Cell & Gene Therapy Products 2021

Join Emerging Scientists Event

Motivations for an Early Career Researcher in Cell and Gene - Session Speaker Tiffany Hood

The Transition from Academia to Industry: Lessons Learned - Session Speaker Yazmin Rovira Gonzalez

Challenges for Gene and Cell Therapy in the 21st Century: From Child Prodigy to All-star Treatment for Incurable Diseases - Session Speaker Riccardo Biavasco

In-depth characterization of Adeno-Associated Virus (AAV) is important for quality assurance and safety of AAV products in gene therapy industry. Capillary Electrophoresis (CE) is a technology which could provide fast, reliable and robust analysis of AAV capsid protein purity with high sensitivity, AAV full and empty ratio determination, AAV charge variants and integrity analysis of genome packaged in AAV capsids which are critical workflows for AAV product analysis. Additionally, advancements in pharmaceutical development have led to novel ways in which therapeutics are delivered. Emerging drug delivery mechanisms are liposomes, currently being utilized as therapeutic transport systems. The expansion of liposomes to more specialized lipid nanoparticles (LNPs) has further developed this area of therapeutics and LC-MS has emerged as a robust technique for their profiling and quantification.

The separation of Adeno-associated virus (AAV) Empty and Full by charge-based techniques have been development on several serotypes using ion-exchange chromatography. However, the separation is quite serotype dependent and sometimes process dependent on other factors. Another technique is needed to separate hard-to-separate AAV in order to characterize the empty species. Here we will explore the use of ICIEF to separate a previously failed-to-separated AAV drug substance, and present the method development and assessment of empty species. Talk will cover:
-Introduction of iCIEF and empty/full separation.
-Development of empty and full characterization by iCEIF.
-What has the empty/full characterization by iCIEF tell us.

As a class of therapeutics, cell and gene therapies are remarkably diverse in their modes of action and composition. But perhaps even more remarkable is how the diversity of these modalities continues to expand, powered by transformational scientific advancements. Over the past few years, we have witnessed how induced pluripotent stem cells, gene replacement therapy, and genetic editing of various different cell types (T-cells, NK cells, stem cells, etc.) have made the transition from research tools to become the basis of clinical candidates in development. Cutting edge analytical methodologies which once were firmly in the sphere of discovery biology have been adopted into product development workflows. Personalized medicine approaches, such as the identification and targeting of tumor-specific neoantigens, are quickly evolving. Strategies are under constant development to better understand the regulatory implications of these new technologies.

In this session, we will explore examples of how new technologies have emerged in application to potential therapeutic products and discuss the practical CMC challenges that face those who develop and regulate them.

1. What are the CMC and regulatory factors that need to be considered when developing a pluripotent stem cell-based therapy product?
2. Why is it important to implement state-of-the-art technologies and algorithms into neoantigen identification pipelines?
3. How are innovations implemented in a regulated clinical environment?
4. How do regulators view the integration of emerging technologies in cell and gene therapy products?

Join Session I Deep Dive Panel Discussion

Join Session II Deep Dive Panel Discussion

Analytical characterization of cell and gene therapy (CGT) products remains a challenging, costly, and time-consuming task. Additionally, the relatively high sample volume typically required for analytical testing of such products is often considered a challenge by itself. To overcome those issues, new technologies can be used, and we would like to present a proof-of-concept work demonstrating application of multidimensional chromatography for characterization of Adenovirus type 5 (Ad5)-based product. In our case study, we focused on Ad5 quantitation by AEX-HPLC and identity by RP-HPLC described in the literature [Blanche et al., Gene Ther., 7 (2000) 1055-1062 and Lehmberg et al., J. Chromatogr. B, 732 (1999) 411-423]. In the first step, we were able to significantly reduce the sample run time by using modern chromatographic columns and optimizing gradients, while maintaining selectivity and overall quality of the individual assays. In the second step, we combined two analytical assays into one functional 2D LC assay allowing for Ad5 quantitation and confirmation of its identity.

The resulting 2D LC method includes first-dimension AEX separation, which generates the data that can be used for quantitation of Ad5 viral particles using the area-under-the-curve approach and an appropriate calibration curve, followed by automated transfer of the material representing the Ad5 peak from the first to the second dimension, and second-dimension RP separation, which generates the characteristic pattern of Ad5 capsid proteins that can be used for verifying identity of Ad5.

The approach presented here not only allowed us to increase productivity, but also to limit the sample volume needed for the analysis. We envision that by applying the concept presented in this proof-of-concept work, it will be possible to shorten the time necessary to perform analytical testing of CGT products and reduce the required volume of samples needed to complete the analysis.

The maturing of Cell and Gene Therapy products provides an opportunity to serve patients with options for treatment where none have previously existed. In the past few years, several cell and gene therapy products have gained regulatory approval in the US and EU. The number of products in clinical development in the US continues to increase and many of these products have the potential for accelerated regulatory pathways. Manufacturers of cell and gene therapy products must tackle technological challenges under the pressure of short timelines resulting from streamlined clinical development. This has been further compounded by demands for capacity, human resources, and manufacturing materials resulting from the global COVID pandemic. This session will focus on innovations that focus on the implementation platform processes and technology that will enable rapid product development and in turn aid in Regulatory review and approval.

The goal of platform-based process technology is to bring products to market sooner and to ease the Regulatory burden for sponsors and Regulators.

• What aspects of the platform process approach do you see as the first to gain Regulatory acceptance?
• Where do you see the biggest challenges for the Regulatory relief?
• What technology breakthroughs are on the horizon to overcome the challenges?


The public/private partnership described by Steven Hoffman for the AAV platform is a great opportunity, but even taking the existence of DMF in the US into account (which is not an option in the EU) is this approach a valid one within the current regulatory framework? Does a framework need to be developed.

• To what extent will Regulators accept inter-company platform knowledge, given that it will need to be implemented locally?
• Is this the same as an MF?

What do you see as the main challenges for automated platform manufacturing of cell-based products? (starting with someone other than Qasim)

What is the interplay between platform technologies and GMP?

• Will it make compliance easier, or more difficult? For cell-based products there is a widespread lack of understanding what is required of closed systems.
• Should the approach be tightened based on increased knowledge and scale-up possibilities? (Currently, the EU GMP for ATMPs is seen by many as less strict than standard GMP)

Join Session III Deep Dive Panel Discussion

Join Session IV Deep Panel Discussion

Adeno-associated virus (AAV) has been widely used in gene therapy applications. To fully realize the potential of AAV vectors, reliable and efficient analytical technologies have become increasingly relevant and urgent to help establish a structure-function relationship, guide the development of manufacturing process, and assess the quality of clinical materials. In this talk, we will highlight the novel LC/MS workflows that are developed for structural characterization of recombinant AAV vectors, including capsid protein identification and PTM analysis.

This session will cover cell and gene therapy products in late stage of development and approved by the FDA and/or EMA to demonstrate the main CMC challenges, the regulatory framework, and the overall experience with the Health Authorities to bring these medicines to patients. The innovative approaches and the regulatory outcome will be discussed in case studies to cover different approaches on development, main differences observed between EU and US, and lessons learned.

Dr. Fuller will present on the use of correlative analysis to develop specifications for idecabtagene vicleucel (Abecma®), an FDA approved Bristol Myers Squibb cell therapy to target BCMA, for the treatment of multiple myeloma. His talk will focus on the outcome of correlative analysis and the regulatory feedback on specifications.

Dr. Wagmare will present bluebird bio’s Marketing Authorization Application (MAA) journey for elivaldogene autotemcel (eli-cel, Lenti-D™), an investigational gene therapy for the treatment of patients with Cerebral Adrenoleukodystrophy, a rare, X-linked, metabolic disorder primarily affecting boys between the ages of 3 and 12 years. His talk will focus on potency assay development, process performance qualification strategy development, and regulatory procedures.

Dr. McQueen will present on storage and shipping conditions at ultra-low temperatures and the analytical complexity in support of CMC changes in the post-approval phase. She will present on the FDA and EMA approved IMLYGIC™ (talimogene laherparepvec), a genetically modified oncolytic viral therapy indicated for the local treatment melanoma recurrent after initial surgery.