Significantly reducing development-to-production timescales and enabling faster delivery of critical products is not without its challenges. The safe, efficient and rapid delivery of vaccines will require more efficient production and testing capabilities, along with facilitating a strengthened supply chain.
Cynthia Pussinen, vice president and general manager, Life Sciences, Honeywell Process Solutions discusses the challenges associated with moving from regulatory approval to full production, and walks us through how they can be addressed at each step in the manufacturing process. –KB
Contract Pharma: What are the hurdles in moving from regulatory approval to full production of a vaccine?
Cynthia Pussinen: In an effort to optimally manage risk levels and resources, life sciences companies who are engaged in the discovery, development and commercialization of a new medical therapy have historically waited until the point in time at which confidence in successful outcomes, including safety, efficacy, ability to manufacture in a reproducible and consistent manner and ultimately regulatory approval is high.
In today’s world, there is often an immediate need for a vaccine or therapy. In the past, many life sciences companies have held off on making investments in facilities, infrastructure and materials to produce sufficient quantities of a medical therapy until late stage clinical studies were conducted with a commercial quantity scale up starting during the registration process.
Challenges associated with moving from regulatory approval to full production of a vaccine are focused on speed to deliver an effective vaccine, including:
1) balancing the need to urgently provide as much supply of a vaccine to the world as quickly and safely as possible once clinical trials have proven to be successful while investing in facilities and infrastructure earlier than has been seen historically
2) ensuring a fully functional supply chain and distribution network is in place
3) delivering a scalable manufacturing process, as vaccines are more technically complex to produce compared to a chemically synthesized, small molecule-based medicine.
Contract Pharma: How can this process be safely expedited?
Cynthia Pussinen: The process of delivering a vaccine to the public can be expedited through a variety of actions including repurposing existing facilities for use in commercial production, preparing commercial manufacturing facilities for production in parallel with early phase clinical studies - which involves increased risk if the vaccine in development doesn’t show safety or efficacy, working with the FDA or local regulatory bodies to schedule a facility pre-approval inspection early, understanding and requesting expedited regulatory pathways with the FDA including emergency use authorization.
Preparing your Good Manufacturing Process (GMP) compliant commercial facility for production will include:
1) procuring and configuring the necessary equipment for your scaled up upstream and downstream processes as well as integrating the systems used to manufacture including Manufacturing Execution System (MES), Quality Management System (QMS), and (Supply Chain Management) SCM systems
2) conducting Installation Qualification (IQ)/ Operational Qualification (OQ)/Performance Qualification (PQ) of the equipment, implementing upon a validation master plan and associated protocols
3) readiness of testing labs to support scaled up production – starting activities earlier than would have been done in the past and parallel processing of efforts is a must do.
A key aspect of preparing for commercial production, and accelerating pathways is securing the supply chain and distribution networks; eliminating sources of vulnerability and having redundancy to ensure appropriate quantities of the various components used across expanded supply chain to include raw starting materials, cells banks, manufacturing materials, purification and testing, and buffers is required. Refrigerated storage facilities, necessary temperature-controlled logistics, shipping containers and vehicles will be required to move product around the world at unprecedented speed. Acting on building stock of needed supplies, components and logistics earlier than has been done in the past will facilitate speeding up the delivery to the patient once regulatory approval is granted.
Once a successful clinical outcome is achieved, collaboration and partnership across governments, industry and the medical communities along with comprehensive planning will be required, along with solid execution in manufacturing and distribution to supply a global solution to avoid pockets of unprotected populations in the process.
Contract Pharma: What are some of the process requirement challenges?
Cynthia Pussinen: In vaccines, the product is the process and therefore ensuring a well-controlled and highly consistent manufacturing process, with stringent oversight and data collection, is all the more critical. Quality of design, quality assurance and quality control testing for release of the product is more complex given that production of vaccines involves a biological process. Process development and optimizing your manufacturing process, including using the most productive host cell line available, while limiting sources of variability will help to ensure product batch to batch consistency.
Contract Pharma: How can technology be leveraged to help overcome these challenges?
Cynthia Pussinen: The use of automation and controls technologies include; robotics, distributed control systems and batch production technology, packaging and labelling systems, cameras to aid in visual inspection for release, in process and release testing and data collection, and end-to-end tracking and tracing of products. The utilization of these tools will increase accuracy, precision, speed and operational efficiencies, while decreasing manual errors and shortening the time to deliver vaccines to patients.
Artificial intelligence, machine learning and predictive insights can help life sciences manufacturers enhance manufacturing process operations and consolidate compliance-related manufacturing data contained in disparate systems across the enterprise into a single, visual interface. This includes data from laboratory information management, batch management, control, quality management, manufacturing execution and inventory systems.
Utilization of single-use systems and components, real time process analytical testing and continuous manufacturing, present tremendous opportunities to reduce costs and to shorten supply chain durations significantly.
Contract Pharma: At what stage of development can scale up efforts begin?
Cynthia Pussinen: Commercial scale up to provide a vaccine to the public can begin once a GMP manufacturing facility and testing labs are fully compliant with regulations and ready to manufacture products using the final, locked down process. This process includes having defined and characterized critical quality attributes and process parameters that deliver a product which has been produced via a well-controlled and consistent manufacturing process. Teams that are fully trained in executing the manufacturing process, testing and release of the product are part of the process as well.
Cynthia Pussinen is the vice president and general manager of Honeywell's pharmaceutical business, a strategic business unit within Honeywell’s Performance Materials and Technologies (PMT) division. Cynthia's prior experience includes 20 years with Pfizer in a variety of roles, including the head of strategic portfolio management, global head of supply chain logistics, and various other roles in research and development. Prior to Pfizer, she was president of Ipsen's U.S. subsidiary for about six years, which included technical operations and research and development activities. Most recently, Cynthia served as executive vice president of technical operations and supply chain for Actinium Pharmaceuticals, Inc.