Category: Article

Transferring Potency Assays from Lab to GMP Production: 5 Key Strategies for Success

Posted on by Audrey Chang

Why it Matters

Transferring potency assays is a complex but crucial process in the development and manufacturing of biological products, particularly in the realm of cell and gene therapies (CGTs). These assays play a vital role in ensuring product efficacy, quality, and stability. Unlike biosafety assays, potency assays must be specifically designed for each product, making their transfer process highly specialized.

As a Contract Development and Manufacturing Organization (CDMO), WuXi Advanced Therapies has extensive experience in handling assay transfers from a wide variety of sources at various stages of development. To ensure a seamless transition, we have identified five key factors that can significantly impact the success of potency assay transfers.

Five Key Considerations for Potency Assay Transfers

1.     Timeframes

Establish realistic timeframes that balance speed and quality.

Setting achievable timelines is essential for a successful potency assay transfer. Factors such as standard operating procedures (SOPs), training, scaling, documentation, equipment validation, and regulatory implications must all be considered. Later-phase or commercial potency assays may require additional qualification and validation. Involving key stakeholders and subject matter experts from both parties ensures a well-informed timeline that aligns with project goals.

2.     Agreements

Define clear agreements with detailed scopes and documented expectations.

Each potency assay transfer is unique, requiring a well-documented collaboration between involved parties. Work Orders (WOs) and Master Service Agreements (MSAs) should outline roles, deliverables, pricing, payment terms, and intellectual property concerns. Clearly documenting changes and amendments throughout the transfer process fosters transparency and accountability.

3.     Training

Implement a comprehensive training plan tailored to varying experience levels.

Potency assays rely on diverse scientific technologies that require specialized training for GMP laboratory execution. Hands-on training, documentation reviews, and trainer-to-trainer sessions are all crucial components. You can improve knowledge transfer and consistency in execution by adopting flexible training approaches, such as on-site training by expert trainers or laboratory scientists visiting the originator lab. Establishing clear acceptance criteria and performance assessments will help ensure your training programs are effective.

4.     Material Readiness

Secure critical reagents and establish a robust sourcing strategy.

Supply chain disruptions can significantly impact potency assays, affecting clinical and commercial product timelines. Early planning for sourcing essential reagents and qualifying suppliers can mitigate these risks. Additionally, in-house production of critical assay reagents, such as reference controls, ensures a steady supply and minimizes delays.

5.     Communication

Develop a structured communication plan with escalation paths and regular updates.

Transparent, proactive communication is key to successful potency assay transfers. Establishing a clear cadence of meetings for cross-functional teams and stakeholders helps address potential issues in real-time. A well-documented communication plan, including escalation paths and communication trees, prevents misunderstandings and ensures smooth knowledge transfer.

The Bottom Line

Transferring potency assays is a critical step in the development and manufacturing of biological products, especially for CGTs. Ensuring success requires careful planning, clear agreements, effective training, proactive material readiness, and structured communication. By addressing these five key considerations, organizations can streamline potency assay transfers, minimize risks, and enhance overall product quality and regulatory compliance. As an experienced CDMO, we are committed to supporting seamless potency assay transfers for clinical and commercial success.  Contact us today to discuss the future of your program.

Where Can I Learn More?

If you’d like more insight into improving your approach to tech transfer of a cell potency assay or potency assay development, Dr. Audrey Chang, Executive Director and CMC Scientific Advisor and Joseph Newcome, Senior Director, Analytical Development, recently hosted a webinar in which they discussed how to overcome the challenges the industry faces when developing potency assays for cell and gene therapies. You can watch the full webinar or contact us to speak with our experts directly.

TESSA® Technology Undergoes Peer Review: Published in Molecular Therapy Clinical Methods & Development

Posted on by Amy Lamperti

A team from BridgeBio, including Matthew Roach, Phillip Wirz, Jeremy Rouse, Allison Schorzman, Clayton Beard, David Scott and other team members, recently published an article describing the work they did using the TESSA® platform to increase their yield of rAAV5.

The article, entitled Production of recombinant adeno-associated virus 5 using a novel self-attenuating adenovirus production platform, can be seen and downloaded in the September 12th issue of Molecular Therapy, Methods & Clinical Development. You can find it online here.

Molecular Therapy Methods & Clinical Development is an international, open-access journal that publishes peer-reviewed research on methods, procedures, and translational advances in molecular therapy. The journal focuses on cell and gene therapy, particularly in how these therapies are applied in clinical settings. Key topics include novel gene delivery methods, the use of integrating and non-integrating vectors, gene editing techniques, and the manufacturing of these products under Good Manufacturing Practice (GMP) conditions. The journal also addresses regulatory science and the commercialization of these innovative therapies.

Article Abstract

Recombinant adeno-associated virus (rAAV) has become a prominent vector for clinical use. Despite an increase in successful clinical outcomes, the amount of high-quality rAAVs required for clinical trials and eventual commercial demand is difficult to produce, especially for genetic diseases that are prevalent or require high doses.

Many groups are focused on establishing production processes that can produce sufficient rAAV while maintaining potency and quality. The authors, a group from BridgeBio Gene Therapy in Raleigh, NC, used a novel production platform to increase their yield of rAAV5. The production platform uses tetracycline-enabled self-silencing adenovirus (TESSA®) to deliver the wild-type AAV replication and capsid genes alongside the adenovirus helper genes necessary for production. In the article, the authors describe their efforts to evaluate the TESSA® platform in house. They conducted numerous experiments to determine the optimal conditions for producing rAAV5 from the TESSA® production system and produced rAAV5 from the TESSA® system to compare against rAAV5 produced from triple transfection.

Ultimately, they generated data that showed that the vector genome yield of rAAV5 produced with TESSA® was >20-fold higher than rAAV5 produced with triple transfection. Additionally, their data show that quality as well as potency in mice of rAAV5 produced with the TESSA® system and by triple transfection are equivalent.

To learn more about TESSA® for scalable AAV production visit our web site or contact us to arrange a time to meet with our technical team.

WuXi ATU Sponsors the Believe Ball, Hosts Tom Whitehead, and Launches a Book Club Starting with Praying for Emily: The Faith, Science, and Miracles That Saved Our Daughter

Posted on by Amy Lamperti

WuXi Advanced Therapies had the immense honor of sponsoring this year’s Emily Whitehead Foundation Believe Ball, held on September 27th in Philadelphia. It was a night to remember, filled with hope, inspiration, and community. The event brought together industry leaders, supporters, and patient warriors who have fought and continue to fight for a future with better access to life-saving therapies.

The stars of the evening were without question the numerous CAR-T warriors who took to the stage to share their remarkable stories.  We were privileged to have Laurie Adami seated at our table with her son August. Laurie recently visited our site in Philadelphia and shared her amazing journey and story of resiliency and strength – further inspiring our team who work on CAR-T therapies like the one that saved her life.

The enthusiasm and support in the room were palpable as attendees rallied around the mission to advance therapies like CAR-T, the treatment that saved Emily Whitehead’s life. 

In addition, two remarkable individuals were acknowledged: Victoria Gray, recipient of the Bill Ludwig Pioneer Embassador Award, and Dr. Amber K. Hamilton, who was honored with the Nicole Gularte Fight for Cures Embassador Award. Both have made incredible contributions to the fight for cures, and their stories of resilience and dedication left a lasting impression on everyone present.

As proud sponsors of the Believe Ball, WuXi Advanced Therapies is committed to supporting the Emily Whitehead Foundation’s mission. The foundation, known for its pioneering role in advancing therapies like CAR-T, is helping create a future where more patients have access to these breakthrough treatments.

For more information about the Believe Ball and the foundation’s efforts, visit the official page here.

Tom Whitehead’s Inspiring Visit to WuXi Advanced Therapies

Just before the Believe Ball, WuXi Advanced Therapies had the privilege of hosting Tom Whitehead, co-founder of the Emily Whitehead Foundation, at our Philadelphia site. Tom toured our facilities and then delivered a “True North Town Hall” presentation where he shared the moving story of his daughter Emily’s battle with cancer and her experience receiving groundbreaking treatment with CAR-T cell therapy. Emily was the first pediatric patient to undergo this experimental therapy at the Children’s Hospital of Philadelphia, and her success has given hope to countless others.

Bryan Kennedy and Tom Whitehead of the Emily Whitehead Foundation tour facilities with Jessica

Tom’s visit provided an opportunity for our team to reconnect with the reason we do what we do and the importance of our work.  Tom expressed his gratitude for the work being done at our site by each employee as well as the progress made in the field of advanced therapies. Our team left inspired by his words of appreciation as well as his passion and dedication to raising awareness and advocating for advanced therapies.  He also shared how we can contribute to the foundation’s mission of activating the cure.

Book Club Launches with Praying for Emily: The Faith, Science, and Miracles That Saved Our Daughter

As part of our ongoing commitment to patient advocacy and raising awareness about life-saving therapies, WuXi Advanced Therapies recently launched a company-wide book club which will focus on reading books that center around our industry and the patient communities we serve.

The inaugural book for this initiative was Praying for Emily: The Faith, Science, and Miracles That Saved Our Daughter and right after he spoke to a packed room for our True North Town Hall, Tom joined us for our very first book club discussion, giving readers the unique opportunity to speak directly to Tom about Emily’s journey.

We found the book to be a great read because it not only captures the emotional and spiritual aspects of Emily’s fight but also delves into the scientific breakthrough that saved her life. It clearly demonstrated how and why she has become a beacon of hope for families around the world. It’s an inspiring read that highlights the incredible advancements of CAR-T while also sharing the deeply personal challenges the Whitehead family faced.

The lively, and often poignant discussion, revolved around the book’s themes of perseverance, hope, and the life-saving potential of advanced therapies. The response to the book and the discussion was overwhelmingly positive, with participants expressing how much Emily’s story resonated, not just personally, but in the context of their work developing cutting-edge therapies for patients like her.

For many employees, reading Praying for Emily has deepened their connection to the mission we share—to accelerate access to advanced therapies and ensure that more families can experience the same hope and success the Whiteheads did. We believe initiatives like this book club foster a greater sense of purpose and understanding within our organization, reminding us of the very real lives behind the scientific work we do every day.

If you haven’t had a chance to read Praying for Emily yet, it is available on Amazon and other popular book retailers.

WuXi ATU in Action: Conquering Mountains and 5Ks for Kinder Care and Melanoma Research

Posted on by Amy Lamperti

Recently, teams from the WuXi Advanced Therapies site in Philadelphia and the OXGENE site in the UK participated in events that championed awareness for issues that impact the patient communities we serve.

Climb for Kinder Care: Scaling New Heights for a Worthy Cause

On September 21st, 2024, three of our dedicated colleagues—Mohine Alam, Michael White, and Meenakshi Raghunath—took part in the Opie Jones Foundation’s #ClimbForKinderCare event by hiking to the summit of Mount Snowdon in Wales. This challenging 8-mile trek, representing the uphill battle of fighting childhood cancer, wasn’t just a hike; it was a mission to raise awareness and support for those affected by pediatric cancer.

The weather grew tougher as they ascended, with significant changes in climate near the peak, but their resolve remained unwavering. We couldn’t be prouder of their dedication, not only to completing the hike but also to their impressive fundraising efforts. If you’d like to contribute, it’s not too late! Visit their fundraising page here.

The Cause Behind the Climb

The Opie Jones Foundation organizes this annual fundraiser to advocate for kinder, innovative treatments for childhood cancers, such as CAR-T therapies. Their mission includes:

  • Providing mental health support through grants for families facing childhood cancer.
  • Increasing access to CAR-T cell therapy for patients and their families.
  • Raising awareness of childhood cancer and advocating for accessible, patient-friendly treatments.

Opie Jones, diagnosed with infant leukemia at just 5 months old, faced chemotherapy, a bone marrow transplant, and relapsed shortly after his first birthday. Opie then became one of the first pediatric patients in Europe to receive commercialized CAR-T therapy, and at 4 years old, he remains in remission today. His mother, Lucy Ellerker-Jones, vowed to climb a mountain if they ever made it through this ordeal—and now, she and others are turning that promise into reality.

To learn more about the Opie Jones Foundation or donate, please visit their website.

Running Toward a Cure: WuXi Team Supports Miles for Melanoma

A team of 37 employees, friends, and family members from WuXi Advanced Therapies participated in the August 24th, 2024, Miles for Melanoma 5K at the Philadelphia Zoo. In support of the Melanoma Research Foundation (MRF), the team raised over $2,500 to accelerate medical research, provide educational resources, and advocate for the melanoma community.

Melanoma, the fastest growing and deadliest form of skin cancer, is a cause close to our hearts. By participating in this event, we joined survivors, current patients, and loved ones of those affected by melanoma to rally around the fight for a cure.

Notable Achievements

A special congratulations goes out to several of our team members for their standout performances:

  • Stephen Frasco – 5th overall
  • Benjamin Weber – 7th overall
  • Alyssa Fisher, MS and Sara Benson, MS – 2nd in their age groups, both finished in the top 10 among all female runners

The #MilesForMelanoma event series unites communities nationwide to raise funds and awareness for the Melanoma Research Foundation’s mission. This year’s event drew industry leaders like Pfizer, Merck, and BMS, as well as healthcare providers like Jefferson Health and biotech companies such as Iovance Biotherapeutics, making it an inspiring day filled with solidarity and purpose.

We are incredibly proud of our team’s efforts and the collective dedication to a cause that matters to so many.

Both the Climb for Kinder Care and the Miles for Melanoma 5K reflect our ongoing commitment to making a difference. By supporting groundbreaking research and providing crucial resources, we continue to honor the patients, families, and survivors who inspire us every day.

XOFLX™ Technology Undergoes Peer Review: Published in Molecular Therapy Clinical Methods & Development

Posted on by Amy Lamperti

XOFLX™ stable cell lines technology and corresponding packaging and producer cell lines offer a simplified high-yielding LVV manufacturing system that lowers costs & improves process consistency.

Earlier this year a group of more than 30 contributors from OXGENE, a WuXi Advanced Therapies company dedicated to providing the industry with Discovery Services including design and engineering of plasmids, viral vectors, and cell lines, completed their manuscript and submitted it to Molecular Therapy: Clinical Methods & Development for review. The manuscript went through peer review process and was accepted August 5th, 2024.

The final article, entitled “Lentiviral vector packaging and producer cell lines yield titres equivalent to the industry-standard four-plasmid process” was published online on August 8th, 2024, and can be accessed here.

Molecular Therapy Methods & Clinical Development is an international, open-access journal that publishes peer-reviewed research on methods, procedures, and translational advances in molecular therapy. The journal focuses on cell and gene therapy, particularly in how these therapies are applied in clinical settings. Key topics include novel gene delivery methods, the use of integrating and non-integrating vectors, gene editing techniques, and the manufacturing of these products under Good Manufacturing Practice (GMP) conditions. The journal also addresses regulatory science and the commercialization of these innovative therapies.

Background

Lentiviral vector (LVV)-based cell and gene therapies offer the potential to cure diseases that currently require lifelong treatment. However, large-scale LVV production is hampered by the need for plasmid transfection, which adds operational complexity and cost. To overcome this, we developed LVV packaging and producer cell lines that reduce or eliminate the need for plasmid transfection.

Our team integrated lentiviral packaging genes and transfer plasmids into cell lines using random and transposase-mediated integration, respectively. Through single-cell isolation and testing, we identified top-performing clones. These clonal cell lines produced LVVs with consistent performance comparable to the industry-standard four-plasmid transfection method.

By simplifying the production process, XOFLX™ stable cell lines technology lowers costs and complexity, making LVV-mediated therapies more accessible to patients.

To learn more about the XOFLXTM stable technology and packaging and producer cell lines, visit our web site or contact us to arrange a time to meet with our technical team.

Pioneering Scalable Solutions in AAV Manufacturing and Testing for Gene Therapy

Posted on by Weiheng Su

Gene therapy represents a frontier in medical science, offering the prospect of cure for previously incurable genetic disorders. Central to this promise are adeno- associated virus (AAV) vectors, the vehicles for delivering therapeutic genes to patients’ cells. However, the commercial success and accessibility of gene therapies hinges on overcoming significant challenges in scalability and testing.

The Scalability Challenge in AAV Manufacturing

The scalability challenge in AAV manufacturing is a critical bottleneck hindering the wider application and commercial viability of gene therapies. Traditional AAV production methods are associated with low yields and recoveries, making the process expensive and inefficient. These challenges stem from the complex biological requirements for AAV vector production, including the need for specific helper viruses and the intricate balance of conditions required for effective replication and packaging of the therapeutic gene. As demand for gene therapies grows, the industry grapples with how to scale up production without compromising quality or increasing costs prohibitively. This situation creates barriers to patient access and places significant financial and logistical strain on healthcare systems worldwide, emphasizing the urgent need for innovative solutions to enhance scalability and reduce the overall cost of gene therapy manufacturing.

We have repeatedly heard from industry veterans that AAV production using the triple transfection system is not a logical fit for affordable gene therapy access for patients or feasible gene therapy manufacturing at scale for drug developers. The gene therapy sector has been on a mission to pursue a game changing solution.

Weimin Valenti – Executive Director of Strategic Alliances and Licensing, and TESSA franchise leader at OXGENE, a WuXi Advanced Therapies company.

The WuXi Advanced Therapies Solution

At WuXi Advanced Therapies we have developed Tetracycline- Enabled Self-Silencing Adenovirus (TESSA®) technology, a ground-breaking approach to AAV manufacturing. TESSA® technology transforms the process by enabling transfection-free, scalable production of AAV vectors at Good Manufacturing Practice (GMP) grade in HEK293 cells. This innovative solution significantly reduces costs and complexity, ensuring adenoviral contamination-free AAV production, with patient safety enhanced through the self-silencing of helper adenoviruses. With TESSA®, overall yields can increase more than tenfold due to the combination of improved yield with a significantly higher percentage of full AAV capsids.


TESSA® Pro, an advanced version of this scalable AAV production process, delivers substantial improvements in AAV manufacturing by lowering levels of host cell DNA and reverse packaging contamination. This benefit is evidenced by a study that was completed by Bridge Bio and shared during a webinar conducted in October of 2023 titled ‘Alleviating production bottlenecks in AAV manufacture via platform innovation’ (insights. bio). In practical terms, the TESSA® Pro process has generated up to 23 times more AAV material compared to the 3-plasmid process, with final AAV material quality also favoring TESSA with 100% full capsids versus 51% from the 3-plasmid process.


Recognizing the benefits of the TESSA® technology, Janssen Biotech, Inc., now Johnson & Johnson (J&J) Innovative Medicine, recently entered into a licensing agreement with WuXi and have successfully implemented the TESSA® process, from cloning and virus vector recovery to AdV and AAV production.

Major advance over the state of the art, and competitive in that respect with the best Sf9 platform yields I’ve seen. All in all, my conclusion is that TESSA is a strong contender for anyone considering development of a scalable AAV platform.

Gene therapy expert from a leading pharmaceutical company.

A Partner in Innovation

At WuXi Advanced Therapies we integrate our innovative AAV manufacturing with a comprehensive development and testing platform. By linking process development, assay development, biosafety testing, viral clearance, and product release testing with manufacturing, we ensure the quality and safety of gene therapies. This seamless integration of advanced testing methodologies from early development through to commercialization is crucial for meeting regulatory standards at scale, effectively bridging the gap between scalable production and the market’s demand for safe and effective gene therapies.

Our ethos is to work in close collaboration with our customers, partnering with pharmaceutical and biotech companies to foster innovation in gene therapy. This collaboration extends beyond transactional service provision, addressing industry- wide challenges and pushing the boundaries of gene therapy development and commercialization. Through these partnerships, we leverage our extensive expertise and cutting- edge technology to help bring transformative gene therapies to market, reinforcing our role as a strategic ally in the quest for novel treatments.

Looking Forward: The Future of Gene Therapy Manufacturing and Testing

The future of gene therapy manufacturing and testing is poised for transformative changes. Innovative technologies, changes in the regulatory environment, and the drive towards personalized medicine are expected to shape the landscape. WuXi Advanced Therapies is at the forefront of these developments, ready to lead with ground-breaking solutions that meet the sector’s evolving needs. Our commitment to innovation ensures we will continue to play a pivotal role in advancing gene therapy, making treatments more accessible and effective for patients worldwide.

As we progress through this transformative era of personalized medicine and gene therapy, adopting technological advancements for scaling up manufacturing of these innovative drugs will be critical for their success, and also expand their reach to more patients. TESSA is a breakthrough and built from decades of cumulative virology research, from Atchison’s first identification of AAV particles as contaminants in adenovirus preparations in 1965, to the significant efforts by veterans such as Muzyczka, Samulski, Xiao, Gao, and Grimm, in vectorizing AAV and their attempts to exploit its natural helper, the adenovirus, in generating these efficient gene delivery particles.

We believe TESSA is a significant game-changer for manufacturing AAV medicines, more economically, and help propel them to the clinic and patients.

Weiheng Su, Head of AAV at WuXi Advanced Therapies and inventor of TESSA technology

In Conclusion


Overcoming scalability and testing challenges is crucial for the broader accessibility and efficacy of gene therapies. At WuXi Advanced Therapies we tackle these challenges head on, offering innovative solutions and partnerships to navigate the complexities of gene therapy development and commercialization. Our work not only advances the field but also promises a future where treatments are more readily available to those in need. Partner with WuXi Advanced Therapies to leverage our expertise and technology for the betterment of healthcare outcomes worldwide. Get in touch today and we’ll arrange a time for you to meet with our scientists to learn more. You can also download a copy of this article.

Five Best Practices to Adapt and Improve Quality Control Programs for CGTs

Posted on by Audrey Chang

To launch a successful GMP program for biologics, a robust quality control (QC) release testing protocol is essential. QC testing, which is mandated by global regulatory authorities, helps ensure that a product meets scientific specifications and reaches patients safely. Though each program will have unique parameters, QC testing should gather data to answer the following questions:

  • Identity: Have you produced the correct product? 
  • Purity: What manufacturing and product byproducts are present? 
  • Strength: What is the potency and quantity of your product? 
  • Safety: Is your product safe and free of unwanted adventitious agents, e.g. Virus, bacteria, and mycoplasma? 
  • Product Quality Attributes: Have you demonstrated that product specific attributes are present? 

As biologics continue to diversify beyond monoclonal antibodies (mAbs) and recombinant proteins to include cell and gene therapies (CGTs), QC programs are shifting to accommodate the unique challenges associated with these advanced and novel therapeutics.

Recognizing Important Shifts

CGTs require adaptive and advanced assays for characterization and safety assessments; in many instances, the assays historically used for biologics do not fit the needs of these novel therapies. For example, mycoplasma has long been an area of key testing concern due to its ability to pass through standard sterilization filters. The standard mycoplasma culture-based assay takes 28 days to complete. This cycle is incompatible with the short shelf life of CGT products; as a result, the industry has pivoted to PCR testing for mycoplasma in CGTs, which can be completed in just a few days.

Empty/full ratios for viral vectors are another critical quality characteristic that has been challenging to characterize in the GMP setting thus far. To date, Analytical ultracentrifugation (AUC) has served as the best assessment of empty, full, and partial populations on the market, and as the identification of these ratios grows increasingly vital, AUC will continue to be an important implement for QC programs.

Several other considerations, including defining the critical quality attributes of raw materials and navigating evolving regulatory guidance, have left CGT developers and manufacturers looking for greater insight into how best to design their QC approach.

Identifying Five Best Practices for QC Programs

As you strive to design a strategic QC program, assess how you can leverage the following five best practices in your approach:

  1. Align to Your Risk Assessment:To mitigate risk, begin with a GMP mindset from the start, including sourcing well-characterized cell lines and raw materials while accounting for scale in your processes.
  2. Take a Quality by Design (QbD) Approach: Implementing QbD processes entails several deliberate choices, including ensuring you have the inventory necessary for your product lifecycle, creating a reference standard, and tracking trends as you set specifications.
  3. Leverage Templates and Platforms: Utilizing a templated or platformed approach helps you minimize variation in your process and establish streamlined validations, defined assay parameters, and a thorough understanding of each step.
  4. Gain Proximity to the Manufacturing Floor: The closer the QC lab’s proximity to the manufacturing floor, the better. The goal is to implement real-time, continuous testing in parallel with your manufacturing process.
  5. Participate in Knowledge Sharing: Disseminating key findings between stakeholders across the industry ― particularly around data, technology, and regulatory interactions ― yields major benefits for everyone, including patients.


Where Can I Learn More?

If you’d like more insight into improving your QC program, Dr. Audrey Chang, Executive Director at WuXi Advanced Therapies, recently hosted a webinar in which she highlighted the difficulties of developing QC programs for CGTs and her recommendations for how to improve them. You can watch the full webinar here or contact us to schedule a time to speak with her directly.

6 Key Questions to Cover When Selecting Your Cell Banking Manufacturing Partner

Posted on by Mitch Gore

The purpose of cell banking is to provide cells of a specific genetic and phenotypic profile for use in the production of disease therapies in adequate quantities for the lifespan of the therapeutic. Cell banks and cell lines used for pharmaceutical products are governed by regulatory agencies worldwide. 

Cell banks can be research cell banks (RCB), master cell banks (MCB), working cell banks (WCB), and end of production cell banks (EOPCB). Research cell banks are the result of extensive modification and selection processes that provide the seed stock for the MCB.

Expanding from RCB to MCB, and ultimately, to WCB involves a significant transition of growing cells under research conditions to growing cells using GMP-compliant processes. A large part of what changes during this transition is the extensive testing required to ensure genetic and phenotypic consistency, safety, purity, and functionality. In addition, when creating MCB and WCB especially, there needs to be proper documentation produced for support of regulatory requirements.

Choosing the right cell banking service provider is critical to the speed and success of the production of the therapeutic. Whether you are a small academic medical center provider or a large therapy developer or CDMO, here are six key questions you should be asking to help understand how well your needs will be addressed.

  1. Do they have experience with your cell type?

 It’s vital to choose a manufacturing partner that has demonstrated experience with your cell type and the growth and production targets you need to meet to support your program. Only a provider with prior experience will be able to knowledgeably assess their ability to deliver.

Common cell types used in cell banking include:

Human

Embryonic Retina (PER-C6)

Spleen

Kidney (MRC-5)

Neuroblastoma cells

Embryonic Kidney (HEK 293)

Umbilical cord

Murine

Hybridoma

Hybridoma Sp2/0

Myeloma (NSO)

Monkey

Africa Green Monkey (VERO)

Rhesus Monkey (LLC MK2)

Insect

Drosophila S2

Fall armyworm Sf9

Hamster

Ovary (CHO)

Canine

Kidney (MDCK)

Chicken

Embryo

2. What is the anticipated timeline and approach?  

Even the most robust cells and cell expansion protocols are subject to unknown pitfalls when transferring from provider to a manufacturing partner. Putting emphasis on the technical transfer of the cell bank expansion characteristics from the start will help avoid issues.

Make sure there is a clear and well documented understanding of the expected growth characteristics and a plan to test those before proceeding to the actual manufacturing runs. Minimally, the provider should be proposing that test runs be conducted for at least several passages, with cell counts and viability recorded at each passage.

The timeline for the pre-bank verification can vary, but it’s typically completed in approximately three weeks. Following that, MCB or WCB GMP production is typically three weeks. Two to six additional weeks are needed for testing and two to four weeks for document production should also be included in the timeline.

3. How will the partner manage in-process and release testing?

Understanding how your manufacturing partner will manage the testing of your cell bank during and after the production run is critical to ensure successful project execution. The timeline required for post-bank testing should be established early in the discussion with the provider.

Special attention should be given to the in-process testing as it’s vital to gauge the progress and health of the cells at each passage. The results may indicate a need to adjust expansion plan parameters.  At harvest and vialing there may be a need for quick turnaround of test results (STAT testing) to facilitate conditional release. Make sure your provider can perform STAT testing when needed.

Examples of the types of tests used for cell banking include:

  • Pre-Bank Sterility and Mycoplasma
  • Adventitious Viral Screening
  • Animal-derived Raw Material vVruses
  • Specific Virus Screening (Sf-rhabdovirus, Calicivirus, retroviruses, etc.)
  • Cell Morphology
  • Post-Bank Viability and Usability
  • Post-Bank Sterility and Mycoplasma
  • Cell Line Identification
  • Stability Testing

4. Is the testing done in-house or outsourced?

Find out if your provider will outsource the testing or if they have integrated testing capabilities. In-house testing alleviates the need to ship samples to a secondary site.  This will significantly impact the turnaround time for results and can also influence the number of vials needed for testing.

Your provider should be willing and able to advise you on the appropriate release tests for MCBs, WCBs, EOBCs, and genetic testing for stability studies. Their testing services need to include STAT testing, conditional release, pre- and post-bank testing, all within a proven and robust quality system.  

5. What is the provider’s approach to materials management?

An often-overlooked aspect of cell banking projects is materials management.

Finding a manufacturing partner who can quickly develop the Bill of Materials (BOM) and source the media, media additives, specific culture containers, and culture systems will help avoid delays.  

You may have to consider alternative materials, so choose a cell banking partner that can help suggest, source, and test the new components. It’s important to be sure that your provider has extensive experience in materials management for all types of cell banking and be willing to collaborate with you to quickly obtain and test alternative components.

6. Can the provider analyze for phenotypic / genetic drift?

Phenotypic and genetic drift is a potential risk in cell banking and ensuring that this has not happened should be part of the process. Make sure your provider has knowledge of the appropriate methods to access morphological and genetic changes. These can include microscopic evaluation, short tandem repeat profiling, growth curve comparisons, and testing for mycoplasma presence.

In conclusion, careful consideration of your cell banking service provider is critical to the success and speed of your journey from discovery to commercial manufacturing.  The ideal cell banking service provider has experience with the cell types, systems, and testing needed for your project. Importantly, those services and capabilities should also be part of an integrated development, GMP production, and testing workflow.

WuXi Advanced Therapies has been providing cell banking services, testing, and regulatory support for over 20 years. We can support your cell banking needs at any point in the journey from discovery to commercial production. Our teams also have extensive capabilities and experience in gene therapy and cell therapy processes, furthering our understanding of cell bank use. We conduct all manufacturing and testing from our state-of-the art facilities in Philadelphia, PA. Get in touch today to discuss your cell banking requirements.  

WuXi Advanced Therapies Receives FDA Approval to Manufacture Iovance’s AMTAGVI™ (lifileucel) for Advanced Melanoma

Posted on by Amy Lamperti

AMTAGVI™ is the first and only one-time, individualized T cell therapy to receive U.S. FDA approval for a solid tumor cancer.

PHILADELPHIA, PA.  February 20, 2024 – WuXi Advanced Therapies (WuXi ATU), a wholly owned subsidiary of WuXi AppTec, today announced that the U.S. Food and Drug Administration (FDA) has approved its Philadelphia site to begin the analytical testing and manufacturing of AMTAGVI for Iovance, which received FDA accelerated approval of its Biologics License Application (BLA) on February 16, 2024.

AMTAGVI is a tumor-derived autologous T cell immunotherapy indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. AMTAGVI is also the first and only one-time, individualized T cell therapy to receive U.S. FDA approval for a solid tumor cancer.

With this announcement, WuXi ATU’s Philadelphia site becomes the first U.S. external manufacturing site and the first third-party contract testing, development, and manufacturing organization (CTDMO) to be approved by the FDA to support the commercial manufacturing and release of an individualized T cell therapy for a solid tumor cancer.

 “We congratulate Iovance on this major milestone in their quest to address unmet patient needs in the treatment of advanced melanoma. WuXi ATU has partnered with Iovance since 2015, and we are thrilled to help them through each step of the drug development pipeline – from research to clinical manufacturing to FDA approval,” said Edward Hu, Chief Executive Officer of WuXi ATU and Vice Chairman of WuXi AppTec. “We are proud of our track record of enabling healthcare innovators to advance medical discoveries and deliver groundbreaking treatments to patients globally.”

Iovance, (NASDAQ: IOVA) is headquartered in San Carlos, California with an FDA-approved built-to-suit custom manufacturing facility, the Iovance Cell Therapy Center (iCTC), adjacent to WuXi ATU in the Navy Yard Philadelphia. The company is committed to innovating, developing, and delivering tumor infiltrating lymphocyte (TIL) cell therapies, including gene-edited cell therapies, for patients with cancer.

“The accelerated approval of AMTAGVI is the first step in realizing Iovance’s ambition to usher in the next generation of cell therapy by bringing this breakthrough to patients with advanced solid tumors,” said Frederick Vogt, Ph.D., J.D., Interim Chief Executive Officer and President of Iovance. “Given the significant unmet needs in the advanced melanoma community, we are proud to offer a personalized, one-time therapeutic option for these patients. WuXi ATU has partnered with us to manufacture this cell therapy for close to a decade. It is a great benefit to both Iovance and the healthcare community to have a contract testing, development, and manufacturing partner adjacent to our facilities. Working together our teams can make a meaningful difference for patients.”

About Iovance Biotherapeutics, Inc.

Iovance Biotherapeutics (NASDAQ: IOVA) aims to be the global leader in innovating, developing and delivering tumor infiltrating lymphocyte (TIL) cell therapies for patients with cancer. We are pioneering a transformational approach to cure cancer by harnessing the human immune system’s ability to recognize and destroy diverse cancer cells in each patient. The Iovance TIL platform has demonstrated promising clinical data across multiple solid tumors. Iovance’s AMTAGVI™  is the first FDA-approved T cell therapy for a solid tumor indication. We are committed to continuous innovation in cell therapy, including gene-edited cell therapy, which may be a promising option for patients with cancer. For more information, please visit www.iovance.com.

About WuXi Advanced Therapies (WuXi ATU)

As the advanced therapies business unit of WuXi AppTec, WuXi Advanced Therapies is a Contract Testing, Development and Manufacturing Organization (CTDMO) that offers advanced platforms and end-to-end solutions that enable the discovery, development, testing, manufacturing, and commercialization of cell and gene therapies. Our services and solutions accelerate time to market and support customer programs around the world. For more information visit www.advancedtherapies.com. 

About WuXi AppTec

As a global company with operations across Asia, Europe, and North America, WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable the pharmaceutical and healthcare industry around the world to advance discoveries and deliver groundbreaking treatments to patients. Through its unique business models, WuXi AppTec’s integrated, end-to-end services include chemistry drug CRDMO (Contract Research, Development and Manufacturing Organization), biology discovery, preclinical testing and clinical research services, and cell and gene therapies CTDMO (Contract Testing, Development and Manufacturing Organization), helping customers improve the productivity of advancing healthcare products through cost-effective and efficient solutions. WuXi AppTec received AA ESG rating from MSCI in 2023 and its open-access platform is enabling more than 6,000 customers from over 30 countries to improve the health of those in need – and to realize the vision that “every drug can be made and every disease can be treated.”

CONTACTS

WuXi Advanced Therapies

Amy Lamperti
Executive Director, Global Marketing
amy.lamperti@wuxiapptec.com

WuXi AppTec

Davy Wu
Executive Director, Brand & Corporate Communications
mediainquiries@wuxiapptec.com

Iovance Biotherapeutics, Inc.

Sara Pellegrino, IRC
Senior Vice President, Investor Relations & Corporate Communications
650-260-7120 ext. 264
Sara.Pellegrino@iovance.com

Jen Saunders
Director, Investor Relations & Public Relations
267-485-3119
Jen.Saunders@iovance.com 

WuXi Advanced Therapies Supports First Investigational CD19 CAR-T Therapy Approved by China’s NMPA

Posted on by Amy Lamperti

SHANGHAI, November 8, 2023 – WuXi Advanced Therapies (WuXi ATU), a global Contract Testing, Development and Manufacturing Organization (CTDMO) congratulates its customer, Juventas Cell Therapy, on achieving China’s NMPA approval for Juventas’ New Drug Application (NDA) for Inaticabtagene Autoleucel (CNCT19 Injection), which is indicated for the treatment of adult relapsed and refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

Unique CTDMO Model Accelerates Market Approval Process

As a crucial partner of Juventas Cell Therapy, WuXi ATU has played a critical role in the development and production of key raw materials such as plasmids and lentivirus. The services encompassed process development, support for the IND and BLA filings, registration testing, on-site inspections, market approval, and providing comprehensive CTDMO services to ensure seamless commercial production.

Since 2018, WuXi ATU has worked alongside Juventas Cell Therapy. In August 2023, WuXi ATU received the “Outstanding Supplier of 2022” by Juventas for WuXi ATU’s contributions in developing and manufacturing Inaticabtagene Autoleucel.

Leveraging the advantages of its CTDMO platform, WuXi ATU empowered Juventas to expedite the project across various facets and accelerate the approval for Inaticabtagene Autoleucel. It took only four years from IND submission to NDA acceptance.. As a result, WuXi ATU became the first Cell and Gene Therapy CDMO in China to pass a lentiviral vector on-site inspection by the Center for Food and Drug Inspection of the China NMPA (CFDI).

QbD Concept Embedded, Ensuring Process and Quality

CAR-T cell therapy, representing tumor immunotherapy, was recognized as the top scientific breakthrough of 2013 by Science. As a “living drug”, CAR-T cells exhibits high complexity and variability. Its production process includes (i) two key raw material production:  plasmid production and lentiviral vector production and (ii) CAR-T cell drug production, each of which involves multidimensional, multi-input, and multi-output factors. Therefore, from the initial stage of process design and development, Juventas Cell Therapy and WuXi ATU adhered to the concept of “Quality by Design” (QbD) throughout the drug’s entire lifecycle. The QbD process involves applying a scientific and systematic development approach to efficiently transform laboratory-prepared processes into GMP manufacturing processes that meet IND filing requirements and, ultimately, achieve BLA approval for commercial production. By applying the QbD, Juventas Cell Therapy and WuXi ATU considered the impact of key raw materials on final product quality, as well as its impact on patient efficacy and safety from the early stages of process design.

This approach attempts to mitigate future risks and the high costs associated with changes by doing the following: Fully understanding of the unique requirements for downstream cell products, setting quality target product profile (QTPP) for key raw materials, identifying critical quality attributes (CQA), systematically developing laboratory-scale process models for multivariate experimental research to determine critical process parameters (CPP) and design space, and ultimately establishing an overall control strategy. This strategy has been validated at the commercial production scale, ensuring the robustness of the manufacturing process and the stability of product quality.

About Juventas

Established in June 2018, Juventas Cell Therapy Ltd, a biopharmaceutical company powered by cutting-edge cell and gene technologies, has become the leader of innovative CGT drug development in China. Juventas’ innovation is stemmed from its integrated R&D platforms including CAR, iPSCs, and gene-editing technologies. With more than 10 drug candidates in its pipeline, featured with solo, dual, or multiple target autologous CAR-T and universal cellular products, Juventas is well on its way to fulfil its mission – providing novel solutions to unmet clinical needs in the treatment of blood cancers, solid tumors, and other diseases.

Beside self-driven innovation, Juventas is open for domestic and international collaborations, and has developed close partnership cooperation with China national top scientific institutes and clinical research centers, to diligently translate frontier science and technology advancement into bedside therapies/treatments.

In Nov. 2023, Juventas’ first core product – Inaticabtagene Autoleucel (CNCT19) was approved by NMPA, for the treatment of adult B-cell relapsed and refractory acute lymphoblastic leukemia (B-ALL).

About WuXi Advanced Therapies (WuXi ATU)

As the advanced therapies business unit of WuXi AppTec, WuXi Advanced Therapies is a Contract Testing, Development and Manufacturing Organization (CTDMO) that offers integrated platforms to transform the discovery, development, testing, manufacturing, and commercialization of cell and gene therapies. Our services and solutions accelerate time to market and support customer programs around the world. For more information, please visit https://wuxiadvstg.wpenginepowered.com.

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