Digital transformation is a major undertaking for any manufacturer. But factor in the mission critical, highly regulated, and quality-conscious nature of pharmaceutical production and the effort becomes even more daunting.

Pharma 4.0 is a maturity model-based framework for adapting digital strategies to the unique contexts of pharmaceutical manufacturing—including practical guidance together with quality and regulatory best practices to accelerate transformation and leverage the full potential of digitalization to speed innovation on behalf of patients. The term was coined by the International Society for Pharmaceutical Engineers to envision a digitally mature pharmaceutical industry.

Yet Pharma 4.0 remains just a framework, not a complete roadmap for a company’s transformation. In this article we examine how organizations can put Pharma 4.0 principles into practice, and how a crucial foundation for doing so is the digitation of technology transfer in the life sciences enterprise.

Adapting Industry 4.0 to life sciences and pharmaceutical production

All business sectors recognize the importance of digital transformation, and industrial manufacturers have learned to navigate some unique transformational challenges in their production environments. This latest transformational phase, known as Industry 4.0, emphasizes breaking down the traditional functional and technical silos to enhance collaboration across various business functions and manufacturing units to sustain a coordinated modernization effort. Industry 4.0 focuses heavily on enhanced IT (Information Technology)/OT (Operational Technology) collaboration and new systems for real-time design, collaboration, factory floor insights and decision support.

Pharma 4.0 adapts these Industry 4.0 principles to the realm of pharmaceutical and life sciences production. As an operating model, it’s designed to take a range of innovations—running the gamut from new treatment modalities and enhanced digital connectivity to smart connected machines and advanced analytics—and align them with Pharmaceutical Quality Systems standards such as ICH Q10 and ICH Q12. The ISPE’s Pharma 4.0 website promotes a framework of 12 “theses” to guide transformational efforts:

1. Pharma 4.0 extends/describes the Industry 4.0 Operating Model for medicinal products.
2. In difference to common Industry 4.0 approaches, Pharma 4.0 embeds quality oriented leading practices and places an emphasis on data integrity across the product and process lifecycle.
3. Pharma 4.0 attempts to break silos in organizations by describing how to build bridges between industry, regulators and other stakeholders.
4. For the next generation Medicinal Products, Pharma 4.0 is a key enabler of the business case for digital transformation.
5. For established products, Pharma 4.0 offers new business cases centered around efficiency and continued quality and advanced insights to manufacturing process performance.
6. Investment calculations for Pharma 4.0 require innovative approaches for business case development.
7. Prerequisites for Pharma 4.0 include an established Pharmaceutical Quality System (PQS) controlled processes & products.
8. Pharma 4.0 is not an IT initiative but rather a holistic framework of outlining priorities for business, technology and manufacturing throughout a drug product’s lifecycle.
9. The Pharma 4.0 Operating Model incorporates technology with organizational, cultural, process and resource aspects.
10. The Pharma 4.0 Maturity Model enables aligning the organizations operating model for innovative and established industries, suppliers and the extended value chain to an appropriate aspirational state in the future.
11. Pharma 4.0 is not a must on its own, but a framework for establishing competitive advantages.
12. When evolving from blockbusters to niche products and personalized medicines, Pharma 4.0 offers new mechanisms to derive value from people, process, technology and data.

These are just high-level guardrails for what each organization must ultimately craft as a detailed and highly specific roadmap for transformation in the enterprise. And due to the nature of the end product, patient safety is always the absolute priority, meaning there is no margin for error.

As extended value chains in the pharmaceutical industry become more global and complex in nature, the requirement for visibility of information and structured data across a porous value chain is essential. That means putting Pharma 4.0 principles into practice relies heavily on secure, efficient and digitalized technology transfer capabilities – something that’s still a challenge for many organizations.

The challenge of outdated technology transfer

Enterprises hoping to pursue Pharma 4.0 quickly learn that digitalizing their technology transfer processes is a key strategic priority. Many life science companies today remain mired in a siloed, high latency and paper-based mindset—and eliminating these hurdles to technology transfer is a foundational step in pursuing digital transformation across the value chain.

Outdated technology transfer approaches can mean slower speed to market; duplicated work efforts; labor intensive manual transfer of design, research and production data between disconnected systems and partners; lack of automation; and non-accessibility of systems on a global scale. All of this threatens competitive advantage and long-term growth, especially in the context of what may be next-generation production or therapy systems whose design and operation assume the existence of highly connected, flexible systems for the contextualization, reuse and collaboration of data.

Unfortunately, too many pharmaceutical companies are still saddled with the legacy of multiple, uncoordinated data management systems. Electronic lab notebooks, laboratory information management systems, product lifecycle management platforms and other systems are often misaligned or entirely siloed from one another.

Without a continuous and digitized flow of data, it’s impossible to analyze and reuse the reams of structured, semi-structured and unstructured data residing separately across the enterprise; human analysts and custom reports are needed to share even basic information between such systems. Many companies also suffer from insufficient digitalization from paper-on-glass scans that fail to make all data elements extractable and reusable.

Pharmaceutical companies often struggle to standardize data integrity across research and development, through process development and commercialization and into a production environment. This can be a hurdle to maintaining compliance with strict regulatory agency requirements. The challenge is exacerbated by the fact that a typical global manufacturing operation may have hundreds of process “flavors” representing different critical quality attributes (CQAs) and corresponding critical process parameters (CPPs). There may also be variations in market specific labeling, instructions for use (IFU), packaging and other market specific changes affecting production.

To complicate matters further, commercial pharmaceutical production often involves non-linear scaling, where certain key process parameters may need to be adjusted during scale up. That means constant collaboration on information as teams optimize CPPs during the scaling process in order to maintain CQAs approved by one or many market-specific regulatory agencies.

All these labor-intensive processes for technology transfer are costly and simply don’t enable pharma production to scale quickly and efficiently. Poorly designed technology transfer capabilities can stall ramping to production, introduce transcription related errors and consume valuable resource time needed to double and triple check data. It’s also harder to address security concerns from increasingly interconnected systems that make the entire production environment—including supply chain and external partners—more vulnerable to attack.

Far and wide across the product development lifecycle, outdated technology transfer remains the Achilles heel responsible for stumbling blocks like manual and paper based KPI calculations, data recreation across functional silos, data change latency and failure to aggregate process information or establish a single source of truth across all data management systems.

Digital technology transfer unlocks data for agility and power

In pursuing Pharma 4.0, manufacturers are learning to streamline the flow of data across internal and external architectures and systems for a more powerful, constant and reusable flow of critical data. At its most robust levels, fully digitized technology transfer creates a rich flood of contextualized and reusable digital data streams across the enterprise to unlock new levels of agility and efficiency.

Advanced digital technology transfer solutions allow organizations to weave digital threads of into a digital fabric of continuous product and process information flow across the enterprise. The seamless sharing, reusability and leveraging of contextualized data throughout the production lifecycle enables robust data change control, accelerates innovation and scale-up and shortens time to market to reap significant timeline, cost and profitability improvements.

As technology transfer is increasingly digitalized and the digital thread ties together more data, traceability emerges as a powerful driver for ensuring data integrity, agility, resilience and business value. This is critical, as traceability is key to compliance with numerous drug product production regulations.

The visibility and control that digital threads create enable pharma companies to better project the impact of any changes in materials, process or design while ensuring safety and efficacy of the drug product. This helps the extended enterprise better collaborate and make fast, accurate, actionable and traceable decisions on that information. In essence these digital threads can enable digital twin simulations of automated production processes, a technique that can save significant time and resources.

Digital twin simulations enable companies to create virtual representations of physical assets for virtual line commissioning, subsequently enabling real-time monitoring and control of those assets. This delivers a range of benefits—including fewer late-stage capital intensive changes to a physical production line, increased efficiency of line operators, higher product quality, reduced batch non-conformity and reduction of batch quarantines.

Ultimately, establishing pervasive digital threads and the advanced tech transfer solutions enabled by them gives the pharmaceutical enterprise a holistic view that encompasses people, physical assets, manufacturing processes and value chain performance. Pharmaceutical companies find themselves better able to control production environments and turn data into contextualized information. Secure information exchange between systems and even across the entire network becomes possible—including data shared with external manufacturing parties, third-party logistics providers, researchers, distributors and other partners.

Benefits and applications

The business value of digital technology transfer plays out in ways large and small across the enterprise from the top floor to the shop floor. As life sciences manufacturers benefit from connected development at connected factories with connected workers, the traditional value chain evolves from disconnected islands of automation into a fully connected extended enterprise. This unlocks unprecedented levels of actionable insights—including monitoring the health of equipment and production systems to preemptively identify and head off potential process and or asset failures before they happen.

Such proactive capabilities can transform the job of process engineers and technology operations teams who currently struggle with excessively paper-based and manual technology transfer processes. Digital technology transfer makes everyone’s job easier, including that of Chief Operating Officers, Chief Compliance Officers and other C-Suite executives in charge of making the case and accounting for risk management and value generation in the enterprise.

To reiterate that Pharma 4.0 is a framework, not a detailed road map, for digital transformation and implementing Industry 4.0 principles in the life sciences arena, every organization will have to craft its own unique journey on that roadmap. While each unique journey depends on the unique business terrain and operating conditions involved, there are some common strategies tied to success.

One is to leverage a Minimum Viable Product (MVP) approach, which consists of several distinct phases designed to strike the right balance between value justification and technical feasibility of the tech transfer implementation. The phases are summarized as an initial Demo phase that is often facilitated with generic data; a Proof of Concept phase to evaluate technical feasibility and provide a base to develop a value hypothesis; a Minimum Viable Product (MVP) deployed in a production setting to validate a base data model, design and user interfaces; a Production Hardening phase where key functionalities are finalized and securely embedded in the production environment and server architecture; and Scale Up to further expand features and adoption in the enterprise.

Throughout, it’s important to enact powerful change management, data governance and exchange mechanisms to better map ISA 88/95/99 models and data structures across pharmaceutical production networks. Also, open technology architecture and standardized data models can be leveraged to allow for a continuous digital thread across network boundaries.

Positioning the pharmaceutical operation for resiliency and value

Well-implemented digital technology transfer capabilities facilitate data reuse, continuous flow of information and real-time insights throughout the value chain—encompassing materials, process, equipment, control strategy and validation across the whole industrial landscape of drug discovery, development and manufacturing.

Organizations that succeed in the Pharma 4.0 effort will find themselves able to shorten scale-up time by eliminating tech transfer redundancies, data recreation and transcription errors. The benefits are being realized in a constantly growing list of use cases—from network node management, digital control strategy and site-specific variations in general recipe, to electronic batch record management, digital COAs, digital work instructions and more.
The digital transformation journey in life sciences requires a good deal of strategy and investment. Fortunately, life science enterprises don’t have to start from scratch in charting that journey. More and more companies are beginning to leverage the Pharma 4.0 framework and the benefits of digital technology transfer solutions to drive transformation toward reduced overall costs and increased efficiency of the entire pharmaceutical value chain. 

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Sachin Misra, Principal & Global Practice Leader – Pharmaceuticals and Biotech at Kalypso, brings over 20 years of experience in digital value chain advisory services and technology implementations. In his role, he helps clients define the Digital Thread roadmap, align digital capabilities to tangible business value, and succeed with technology initiatives including Enterprise Digital Architecture, PLM, MDM, MES, IioT, 3D Modeling, Emulation, Simulation, Additive Manufacturing, Smart Connected Operations, and Data Science.