Developing viable biopharmaceutical processes for the manufacturing of biotechnology products requires foundational knowledge of the operational relationship between product, process, and facility attributes.
Here, Jeffrey N. Odum, CPIP, Qualified Instructor, International Society for Pharmaceutical Engineering (ISPE), outlines the three core considerations.
The Manufacturing Enterprise Model
To achieve Good Manufacturing Practice (GMP) goals—such as establishing control, providing proof of control, and ensuring a means of returning to a controlled state in the event of a problem—effective design solutions for the process, facility, and infrastructure must be defined early in the project lifecycle.
Biopharmaceutical facility design is driven by three primary considerations, known as the Facility Design Paradigm:
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Product Attributes
The physical characteristics of the product being manufactured, defined by Critical Quality Attributes (CQAs). -
Process Attributes
The materials, equipment, systems, methodologies, and techniques required to deliver the product (CQA/critical process parameter (CPP) relationship). -
Facility Attributes
The space allocations, environmental conditions, segregation strategies, finishes, and operational procedures required for manufacturing.
Optimised facility design starts with logical and efficient process design. To minimise operational risk in biological product manufacturing, a well-defined process and understanding of unit operations are critical.
The three elements of the Enterprise must be integrated, unit operations defined, and facility attributes coordinated to support segregation strategy and operational approach.
Summation of the Enterprise Model:
The Process is operated in the Facility, under the control of the Infrastructure.
Figure 1: Enterprise Model
Figure 2: The concept of design space and its relation to QbD
Process Design Considerations
The Process is the driving force behind the biomanufacturing enterprise. Process design should begin with these questions:
- Do you fully understand the process?
- What are the process states and requirements?
- Is the process closed?
The Quality by Design (QbD) approach, as outlined in ICH Q8, ensures that:
- Quality Target Product Profile (QTPP) is well-defined.
- CQAs and CPPs are identified and linked to raw materials and process parameters.
- Risk assessment is performed to create a design space and develop a control strategy.
Facility Considerations in Biomanufacturing
Optimising facility design is integral to process efficiency. Key elements to consider:
Process Factors:
- Cell line expansion method
- Cell production platform
- Recovery method & purification approach
- Stability characterization
- System closure & biosafety level
Operational Considerations:
- Single, multiuse, or multiproduct operations
- Process titer and yield
- Equipment utilization & segregation strategies
- Technology platform(s)
Regulatory & Compliance Considerations:
- Governing agency requirements based on where the product will be sold
- Classification of product
- Single vs. multi-product manufacturing
By integrating these considerations, manufacturers align process design with facility constraints to maximise efficiency while maintaining regulatory compliance.
The Role of Control Strategy in Manufacturing
A viable control strategy is the backbone of cGMP compliance. Effective implementation requires:
- Defining control parameters for the product, process, and facility.
- Integrating automation and control to ensure consistent quality.
- Cross-functional collaboration among drug development, process engineering, facilities engineering, and automation teams.
With the Manufacturing Enterprise Model, the goal is to operate the process within the facility, under the control of the infrastructure.
Conclusion
As the biopharmaceutical industry continues to evolve, experienced engineers must find innovative ways to reduce HVAC energy consumption, optimise facility design, and improve operational efficiency—while ensuring global patient safety compliance.
By focusing on:
- Process closure & microenvironments
- Optimising airflow and energy efficiency
- Aligning facility attributes with regulatory requirements
Manufacturers can balance sustainability with cost efficiency and product quality, creating a more resilient and adaptable biomanufacturing ecosystem.
About the Author
Jeffrey N. Odum, CPIP, is a subject matter expert and Qualified Instructor with the International Society for Pharmaceutical Engineering (ISPE). He has over 30 years of experience in facility design, regulatory compliance, and process engineering for the biotechnology and pharmaceutical industries.
