in Line With USP <86>

Nicola Reid, Associate Director of Endotoxin Products, Charles River
Presenting: A 3-Step Validation Blueprint for Recombinant Method Implementation

Lamin Jallow, Microbiology Technology Specialist at Merck KGaA
Presenting: Early detection of microbial contaminants in cell-based products using the Milliflex® Rapid System

Félix Montero-Julian, Scientific Director of Pharma Quality Control at bioMérieux
Presenting: Implementation of BACT/ALERT® 3D in light of the USP <72> Chapter: Respiration-Based Microbiological Methods for the Detection of Contamination in Short-Life Products

Followed by a live Questions and Answers session.

Current Status and Overview of the RMM and Endotoxin Microbiology USP Chapters under Development

The desire for innovative technology that can eventually cause disruptive changes remains high in the biotech pharmaceutical industry. The road between pursuing and developing that technology to genuine implementing is not a smooth ride. In this webinar, the presenter identifies key challenges of implementing innovative technologies and the major drive for implementing innovative technologies and process upgrades. The presenter will share some case studies of implementing successful innovation tools and provide comparative economic analysis based on the understanding the true value of innovation driven process design. The webinar also provide the insight of the balance needs for quality, cost and speed.

Evolve Manufacturing Processes by Implementing Disruptive Technologies

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Grifols pharmaceuticals

Disruptive Technologies

Continuous Bioprocessing

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Evolve Manufacturing Processes by Implementing Disruptive Technologies

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