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Formazione >> Webinar e Formazione Online >> Navigating Extractables and Leachables (E&L) in Cell and Gene Therapy (CGT) Manufacturing

Navigating Extractables and Leachables (E&L) in Cell and Gene Therapy (CGT) Manufacturing

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DATE: 12 June 2024 | 3.00 PM - 4.00 PM CET

EVENT: Free Webinar

OFFICIAL LANGUAGE: English

AUDIENCE CAPACITY: 500 Attendees

REGISTRATION LINK: https://attendee.gotowebinar.com/register/5871989566221983576

The event will be hosted within Go ToWebinar platform. To continue supporting our customers' needs, this webinar is dedicated to manufacturers only. Due to the type of event and limited audience capacity, participation of companies not included in this topic category will not be accepted. Attendance will be confirmed from the event's organizers. You'll receive a confirmation email with a unique link to join the session, not to be shared with others.

Webinar overview

Cell and Gene Therapies (CGTs) are shaping the future of medicine offering groundbreaking treatments for patients battling with diseases that span from rare genetic disorders to oncological and long-term chronic conditions. The significant advancements made in the recent years yet need to face several unique challenges, such as addressing the risk presented by extractables and leachables (E&L).

CGTs are primarily manufactured via single-use systems (SUS) which consist of many different components, including bags, tubing, filters, pumps, etc. The compounds possibly released from these materials can have a direct and significant impact on both the safety and the potency of the CGT final products. When cells contact the SUS indeed, it can cause the release of extractable substances, referred to as process equipment-related leachables (PERLs) that may accumulate throughout the manufacturing process, potentially compromising the quality of the product and the patient safety.

Given the potential for these compounds to accumulate, a thorough E&L testing strategy should extend beyond the final stages of drug product manufacturing to encompass earlier manufacturing steps as well. Regulatory authorities require extractables and leachables testing of any materials in the manufacturing stream that come into contact with the drug product and the most effective way to ensure that SUS are suitable for the intended use, is to select well-characterized components. Of note, although not mandatory, where appropriate, considerations for E&L testing may also extend to critical raw materials: indeed, the complex biological structure of cells and viral vectors can have important, and difficult to predict, impacts on E&L accumulation and metabolization.

While USP chapters 665 and 1665 provide valuable guidance for extractable and leachable (E&L) testing in biological products, they lack specific recommendations for C&GT therapies. Therefore, a tailored strategy for risk assessment and analytical activities is necessary.This webinar will delve into the challenges faced by manufacturers in developing a successful E&L testing strategy, offering practical advice on study design and result interpretation. Our expert speakers will provide insights into handling E&L studies for components that are specifically utilized in cell and gene therapies, in order to meet regulatory requirements and expectations, and ultimately ensure product quality and patient safety. In particular the webinar will address the risk of extractables and leachables in cell therapy manufacturing and how the new USP<665> and <1665> chapters could be adapted to CGT products.

The webinar will establish the foundation for manufacturers of cell and gene therapies on what to expect when it comes to regulatory requirements and develop a study program that will assist them in achieving approval from regulatory authorities when they submit their packages.

Agenda

E&L Fundamentals and Regulatory Landscape

  • Overview of regulatory guidelines for E&L in biologics, including USP chapters 665 and 1665
  • Defining extractables and leachables (E&L) and their significance in CGT
    • Leachables impact on safety and quality
    • Understanding the potential impact of E&L on protein products, particularly monoclonal antibodies (mAbs)
    • CGT
  • Addressing the unique E&L challenges in CGT, considering the absence of specific guidance in USP 665 and 1665

Risk Assessment and Analytical Strategies for CGT E&L 

  • Introducing a tailored risk assessment approach for E&L in CGT products
  • Assessing biocompatibility, viability, cell growth, and mutagenicity as key risk factors
  • Evaluating patient safety considerations, including threshold trigger concentration (TTC) selection  
  • Addressing E&L in the drug product (DP) and internalized E&L in cells
  • Delving into the analytical approach for E&L assessment
    • Selecting appropriate extraction solvents
    • Optimizing extraction time and temperature
    • Understanding the role of extraction ratios
    • Addressing the challenges associated with DMSO as an extraction solvent
    • Identifying internalized leachables and their potential impact

Balancing Risk and Benefit in CGT E&L Management 

  • Discussing the importance of risk-benefit considerations in E&L management for CGT products
  • Evaluating the potential risks of E&L versus the therapeutic benefits of CGT

Conclusion and Q&A 

 

 

Industry experts

Stefano Baila
Stefano Baila received his PhD in 2007 based upon translational research and development of gene therapies for hemophilia at the Children’s Hospital of Philadelphia. Since that time he has been actively involved in the process development and manufacturing of advanced therapeutic medicinal products through business development and strategic marketing roles at Areta International, a CDMO, and by leading field implementation and commercialization activities for the cell processing unit of Terumo BCT. Stefano worked as Industrialization Manager at Celyad where he led process development and automation efforts for CAR-T and later on he did join Anemocyte as Director of Operation and Business Development. Now he serves as Managing Director for Eurofins.

Daniele Zarini
Daniele Zarini earned a bachelor's and master's degree in industrial biotechnology (bioinformatics field) in 2014 and 2016, respectively, and he started working as a toxicologist in the electronic cigarette industry from 2017 to 2021. Daniele joined Eurofins BioPharma Product Testing Italy in 2021 as a toxicologist in the Extractable and Leachable sector of the pharmaceutical industry, holding also the role of project manager (E&L, biological, chemicals). Daniele is currently team leader for the pharma consulting group within Eurofins Regulatory & Consultancy Services Italy.