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Applying Quality By Design Principles to AAV Manufacturing

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The expectation to apply quality by design (QbD) principles to new manufacturing processes has been voiced by regulatory authorities for over a decade (1, 2). They recognize that because of the generally low patient populations for emerging therapies, such as adeno-associated virus (AAV)-based therapeutics, available chemistry, manufacturing, and controls (CMC) information might not be as exhaustive as for other biologicals such as monoclonal antibodies (3, 4). Other challenges include the need for rapid development to address currently unmet medical needs…

October 20, 2022

A Plug-and-Produce GMP Plant for Cell and Gene Therapies Part 2: Rapid Deployment of a Commercial-Scale Facility

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Extending the use of approved advanced-therapy medicinal products (ATMPs) to the tens of thousands of patients who could benefit from such treatment requires a 10- to 100-fold production scale-up. Given that each autologous ATMP batch yields one dose for one patient, expanding production throughput is not a question of boosting volume, but rather of amplifying single manufacturing runs. That is, scale-up is actually scale-out, and the dimensions of the ensuing endeavor extend beyond what occurs in the cleanroom. Coupled with…

October 20, 2022

Two-Step Monoclonal Antibody Purification Using a Multicolumn Continuous Chromatography Platform

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Biomanufacturers typically have relied on multistep processes for optimal removal of impurities such as host-cell proteins (HCPs), DNA, adventitious viruses, and aggregates. However, additional purification steps increase downstream expenses significantly, including costs of supplementary resin, hardware, and buffers. The substantial footprint required at a processing site and additional time needed to perform a complete multistep purification process also increase production costs and complicate process execution. Thus, it is imperative to design and test effective purification procedures for high-quality biotherapeutics, but…

October 20, 2022

Investigation of HCP Enrichment During CGMP Scale-Up

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On paper, scaling a bioprocess from a 10-L to a 100-L to a 2,000-L bioreactor may seem like a straightforward math problem that could be solved by software. In practice, however, the exercise relies on a complex set of biological, chemical, and engineering assumptions; on maintenance of healthy cell cultures; and on management of equipment and analytics while adjusting to each increase in scale (1). Process development and quality control groups need to monitor how scale-up might affect critical quality…

October 20, 2022

Bridging Anti-CHO HCP Antibodies: From Two Third-Generation Cygnus CHO HCP ELISA Kits By AAE-MS

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A well-developed, broadly reactive, and qualified enzyme-linked immunosorbent assay (ELISA) is the gold-standard method for ensuring removal of host cell proteins (HCPs) and demonstrating process consistency and final drug substance (DS) purity. Regulatory guidelines require sponsors to use orthogonal methods for demonstrating antibody coverage of individual HCPs and provide a comprehensive assay qualification package to ensure that the ELISA is fit for purpose. In a June 2022 webinar, Eric Bishop (head of R&D and custom development services at Cygnus Technologies)…

October 20, 2022

Streamlined AAV Manufacture: From Plasmid Design to GMP Production

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This webcast features: Bo-Jhih Guan, PhD, Senior Scientist, Department of Viral Vector Process and Technology Development, WuXi Advanced Therapies. Adeno-associated virus (AAV) vectors are important gene delivery tools for gene therapies. To ensure that novel treatments can be effective and can reach as many patients as possible, AAV vectors must be produced at high quality and high titres – and manufacturing approaches must keep pace with an increased demand for treatments. AAV quality and titre can be improved by optimizing…

October 20, 2022

Addressing Purification Challenges for Complex Therapeutics with Custom Chromatography Resins

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This webcast features: Laurens Sierkstra, Business Segment Leader, Bioproduction Group, Thermo Fisher Scientific. Ongoing progress in biotherapeutics development has initiated an increasing range of complex molecules entering the drug development pipeline such as novel vaccines and therapeutic proteins. This often rises challenges in the manufacturing process of these newer modalities, with downstream operations as a focus point as this part of the production process frequently represents a bottleneck. Addressing downstream challenges requires novel purification strategies for commercial manufacturing which may…

October 20, 2022

Analysis of Subvisible and Visible Aggregation in Lentiviral Vectors with Aura GT

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Characterizing LVV stability just got a whole lot easier. As a developer of genetic therapies, do you find yourself struggling with the complexity of lentiviral vectors (LVV)? If so, you’re not alone. Compared to protein biologics, LVVs can be more difficult and expensive to manufacture. The scarcity of LVV material also makes scale-up difficult and adds additional complexity when qualifying subvisible particles, the most indicative critical quality attribute for biologic stability. But what if there was a way to overcome…

October 20, 2022

Validation 4.0: An industry transformation

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The life sciences industry is on the precipice of a new frontier — a future that is digital-first and technology-led. With the mass acceleration and adoption of software-as-a-service (SaaS) cloud systems—from discovery through to point of care—widespread digital transformation is a key business driver, saving companies critical time, resources, and spending. Despite this ongoing industry-wide shift, one business-critical aspect common to regulated companies lags: validation. Historically, compliance has followed the industry practice of Computer System Validation (CSV), which is paper-driven,…

October 19, 2022

AAVs: The future of gene therapies, but what will it take to make them stable?

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Characterize adeno-associated viruses (AAVs) for aggregation, stability, and particles at low volume for accelerated development of life-saving gene therapies. Development can further be accelerated by monitoring critical quality attribute parameters like subvisible particles (SVP) concentration early in the development process. Capsid degradation and nucleic acid leakage can both occur under different formulation and storage conditions and contribute to the accumulation of aggregates. Characterizing candidates earlier in the development process is best as it identifies and eliminates inherently unstable candidates before…

October 17, 2022