Name: Analytical Assessment of Leachables in Biological Drug Products: ...
Start: 2024-09-04T14:00:00Z
End: 2024-09-04T14:02:00.000Z
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.

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

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

Nicola Reid, Associate Director of Endotoxin Products, Charles River

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

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: 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...

Minute virus of mice (MMV) has contaminated biotechnological processes in the past and specific MMV testing is therefore recommended, if the production cell line is known to be permissive for this virus. Testing is widely done using cell-culture based adventitious virus assays, yet MMV strains may differ in their in vitro cell tropism. Here, I present growth characteristics of different MMV strains on A9 and 324K cells and identified significant differences in susceptibility of these widely used indicator cell lines to infection by different strains of MMV, which has implications for MMV detectability during routine testing of biotechnology process harvests [1]. An MMV specific PCR was evaluated as a more encompassing method and was shown as suitable replacement for cell culture-based detection of the different MMV strains, with the additional benefit that detection is more rapid and does also cover other rodent parvoviruses that might contaminate biotechnological processes. Although no MMV contamination event of human-derived cell lines has been reported in the past, biotechnological processes that are based on these also need to consider MMV-specific testing, as we showed e.g. HEK293, a human-derived cell line commonly used in biopharmaceutical manufacturing as susceptible to productive MMV infection.

[1] Farcet et al., Biotechnology & Bioengineering 2024; 121:131-138; DOI: 10.1002/bit.28573

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

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...

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

Presented by Paolo Grisostomi, Senior Engineer, Materials Science at Biogen and Donald Young, Sr. Product Manager at Thermo Fisher Scientific

Challenges In Therapeutic Biological Products

John R. Logar, Senior Director, Sterility Assurance at Johnson & Johnson 

The concept of a Microbiological Quality Level (MQL) has been proposed as a method for determining the acceptable level of microbial contamination permitted during the manufacturing of or on a finished pharmaceutical, biopharmaceutical or combination product. The Kilmer RMM and PAT collaboration teams, along with ASTM Committee E55, have been exploring the use of Microbiology Quality Level (MQL) as means to enabling this future and this webinar will introduce and eexplore this concept as a means of determining probability/quantification of microbial risk for each step and its contribution to the final product as a mechanism to differentiate the microbiological quality of finished product.

Followed by Sebastian Scheler, Co-Founder, Managing Director, Chief Methodologist, Frame-by-Frame Risk Profiling Supervisor at Innerspace

A Future of Microbiological Quality Levels and Managing Risk Release

Full title: ICH Q3E Impurity Guidelines: Assessment and Control of Extractractables and Leachables for Pharmaceuticals and Biologics.

ICH Q3E Impurity Guidelines: Assessment and Control of Extractractables...

Industry 4.0 comes with an impressive collection of assets and capabilities. However, although the degree of applicability in Bioprocessing is high, the origin of these technological innovations is exogenous. This is not without implications and in this talk we are concerned with their identification and quantification. We commence with the onboarding of an exogenous technology problem. Industry 4.0 tools have been developed with different objectives in mind. Integrating them in Bioprocessing requires a critical a priori analysis of similarities and transferability.  We then move on to address a fundamental question: is this exogeneity positive or negative for Bioprocessing?  The answer is drawn from historical case studies, stemming from different industries. This naturally leads us to the concept of  the fallacy of division and the associated dangers of disruption. Finally, we go a step further and explore how the addition of 4.0 in Bioprocessing can alter the core business activities and what this implies for the insourcing vs outsourcing dilemma that both big and small corporations have to face.

The exogenously driven disruption of Bioprocessing

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 and Experience in Reviewing Information

Followed by Sona Kovackova, PhD, Scientific Expert – E&L at Nelson Labs. 
Presenting: Extractables & Leachables Qualification of the Primary packaging for Biological Products

Followed by Tine Hardeman, Manager Material Development bij at Datwyler.
Presenting: Selecting the Right Primary Packaging Materials for Biological Drug Products

This webinar ends with a live Q&A session.

Analytical Assessment of Leachables in Biological Drug Products: ...

therapeutic protiens

vaccines

gene therapies

cell therapies

analytical assessment

leachables

extractables

Biological drug products

EandL

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