Walter E. Washington Convention Center
Washington, D.C.
May 16-19, 2022

Andelyn Biosciences  

Columbus,  OH 
United States
  • Booth: 148

Andelyn Biosciences invites you to visit us at Booth 148.

Andelyn Biosciences is a pioneering gene therapy organization born out of Nationwide Children's Hospital that helps clients innovate and produce new gene therapies that transform, extend and save lives. Andelyn has partnered in over 75+ US, EU and ROW clinical trials including the innovation of Zolgensma – the first FDA approved gene therapy for Spinal Muscular Atrophy. The name “Andelyn” was chosen to pay tribute to two patients that participated in pivotal clinical trials for Zolgensma. Their combined names serve as a reminder that while Andelyn is a biopharmaceutical business, the patient is always first. Andelyn Biosciences supports clients from preclinical through Phase I/II trials. Our 185,000 square-foot late stage and commercial manufacturing facility will be operational in 2H2022, allowing Andelyn to be a full spectrum Gene Therapy Partner. Our capabilities include Viral Vector process and analytical development, small to large scale cGMP manufacturing, Fill/Finish and quality release testing. We also offer plasmid manufacturing services and vector development (GMP, Tox grade and Research grade). Our experts can help take you through all stages of making your ideas reality, reducing the need and time for tech transfers. We are your trusted partner for accelerating the development and manufacturing of innovative therapies to bring more treatments to more patients.

 Press Releases

  • Dear Current and Future Andelyn Partner,   

    We would like to invite you to join us at the ASGCT 25th Annual Meeting booth 148 this year in Washington D.C. The conference will be held from May 16th -May 19th at the Walter E. Washington Convention Center. We will have representatives from Operations, Analytical & Product Development, Human Resources, and the Business Team attending the conference. We have a meeting room reserved at the Residence Inn Hotel next to the Convention Center (Lincoln Room, on the 2nd floor), Monday, May 16th through Wednesday, May 18th from 9 a.m. to 5 p.m. to meet with you and your team about current planned productions, future productions, and potential visits. We will also be available outside these times as needed to facilitate your schedules.

    If you will be attending the conference and would like to schedule a time to meet, let us know which Andelyn representatives you are interested in speaking with along with a couple of possible times and your contact information.  We will send you a meeting invite to confirm your time.  We look forward to meeting with you and your team.

    Best Regards,

    Eric Blair - Chief Commercial Officer

    Wade Macedone – Chief Operating Officer

    Andy Moreo – Head of Process Development

    Will Fountain – Head of Analytical Development

    Kristin Heller – GMP Manager

    Samir Acharya - AD of Process Development

    Chrystal Montgomery – AD of Contracts

    Vera Araujo – Business Development Manager

    Josh Kime – Business Development Manager

    Dan Butler – Business Development

    Pamela Backus-Diggs – Human Resources

    Sara Bergman – GMP Scientist

    Hannah Roodhouse - GMP Scientist

  • By Andy Moreo, Head of Process Development, Plasmid and Viral Vector Core Facilities, and Lenore Giannunzio, principal research scientist, Andelyn Biosciences


    Viral vectors are more than a vehicle for a payload – their ability to target specific cells has made them one of the most promising treatment modalities to emerge in recent years. But the specificity enabled by this tropism has created complexities impacting their scale-up.

    Ensuring optimal yield for engineered viral vectors is crucial to ensuring their eventual commercial viability. Despite this, it can be easy to overlook the factors that impact yield performance early enough, resulting in suboptimal yields, rework, and the potential scrapping of an otherwise promising therapeutic. Frequently, issues related to yield are not uncovered until toxicology testing has already commenced, and considerable time and cost investment has already been leveraged toward a transgene that, while effective, is production-inefficient.

    The heavy lifting inherent to development in cell and gene therapy contributes to the high costs of production for these therapeutics, and the commensurately high cost for a patient. Zolgensma, a gene therapy for spinal muscular atrophy, is the most expensive drug on the planet, averaging more than $2 million for a single dose. It is critical to drive down the cost of viral vector development to make these life-changing therapies more accessible, facilitating more targeted treatments for a greater range of diseases and quality-of-life improvements.

    The Variables that Impact Yield Optimization for Viral Vectors

    Scientists have greatly advanced the field of engineered serotypes by fine-tuning their epitopes and proteins to improve tropism, transduction, and specificity. In contrast, “wild serotypes,” such as rh74 or AAV9, have had over a billion years to optimize their packaging efficiency, resulting in a superior yield profile in a production setting.

    Another core focus of this research has been transgene development, with a particular emphasis on expression. Early in a product’s life cycle, the driving question centers on how to design a transgene that achieves optimal expression with an already limited payload capacity. This is a complex endeavor in itself, as a portion of that capacity is earmarked for inverted terminal repeats (ITRs), promotors, poly(A) signals, and other features that must be present to meet regulatory requirements. Therefore, the molecular development needed to produce a functional coding sequence, with a high expression level, able to be packaged in a tailored capsid is already a difficult task; working concomitantly to ensure yield may fall to the wayside as a result of this complexity.

    Optimizing a yield profile early, and subsequently scaling with yield performance in mind, can help companies more easily achieve the productivity demands required for the whole product lifecycle. Downstream purification losses average between 50 and 70 percent for non-optimized processes. Ultra-centrifugation is one of the most notorious points that spur product loss, as well as one of the most common workhorse steps to purification; transitioning entirely to column purification would be one potential solution to minimizing that loss. But purification losses are typically compounding; while a discrete purification step may boast an average 20 percent product loss, previous and subsequent purification steps with the same average loss will contribute to the majority of a product lost to purification when evaluated holistically. Some level of static, adsorptive loss is unavoidable at each step, but improving upfront yield can serve to mitigate losses and improve downstream purification.

    Mitigating Costs Through Standardized Platform Technology

    It is important for biopharmas to understand that yield profiles of a product can vary greatly based on serotype and DNA sequence. Therefore, researchers must go through a thorough screening process of transgenes, backbones, and serotype configurations to establish critical production parameters prior to selecting the best candidate for production and clinical performance. To achieve this, AAV candidates can be sent to a platform development lab with standardized processes, equipment, materials, and expertise to evaluate their performance through a standardized Design of Experiment (DoE) study in adherent or suspension cultures. By balancing customization and standardization through flexible approaches, companies can gain important insights on both upstream yield and downstream purification.

    While prioritizing tropism and transgene expression is integral, focusing on other variables, such as cell density, packaging efficiency, incubation, and hold time duration, stability, and impurity profiles are critical to mitigating costs and creating efficiencies. Enabling the interchangeability of materials and working toward process standardization across as many serotypes as possible is key to the future of the cell and gene therapy space. At present, the proliferation of custom-built platforms for specific transgenes has created a flood of siloed, individualized processes, impacting cost, time to market, and manufacturing efficiency.

    Optimizing viral vector yield also means right-sizing processes. Accurate lot sizing is critical for this optimization; the ability to operate at multiple scales, considerations such as sub-lot production size to minimize pooling, or other considerations can reduce waste and lower cost of production. This standardization can be elusive for some therapeutics, but for those whose projects can accommodate it, it can serve as an important tool for optimizing yield at a reduced long-term cost. Many of the nuances in AAV production and scale-up can only be identified and addressed over multiple production runs. Experience and standardization on the part of a manufacturer can prove critical in avoiding unnecessary delays.

    Future Trends in Standardizing Yields for Viral Vectors

    The current AAV research landscape is still far from achieving the standardization of other parts of the biopharmaceutical market, because of the inherent variability of the biological process. The sheer amount of data needed to enable predictive analytics is still a long way off for many developers, most of whom are working with highly proprietary, engineered serotypes in a highly competitive market. But achieving product equivalency will be critical to maturing the market in the coming years, and the maturation of the analytics behind that market will be key to achieving that equivalency.

    The variability between vectors is immense, owing to both the selected serotype and transgene, as well as other factors like size of the genetic payload and sequence, which can affect its packaging, density, buoyancy, or affinity. The intersecting variables that inform an AAV’s development, coupled with the competition and evolving regulatory standards that attend these therapies, has made developing a standard approach difficult. This, along with interchangeability and a push for harmonization, represents the future of AAV therapies that are affordable and accessible.

    Ultimately, partnering with a contract development and manufacturing organization (CDMO) with the expertise and platform technologies to help balance a project’s customization and standardization can help companies avoid the more common pitfalls of AAV development. Ensuring optimal yield for these therapeutics is a complex endeavor; it is also a crucial one, as many projects with immense therapeutic potential have been waylaid by poor yield. In a market prohibited by costs, both on the part of the developer and the end user, pursuing long-range advancements in process standardization, data collection, and yield optimization will serve to stabilize the space and advance more targeted therapies.

  • Source: Andelyn Biosciences
    By Kristin Heller, Plasmid Core Manager, and Andy Moreo, Head of Process Development, Plasmid and Viral Vector Core Facilities, Andelyn Biosciences

    The proliferation of targeted cell and gene therapies as first-line treatments for many rare and complex disease states has spurred demand for materials that meet the downstream needs for these applications. Plasmid DNA, purified from bacteria, serves several important roles in the biologics and cell and gene therapy spaces – from transfection to sequencing, cloning to PCR, plasmids have a ranging utility that has helped drive personalized medicine innovations.

    Securing the right plasmid for a given application can be a complex endeavor. Between the wide variance that can occur in their development to the shifting regulatory standards that define their production, plasmids require the right expertise and experience to optimize their development for varying manufacturing paradigms.

    Choosing the right plasmid can help prevent costly delays in the development lifecycle. Core to this is selecting a supplier with the quality assurance protocols and Good Manufacturing Practices (GMPs) in place to facilitate optimized plasmid production.

    Finding the Right Plasmid: Considerations

    Plasmid DNA – small, double-stranded DNA molecules independent from a cell’s chromosomal DNA – is often a highly varied material, developed with unique considerations for bespoke pharmaceutical applications. In response to increased demand for pDNA to keep pace with personalized medicine innovations, contract development and manufacturing organizations (CDMOs) have begun pioneering a greater range of plasmids with more utility than ever before.

    As with many aspects of the space, companies have trended toward securing the highest-quality plasmids available for a given application. This has largely been in response to evolving regulatory standards – many companies, keen on staying ahead of the curve, have sought out materials well above what is necessary for their process. As a result, many have begun to incur the cost constraints inherent to that approach. Right-sizing with a supplier able to meet evolving needs for a project along its development can help companies mitigate those costs and optimize productivity.

    There are essentially three grades of plasmid DNA: research-, clinical-, and commercial-grade. But within these categories exist levels of nuance; commercial-grade plasmids that are intended to serve as raw materials, for example, possess regulatory standards much less stringent than for plasmids selected to serve as active pharmaceutical ingredients (APIs). That stringency is even greater for plasmids that function as a finished product. These varying degrees of regulatory rigor, dependent on a plasmid’s intended use, result in compounding cost and time constraints for companies working toward return on investment.

    In response to progress across the cell and gene therapy field, many biopharmas are working now to identify efficiencies in their manufacturing processes and create more sustainable, scalable production. As plasmids have become a more common component to these therapies, the FDA and other regulatory bodies have continued to iterate on their quality standards. Under existing regulations, there are no allowable contaminants for plasmids, which makes the purification processes fundamental to their manufacture a critical focal point for innovation. This consideration goes hand in hand with a plasmid’s initial design – its functionality alone is insufficient to guarantee its scalability as part of a manufacturing paradigm. Companies must also consider other factors inherent to its design, including yield, transient transfection rates, and its capacity to stably transduce cell lines in downstream applications.

    For companies at the proof-of-concept stage, these and other considerations, such as the antibiotic resistances of different plasmid backbones or how many generations a backbone is removed from its genesis, all serve to impact the yield and contamination profile of the pDNA. Decisions related to these considerations, made as early as possible, can help companies avoid the delays associated with reworking a plasmid that demonstrates suboptimal yield or a tendency toward contamination at later stages of development.

    Optimizing Plasmid Design and Production

    Poor plasmid design can lead to a range of issues, from issues regarding the integrity of inverted terminal repeats (ITRs) to partial transgene packaging and everything in between. There are a wide variety of factors, energetically, stoichiometrically, and chemically, that can impact this design. Ideally, companies can access the necessary data, either internally or in concert with a partner, to address each in turn – data that illustrate the issues that can influence backbone packaging, such as transgene size, or that support the selection of helper plasmids capable of reducing or virtually eliminating replication-competent adenovirus.

    Finding a plasmid supplier able to support a project’s vertical integration from early research grade through toxicology, clinical manufacturing, and commercialization is paramount to ensuring its success. Capacity is nearly as important a consideration as competency in this respect – plasmid suppliers that have invested in their capacity to meet market demand, as well as those able to demonstrate their ability to control lead times in the face of potential supply chain constraints, are invaluable to companies looking to scale a therapy commercially. Access to pDNA is one of the biggest bottlenecks in downstream biopharmaceutical manufacturing; instability in manufacturing or the identification of issues post-sequencing are perhaps a bigger factor in this problem than capacity, but both are important considerations for biopharmas seeking to streamline their development efforts.

    One of the best ways for companies to ensure this streamlining is by partnering with a plasmid supplier capable of transitioning alongside them through every phase of development. This lack of third-party intercession, coupled with a continuity in data collection, serves to close gaps, both in the time needed to scale up and the communication required to scale up the right way. Squaring the scale of manufacturing a plasmid against the yield profile of the commensurate vector manufacturing to determine how to produce enough material for each phase of development is a complex endeavor. Being able to communicate with a provider that can help companies understand their yield goals and the variables that can impact achieving them is key to avoiding the pitfalls that insufficient pDNA can have on the overarching manufacturing process.

    Selecting the Right Partner for the Future

    Traditional plasmid manufacturing has been around for a long time, and most plasmid manufacturers are working with a similar and well-codified process. But as gene therapies continue to proliferate, innovations to the status quo surrounding plasmid manufacturing are becoming more common. Things such as new resins introduced to the purification process, as well as single-use disposable fermenters in place of traditional stainless-steel ones, have helped minimize the potential for contamination. Similarly, the traditional approach to bacteria growth was to centrifuge bacteria in order to pellet it down; today, new technologies are starting to emerge that allow users to filter out media and replenish it with new media or solution that aids the downstream purification processing, as well.

    There are even more promising developments on the horizon that portend even greater advancement for the space: innovations like the “doggy bone” DNA technology, a synthetic, rapid, cost-effective alternative to backbone plasmids that eliminates antibiotic resistance genes, which can represent a “contaminant” for plasmids due to their potential to introduce antibiotic resistance in patients. This and other developments that represent the next frontier of plasmid development are important milestones for the space, but equally important is a commitment to the state-of-the-art: by streamlining and optimizing plasmid DNA in the short term, companies are well-positioned to reap compounding benefits as they scale their therapies.

    Ultimately, partnering with a plasmid supplier that can scale alongside a therapy’s development can save biopharmas time and money through standardized, connected protocols, comprehensive data aggregation, and in-house expertise. Companies should consider their plasmid and plasmid supplier as early as possible in the development pipeline; doing so in a way that accounts for the factors that can impact yield and stability, as well as the changing regulatory considerations that surround plasmids, can help biopharmas ensure their long-term commercial success in a rapidly evolving landscape.