Pharma 4.0: A Look Inside the Digital Future of Drug Development

A Digital Approach to Continuous Process Validation

Authors: Lewis Shipp, Sana Ahmed, and Patrick Riordan

Have you ever wondered what validation looks like in the Validation 4.0 concept?

Let’s take a look at the different aspects and milestones of what this entails, by using a Quality by Design (QbD) approach with knowledge and risk management as enablers. To demonstrate these key concepts, let’s first take a look at a video that explores the ACE Case study in order to demonstrate how to create effective knowledge management in a digital system using a QbD approach following ICH Q8 through ICH Q12.

Validation 4.0 seeks to develop a cohesive harmonized, integrated, holistic, risk-based approach for process performance qualification that incorporates computer system validation building on the Pharma 4.0™ operating model. This includes a holistic control strategy that focuses on digital maturity and data integrity by design. This works hand in hand with Quality by Design which is meant to create a systematic approach to drug development, starting with pre-defined objectives, with emphasis on both product and process understanding. In addition to risk control based upon sound science and quality risk management.

The Current Landscape

Currently, the integrated approach for risk management through the patient, product and process is introduced both reactively and retrospectively. This is due to the overt focus on compliance, which should be automated, rather than quality. However, a holistic approach to knowledge management encompasses the identification, control, and verification of risks to end product quality and safety, in a continuous loop. This touches on what we may think of as them control strategy framework, which enables the prediction or simulation of impact in real time and the subsequent proposition of the necessary process adjustments . Moving away from reactive decision making, and into a new paradigm of developmental agility, built upon a holistic overview of production.

Quality by Design and its implementation are no longer optional, but mandatory, for achieving the aims of Pharma and Val 4.0 as well as, the transformation of our industry.

It is clear, from a regulatory and industry standpoint, that Quality by Design and its
implementation are no longer optional, but mandatory, for achieving the aims of Pharma and Val 4.0 as well as, the transformation of our industry. Digital tools that enable the continuous flow of data for iterative QbD and Knowledge Management as well as the ability to continuously demonstrate Control, and consequently facilitate a continuous state of Validation represent a great leap forward for Pharma.

QbD and Val 4.0 Go Hand in Hand

QbD is an enabler of Val 4.0, as validation is based upon continued process control through iterative knowledge management and Quality Risk Management (QRM) from concept through to post-marketing. The achievement of Val 4.0 is predicated on approaching knowledge management both sequentially and methodologically, which is QbD, but it is often hindered by the lack of adoption and utilization of structured knowledge repositories.

The achievement of Val 4.0 is predicated on approaching knowledge management both sequentially and methodologically, which is QbD, but it is often hindered by the lack of adoption and utilization of structured knowledge repositories

Recently, an article was published from the Val 4.0 Working Group working group detailing the challenges of Oral Solid Dose (OSD) manufacture, and illustrating the relationship between Val 4.0 and QbD. The authors note that there are “Major issues in the traditional approach to validation are the lack of information on representative sampling; the difficulty of real-time monitoring and control; and the snapshot, rather than continuous manner, in which validation is performed.”

Swarbrick and Margetts also note that the key takeaway from their analysis of three OSD case studies is that “the principles of Validation 4.0 are proactive, not reactive. Under the old paradigm, traditional approaches were biased and based on selecting batches with the best raw material, operators, and analysts as a baseline to pass product for release. In Validation 4.0 and a truly QbD system, the use of data models, PAT, and feed-forward/feedback control establishes a process chronology and digital signature for comparison to past and future batches. Therefore, digitization and QbD allows for true validation of every batch.

The Case for Digital Tools

To illustrate the capability of a digital tool to demonstrate CPV, QbDVision works as a Digital CMC Platform and follows the Acetriptan CMC Tablet Case Study produced by the CMC-IM Working Group in 2008. The case study uses a QbD approach and embeds risk from the QTPP stage, through to scale up and optimization of the processes. The purpose here was to aggregate all this information into a central repository and import it to not only provide more context but to provide templates, tables, maps and charts/matrices that can be utilized throughout the validation lifecycle as outlined in the video below.

In the ever-evolving world of drug development, digital tools like QbDVision are creating a transformative path forward by combining digital innovation, effective knowledge management, and Quality by Design principles to shape the future of Continuous Process Validation.

As our industry embraces Validation 4.0’s holistic and risk-based approach, guided by the Pharma 4.0 model, the integration of QbD principles and digital technology adds depth and precision to the process. The insights gleaned from these collaborative efforts underscore the critical importance of knowledge management, proactive risk control, and real-time adaptation. By leveraging new technologies and new processes, our drug development era stands at the brink of a new era marked by agility, efficiency, and a commitment to product quality and patient safety.


Learn more about what QbDVision and Validation 4.0 can do for your drug development program.

Reach out to our team of experts any time to start a conversation about how you can protect your mission-critical product and process data.

Shameek Ray

Head of Quality Manufacturing Informatics, Zifo

Shameek Ray is the Head of Quality Manufacturing Informatics and Zifo and has extensive experience in implementing laboratory informatics and automation for life sciences, forensics, consumer goods, chemicals, food and beverage, and crop science industries. With his background in services, consulting, and product management, he has helped numerous labs embark on their digital transformation journey.

Max Peterson​

Lab Data Automation Practice Manager, Zifo

Max Petersen is the Lab Data Automation Practice Manager at Zifo responsible for developing strategy for their Lab Data Automation Solution (LDAS) offerings. He has over 20 years of experience in informatics and simulation technologies in life sciences, chemicals, and materials applications.

Michael Stapleton

Board Advisor, QbDVision

Michael Stapleton is a life sciences leader with success spanning leadership roles in software, consumables, instruments, services, consulting, and pharmaceuticals. He is a constant innovator, optimist, influencer, and digital thought leader identifying the next strategic challenge in life sciences, executing and operationalizing on high impact strategic plans to drive growth.

Matthew Schulze

Head of Digital Pioneering Medicines & Regulatory Systems, Flagship Pioneering

Matt Schulze is currently leading Digital for Pioneering Medicines which is focused on conceiving and developing a unique portfolio of life-changing treatments for patients by leveraging the innovative scientific platforms and technologies within the ecosystem of Flagship Pioneering companies.

Daniel Matlis

Founder and President, Axendia

Daniel R. Matlis is the Founder and President of Axendia, an analyst firm providing trusted advice to life science executives on business, technology, and regulatory issues. He has three decades of industry experience spanning all life science and is an active contributor to FDA’s Case for Quality Initiative. Dan is also a member of the FDA’s advisory council on modeling, simulation, and in-silico clinical trials and co-chaired the Product Quality Outcomes Analytics initiative with agency officials.

Kir Henrici

CEO, The Henrici Group

Kir is a life science consultant working domestically and internationally for over 12 years in support of quality and compliance for pharma and biotech. Her deep belief in adopting digital technology and data analytics as the foundation for business excellence and life science innovation has made her a key member of PDA and ISPE – she currently serves on the PDA Regulatory Affairs/Quality Advisory Board

Oliver Hesse

VP & Head of Biotech Data Science & Digitalization, Bayer Pharmaceuticals

Oliver Hesse is the current VP & Head of Biotech Data Science & Digitalization for Bayer, based in Berkeley, California. He has a degree in Biotechnology from TU Berlin and started his career in a Biotech start-up in Germany before joining Bayer in 2008 to work on automation, digitalization, and the application of data science in the biopharmaceutical industry.

John Maguire

Director of Manufacturing Sciences, Sanofi mRNA Center of Excellence

With over 18 years of process engineering experience, John is an expert in the application of process engineering and operational technology in support of the production of life science therapeutics. His work includes plant capability analysis, functional specification development, and the start-up of drug substance manufacturing facilities in Ireland and the United States.

Chris Kopinski

Business Development Executive, Life Sciences and Healthcare at AWS

As a Business Development Executive at Amazon Web Services, Chris leads teams focused on tackling customer problems through digital transformation. This experience includes leading business process intelligence and data science programs within the global technology organizations and improving outcomes through data-driven development practices.

Tim Adkins

Digital Life Science Operations, ZÆTHER

Tim Adkins is a Director of Digital Life Sciences Operations at ZÆTHER, serving the life science industry by assisting companies reach their desired business outcomes through digital IT/OT solutions. He has 30 years of industry experience as an IT/OT leader in global operational improvements and support, manufacturing system design, and implementation programs.

Blake Hotz

Manufacturing Sciences Data Manager, Sanofi

At Sanofi’s mRNA Center of Excellence, Blake Hotz focuses on developing data ingestion and cleaning workflows using digital tools. He has over 5 years of experience in biotech and holds degrees in Chemical Engineering (B.S.) and Biomedical Engineering (M.S.) from Tufts University.

Anthony DeBiase

Offering Manager, Rockwell Automation

Anthony has over 14 years of experience in the life science industry focusing on process development, operational technology (OT) implementation, technology transfer, CMC and cGMP manufacturing in biologics, cell therapies, and regenerative medicine.

Andy Zheng

Data Solution Architect, ZÆTHER

Andy Zheng is a Data Solution Architect at ZÆTHER who strives to grow and develop cutting-edge solutions in industrial automation and life science. His years of experience within the software automation field focused on bringing innovative solutions to customers which improve process efficiency.

Sue Plant

Phorum Director, Regulatory CMC, Biophorum

Sue Plant is the Phorum Director of Regulatory CMC at BioPhorum, a leading network of biopharmaceutical organizations that aims to connect, collaborate, and accelerate innovation. With over 20 years of experience in life sciences, regulatory, and technology, she focuses on improving access to medicines through innovation in the regulatory ecosystem.

Yash Sabharwal​

President & CEO, QbDVision

Yash Sabharwal is an accomplished inventor, entrepreneur, and executive specializing in the funding and growth of early-stage technology companies focused on life science applications. He has started 3 companies and successfully exited his last two, bringing a wealth of strategic and tactical experience to the team.

Joschka Buyel

Process & Knowledge Management Scientist, Bayer Pharmaceuticals | Ph.D., Drug Science

Joschka is responsible for the rollout and integration of QbDVision at Bayer Pharmaceuticals. He previously worked on various late-stage projects as a Quality-by-Design Expert for Product & Process Characterization, Process Validation, and Transfers. Joschka has a Ph.D. in Drug Sciences from Bonn University and a M.S. and B.S. in Molecular and Applied Biotechnology from the RWTH University.

Luke Guerrero

COO, QbDVision

A veteran technologist and company leader with a global CV, Luke currently oversees the core business operations across QbDVision and its teams. Before joining QbDVision, he developed, grew, and led key practices for international agency Brand Networks, and spent six years deploying technology and business strategies for PricewaterhouseCoopers’ CIO Advisory consulting unit.

Gloria Gadea Lopez

Head of Global Consultancy, Business Platforms | Ph.D., Biosystems Engineering

Gloria Gadea-Lopez is the Head of Global Consultancy at Business Platforms. Using her prior extensive experience in the biopharmaceutical industry, she supports companies in developing strategies and delivering digital systems for successful operations. She holds degrees in Chemical Engineering, Food Science (M.S.), and Biosystems Engineering (Ph.D.)

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