Stefan Hyde Automation Manager, Asahi Kasei Bioprocess America
Asahi Kasei Bioprocess America, Inc. (AKBA) firmly believes that Oligonucleotides are one of the most promising therapeutic modalities for today and the future. Already, the industry is struggling with the exponentially growing demand for Oligo drug substance – and as the race to keep up continues, adding/onboarding knowledgeable resources becomes increasingly difficult. This means that the solution to the supply problem may very well require an evolution of the industry’s manufacturing facilities to
By Stefan Hyde Automation Manager, Asahi Kasei Bioprocess America
employ Pharma 4.0™ concepts to support not only the growth of the workforce but also increased per-head productivity. New digital technologies must be implemented to reduce testing and installation time, ease training for new operators and scientists, streamline production, and deliver real-time batch results for clearance and approval. Pharma 4.0 factories will become predictive and even adaptive in their operation, heading off risks and issues before they impact production. But before we begin to employ any of these concepts, we must first understand the fundamentals of just what defines Pharma 4.0.
Industry 4.0
Pharma 4.0 (as coined by the International Society for Pharmaceutical Engineering – ISPE) is a specific introduction of “Industry 4.0” concepts to the pharmaceutical industry. The term "Industry 4.0” refers to the so-called “fourth industrial revolution,” which is preceded by the first, second and third industrial revolutions.
The boundaries of these periods are defined differently by different groups, and they often overlap since adoption times varied drastically by region. But it is generally agreed that the first industrial revolution is defined by the steam engine and the weaving loom (early mechanization), the second with the adoption of electricity and assembly lines, the third with the introduction of computers and automation, and the fourth (current) industrial revolution with the Internet of Things (IoT) and large networks.
Pharma 4.0 Operating Model
Pharmaceutical production based on Industry 4.0 factory design becomes “Pharma 4.0” when these same ideas are applied to GMP compliance, validation, and GAMP® requirements. Pharma 4.0 is not a product, but rather a framework. ISPE has developed an operating model to apply the concepts of Industry 4.0 to the pharmaceutical industry. This operational model is a methodology for processes from product development all the way up to commercial manufacturing. It is summarized in a graphic1 consisting of Elements – Resources (Digitalization, Workforce of the Future, Available/Qualified), Information Systems (Holistic Value Network, Integration/Traceability), Organization and Processes (ICH Holistic Control Strategy, Lifecycle Management, and Culture (Communication, Decision Making); as well as Enablers – Digital Maturity and Data Integrity by Design.
ICH Q10
These terms, Elements and Enablers, come from the International Council for Harmonisation of Technical Requirements for Human Use (ICH)’s Q10 guidelines. In the ICH Q10 model2, elements and enablers are shown in grey (e.g., CAPA System, Change Management, etc.) and are quite familiar in the pharmaceutical industry. New elements made possible by digitalization (see Pharma 4.0 model) are shown in blue. When these elements are combined with the new enablers (Digital Maturity and Data Integrity by Design), they form a holistic control strategy for the complete product life cycle. It’s important to note that this digitalization effort is not an IT project – it is a project for the entire organization. This model requires information exchange both vertically and horizontally throughout the plant, meaning that all departments and stakeholders need to collaborate to enable Data Integrity by Design. Broad collaboration is imperative to properly Critical Quality Attributes (CQAs) and Critical Process Parameters (CPPs), which are tenants of ICH Q10.
Digital Plant Maturity Model
Of course, all these guidelines are helpful to achieve industry alignment, and we must maintain a vision of the future to ensure that we are on the right track today, but this perfectly digitalized, adaptive, Pharma 4.0 plant can sometimes feel like a pie in the sky. It can be difficult to understand where we stand today and what the next incremental steps are to get there. To support this evaluation process, the BioPhorum IT Collaboration Group (BPIT) created a “Digital Plant Maturity Model” (DPMM)3. This DPMM can be helpful in evaluating where a plant currently stands and what a reasonable next step might be, while keeping the end goal in mind.
Levels 1, 2, and 3 of this model are quite recognizable to those in the industry. As such, it may not come as a surprise that BPIT conducted a survey upon completion of the DPMM and found that most Pharma companies are at level 2 or 3, with some incorporating level 4 concepts.
Benefits of Digitalization
While a “Level 5 – Adaptive Plant” may not be immediately within reach, incremental steps are often easy to define and have a big impact:
Some digitalization efforts may carry a significant cost and require large-scale buildouts; but it is equally common that technology already in place can be used in a more connected or predictive way – allowing the benefits of Pharma 4.0 digitalization to be enjoyed almost immediately and not necessarily with major capital expenditure.
Resources 1. https://ispe.org/initiatives/pharma-4.0 2. https://ispe.org/pharmaceutical-engineering/july-august-2018/pharma-40tm-hype-or-reality#footnote3_3tsx327 3. https://www.biophorum.com/wp-content/uploads/bp_downloads/BPOG-DPMM-Best-Practice-for-Plant-Assessments-May-2018.pdf
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