Expedite Entry Into Clinical Trials With The WuXi Hyper-PRO Platform For Viral Vector Manufacturing
With the increasing demand for GMP (Good Manufacturing Practice) viral vector production – a critical component in the gene therapy and gene-mediated cell therapy supply chain – WuXi AppTec has allocated significant resources toward the development of a platform process to assist customers with an expedited entry into clinical trials. The platforms focus on lentiviral and AAV (adeno-associated virus) vectors and include a manufacturing process flow that encompasses the consumables, standardized base media, and the ability to utilize a WuXi cell line and plasmids, or one’s own cells and plasmid. The platforms include the corresponding QC (Quality Control) test protocols for in-process, DS (Drug Substance) and final DP (Drug Product) samples. Industry-wide capacity constraints for GMP viral vector production have necessitated the development of an accelerated pathway for GMP drug product supply for lentiviral and AAV vectors. WuXi AppTec’s process development and QC/technical development teams comprise more than 50 scientists. Together, over the past two years, these teams have dedicated vast resources into the development of these platforms, and are available to expedite any process or QC custom adjustments that are required for more rapid entry into first-in-human trials or to otherwise establish external manufacturing/sourcing.
Industry GMP viral vector manufacturing capacity, especially as it pertains to lentiviral and AAV vectors, has become increasingly saturated. There are currently more than 500 gene therapy candidates in different stages of clinical development with approximately 1,700 clinical studies being conducted in various regions across the globe. Coupling this number of clinical trials with the staggering pace at which many of these assets are securing accelerated regulatory approval pathways, the bottleneck for manufacturing capacity is likely to only worsen for the foreseeable future. Capacity constraints exist despite the fact that the total cell and gene therapy production worldwide is only approximately 10,000 patient units/year at present. Therefore, orders of magnitude growth in manufacturing capacity will be required – first for later-stage clinical stage trials, and multiplied for commercial manufacturing.
The WuXi Hyper-PRO Platform
The WuXi Hyper-PRO Platform for the GMP manufacture – and corresponding analytical testing – of lentiviral and AAV vectors provides a streamlined approach to viral vector production. Through focused evaluation, via hundreds of DoEs (upstream and downstream), WuXi AppTec has developed vector processes that either use WuXi-licensed plasmids and a WuXi-licensed cell line, or utilize a client’s plasmid and cell line, or any combination. As a result of these studies, WuXi AppTec’s team of process development scientists has developed an approach that consistently produces lentiviral and AAV vectors at or above typical target titers.
Additionally, because the vast majority of raw materials are not custom (aside from the transgene), the team is able to stockpile the most crucial materials, effectively eliminating critical time bottlenecks in the tech transfer process. The upstream process for the WuXi Hyper-PRO Platform can be maximized to 60 Corning CellBIND 36-Layer HYPERStacks® in a single production run, which results in bulk harvest of approximately 250 Liters of viral vectors. WuXi-licensed plasmids and a WuXi-provided cell line (HEK-293T) are standard with the WuXi Hyper-PRO Platform for lentiviral vectors. However, the platform allows for utilization of client-specific plasmids and/or cell lines through inclusion of verification runs that determine performance and process fit and/or suitability. For AAV, the overall process will remain locked for upstream, and semi-custom for the downstream portion as the multitude of serotypes available may require some optimization to the process. WuXi AppTec’s experience with different serotypes will be leveraged to maximize output while keeping timelines as short as possible. With respect to the lentiviral platform, WuXi AppTec has developed a closed downstream purification process that utilizes clarification and concentration techniques to provide vector suitable for most currently clinical trials/indications. This downstream process has also been thoroughly vetted through multiple DoEs, resulting in titers that are equal to – or exceed – typical target titers by common titer methods.
The WuXi Hyper-PRO Platform provides the potential for rapid initiation and release of first GMP grade product. The goal is to deliver GMP product for clinical use within months of signing a contract. If plasmids are readily available and provided by the client, only minimal changes are required for preset batch records. If the standard characterization assays fall within platform expectations and custom target assays (like specific construct/transgene targeted GC – PCR titer) are required, then WuXi AppTec can initiate process development activities in a parallel path for the custom assays and the GMP production in order to initiate the manufacturing activities almost immediately upon signing the contract. If a given client elects to use WuXi-licensed plasmids and WuXi-licensed cells, agreements are already in place for cloning and amplification of a transgene plasmid for use with our licensed helper plasmids in order to minimize additional time for that activity.
Platform Benefits vs Technology Transfer
While platforms offer benefits, the process development team at WuXi AppTec remains open to transferring in clients’ unique processes. WuXi AppTec will continue bringing on a variety of cell therapy and viral vector manufacturing processes into each of the three specialized manufacturing facilities in Philadelphia. WuXi AppTec has numerous clients who prefer to utilize their own processes for generation of comparable product or continuity with existing clinical data. However, the WuXi Hyper-PRO Platform provides an alternative to this traditional methodology for certain contract manufacturing services. This alternative allows for pre-trained personnel to use WuXi AppTec’s own fully characterized master and working cell banks in conjunction with WuXi AppTec’s standardized methodology media for
platform manufacturing and associated testing. The aforementioned process results in a shortened timeframe from the point of process initiation to the production of GMP material. This represents a tremendous advantage for those racing to get into the clinic and for those clients with even the most aggressive regulatory timelines. Both strategies have their individual advantages, but the WuXi Hyper-PRO Platform allows for a separate path to production for those seeking to avoid the time needed for a full tech transfer path. Additionally, for those who do not yet have a refined process in place, there is significant conservation of time and resources by not having to dedicate additional finances and personnel to process development. All process and technical development activities are effectively provided in advance, by WuXi AppTec, as part of implementation.
The WuXi Hyper-PRO Platform encompasses manufacturing and is paired with the associated analytical assays for lentiviral and AAV vectors, integrating a complete panel of on-site QC analytical testing to seamlessly complement the flow of production. By deploying the requisite qualified GMP analytical release assays for both AAV and lentiviral vectors, the platform alleviates yet another potential bottleneck. For AAV and lentiviral vectors, the testing panels include assays for upstream in-process samples, harvest material samples, downstream in-process material, bulk drug substance characterization and final product samples. WuXi AppTec has dedicated substantial technical development resources into bringing assays online for determination of identity, purity and potency. This includes, but is not limited to: replication-competent lentivirus or rcAAV testing, infectious titer assays, and other related or standard assays such as residuals and safety testing. In-house analytical testing for in-process and final drug product materials creates obvious advantages related to client convenience and speed to product release.
WuXi AppTec has thoroughly recognized that time is critical for most clients seeking to enter the clinic or pursue the next step toward commercialization. The introduction of these platforms is one of the primary ways that WuXi AppTec is utilizing its capacity for upfront technical/process development and its broad array of analytical capabilities to assist our clients with an accelerated course to GMP material for human clinical trials – enhancing the opportunity for a path to commercialization for these important advanced therapies.
Not sure if the platform approach to viral vector manufacturing is right for you? Avoid the lengthy tech transfer process with the WuXi Hyper-PRO. Click here to speak with a technical expert to learn more.