Dan UpDyke - Strategic Marketing Manager, Life Sciences, Rockwell Automation
Of the many different industrial manufacturing environments, the pharmaceutical sector can be a particularly daunting one. Beyond the common issues that any factory will face in maintaining efficient and high-quality production at scale, biopharma manufacturing must master additional challenges with regards to highly sensitive ingredients, strict regulations, and a mission-critical focus on quality for the often life-saving products destined for human consumption.
One in every 10 Americans is now affected by a growing array of more than 7,000 classified rare diseases, raising pressure on pharma to address a broader range of illnesses. As a result, biopharma companies are pivoting to shift some operations away from large-scale bulk manufacturing and toward more agile and flexible production environments, as they seek to maximize the use of available capacity to meet specialized demands.
This pressure is prompting the need for factories to produce a variety of new, targeted drugs in smaller volumes – a multitasking production scenario involving more complicated batching, meticulous tracking and frequent changeover requirements. In the face of these rigorous production demands, biopharma manufacturers are leaning into digital transformation. Specifically, they’re looking to adapt proven Industry 4.0 innovations – including enhanced connectivity, automation and real-time analysis of data and operations in the factory – to the highly specialized pharmaceutical sector.
The fact that pharmaceutical manufacturing is now such a specialized field has given rise to Pharma 4.0, the International Society for Pharmaceutical Engineering (ISPE) initiative to adapt these Industry 4.0 modernization efforts to life sciences and pharmaceutical production. It’s worth examining the ways these manufacturers are embracing these transformations, and how they’re positioning these digital enhancements for a factory of the future that is flexible, agile and adaptable in meeting market demands for more new drugs and treatments than ever before.
Applying Industry 4.0 Transformation to Pharmaceutical Manufacturing
To cope with today’s fast-shifting production requirements, manufacturers are relying on a growing range of Industry 4.0 technologies that leverage intelligent digitization to streamline operations. Major investments in new systems for real time design, seamless IT/OT integration and enhanced shop floor data for real-time production insights and decision support are paying off in the form of more efficient, high-quality, and compliant production environments. These innovations help break down organizational silos and enhance collaboration across the spectrum of manufacturing and supply chain operations. The ISPE laid out 12 widely accepted “theses” on its website as a Pharma 4.0 framework for adapting digital strategies to the unique contexts of pharmaceutical manufacturing:
- Pharma 4.0 extends/describes the Industry 4.0 Operating Model for medicinal products.
- In contrast to common Industry 4.0 approaches, Pharma 4.0 embeds health regulations best practices.
- Pharma 4.0 breaks down silos in organizations by building bridges between industry, regulators and healthcare and all other stakeholders.
- For the next Generation Medicinal Products, Pharma 4.0 is THE enabler and business case.
- For the established products, Pharma 4.0 offers new business cases.
- Investment calculations for Pharma 4.0 require innovative approaches for business case calculations.
- Prerequisite for Pharma 4.0 is an established PQS and controlled processes and products.
- Pharma 4.0 is not an IT Project.
- The Pharma 4.0 Operating Model incorporates next to IT also the organizational, cultural, processes and resources aspects.
- The Pharma 4.0 Maturity Model allows aligning the organizations operating model for innovative and established industries, suppliers and contractors to an appropriate desired state.
- Pharma 4.0 is not a must, but a competitive advantage. Missing Pharma 4.0 might be a business risk.
- When moving from blockbusters to niche products and personalized medicines, Pharma 4.0 offers new ways to look at business cases.
In practice, these guidelines serve as a model for implementing a range of manufacturing initiatives that modernize operations while strictly adhering to pharmaceutical quality systems standards like ICH Q10 and ICH Q12. As such, they serve as an outline for innovation, a high-level framework for how to tailor the digital transformation effort to pharma. Each organization must put these principles into practice with a detailed road map that’s tailored to the unique manufacturing needs with a specific factory setting.
This is easier said than done, especially considering the growing flexibility and agility that the expanding range of treatments for rare diseases demands of pharmaceutical manufacturers. All the while, tight regulations and strong penalties for noncompliance require that high quality be maintained and documented across the production environment.
Pharma 4.0 Enables “Plug-and-Play” Agility on the Factory Floor
Pharma 4.0 innovation can’t happen fast enough for manufacturers who face the added challenges to bring more drugs quickly to market to treat a burgeoning range of diseases. This trend is driving an evolution away from centralized facilities serving global markets in favor of more localized and smaller scale facilities. Such manufacturing agility relies on a technical foundation that consists of more tightly integrated IT and OT systems, more dynamic R&D operations and data driven feedback loops for continual process optimization.
Fortunately, the right up-front design and proven technologies can bring active pharmaceutical ingredient production to lower-cost locations, and personalized drugs closer to patients. This is made possible through a flexible operations environment that leverages a combination of single-use technologies and pre-validated, modular equipment, advanced communications infrastructure and IoT capabilities to effortlessly repurpose assets.
Such flexibility in the factory of the future comes about through connecting systems both horizontally and vertically, with a “plug-and-play” approach to factory floor operations that involves more modular and mobile equipment that can be easily repositioned and reconfigured to adapt to changing production needs. Whereas bioreactors in a traditional facility are typically rooted in fixed locations on the factory floor, reactors and other crucial equipment in the factory of the future can be wheeled into position. This plug-and-play factory of the future ensures these assets are modular and mobile – capable of being moved and docked wherever they are needed most. And each unit is identified by a unique IP address, so workers can track how and where these assets are positioned and used.
Of the many benefits that come with this plug-and-play factory design, one of the most impactful is the drastic reduction in downtime required for cleaning and sterilization of equipment. Especially given the many biochemical ingredients involved in pharmaceutical production, mixing tanks and other equipment must be routinely cleaned. Rather than pausing operations to do this, the modular factory of the future allows such equipment to be swapped out for cleaning in a separate location that doesn’t interfere with production, or for disposable piping and other single-use components to reduce the number of factory components to be cleaned in the first place.
It’s not unusual for a biopharma company’s transformation effort to reap 25% greater yield by reducing costly cleaning downtime. Consider how a traditional stainless-steel reactor can take up to two days to clean and sterilize; but flexible operations can support new processes that employ single-use reactor bags that can be changed out in just a couple of hours. That is just one of many examples across the production environment that demonstrate the tremendous value to be gained from Pharma 4.0 modernization.
Throughout, tangible benefits are derived from a common data structure, helping give workers access to real-time data in a single, consistent format to elucidate valuable production insights. For instance, an Enterprise Resource Planning (ERP) system can be connected down to individual equipment, raw materials and end products, and back up again. Such two-way communication for both vertical and horizontal processes empower factory personnel with optimized control when it comes to maintaining high standards around data integrity and batch quality.
In a similar way, Pharma 4.0 transformation helps put the organization on a better security footing. Thanks to the enhanced visibility and control that comes from intelligent digitization, security teams can take a much more proactive posture to anticipate cyber-risks that could disrupt operations. The best of these modernization efforts ensures this through close integration of both IT and OT network security design.
Key Focus Areas for Pharma 4.0 Implementation
Well-implemented Pharma 4.0 modernization efforts radically improve speed to market. Startups as fast as six to 12 months are possible using pretested and validated equipment, and a smaller building footprint is needed, thanks to removal of hard piping for utilities and the reliance on easily repurposed, modular equipment. This brings many advantages that simplify processes and speed cycle times.
One particularly relevant focus area to help achieve these outcomes involves the many Distributed Control Systems (DCS) in a factory that help monitor and orchestrate production processes. When first introduced, DCS solutions were a reliable way to connect multiple controllers and points of access throughout a plant. But the traditional DCS is no match for the plug-and-play environment that modern pharmaceutical manufacturers require to be competitive and compliant.
For starters, many traditional DCS scenarios involve proprietary technology that is disparate from other control systems. This divergence results in fragmentation between process, packaging, utilities and other critical areas. Separate systems are costly, difficult to integrate and can restrict factory floor agility and responsiveness to future needs.
By contrast, a modern DCS configured for plug-and-play operations can offer the same core capabilities of a traditional system, but with enhanced functionality designed for a scalable facility of the future. Specifically, a modern DCS can support smart docking stations and seamless plug-and-play connectivity for mobile equipment. This approach minimizes alarms and ensures data transfer to the DCS remains consistent and with minimal system disruption – not unlike how a laptop can be undocked and plugged into the network in a different location.
A modern DCS will automatically reject controls for mobile equipment that is docked in the wrong location, and can support the scanning of materials, pipes and other components to confirm they’re used with the right equipment at the right time. These characteristics helps mitigate human error and save valuable validation time for operators and engineering staff.
To illustrate how this works, consider the use case of smart totes, which are critical for shuttling materials through the facility of the future. Advanced smart totes typically have sensors, temperature probes and level switches that require I/O and wiring back to the DCS. This can quickly lead to integration headaches that cost time and money with engineering interventions and production delays. To avoid these drawbacks, a modern DCS can employ hardened I/O modules connected to docking stations via Ethernet cables. This reduces the amount of wiring required and enables automatic alerts for instances where a tote may have been connected improperly – allowing operators to proactively fix the problem before it impacts production.
It’s important to recognize that Pharma 4.0 modernization optimizes more than just technology and equipment; it can also be a game changer for the workforce. A factory of the future can arm manufacturing team members with modern visualization solutions to guide them seamlessly through process steps, with automatic equipment recognition and verification systems that can track and confirm equipment placements.
This eliminates the need for fixed operator terminals, instead allowing workers to use tablets or mobile screens anywhere in the factory. Location-based mobility solutions can recognize an operator’s physical location and then automatically enable relevant access, via the user’s mobile device, to the right visualizations and controls. At the same time, the system can disable controls as the worker moves away from a piece of equipment on the factory floor. So, whether a piece of equipment is moving, a worker is moving, or both – the right operational context and controls are instantly available.
Conclusion
As biopharma companies face new and evolving challenges in meeting demand for a broader range of medications and health products than ever before, they are increasingly turning to Pharma 4.0 transformations to reap the benefits that have revolutionized other industry sectors. As this happens, production quality, flexibility, efficiency and compliance are all enhanced – allowing these companies to better compete and better serve the needs of citizens who rely on their manufacturing output for life saving drugs and treatments.
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