Preparing Pandemic Vaccine Capacity

Among the challenges of a pandemic is the need to scale up to billions of doses, at a larger scale than typically needed for vaccines, from raw materials all the way through to the materials for the containers for fill/finish. Having adequate raw materials, building and staffing the facilities, and tech transfer are all keys to success. [...]we can plug into existing infrastructure, including services (gas, water, waste, etc.) as well as analytics and quality labs." Emergent BioSolutions says that its flexible CDMO capacity deployment model can respond quickly to demand fluctuations. The company's facilities in France, Switzerland, and the US are working on the project;at CordenPharma Colorado, unique high-pressure chromatography systems usually used for manufacturing peptides have been reallocated for purifying lipids.

Breaking Through Barriers to Continuous Manufacturing

The success of the cooperation between government and the private sector to rapidly develop and build capacity for vaccines and treatments to combat the COVID-19 pandemic is an example of what is possible, in the normally slow-acting and risk-averse pharmaceutical sector, say industry experts. Reducing barriers to CM One positive sign is greater acceptance of public-private partnerships by the United States (US) Food and Drug Administration (FDA) and the US Congress, due to the successes demonstrated during the pandemic response, said Jennifer Luray, vice-president of strategy and communications at ResearchlAmerica, during a panel discussion hosted by the US Pharmacopeia Convention (USP) (2). USP can help fill the gap that exists in access to knowledge, experience, and laboratory capabilities for PAT model development and process development, adds De Belder. " "Some PAT systems are more suited to a development environment, where the goal is to gain process understanding and knowledge about the product, but those systems may not be robust enough for routine deployment on a commercial process," adds Connelly.

Automating Biopharma Manufacturing

"With the advance of data science enabling factors such as easy access to scalable memory and computing resources;our growing competence in collecting, storing, and contextualizing data;advances in robotics;[and] the quickly evolving method landscape driven by the open-source community, the benefits of automation and simulation are becoming accessible in the notoriously complicated realm of biopharma manufacturing," says Marcel von der Haar, head of product strategy data analytics at Sartorius. "Plug-and-play" capabilities of automation systems, which enable flexible manufacturing and faster technology transfer, are more important than ever, he says. Walvax Biotech's new COVID-19 mRNA vaccine plant in China is another example of an intelligent and digital plant;it uses Honeywell's batch process control, building and energy management solution systems, and digital twins to monitor assets (5). "Automation brings in the data for machine learning to model the dynamic processes of cell growth and map it against the multiple dimensions provided by advanced sensors," explains Brandl.

Equipment Suppliers and CDMOs Advance Process Development

Rapid growth in biopharma is driving faster process development, more efficient manufacturing, and increased manufacturing capacity Process development is moving at unprecedented speed as manufacturers race to produce COVID-19 vaccines and treatments and the products needed to make them, such as viral vectors, as well as keep up with the burgeoning cell and gene therapy sector. Since 2020, EMD Millipore has been hard at work supporting developers of treatments for COVID-19. Because rapid scale up to high volumes of commercial product were needed, AstraZeneca called on multiple CMOs for production. Glover notes that, through the consortium, the CMOs worked to each use as similar a process as possible, which simplified the supply chain for equipment and raw materials.

Digitalization Moves Forward in Pharma Equipment and Processes

Digital technologies that could meet these new challenges and aid manufacturing scale-up and speed to market, such as automated digital data collection and augmented and virtual reality (AR/VR) remote collaboration tools, were already available and had been adopted by some, but the new demand spurred greater adoption. "There is a cultural aspect to digitalization because it's a significant investment that results in changes to the operational structure of a facility;it is beneficial when the digitalization comes from the top," explains Yvonne Duckworth, automation engineer and Industry 4.0 subject matter expert at the CRB Group, a life sciences engineering and construction company. Machine sensors and process analytical technology (PAT) instruments can communicate directly with data collection systems using the NoT. Efficient development and tech transfer for mRNA vaccine manufacturing The data analysis and clear communication allowed by digital tools has demonstrated its benefits for process development and technical transfer, making time to market faster.

Advanced Manufacturing Technologies Shift # Outside the Box

The call for reshoring manufacturing may be answered in part by using these advanced technologies to produce APIs or to continuously manufacture drug products end-to-end, beginning with basic raw materials and ending with a finished drug form. The US Department of Defense's Defense Advanced Research Projects Agency (DARPA) has funded several continuous flow chemistry projects, promoting portable technologies that can be used to make medicines on-site in the field for the US military using a few essential raw materials. "To compete with the cost-effectiveness of offshore API manufacturing, innovative streamlined and automated systems are needed," notes Nathan Collins, chief strategy officer of SRI's Biosciences Division and the principal investigator for the ProSyn project. In mid-2020 the process development company doubled its R&D capacity and opened a lab to produce gram to kilogram-scale APIs and demonstrate its continuous flow manufacturing technology at pilot scale.

Modular Processes and Facilities Enable Flexible Vaccine Manufacturing

The COVID-19 pandemic has accelerated the need for modular designs to rapidly expand vaccine production capacity. Speed to market An established benefit of modular facilities is that they are constructed off-site and then delivered to the site where they will be put into use. CRB's SlateXpace was introduced in September 2020 as a "suitebased" modular facility design for cell and gene therapy. Modular systems enable the manufacturer to produce regionally on the required scale and thus to react flexibly to the current situation and local requirements," says Kappeler.

Manufacturing Materials for Clinical Trials

CDMOs need to gauge their internal capacity of temperature storage units, form strategic partnerships with logistics companies, and potentially offer validated temperature storage of clinical trial material. Through the use of secure document sharing platforms, remote viewing systems, and virtual site tours, clients can be assured they will be able to perform a thorough review of facilities and quality systems and have connections with the subject matter experts and remote access to live action activities to meet their programme requirements and quality standards. To ensure projects continue to run to time, it is vital that upper management and business development have the ability to check in constantly. Hoerner (Purisys): Modelling and simulation tools have been extremely valuable to reduce the amount of work required for scale-up;for example, engineering technologies such as Scale-up Systems' Dynochem can model solvent swaps, drying, distillation, off-gassing, and many other fundamental elements of synthetic and chemical processes.