1. Industrial Revolutions – Then and Now
While the First and Second Industrial Revolutions each lasted about 75 years, the Third (or Digital) Revolution powered on for only about 30 years before triggering its successor, the Fourth and current era. This 4.0 Revolution phenomenon has been characterized by the dramatic increases in connectivity, communication, and rapid integration of emerging technologies. In other words, we are undergoing an unstoppable fusion of physical, digital, and biological systems of exponential proportions!
This change is global and traverses all industrial sectors and socio-economic conditions. Since the World Economic Forum in 2016, various influential leaders have affirmed that we are now experiencing what experts believe to be a disruptive force for change far greater than the combined impacts all three prior industrial revolutions, and that the 4.0 will lead to unimaginable advances for humankind.
2. Where did the term Pharma 4.0 come from?
Industry 4.0 was originally a German concept involving increased connectivity and automation of cognitive (or analytical) tasks mainly performed by humans. In 2015 the International Society for Pharmaceutical Engineering’s Germany/Austria/Switzerland (ISPE D/A/CH) affiliate introduced the concept of “Pharma 4.0” to describe application of Industry 4.0 concepts to pharmaceutical manufacturing. This involves moving away from simply manufacturing according to strict recipes and specifications and adopting an interconnected, dynamic, and more reliable system of simulation, real-time monitoring, and “self-correcting” by the control systems of manufacturing processes.
This brings the principles of quality by design (QbD) and process analytical technology (PAT) to life rather than having design details and experiential data simply trapped within documents. It also allows data held there or in the minds of a select few subject matter experts to be historized and, in real time, disseminated and exchanged between functional groups and teams.
These concepts extend beyond simple manufacturing to include the entire pharmaceutical value chain.
3. What does Pharma 4.0 mean exactly and how is the pharma industry responding?
Pharmaceutical companies, equipment providers, and suppliers of goods and services have embraced the concepts of Pharma 4.0. Key industry forums are playing a major role coordinating and building momentum helping to shape and define the responses.
Specifically, in 2017, the International Society of Pharmaceutical Engineers formed the Pharma 4.0 Special Interest Group (SIG) and concepts have been merging with the ISPE Holistic Production Control Strategy Working Group recommendations.2
The full meaning of Pharma 4.0 is becoming clear. It has best been described by Christian Woelbeling, Chairman ISPE Special Interest Group “Pharma 4.0”, as follows. “From Industrie 4.0 to Pharma 4.0, the ISPE initiative driven by the Special Interest Group “Pharma 4.0” created the Pharma 4.0 Operating Model for the Factories and the Supply Chains of the Future. Pharma 4.0 is fueled by e.g. the processing of big data, interconnectivity, collaborative robotics, artificial intelligence and distributed cloud service-based architectures. Digitalization enables the change across the organization and along the complete value chain network. The formula “Industrie 4.0 + ICH Guidelines = Pharma 4.0 Operating Model” is calculated in this ISPE Special Interest Group and it adds additional Enablers and Elements to the ICH Q10 Pharmaceutical Quality System which are based on the defined Companies Structural Areas of the acatech Industry 4.0 Study. The Pharma 4.0 Operating Model (Picture 1) is the pharma specific interpretation of the Industrie 4.0 capabilities across the functional areas of the business: Resources, Information Systems, Culture and Organization & Processes. ICH is the regulatory standard for this Pharma 4.0 Operating Model. The concept of the ICH based Control Strategy is the basis for the holistic approach of enabling “lab to patient” or even “patient to patient” value chains for the Next Generation Therapies controlled by the ICH Q10 Pharmaceutical Quality System/PQS.” 3
In December 2017 the Parenteral Drug Association and Manufacturing Science and Operations ProgramSM (MSOP) sponsored a Task Force on Big Data. Several workstreams (Process Robustness, Data Control, and Data Model) were identified as critical to modernizing manufacturing practices by bringing together big data, digital quality management, machine learning, and information security to create a future state of intelligent pharmaceutical development and manufacturing.4
These groups are actively working to define frameworks for implementation of best practices. In addition, several draft guidance documents are being drafted.
To further assist efforts of companies undertaking this transformation, the Biophorum Operations Group (BPOG) recently published “The Development of a Digital Plant Maturity Model to Aid Transformation in Biopharmaceutical Manufacturing”.5
This excellent resource describes what it means to become a factory of the future, otherwise known as a “digital plant”. The detailed guidance and framework provide common terminology for five levels of digital maturity helping companies determine their current position on their own digital journeys and communicate with their peers and partners as they mature. Moreover, it provides a well-defined pathway for advancing digitalization of pharmaceutical physical equipment and enterprise system capabilities.
OPC Foundation and the Industrial Internet Consortium
Meanwhile, the OPC Foundation and the Industrial Internet Consortium have published international standards, known as the OPC Unified Architecture for vertical and horizontal industrial communications. This allows for consistent design of safe and reliable communications between manufacturers, disparate operating systems, from the edge to the cloud and allows for rapid expansion of semantic interoperability for the smart world of connected systems.
Improved integration of pharmaceutical equipment and systems and digitalization of the process operations and equipment using latest sensors and IIoT according to standard conventions such as IIRA, ISO/IEC/IEE42010:2011 and RAMI4.0 gives GxP manufacturers the framework to modernize atop existing automaton and infrastructure. This means we utilize the “big data” that exists in pharma to make end-to-end product and process control strategies more robust than ever before.
4. What are the benefits of Pharma 4.0?
As described by ISPE Pharma 4.0 SIG team, the idea is that we are seeking a transformation from today’s current submission-based control strategy, in which a strategy for commercial manufacturing is transferred or scaled up from the development phase, to a holistic strategy that includes equipment, facility, GMP, and business controls, which includes adaptation throughout the product development and commercial lifecycle as learning is captured. It also extends up and down the pharmaceutical value chain. This holistic strategy is the basis for the automation and digitization program and for lifecycle management as outlined by the upcoming International Council for Harmonization Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management guideline.
Pharma 4.0 is the next step toward “smart manufacturing”. The product/process control strategy effectively serves as the “central nervous system” upon which machine learning and artificial intelligence can continually occur as inputs and outputs flow in real-time from edge OT sensors and controllers and to and from Quality Management Systems (QMS) and business systems (E.g. ERP, MES, etc.). These IIoT engines and Intelligence engines can then drive improvements making operations more efficient and more robust, and predictable operations.
5. How are Regulatory Agencies Responding?
The FDA has supported a risk-based approach to quality management including a range of process analytical technologies (PAT) for decades. In particular, FDA expects that the product and process designs and supporting QMS elements work together as part of an integrated control strategy. The optimal approach involves real-time monitoring and control of flexible process parameters that can respond to variability of process inputs and performance.6
See Figure 1.
FDA Emerging Technology Team (ETT)
FDA recognizes that adopting innovative approaches to manufacturing may present both technical and regulatory challenges. Pharmaceutical companies may have concerns that using such technologies could result in delays while FDA reviewers familiarize themselves with the new technologies and determine how they may be evaluated within the existing regulatory framework.
More recently, in an effort to accelerate modernization of pharmaceutical methods of manufacture and enhance product quality assurance, CDER’s Office of Pharmaceutical Quality created the Emerging Technology Program to promote the adoption of innovative approaches to pharmaceutical product design and manufacturing. Through the program, industry representatives can meet with Emerging Technology Team (ETT) members to discuss, identify, and resolve potential technical and regulatory issues regarding the development and implementation of a novel technology prior to filing a regulatory submission.7
6. How is Quartic.ai Enabling Pharma 4.0?
Our Life Sciences Team includes experts with years of experience working across the pharmaceutical value chain. We are passionate about placing the power of IIoT and Artificial Intelligence in the hands of pharmaceutical scientists, engineers, operations, and quality assurance reps.
We built our Quartic PlatformTM with direct inputs and feedback from top 10 global pharmaceutical companies. Our all-in-one system, with an illuminatorTM IIoT engine and an eXponenceTM intelligence engine, is meant to be used by anyone that wants to gain insights about their processes and make them better.
We are active members of the aforementioned special interest groups and committees. We continue to enhance functionality consistent with the frameworks and guidance from OPC, ISPE, PDA, etc., as well as feedback from FDA.
7. How can I get Started?
Our team is ready to support your journey and will help you begin your first hands-on experience with artificial intelligence. Simply give us a call or email us at ACCELERATE@Quartic.ai
REFERENCES and LINKS
1. What is the Fourth Industrial Revolution https://www.youtube.com/watch?v=kpW9JcWxKq0&feature=youtu.be