From the isolator to the integrated production unit

The IAC methodological framework defines the principles that guide the design of GMP pilot plants. To turn those principles into an applicable methodology, it is necessary to identify a new design unit capable of integrating the manufacturing process, containment, infrastructure and support systems.

In traditional approaches, the project is generally developed by dividing the facility into independent disciplines. Building, layout, equipment, utilities, automation and qualification are designed separately and then coordinated during the different phases of the project.

IAC introduces a different logic. The primary object of design is no longer the individual room, the isolator or a single piece of equipment, but a new integrated design unit in which all the elements required to perform a specific process function converge.

The entire facility is therefore built through the integration of autonomous design units, connected by the manufacturing process and supported by common containment, automation and engineering infrastructures.

Integrated Production Unit (IPU)

The IPU is the smallest complete design unit within the facility.
An IPU does not correspond to the production room or to the isolator alone. It encompasses all the elements required to perform a specific stage of the manufacturing process, integrating the production area, containment system, technical zone and all supporting infrastructures into a single design solution.

It includes isolators, process equipment, dedicated utilities, HVAC systems, local automation, maintenance spaces, transfer systems and all the functional connections required for the unit to operate correctly.
The objective is not simply to group different components together, but to create an autonomous, complete and reconfigurable design structure capable of evolving while maintaining its functional coherence.
The IPU thus becomes the main building block of the facility, replacing the traditional concept of the production room as the basic unit of design.

Reconfigurable Process Train (RPT)

The RPT represents the process architecture of the facility.
The manufacturing process is no longer defined as a rigid sequence of equipment installed within predefined rooms, but as a dynamic succession of IPUs connected according to process needs.

Each IPU performs a specific function and can be added, removed, replaced or reconfigured without changing the overall architecture of the facility.

From this perspective, reconfigurability is not a feature of individual pieces of equipment, but a property of the entire manufacturing process.

The RPT therefore enables the facility to accompany the evolution of NCEs while maintaining operational continuity, plant coherence and regulatory compliance.

Containment Infrastructure

The Containment Infrastructure is the infrastructure that ensures the required level of containment throughout the manufacturing process.
Containment is no longer treated as a characteristic of an individual piece of equipment, but as a distributed property of the entire system.

Each IPU integrates its own containment strategy according to the operations to be performed, while the overall infrastructure coordinates isolators, transfer systems, airlocks, pressure cascades, HVAC, washing systems, environmental monitoring and performance-verification criteria.
This approach makes it possible to modify or reconfigure an individual IPU while preserving the continuity of the overall containment strategy and limiting the impact on the rest of the facility.

Automation Infrastructure

The Automation Infrastructure is the digital infrastructure of the facility.
Within IAC, automation is not a system developed at the end of the design process, but one of the foundational elements of the methodology.

The infrastructure includes process control, supervision, recipe management, data acquisition, PAT systems, electronic traceability, data integrity, Computerized System Validation and integration with corporate information systems.

Unlike the traditional approach, in which software is developed mainly around the installed hardware, IAC adopts a perspective in which software becomes the primary layer governing plant functionality, while hardware provides the physical platform on which those functions are implemented.

Operational functions, process management, recipe reconfiguration, data integration and system evolution are therefore assigned predominantly to the software layer, reducing the impact of hardware modifications and preserving operational continuity throughout the plant lifecycle.
Automation Infrastructure thus becomes a key enabler of both digital transformation and the facility’s ability to evolve.

Engineering Backbone

The Engineering Backbone provides the common technical and information framework for the entire facility.
Each IPU is designed, qualified and managed through a shared body of information that includes user requirements, risk analyses, PFDs, P&IDs, three-dimensional models, qualification strategies, technical documentation, change management, maintenance and asset management.

The objective is not only to ensure document traceability, but to maintain technical coherence across all disciplines throughout the plant lifecycle.

The Engineering Backbone ensures that every evolution of the manufacturing process is consistently reflected in technical documentation, qualification and the operational management of the facility.

The facility as an integrated system of IPUs

Within IAC, the facility is no longer conceived as a collection of rooms, equipment and auxiliary systems developed separately.

The overall architecture is created through the integration of multiple IPUs, each designed by simultaneously applying the principles of integration, modularity and adaptability defined by the methodological framework.

These principles are translated into the operational structure of IAC through the coordinated integration of IPUs, the RPT and the supporting containment, automation and engineering infrastructures.The result is a system in which the manufacturing process, containment, infrastructure and information evolve in a coordinated way, enabling the facility to adapt to the needs of future NCEs without compromising its overall architecture.

Designing for evolution

The evolution of NCEs represents much more than a change in the types of molecules being developed by the pharmaceutical industry. It changes the assumptions on which GMP pilot plant design has been based for decades.

Increasing process complexity, the uncertainty typical of early development, rising containment requirements, the continuous introduction of new technologies and the need to reduce time to market are making design approaches based on static configurations progressively less effective. In this scenario, a facility’s ability to adapt to process evolution is no longer an accessory requirement, but an essential condition for ensuring operational continuity, investment sustainability and long-term competitiveness.

IAC proposes a design model capable of interpreting this transformation by integrating the principles of IPA, MPA and APA within a single coherent architecture. The RPT is the operational translation of these principles, allowing the manufacturing process to be reconfigured without compromising the coherence of the plant infrastructure.

The objective is not to design a facility today that can anticipate every future requirement, but to create an architecture capable of evolving over time together with processes, technologies and regulatory requirements.
From this perspective, reconfigurability becomes an intrinsic property of the facility rather than the result of subsequent design modifications.

The pharmaceutical industry has always driven its evolution through scientific and technological innovation. Today, that evolution also extends to plant engineering. Just as standardisation defined an earlier generation of manufacturing infrastructures, reconfigurability is set to become one of the fundamental criteria in the design of future pilot plants.

From this perspective, IAC is neither a new plant configuration nor a particular technological solution. It represents a different way of conceiving GMP pilot plant architecture, in which evolution is not an exception to be managed, but a requirement anticipated from the earliest stages of design.
The next evolution of GMP pilot plants will not be driven by new equipment, but by a new engineering methodology.

THE SERIES

This article completes the series launched in MakingPharma&Future with “Pilot plants for the new era of New Chemical Entities” and continued online through the analysis of the relationship between process evolution and infrastructure and of the three core principles of the Isolator Atoll Concept. This third article describes their operational translation through the Integrated Production Unit, Reconfigurable Process Train, Containment Infrastructure, Automation Infrastructure and Engineering Backbone.