Miltenyi Bioindustry focuses on harnessing the power of lentiviral gene delivery and expression technology. With decades of experience (which includes Lentigen Technology Inc., now part of Miltenyi Biotec) and a scalable lentiviral vector (LVV) platform, Miltenyi Bioindustry provides critical material to enable CGT applications. Our platform includes rapid and consistent production of high-quality vectors with reduced process development, thus bringing urgently needed therapies closer to various therapeutic programs.
LVVs are gene delivery vehicles that facilitate genetic modification of mammalian cells. Once inside the cell, LVVs integrate into the host cell genome and provide a stable, long-term expression of the gene of interest (GoI). Unlike alternative vector systems, LVVs transduce both non-dividing and dividing cell types with high efficiency, making them the preferred tool for transduction of cell populations of interest.
From molecular cloning to large-scale manufacturing and final batch release, our platform process is designed to provide flexibility and scalability at consistent quality. It all starts with the plasmid design, which is crucial for balancing both the need for a robust manufacturing with high LVV titer yields and the therapeutic functionality in the transduced CGT product being developed. In combination with a suspension-adapted and well-characterized packaging cell line, the process allows for easy and direct transition from a scaled-down 4L demonstration batch to commercial bioreactor-scale manufacturing. Once the newly formed LVV particles are secreted into the media, the crude material is harvested and purified in multiple downstream processing steps to ensure the right product purity and quality. Finally, the purified LVV material undergoes industry-standard QC testing and characterization before formal QC disposition and release.
We have developed a scalable LVV platform for rapid and consistent vector production with minimal process development. With decades of experiences and reproducible process data, we use results from the smallest pilot scale to predict larger-scale GMP manufacturing outcomes, thereby reducing process development efforts. It is based on our proprietary 3rd generation self-inactivating (SIN) vector system, designed to provide a more robust clinical translation experience.
We have taken advantage of our proprietary suspension-adapted 293T cell line to shorten process development time and enable larger batches and thus higher yields. Our 293T cell culture is suited for true upscaling and is less labor intensive than conventional processes. We have mastered scale-up into 50 and 200L single-use bioreactors and parallelized production for larger project requests. In conjunction with chemically-defined cell culture media, our platform reduces concerns related to safety, regulatory compliance, and the supply of animal- and human-derived materials.
Our LVV material was first used in 2009 to treat patients. Since then, we have advanced our entire CMC and regulatory expertise. Today, we can look back at thousands of liters of processed cell culture volumes and the execution of more than 300 successful GMP runs. In consequence, our experience as a CDMO allows us to reliably predict from 4 L demonstration batch results the outcome of 50 and 200 L GMP manufacturing runs. Client projects can therefore go directly to GMP manufacturing and reduce project time requirements and reduce process development costs. As a result, our vector manufacturing platform enables a streamlined path to GMP-compliant vectors with reduced development effort.
We support customers on their journey from initial clinical trial submission (IND/CTA) to marketing authorization (BLA/MAA). For LVV material, we provide cross reference letters to Biologics Master Files (BMF) that have been registered with the US Food & Drug Administration (FDA) and Health Canada. For regions without an equivalent BMF mechanism, our regulatory affairs team prepares Regulatory Support Files (RSFs) to support individual customer applications to enable fast clinical trial approval. Such RSFs have already been successfully implemented with multiple permitted gene-modified cell therapy trial applications.
Our CDMO Service team provides detailed information on our specific support for North America, Europe, Asia Pacific, and other regions.