Immeasurable efforts are underway to develop treatments and vaccines to address the COVID-19 pandemic. Numerous discovery methods and technologies are currently being explored in clinical trials such as DNA and RNA-based vaccine candidates, adjuvant platform technologies, recombinant nanoparticles, and monoclonal antibodies, to name a few. As promising therapies begin to emerge, they’ll need to be rapidly scaled up for trials and potential commercialization, which is not without its challenges in a pandemic setting.

iBio, Inc., a biologics CMO and biotechnology company, is working to develop vaccine candidates to prevent infection from the SARS-CoV-2 virus that causes COVID-19 disease. iBio created its SARS-CoV-2 Virus-Like Particle (VLP)-based constructs in just a few weeks using its FastPharming System to produce the nanoparticles in, and purify them from, plants. The manufacturing platform allows for rapid development of research quantities of product, as well as high-quality material that is readily scalable for producing doses for clinical trials and commercial use.

Originally built in 2010 with funding from the Defense Advanced Research Projects Agency (DARPA), part of the U.S. Department of Defense, iBio’s FastPharming Facility was part of the “Blue Angel” initiative to establish facilities capable of rapid delivery of medical countermeasures in response to a disease pandemic. The factory is equipped with automated hydroponics and vertical farming systems for the production of a wide array of biological medicines using a relative of the tobacco plant as the “bioreactor.”

Contract Pharma spoke with Robert L. Erwin, president of iBio about the manufacturing platform and potential timeline for the delivery of COVID-19 medical countermeasures.

Contract Pharma (CP): Please describe iBIO’s manufacturing platform being leveraged to develop vaccine candidates.

Robert Erwin: iBio’s FastPharming System uses plants as bioreactors, rather than traditional mammalian or microbial cell culture bioprocesses. The plant bioreactors are grown in a specially designed, optimized, and controlled indoor vertical farm environment employing large-scale hydroponics and LED lighting tuned for consistent growth. The gene encoding the specific protein of interest is cloned into a plant-specific expression vector and transfected into Agrobacterium tumifaciens. The expression vector housed within Agrobacterium is then delivered into the leaves of iBio’s proprietary Nicotiana benthamiana plants, which are close relatives of common tobacco plants, by a process called vacuum infiltration. After infiltration, the target protein is expressed in the leaves and, approximately one week later, high-throughput harvest of the leaves is followed by extraction of the target protein, purification, formulation into the desired final product, and appropriate fill/finish processes.

Transient plant-based production significantly reduces the time and cost associated with: (i) the initial upstream setup and execution, (ii) production scale-up, and (iii) characterization and quality assessments compared with conventional bioproduction methods. As each plant serves as a standalone bioreactor, there is a very high degree of consistency between material produced at the research stage and commercial-scale production, and scaling to any level can be directly achieved by simply growing more plants. The FastPharming platform provides confidence that critical consistency is maintained under the accelerated timelines for vaccine and/or therapeutic development and manufacturing during a pandemic.

CP: What development progress have you seen thus far and do you anticipate any specific challenges going forward?

Erwin: iBio’s FastPharming Technology has been previously deployed for development, manufacture, and evaluation of vaccine candidates for viral and bacterial pathogens in clinical trials. That experience was rapidly put to use in January to design, express, and produce COVID-19 vaccine candidates. These candidates are undergoing additional development to select a lead candidate and formulation for extensive animal testing and initial human clinical evaluation. Based on existing data and experience, we do not anticipate manufacturing challenges, and we believe most safety questions can be addressed within a matter of weeks.

CP: What are the major challenges conducting clinical trials during this pandemic?

Erwin: There are a myriad of challenges to the manufacturing and clinical trial supply chain already occurring, with likely broader impacts that will continue to ripple across the industry. Efficient clinical trials require the coordination of supply of not only the experimental drugs, but also comparator drugs, ancillary supplies, and laboratory equipment. These are overlaid with proper clinical packaging, oversight of blinding, and the protection of patient data. Bottlenecks in supply chain links to any of the relevant supplies can potentially compromise a clinical trial, and shortages of even simple routine supplies––like surgical gloves and masks––have already manifested.

Additionally, there are growing concerns about the risks of exposure of vulnerable, potentially immunocompromised patients to SARS-CoV-2 at traditional clinical trials centers, and as such the need for direct-to-patient (DTP) clinical trials models and associated services have become even more acute. Clinical trial logistics organizations are already being tested to secure the supply of existing DTP trials, and this will grow as more previously centralized trials transition into DTP models. Many clinical trials unrelated to COVID-19 have been delayed or even suspended within the last two weeks.

CP: What is the potential timeline for the delivery of medical countermeasures in response to the COVID-19 pandemic?

Erwin: Aside from protective equipment for healthcare workers, diagnostic tests, and critical care equipment, all of which have seen significant delivery shortfalls, there are still opportunities for government and industry partnerships, to speed the development, testing, and delivery of therapeutic and protective (i.e., vaccine) countermeasures to combat the COVID-19 pandemic.

Some therapeutics can be repurposed from applications already approved by the FDA and are in clinical trials already, with mixed success to date. More promising experimental therapeutics are in various stages of early development, and the FDA has created accelerated review pathways to facilitate rapid initiation of clinical trials. The timelines for delivery of promising experimental therapeutics depend on the rate at which patients are accrued to clinical trials, the efficacy and safety of the novel drugs, and the speed with which cGMP manufacturing capacity can be developed or accessed. The better of these new drug candidates are likely to be used in emergency treatment in parallel with careful evaluation of their safety and efficacy in patients who are not critically ill. Conditional FDA approvals, if supported by compelling clinical data, could occur as soon as this year.

Vaccines represent a different challenge in that they must be safe enough to administer to healthy people who may or may not be at risk of infection. This requires careful, early clinical evaluation followed by more extensive testing in larger groups to assess the protective value of a new vaccine. The FDA has already selectively relaxed requirements for preclinical safety evaluation of vaccine candidates for SARS-CoV-2 prior to approving initiation of human clinical trials.

iBio’s plant-based vaccine candidates combine two of the critical features required for rapid deployment. The first is a formulation that is likely to rapidly prove to be safe and effective, based on prior experience with plant-based VLPs tested against other targets and current knowledge of vaccine design alternatives intended to be effective in stimulation of a protective immune response. The second critical feature enabling rapid delivery of iBio’s vaccine countermeasure(s) is the combination of FastPharming technology with iBio’s cGMP manufacturing facility. Together, these are capable of assuring delivery of millions of doses of vaccine every month beginning immediately upon FDA approval, much faster than traditional approaches to manufacture of protein subunit vaccines.