NEWS

Introducing BioPhorum’s Closure Playbook 

3 October 2023
Drug Substance
Paul Osbourne
Global Change Facilitator

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 alignmentindustry 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.

Optimized decision-making

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 paul.osborne@biophorum.com

NEWS
The results are in – BioPhorum’s survey on sterile filtration integrity testing
Medication
NEWS
Using a closure analysis method to reduce CGT contamination risks
NEWS
Survey of industry practice for PUPSIT in 2024
PODCAST
The implementation of Annex 1 and beyond – how BioPhorum supports members now and in the future
NEWS
How our value-driven FIT approach can increase your process reliability and patient safety

Advanced Therapy Medicinal Products

Advanced Therapy Medicinal Products support the quest for better and faster development of cell, gene and RNA therapies​ through connecting therapy developers, contract manufacturing, and testing organizations to gain an understanding and respond to the challenges faced by the advanced therapeutics industry.

Development Group

Development Group accelerates and improves the development process of biopharmaceutical medicines for the benefit of the patient. Replacing isolation with collaboration by providing a “safe” space where subject matter experts can work on sharing solutions and best practice on emerging industry trends, implementation of new technologies and common issues whilst ensuring their intellectual property and confidentiality is protected.

Drug Substance

Drug Substance advances excellence in drug substance manufacturing and testing, acting as an industry voice to accelerate technology adoption, implement post-approval change more rapidly and increase confidence in maintaining compliance.

Fill Finish

Fill Finish accelerates development and acceptance of sustainable world-class filling and packaging operations for drug product which meets the future needs of patients. Through innovative solutions resulting from the sharing of expertise, we can overcome common performance challenges and deliver on quality and regulatory compliance.

Information Technology

Information Technology accelerates digital maturity across the ​global pharmaceutical manufacturing industry.

Quality

BioPhorum Quality provides a dedicated, safe space for quality professionals from biomanufacturers and contract organizations to coalesce and enhance effective collaboration to address shared industry challenges.

Regulatory-CMC

Regulatory CMC brings leaders together who have a common goal – to improve access to medicines through innovation in the Regulatory ecosystem. It provides a dedicated space for strategic leadership and a coordinated industry voice, to move from divergence to convergence.

Supply Chain to Patient

Supply Chain to Patient transforms the performance of global pharmaceutical clinical and commercial outbound supply chains through industry collaboration by creating transparent patient-centric, resilient and agile E2E supply chains, that consistently deliver high-quality medicines ensuring an uninterrupted supply to patients.

Supply Partner

Supply Partner is a trusted advisory group and collaboration that is the engine for driving change across the global industry for all things relevant to the inbound supply chain. Addressing the challenges of complexity, resilience, cost, sustainability, and innovation.

Sustainability

Sustainability enables the industry’s transition to a low carbon, circular future – supporting members to improve patient health while respecting the planet. We activate multi-disciplinary teams drawn from our network to deliver environmental sustainability improvements across the value chain.

Technology Strategy

Technology Strategy acts as one voice of the industry to define strategy, accelerate technology transformation and support technology translation and adoption. With a purpose of enabling the future state of flexible, resilient, sustainable end-to-end biomanufacturing.

DOWNLOAD
An industry perspective on understanding AAV capsid content variants
Needle On Yellow Background
EXTERNAL-RESOURCE
An intercompany perspective on practical experiences of predicting, optimizing and analyzing high concentration biologic therapeutic formulations
DOWNLOAD
The Drug Substance 2.0 Strategic Value Framework
Coloured dots on teal, next to vial
DOWNLOAD
BioPhorum’s holistic approach to container closure integrity
Magnifying glass over a tablet all coloured blue
DOWNLOAD
Digital Plant Maturity Model 3.0
NEWS
Inaugural BioPhorum Quality face to face – get involved
PODCAST
The next step in building regulatory as a capability to enable strategic innovation across the BioPhorum community
PODCAST
Delivering a Cell and Gene Therapy Outbound Supply Chain Pathway for the Industry
DNA and Earth on blue background
DOWNLOAD
A vision for the biopharmaceutical industry’s inbound supply chain
NEWS
A major milestone – a harmonized approach to product carbon footprint data
Technology Roadmap V 2.0
DOWNLOAD
BioPhorum Technology Roadmapping roadmap vision 2.0

Publications

Documents including best practices, vision statements and peer reviewed papers to help you take value back to your business.

Webinars

Discussing all aspects of the biopharmaceutical industry, from digitization and knowledge management to raw materials, supply chain, sustainability and more. Learn from the perspectives of those at the forefront of the industry.

Podcasts

BioPhorum Connect is our podcast series that keeps you up to date with the latest news and trends in the biopharmaceutical industry. From experienced professionals to thought leaders, these podcasts bring you the insights and perspectives of experts from around the world.

Tools

A variety of resources including design tools and user requirement specifications to help you improve and streamline your business processes.

Benchmarks and Surveys

Research conducted among the BioPhorum membership providing evidence to support change and identify best practice.

Browse all

Access a variety of free tools and papers and other resources designed to provide you with up-to-date information and insights to help you make informed decisions and maximize your success. Access our resources today and start making improving and streamlining your business processes.

WEBINAR
Bioreactivity testing in single-use system biomanufacturing
WEBINAR
Bioreactivity testing in single-use system biomanufacturing
WEBINAR
Bioreactivity testing in single-use system biomanufacturing
Magnifying glass over a tablet all coloured blue
DOWNLOAD
Digital Plant Maturity Model 3.0
WEBINAR
Bioreactivity testing in single-use system biomanufacturing