Name: Analytical Assessment of Leachables in Biological Drug Products: FDA Approach in Reviewing Information
Start: 2025-09-04T14:00:00Z
End: 2025-09-04T14:02:00.000Z
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.

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

Presented by Ron Brown, Toxicologist at Risk Science Consortium

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

Presented by Friedrich von Wintzingerode, PhD. Director, Microbiology and QC individualized and cell therapy at Genentech and Cheryl Essex, MS. Head of Contamination Control, R&D Global Quality at Sanofi

Microbial Impact Assessment of In-Process Bioburden Limit Excursions

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

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

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 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

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

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...

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

therapeutic protiens

vaccines

gene therapy

cell therapy

analytical assessment

extractables

leachables

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

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