Closing systems can promote innovation when designing new biologic facilities by minimizing the need for environmental control while providing better product protection. Designs based on closed systems operating within a ‘non-classified’ space can also be quicker and cheaper to build, cheaper to operate and more sustainable.
However, while closed systems technology has been readily available for some time, facility design has not advanced at the same pace. Closed systems are still often housed in classified areas. There has also been no best practice alignment—industry has been searching for a consensus strategy to implement closed system design and operation.
BioPhorum’s new publication, Closure Playbook—Introduction, is a timely input to the solution, as it describes the tools, steps, and documents required to assess risk and qualify biomanufacturing facilities that use closed-system technologies.
The highly anticipated Playbook has been developed to optimize industry-based decision-making when designing, constructing, or modifying biomanufacturing facilities or processes. It focuses on closed systems in a low-bioburden drug substance manufacturing space.
By following the strategy, one can ensure that the right controls are in place to use closed systems in a non-classified manufacturing space. The gains made will be significant by reducing the time to deliver these facilities and lowering associated capital and operational expenditures.
Classified cleanrooms increase costs, and slow product development and manufacturing unnecessarily. It has been estimated that each increase in classification adds 25% to labor costs, so moving down in classification gives you a similar saving.
“What is most costly is not building a facility, but operating it,” said Alejandro Kaiser, Process Engineer at CRB Group and an author of the Playbook. “If my bioreactors don’t have to be in a Grade C room but in a CNC space, then they’re cheaper to build and much, much cheaper to operate. That’s when the Playbook is best used – when you have a greenfield building, a brownfield refurbishment, or even when you are making some operational changes.”
The Playbook’s principle is to use a risk-based approach to determine key facility and process attributes and controls. These include equipment design, manufacturing environment cleanroom classification, viral segregation, gowning, cleaning, and environmental monitoring and sampling. This risk-based approach allows companies to leverage recent advances in equipment design and process closure technologies (e.g., single-use bags, aseptic connectors, and improved filters) as part of an industry-recognized framework. The assessment aims to demonstrate that the risk of contamination from the environment has been reduced to an appropriate level (whether aseptic or low bioburden) in the closed system before introducing the process.
The Playbook has been developed around three fundamental areas: process definition, risk assessment, and the attributes that identify current best practices in designing and building a biomanufacturing facility that meets current global regulatory guidance around closed systems.
Lars Hovmand-Lyster, Senior Engineering Specialist at Novo Nordisk and an author of the Playbook, said, “By looking at the risks to patient safety and product quality, the Playbook provides tools that can help you explain internally and to regulators that you can get a much higher level of protection than by classifying our open operations.”
Making your facility design ‘right-classified’
The Playbook includes a roadmap for biopharmaceutical manufacturers and their partners when developing, assessing, and verifying unit operations, leading to a facility design that is ‘right-classified’. It also provides technical and operational solutions in the form of specific tools, examples, and approaches to help companies execute and document a system closure risk assessment and verification, and develop a strategy for facility design of modern, flexible biomanufacturing facilities.
“With legacy thinking, we tend to put our processes in a legacy environmental grading, so in much more protected rooms than required,” added Kaiser. “The Playbook really helps you ask: am I touching all the right points to ensure my process will be in an adequate environment?”
Closed processing is now accepted as the most effective contamination risk mitigation strategy. The time is right to implement these best practices for facility, equipment, and process design that promote closed processing in non-classified environments. The Playbook sets the scene for closed systems and discusses the right approach, tools, and methods of implementing them in appropriately operated and non-classified zones.
How do you implement your closed systems?
This is the first of several chapters of the Closure Playbook. Over the coming months, subsequent chapters will be published on:
- general philosophy of closed systems
- standard terminology
- how to apply the risk assessment model
- the impact that closed systems may have on your facility design
- documentation needed to qualify the uses of closed systems in an appropriately classified environment.
For more information, download the paper here and contact Paul Osborne, Global Change Facilitator, at firstname.lastname@example.org