Part 2: Digital transformation - 10 Years after the Start of Pharma 4.0
This special three-part series explores the transformative impact of Pharma 4.0 on the pharmaceutical industry, focusing on digitalization, business strategy, and operational excellence. Part 2 focuses on digitalal transformation after 10 years of Pharma 4.0.
By Michelangelo Canzoneri, Hans Heesakkers, Teresa Minero, Christian Wölbeling and Thomas Zimmer, ISPE
The idea of the digital transformation is not new. The “FDA's Pharmaceutical Quality for the 21st Century Initiative” was launched on August 21, 2002, coming along with the concept of a Risk Based Approach which aimed to modernize the regulation of pharmaceutical manufacturing and product quality. This was intended to be achieved by implementing a risk-based approach to current good manufacturing practices (CGMPs) in a Final Report from September 2004. FDA's Process Analytical Technology (PAT) guideline was published in October of the same year, outlining “A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance” paving the road for applying Quality by Design and process understanding. Both, Quality by Design as well as process understanding need accurate and reliable data for decision making. Pilot projects started to design process models and control strategy mechanisms to better control our complex pharmaceutical processes. Lighthouse projects had been prototyped, but the overall understanding on the management level wasn't there.
PAT was seen as a technical initiative not as a strategic initiative - and more or less failed. In addition, many decision makers drew back from cost of implementation without applying a holistic view on the total optimum for the business.
The Operating Model – The Key Enabler
10 years later, the term digital transformation was brought into the industry by the initiative of Industry 4.0. Digital transformation was the strategic goal for the management and the European government – but the question was how to bring it into the pharmaceutical industry? The Special Interest Group Pharma 4.0 had been created ISPE and the term Pharma 4.0 was born. A strong community of engaged engineers, quality experts and operations practitioners started to think holistically.
This operating model is based on a holistic approach for the creation of the pharma specific “Holistic Control Strategy” which is referencing to the regulatory framework of ICH Q 8-12 guidelines along the whole pharmaceutical lifecycle. As a holistic model, Pharma 4.0 includes already the additional aspects of Industry 5.0 as there are sustainability (Community of Practice), human-centricity (Cultural Excellence) and resilience (Drug Shortage Initiative), which are initiatives in ISPE already for a long time.
Time to market and drug availability with the right quality are the major challenges for the pharmaceutical organizations to serve the patients.
Key challenge to achieve this, is the preparedness to reach the right digital maturity level based on data availability, data accuracy and all ALCO+ criteria to meet performance and compliance expectations.
Pharma 4.0 Surveys: Industrial Uptake in Life Sciences
Since 2017, the Pharma 4.0 Survey—initiated and conducted nearly annually by ISPE volunteers—has served as a vital transversal and longitudinal study supporting industry stakeholders and the whole ecosystem of End Users, Vendors, Academy and Regulators. It provides data-driven insights to inform decision-making and track the evolution of Pharma 4.0 initiatives within GxP-regulated domains of the Life Sciences sector.
Certain questions remain stable over the years—such as those concerning maturity levels, technology adoption, benefits, and challenges—enabling meaningful trend analysis. Meanwhile, other topics, including data management, cyber risks, and technical pitfalls, have been recently included to explore emerging frontiers.
Respondents to the survey represent a diverse cross-section of the global industry, encompassing various geographic regions, company types, site sizes, and activity sectors. While predominantly drawn from the ISPE network, participation is open to external entities. To ensure candid and unbiased responses, anonymity is strictly maintained, fostering honest personal insights, without the need for prior approval. Each edition typically receives around 400 responses to a core set of ten questions.
Although raw data remain confidential as part of ISPE’s knowledge assets, summary insights have been presented at numerous ISPE and third-party conferences worldwide. These findings offer a comprehensive overview of Pharma 4.0’s progression, highlighting benefits, challenges, and notable correlations among demographics and trends over time.
The most recent edition—the 8th—was open from late 2024 to early 2025, reflecting the industry’s global reach. The respondent pool comprised approximately 35% from multinational corporations, with regional distribution as follows: 27% Europe, 12% North America, 10% Asia-Pacific, 10% Latin America, and smaller contributions from Oceania, Africa, and the Middle East & North Africa (MENA). The sample also maintained a balanced representation across organizational sizes: 15% small (fewer than 50 employees), 25% small-medium (fewer than 500), 26% medium-large (fewer than 5,000), and 32% large global corporations (more than 5,000).
Pharma 4.0 Maturity Levels
For analytical simplicity, maturity levels are categorized into four stages: not started, just beginning, piloting, and systematic ongoing actions. The survey indicates a notable shift towards higher maturity levels in Pharma 4.0 adoption. As illustrated in Figure 2, 2023 and 2024 data reveal a clear transition from initial planning and evaluation to active pilot projects and systematic implementation at scale.
Aligned with the ISPE Baseline Guide Vol. 8: Pharma 4.0, the survey examined 19 enabling technologies across various stages of adoption: planning, pilot testing, small-scale implementation, and large-scale implementation. The analysis identified four key clusters with related specific technologies:
1. AI/ML: Highest number of pilot projects, yet relatively few small or large-scale implementations.
2. Well-established on a large scale: Big data analytics, advanced analytics, robotic process automation, GxP cloud solutions, IIoT, and collaboration platforms.
3. High number of pilots and small-scale: Technologies such as augmented reality, virtual reality, advanced modelling, image recognition, process mining, wearables, additive manufacturing, advanced robotics, and natural language processing.
4. Less adopted technologies: Blockchain, speech and gesture recognition, quantum computing
Overall, all technologies exhibit similar levels of planning or evaluation across the industry. Notably, this seems indicating a remarkable ongoing innovation and exploration of new business cases within the sector.
Pharma 4.0 Benefits
Figure 3 highlights the perceived advantages of Pharma 4.0 initiatives, with the most frequently cited being improvements in quality and compliance, increased efficiency, and productivity—recognized by 65% to 50+% of respondents respectively. The prominence of quality and compliance underscores a strong awareness of digitalization’s positive impact on product integrity and patient safety. Notably, expectations around productivity, business transformation, sustainability, and risk mitigation have significantly increased.
The survey reveals resource shortages, cultural resistance, and skills gaps as the most prominent barriers—challenges that have intensified over recent years, emphasizing the importance of effective change management and fostering a supportive organizational culture (see Figure 4). An increased perception of validation complexity and technical challenges is also evident, likely linked to the rising number of AI/ML pilots, where implementation and validation, especially within GxP-regulated environments, remain largely uncharted.
Integration issues, interoperability challenges, and insufficient preparedness are identified as the top technical pitfalls—highlighted by 60 to 45% of respondents. Less frequently reported but nonetheless present are issues such as poor system design, scalability problems, and security risks, affecting approximately 30% to 20% of respondents. Interestingly, reliability concerns, unwieldy functionalities, and inadequate testing are reported by only 20% to 10%, suggesting that robust methodologies are in place for project execution and testing. Nonetheless, the analysis seems to indicate a need to improve the approach during the early phases like concept, analysis and design of Pharma 4.0 projects.
Cybersecurity and Pharma 4.0
Approximately 44% of respondents from global or corporate roles perceive high or very high cybersecurity risks within their Pharma 4.0 initiatives. The primary challenges include adapting to evolving threats, integrating new technologies, and addressing skill shortages. As expected, a clear correlation exists: the more advanced a company’s Pharma 4.0 initiatives, the higher the perceived – and for sure real - cybersecurity risks.
Looking Ahead: The 9th Edition of the Pharma 4.0 Survey
As preparations begin for the 9th ISPE Pharma 4.0 Survey, scheduled for launch at the end of 2025, the focus remains on monitoring the always changing landscape of technology adoption, associated benefits, and obstacles. Special attention will be given to critical topics such as AI/ML and Generative AI, with joint efforts underway between ISPE Pharma 4.0 and the AI Global Community of Practice to develop targeted questions. The survey team invites all stakeholders to contribute ideas and suggestions, aiming to expand the sample size and enhance the study’s relevance by addressing industry-relevant emerging issues.
