September 17, 2021 PAO-09-21-CL-09
Michael Alston (MA): Myford was initially designed and built in preparation for the commercial activity of Bavituximab (Bavi). When Bavituximab failed to gain marketing approval, the decision was made to convert it into a full-scale CDMO operation. The facility was built in 2015 and commissioned for operation in 2016. We’re currently running 3×2,000-liter and 2×1,000-liter production bioreactor capacity at the site and are in the process of expanding. The facility was designed from the start with maximal modularity, which means that it’s flexible and alterations can be made easily limiting disruption to the existing operations.
MA: Since the separation of Avid and the decision to focus solely on biologics drug substance manufacture, the market has picked up on the tremendous pedigree Avid has in terms of biologics manufacture. It is generally accepted there is a tightness in the supply side of the market, and this would appear even tighter when it comes to CDMOs with a track record of commercial versus clinical manufacture over a long period of time. I also think Avid’s regulatory track record is another enormous plus and one that enables customers to feel confident that their CDMO (Avid) can be relied upon to transition successfully from clinical to commercial manufacture. Our quality track record speaks for itself; as we’ve had zero 483s observations from FDA audits over the past five inspections. These and other factors have led to significant increases in demand for our services and, to continue to meet the demand for added capacity and services, we’re expanding the current purification capacity of our existing operations. Time to market has always been a key success factor for innovators, and we have always tried to ensure that we can facilitate our clients in moving rapidly through the clinical process. A key element of this is that, as a CDMO, we have to have capacity for existing clients as well as new clients.
MA: The Myford facility was designed with macro trends in mind, specifically around single-use technology, automation, and modular construction. Avid was an early adopter of single-use technology platforms, which allow us to take advantage of the operational and quality efficiencies to manufacture a high-quality product every time. As we move forward with our expansion, we’re always looking for more opportunities where we can apply automation across different process steps, become more efficient, and continue to maintain our focus on single-use technologies. Additionally, Myford was constructed using a modular system, which is another macro trend. The modular system allows for flexibility and adoption of manufacturing processes, ensuring that all needed capabilities can be easily adjusted. For Avid, single-use technologies, automation, and modular construction go hand in hand and align with our goal of creating integrated flexibility for our customers.
MA: When evaluating our expansion vision, we looked at opportunities around continuing to expand the existing Myford site versus building additional capacity at a new site. With the existing infrastructure and personnel already in place at the Myford facility it made sense to continue with expanding the site.
We’re currently in phase one of the expansion, which involves adding a second purification suite to the Myford North facility; at present we have 2,000-L capacity and 1,000-L bioreactor capacity with one purification suite. The second purification suite will ensure we can fully utilize existing bioreactor capacity in Myford North. For our Myford South facility, the expansion focuses more on the larger-scale platform, with 6×2,000-L capacity with two downstream purification suites and an integrated buffer media prep. We also have the ability to multiplex (combine multiple 2,000-L reactors), as well as space to potentially accommodate even larger disposable bioreactors should we see the need. By adding on this capacity, the Myford site will become a high-throughput facility leaning more toward commercial manufacture and the efficiencies one would expect when one gets to this stage.
The Myford North expansion is due to be qualified and online by Q1 2022. Myford South is currently slated to come online in early 2023.
MA: Integrating flexibility is a major theme for all of our expansions. As a CDMO, we have to accommodate a wide range of variability associated with the differing needs of a broad range of different clients and products. While the vast majority of our process steps are similar in mAb processing, we always have to account for process variability, whether it comes from changes in cell growth timing, titers, or a number of other variables from that are not related to processes per se but more to client needs. This is where we really look to use the modular system and single-use technologies to our advantage.
MA: Clearly, with 6×2000-L bioreactors in Myford South, this facility is ideally set up for larger scale/volume processes. This will enable increased flexibility across the businesses to accommodate both large- and small-scale and early- and late-phase processes and in so doing take full advantage of the bioreactor capacity in Myford North (3×2,000, 2×1,000, and 4×200 L) and in Myford South (6×2,000 and 4×500 L). Additionally, both expansion efforts have been designed to allow us to run higher-titer processes, even multiplexing bioreactors so we can run bigger batches when needed. All in all, the broader range of capacities, increased numbers of reactors, the ability to multiplex capacities, and the equipment capable of handling higher titers increases the breadth of process and the underlying economics we can offer across this range.
MA: There is additional real estate on the site that we’re already considering for future use and expansion. We have our existing Franklin facilities that are also on the same campus, where we house additional GMP manufacturing operations, process development operations, and QC labs. With Myford and the two Franklin facilities, we are always considering how we can continue to expand and optimize those footprints, as well as other opportunities on the campus and within the surrounding area.
MA: In theory, all automation sounds great — the machines run themselves, people supervise, product is created, and all is well. However, the reality of automation is that it has to pay for itself. We’re doing an evaluation to ensure that we’re putting automation in the right places as we go, which is based on the unit operations or processes that are going to be high-throughput, low turnover in products. We view automation as a major opportunity to stay efficient in our operations and competitive in our pricing.
MA: The challenges are different. For upstream, you’re typically taking bioreactors through four to six different expansion steps where the bioreactors are highly automated. It’s possible to do some automation control and remote monitoring, which can provide advantages, though it’s debatable how far that can go. Electronic batch records could be one of the major areas used in the upstream space.
On the downstream, there is a lot more opportunity for automation, because there are more buffers as well as different process steps with chromatography and TFF. Optimizing the downstream process with automation requires a keen focus on process integration and understanding critical process parameters to determine how the equipment is to behave. As we consider high-throughput operations, we are evaluating how we can properly utilize this opportunity.
Data mining is another area that we will look into as we move forward. Being able to identify trends is another opportunity to improve processes and help clients reduce cost. Clearly, the more batches of the same product one manufactures, the easier it is to find meaningful trends.
MA: For the phase one expansion, we’ll be able to fully utilize our existing 9,800-L bioreactor capacity, and we’re approximating it will cost $15 million. For Myford South, which is a 14,000-L expansion, we’re estimating to spend in the $45–55 million range.
MA: At Avid, we see the supply chain as a major advantage to our operations. We have been standardizing our equipment platforms; which allows us to build strategic partnerships with key suppliers. This alignment has been critical to our operations and has proved successful even through COVID.
MA: It was definitely already in the works. As you grow, it’s one thing to have process flexibility, but you also have to have a good basis upon which to build your business. As we grow in volume, those critical partnerships become much more so, which was a big push for us. Our supply chain and construction strategies have proven to be successful; even as COVID hit, we installed and qualified a new water-for-injection (WFI) system in the Myford facility, continue to build our purification expansion, and breaking ground on Myford South; all while working through the different COVID protocols and situations that the pandemic has presented.
Michael Alston, Jr. is Director, Project Engineering for Avid Bioservices, Inc. in Tustin, CA; where he is responsible for engineering, project, and portfolio management of the company's capital projects and change initiatives. He has 15 yrs. experience leading projects and teams in engineering, maintenance, operations, and continuous improvement in the biopharmaceutical and food processing industries; working for ConAgra Brands, Unilever, Merck, and Sterogene Bioseparations prior to Avid. He is an active advisory board member of the National Society of Black Engineers (NSBE); along with membership in International Society of Pharmaceutical Engineers (ISPE) and Parental Drug Association (PDA). Michael is a graduate of California State University, Fullerton, with a B.S. in electrical engineering and also holds a Graduate Certificate in project management from Lehigh University.