Name: CMC Progression from Early to Late Phase – Practical Considerations for Gene Therapy
Start: 2025-03-27T14:00:00Z
End: 2025-03-27T14:02:00.000Z
Location: BrightTALK
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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.

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

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

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

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

Full title: Fully Continuous Purification Platform Using Nanoparticles With Ligands and Ultrafiltration

We present on a truly continuous purification technique with potential to reduce costs-of-goods for mAbs, over conventional chromatography-based separations.

We demonstrate the development and proof-of-concept application of a self-assembling affinity nanoparticle to enable affinity ultrafiltration of mAb from an impure mixture.

This technique leverages counter current flow ultrafiltration, concentration gradients between feed and product, in a series of filters representing the phases of the process. Impurity clearance can remain high while minimizing overall buffer consumption and consequently PMI for water.

Overall, these data represent an early advancement toward the development of a truly continuous, counter-current, and column-free method to capture and purify mAb without expensive conjugated resins. We envision further expansion of commercially available nanoparticles towards modality and application specific designs to enable PMI savings across therapeutic areas, delivering lower cost medicines to patients.

Fully Continuous Purification Platform Using Nanoparticles...

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

Process Equipment Related Leachable Compounds – 3 case studies

Case 1: Over sterilized filter, 3 days instead of 3 hours – process leachable compounds in the parenteral drug product

Case 2: Solid, white, 5 mm flakes in process equipment – effects on the parenteral drug products

Case 3: What is wrong with the process equipment? – PERL investigation continued as a stopper related leachable analyses.

Process Equipment Related Leachable Compounds - 3 Case Studies

The current “continuous” downstream is a complex sequence of batch operations, almost a slight-of-hand continuous process that cannot take advantage of most of the value of truly continuous processes. While the current chromatography-based processes are sufficient to bring the cost of goods manufactured down by 40-60%, there is significant benefit from a truly continuous process.

We have demonstrated the use of recombinant affinity nanoparticles and complexes in a dialysis and tangential-flow filtration-based capture step. The development of the nanoparticles is challenging and we have tested over 100 nanoparticles evaluating expression, their ability to bind antibody, and their stability under acidic elution conditions. We believe many are economical enough to allow commercial use, though we have found many to have suboptimal stability at low pHs and that most of the high-pH constructs have significantly reduced capacity. Finally, we have found that the wide pore-size distribution on UF membranes have allowed 10% or more of the nanoparticle to pass through along with the antibody.

We will discuss general methods we’ve used to quickly evaluate nanoparticles including small scale, ~1000kDa MWCO dialysis, and centrifugal dead-end ultrafiltration.  We will also discuss associated analytical techniques including mass photometry, SEC, and native blue electrophoresis.

The data we have generated allows us to be confident that these methods are worth continued effort. Truly continuous processing allows the reuse of solutions from a cleaner downstream to a dirtier upstream. This reuse of solution, and the continuous nature of the process, should decrease cost of goods beyond the current ICB processes while increasing the level of sustainability.

Achieving Fully Continuous End-to-End Processing

Full title: Evaluating Analytical Strategies to Quantify Capsid Titre: Towards a Platform-Method Approach to Accelerate AAV Drug Product Development

Traditional capsid titre methods rely on ELISA which commonly suffers from long turnaround times, low throughput, and large volume sample requirements. This limits the application of ELISA-based methods to routine analysis, thus requiring development of alternative high-throughput (HTP) capsid titre methods. We have performed a comprehensive assessment on currently available orthogonal capsid titre methods using multiple serotypes at concentration range relevant in IND-enabling preclinical and first-in-human (FIH) clinical studies.

Evaluating Analytical Strategies to Quantify Capsid Titre...

The advancement in technologies and innovative thinking are profoundly changing biopharmaceutical drug production industry holistically, giving rise to “the factory of the future.” What will the factory of the future with respect to its structure, technologies, processes, and drug product delivery to the patient be? What enablers will manufacturers need in terms of strategy, leadership, employee skills, IT/OT infrastructure, regulatory oversight, and suppliers to make this a reality?

The factory of the future is an innovation vision on how manufacturers should enhance production by transforming manufacturing in three dimensions: plant structure, plant digitization, and plant processes.

Having a holistic vision of the process

Designing and implementing a flexible framework

Evaluating and implementing proper technology and skill

Emphasizing safety, quality, purity, efficacy and regulatory mandates

The bottom line – delivering ROI

The Factory of the Future

Defining limits for analytical method outputs is a central element of a control strategy. Traditional approaches usually focus on ensuring process consistency, while in more advanced approaches the understanding of structural-function relationships are utilized. This enables definition of patient centric limits that focus on controlling the impact of CQAs on product efficacy and patient safety. In certain cases, those limits and can be defined independent from a specific analytical method and where indicated can extend beyond a therapy specific clinical history. Process consistency control and change management are an integral part of the patient-centric specification and risk-based control strategy approach. The presentation will provide some practical examples for the definition of patient-centric specifications and process consistency control.

Defining Patient-Centric Specification in a Risk-Based Control System

Full title: Downstream Platform Process Development for AAV viral vectors; Challenges and Opportunities

This talk is designed for professionals and researchers from the scientific community, particularly those engaged in industry applications. In this session, I will delve into the concept of platformability in the context of AAV downstream processes. I will examine the opportunities this approach offers for enhancing efficiency, scalability, and reproducibility in viral vector production.

Key topics will include: -

Defining Platformability: Understanding its significance in streamlining AAV production.

Technological Opportunities: Innovative methods and tools available for optimizing downstream processes.

Challenges and Solutions: Identifying common obstacles and discussing potential strategies to overcome them.

Attendees will gain valuable insights into the latest advancements and practical solutions for developing robust downstream processes, positioning them at the forefront of AAV vector production technology.

Downstream Platform Process Development for AAV viral vectors...

Maria Farcet, Head of Cell Culture, Virus Models & Serology in the Global Pathogen Safety / Global Quality team at Takeda
Presenting: Adventitious Agent Testing For MMV: How Much Do We Really Know?

Amina Cherif Louazani, PhD, Viral Safety Manager at PathoQuest
Presenting: Advancing Viral Safety in Biologics: Comprehensive Virus Detection with iDTECT® Transcriptome NGS-Based Assay

Dr. Denise Teber, Scientific Expert of the PCR department at Charles River Laboratories
Presenting: Viral safety testing of human cell lines used for biopharmaceutical manufacturing.

Adventitious Agent Testing For MMV: How Much Do We Really Know?

Medical device chemical toxicological risk assessment is challenging because the risk assessor often needs to consider the many types of device intended uses, many types of materials used in design and manufacturing, and many types of intentional and unintentional chemicals that are or could be present in the final finished device. Medical device intended uses include the type of tissue contact, the contact frequency and duration, and the susceptibility of the device user to chemical exposure. Material factors include the material type (e.g., alloy, polymeric, ceramic, or natural), material properties (e.g., alloy surface characteristics, polymer plasticity, or polymer manufacturing process), and material chemical composition (e.g., chemical formulation, potent toxicants (if present), and the rate and duration of release). How to apply these considerations is described in the U.S. Food and Drug Administration (FDA) 2023 guidance Use of International Standard ISO 10993-1, “Biological evaluation of medical devices: Part 1: Evaluation and testing within a risk management process,” International Standard Organization (ISO) 10993 series, and ISO 14971. This presentation will describe how chemical toxicological risk assessment fits into the overall medical device biological risk management process (i.e., risk analysis, risk evaluation, or risk control). Additionally, what medical device use and chemical toxicological information to consider from the U.S. FDA 2023 guidance and ISO documents when estimating chemical toxicological risk will be covered, such as: approaches for characterizing the applicable chemical specific harm(s), estimating an exposure dose, deriving a tolerable intake (TI), and other critical factors to consider that could be useful in the determination of whether exposure to a medical device chemical presents a tolerable risk or could present a possible toxicological risk.

Medical Device Chemical Toxicological Risk Assessments...

Full title: Established Conditions in Analytical Procedure: Overview, Regulatory Examples and an FDA Laboratory Study

Established conditions (ECs) are manufacturing and control elements considered necessary to assure product quality (e.g., ECs in manufacturing process) and to help assure method performance (e.g., ECs in analytical procedures). ECs in analytical procedures help to maintain reliable results that can ensure the efficient product control strategy during the product life cycle. Changing ECs in analytical procedures may necessitate a certain level of regulatory activity and the level of regulatory activity can be different depending on the strategy defining ECs and the extent of changes. The presentation will first provide a high-level overview of harmonized scientific risk-based approaches for identifying ECs and determining the corresponding reporting categories based on scientific principles described in ICH Q12 and Q14 guidelines. Then, two regulatory examples involving ECs in analytical procedures will be discussed. It is noteworthy mentioning that both parameter and performance-based ECs in an analytical procedure are defined in these two examples. The last part of the presentation will be an FDA laboratory study on a mass spectrometry method for a recently identified NDSRI (Nitrosamine drug substance-related impurity). In this case study, analytical variables and method robustness were investigated according to recommendations from the ICH Q2R2 (draft) Guideline. Based on the impact of each variable on method performance, categorical and numerical ECs were proposed.

Established Conditions in Analytical Procedure: Overview, Regulatory Examples

As gene therapies move toward commercialization, the journey to manufacture a high-quality product while achieving economies of scale and reducing facility footprint, can be challenging. Developing and optimizing your process development early on is critical for your company’s long-term success.

In this webinar, we will present our scalable integrated platforms for viral vector production in both adherent and suspension cell cultures. Key factors to consider in choosing the right technology for scaling up will be discussed in terms of factors such as cost, time, and risk. You will hear from Andelyn’s process development team and Pall’s Accelerator℠ process development experts on their strategy, proven methods, and bioprocess solutions, and on how they scaled up an Adeno-Associated Virus (AAV) manufacturing process using FectoVIR®-AAV transfection reagent to up to 500 L.

Attendees will learn how to:

Achieve versatility with a scalable, single-use end-to-end platform


Optimize small-scale expression systems into a scalable process


Achieve goals faster and better with Pall process development team

Successful Scale Up of a High Yielding Viral Vector Suspension Platform to 500 L

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

Gene Therapy

GMP compliance

biologics

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

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