July 25, 2019 PAO-NI-0719-CL-003
iBio has expanded its CDMO service offerings to include independent sterile liquid cGMP fill-finish services to support the preclinical and clinical trial needs of drug developers. This new service complements iBio’s existing biologics bulk drug manufacturing capabilities and is seen as the next step in creating end-to-end solutions for its clients.
Aseptic fill-finish of parenteral products in bottles, vials and syringes is a complex operation that many small and emerging biotech firms and large biopharma companies outsource to third-party service providers. In fact, a HighTech Business Decisions survey in 2018 revealed that 70% of biopharmaceutical companies view fill-finish as a non-core operation, and many expected to work with more contract development and manufacturing organizations (CDMOs) that offer fill-finish support.1 In 2019, the greatest areas of interest include services for ADCs, live viruses, cytotoxics with slow-release formulations and small-batch runs.2
There is, however, limited available fill-finish capacity at CDMOs for early-stage preclinical and clinical projects. Pharma and biotech companies that outsource their smaller-scale fill-finish often experience long wait times and rising project costs. There is, consequently, a significant unmet need in the marketplace.
At BIO 2019, iBio launched cGMP sterile fill-finish services for monoclonal antibodies (mAbs) and other biologics for clients with preclinical and clinical-stage projects. This offering enables iBio to leverage fill-finish equipment when it is not in use for integrated client projects.
The new services complement iBio’s core bulk drug substance manufacturing capabilities as a plant-based biopharmaceutical CDMO leader. With our FastPharmingTM protein expression and glycan engineering technologies, we consistently and rapidly generate high-quality biologics in plants using automated hydroponic systems at our state-of-the-art facility in Bryan, Texas. In addition to cGMP contract manufacturing and factory solutions for the design and construction of facilities for plant-made biopharmaceuticals, we offer process development and bioanalytical services.
iBio’s fill-finish operations are housed at our CDMO facility in Texas and performed in a dedicated, cleanroom pod that includes both a filling machine and an inline labeler with serialization capabilities. The filling machine is capable of filling up 9,000 100-mL bottles or up to 16,000 5-mL serum vials per day. Vials and bottles are packaged and shipped, or frozen and stored, as required by the client. We have established operating procedures, environmental monitoring programs and all of the systems required for compliance with cGMP guidelines.
Fill-finish services can be combined with formulation development, container closure selection, method development and validation, labeling and packaging services for clients that require additional assistance in these areas.
iBio’s new cGMP sterile fill-finish services operations were activated on June 19, 2019, with the signing of a supply agreement with a clinical-stage biopharmaceutical company developing breakthrough gene and cell therapies. This first agreement was secured as a stand-alone project, and it helps to validate our ability to work with a variety of cell-based and other biopharmaceutical products in different formats.
Given the significant demand for cGMP sterile fill-finish services, iBio is already planning to double our capacity with the addition of a second filling machine for small-volume projects. At this time, we are assessing the specific needs in the marketplace to determine what specialized capabilities should be included in the expansion.
Our current cleanroom can operate up to BS-L2 conditions with positive pressure applied to guarantee an aseptic environment. Depending on the level of need that we assess for aseptic filling of viral vectors, we may design the new facility with the appropriate containment and pressure cascade required for safe handling of these types of products.
Plant-based expression systems can be used for the production of antibodies, vaccines, enzyme therapies and other therapeutic proteins without the need to develop optimized cell lines or invest in expensive bioreactor technologies for large-scale production. Potential contamination from adventitious agents is also reduced. Scale-up involves adding more plants, allowing rapid expansion and consistent product quality at any volume.
Overall, iBio’s plant-based system offers rapid evaluation of protein expression at a lower cost and often more quickly (up to six months faster) than CHO-based systems. It has been estimated that the cost of goods (COGS) for a mAb produced by iBio is approximately 50% less than published COGS values for mAbs produced using CHO systems.3
Our CDMO facility in Texas is designated to bring product from development to commercial launch with a total capacity of about 50 kg of mAbs per year (and is rapidly expandable to 150 kg if needed). Because the bioreactor unit used at iBio is a single plant, product yield and consistency remain unchanged as the process scales up to millions of plants for large-scale production. IBio supports clients with cloning of the necessary vectors, process development, biomass production, protein extraction and purification, buffer exchange, formulation and automated/ manual sterile fill and finish services. We can also conduct feasibility studies.
iBio is interested in supporting both early-stage biotech and large pharma companies, as well as universities, spinouts and government agencies. The simplicity of our plant-based expression technology makes it well-suited for implementation in areas of the world where there is limited access to capital or highly skilled biopharmaceutical workers. The short project timelines also make it attractive for the development of drugs and vaccines in response to pandemics.
We are excited to offer support for cGMP sterile fill-finish operations as a standalone service, but also hope that clients will recognize the value proposition of plant-based protein production.
Brian R. Berquist, Ph.D. is the Vice President of Process Development and Technology Transfer at iBio. Dr. Berquist has been leading downstream process development and manufacturing scale-up for plant-made recombinant proteins using iBio’s FastPharming™ System since 2013. He performed postdoctoral studies at the National Institutes of Health, purifying DNA repair enzymes from more traditional expression systems and characterizing their biochemical activities. He received his Ph.D. from the University of Maryland, School of Medicine in molecule medicine in 2006.