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Jennifer Markarian is manufacturing editor of BioPharm International.
Continuus Pharmaceuticals is building the first GMP facility using integrated continuous manufacturing technology for end-to-end production of small-molecule APIs and finished dosage forms.
Continuus Pharmaceuticals received a $69.3 million US government contract in Jan. 2021 to build a continuous manufacturing facility for US-production of critical APIs and finished dosage forms and bring the company’s Integrated Continuous Manufacturing (ICM) technology for end-to-end production of small-molecule drugs to commercial scale. Continuus, which was launched in 2012 from the Massachusetts Institute of Technology (MIT) using technology developed at the Novartis–MIT Center for Continuous Manufacturing, currently has a functioning pilot plant at its Woburn, MA site. The new ICM facility at the site, slated to start up within two years, will be the first US current good manufacturing practices (cGMP)-certified facility for end-to-end, ICM-based production of small-molecule drugs.
The ICM technology shortens drug production time from months or years to days, which will help to mitigate shortages of critical drugs. Under the US government contract, Continuus will produce vital medicines, including medicines that have been in short supply. With additional available capacity, the company plans to manufacture generic medications as well as provide contract manufacturing services to the industry.
The ICM technology also enables distributed manufacturing, because it can produce multiple types of drugs and can be set up to be portable. The April issue of Pharmaceutical Technology will discuss this subject in further detail.
Pharmaceutical Technology spoke with Bayan Takizawa, co-founder and chief business officer of Continuus, about the technology and what end-to-end continuous manufacturing offers for the pharmaceutical industry.
PharmTech: What needs have been driving your work in end-to-end pharma manufacturing? Has the pandemic accelerated plans for commercialization?
Takizawa (Continuus): There definitely is a positive trend of increased interest in continuous manufacturing from pharma companies, both innovator and generic. We observed this before the pandemic, and were able to grow our pipeline significantly from when we first started eight years ago. There are several reasons for this rise in interest, and I will name just a few. First, several companies have successfully submitted drug applications with significant continuous manufacturing components, such as Vertex and Johnson & Johnson. Thus, there is a regulatory pathway. Second, related to the first, the US FDA and other regulators have provided guidance on the topic, and have been active in engaging companies implementing advanced manufacturing through their Emerging Technology Team at the Center for Drug Evaluation and Research. Third, US government agencies such as the Biomedical Advanced Research and Development Authority (BARDA) and the Department of Defense have been keenly aware of [US] foreign dependence on critical drugs and have been working with companies to develop advanced manufacturing capabilities at home, even before the pandemic. Drug shortages have been a problem for many years. Finally, from our own company perspective, with each successful project, pharma companies have been able to understand better the advantages of ICM. The COVID-19 pandemic highlighted our pharma supply chain vulnerabilities in a big way. As a result, I believe, many ongoing activities and planned projects were accelerated with the intent of combatting the current crisis and preparing for future events.
PharmTech: What are some of the challenges you are addressing as you scale up from your pilot plant facility to the cGMP facility?
Takizawa (Continuus): An example of a challenge is long-term processing equipment reliability. ICM will require 24/7 operations of processing equipment, which is different from the campaign model used in batch manufacturing. To ensure that they are functioning within their respective parameter limits, we will utilize real-time monitors and employ rigorous predictive maintenance strategies and tools. Regular maintenance schedules will complement these preemptive measures, and when appropriate, we will introduce redundancy into the system.
PharmTech: Can you explain the differences between the multisuite model and the mobile pharmaceuticals (MoP) model that Continuus offers?
Takizawa (Continuus): Both models, the multisuite and MoP, leverage ICM lines, which is the underlying technology platform. A multisuite refers to a facility that can house a number of ICM lines in the same building infrastructure, which is generally not mobile. For example, with our planned cGMP facility, we will have two different ICM lines with different throughputs that can produce both oral solid dosages and sterile injectables. ICM is especially suitable for this strategy because its manufacturing lines are much smaller than conventional batch technologies. MoPs refers to an entire ICM line located in a mobile pod that can be transported across sites. Again, this is enabled because of the small size of our manufacturing lines. With MoPs, there is tremendous flexibility to place entire manufacturing lines in facilities that contain a minimum amount of infrastructure, as the pods basically provide the environment required for cGMP manufacturing. It is important to note that multisuites and MoPs are not mutually exclusive, as a multisuite can consist of multiple MoPs. Furthermore, within the multisuites and MoPs, the individual unit operations can be quickly reconfigured in a plug-and-play fashion to produce different drugs. The bottom line is that ICM provides a lot of flexibility.
PharmTech: Where you see the industry headed in the future?
Takizawa (Continuus): We are moving in the right direction. Most people recognize the strategic importance of developing advanced pharmaceutical manufacturing infrastructure so we will never be without the critical drugs that Americans need, especially during healthcare crises. So, I do not think this is a movement that will lose momentum. Additionally, a very important benefit is the impact on drug development. For example, with ICM, bottlenecks associated with scaling-up manufacturing across clinical phases will no longer be an issue. We would just produce for longer periods of time. In this way, life-saving drugs will become available more quickly, again, ultimately benefiting the patient. We look forward to continuing to lead this effort.