The Paul-Ehrlich-Institut has been able to provide regulatory and experimental research support to help fight the pandemic. Our activity focus included (i) scientific advice on COVID-19 vaccine development and clinical trial authorization, benefit-risk assessment in the CHMP at the European Medicines Agency and governmental batch release testing, (ii) national authorization of neutralizing monoclonal antibodies for the treatment of infected persons at risk of severe COVID-19 disease course, (iii) experimental investigation of SARS-CoV-2 rapid antigen test performance and (iv) pharmacovigilance incldg. reports to the public. The COVID-19 pandemic has brought to light several lessons learned from vaccine and biomedicine development. One key factor has been the unexpectedly high efficacy of the COVID-19 vaccines, which is generally attributed to effective antigen design. Higher efficacy of COVID-19 vaccines has been linked to higher serum titers of CoV-2 neutralizing antibodies, as for example demonstrated by the 4th Wuhan mRNA vaccination (2nd booster), which increases anti-Omicron antibody titers to the level detected early after the 3rd mRNA vaccination (1st booster). In response to the pandemic, there has been a push for greater regulatory flexibility to rapidly adapt drug legislation and support the development of vaccines and biomedicines. Neutralizing antibodies were thus made available for treatment of infected persons at risk of severe COVID-19 by national authorization. Comparative experimental evaluations of the sensitivity of marketed SARS-CoV-2 rapid antigen tests have been conducted by the Paul-Ehrlich-Institut to enhance pandemic preparedness. Periodical Safety Reports on COVID-19 vaccine pharmacovigilance were made available to the public and helped to enhance vaccine confidence and rational discussions about vaccine safety. The newly inaugurated Center for Pandemic Vaccines and Therapeutics (ZEPAI) at the Paul-Ehrlich-Institut (PEI), with its vision and mission to provide expertise in pandemic preparedness regarding pandemic vaccines and antivirals, will support pandemic preparedness on the basis of lessons learned from the SARS-CoV-2 pandemic. Research activities at PEI include non-clinical research on model vaccines and vaccine-induced immune responses. The regulatory support provided by PEI to vaccine and biomedicine developers has been instrumental in the successful response to the pandemic.

The digital transformation of the chemical industry is picking up speed. Hardly any company can avoid digitizing its processes, but the extent and speed of digitization projects vary widely. Evonik wants to be a pioneer and has set out on the road to becoming a "Data Driven Company”. The aim is to understand data as a corporate asset and use it as a lever for growth and optimization of its own business. At the end of 2021, the Essen-based Group received an award from the Competence Center Corporate Data Quality (CDQ) for its exemplary data management initiative. Gunnar Weider, Head of IT Strategy, Processes & Architecture explains the development, the status of the initiative and further plans.

 DiaSorin, the Diagnostic Specialist in the IVD Medical Device market, supports the entrepreneurial spirit through DiaSorin Values: - Operational Excellence: lean journey, brief history, methodology, tools and main results (from the impact assessment to the final verification) - Digital Transformation: enabling digitalization and integration among machines and systems; harmonization process of a multi-Site platform.

The experience of the COVID pandemic showed that a reinforced framework to strengthen structures and mechanisms can ensure better EU level protection, prevention, preparedness and response in crisis situations. Coordination and cooperation between Member States and Third Country Authorities is crucial. EMA’s activities to tackle shortages, scientific review and coordination of clinical trials, as well as alternative tools for the GMP verification of facilities  provided us  with valuable lessons. Europe’s regulatory response to the pandemic is a success story. How can we build on this to prepare and prevent future crises?

The Pharma 4.0™ 6th edition Survey (and its latest deep dive) aim to share the ISPE Pharma 4.0 update on maturity, enabling technology adoption, the benefits, challenges and general sentiment around 4.0 from Life Science protagonists. The deep dive of the 6th edition presents an extended analysis into planned projects by the industry in the two years and a few additional intriguing correlations and trends when analyzing current versus previous editions results together with demographics.

As COVID-19 started to spread across the world, Johnson & Johnson (J&J) initiated global efforts to develop a potential vaccine against the coronavirus. Soon, successful vaccine candidates were developed. To provide the world with COVID-19 vaccines, J&J needed to increase production capacity. Janssen Biologics, a production facility of biotherapeutics and vaccines in Leiden and part of J&J, was identified to potentially have this capacity. To become one of the main suppliers of J&J’s COVID-19 vaccine, the Vaccines Facility (VF) needed to be expanded at a fast pace. A project team was installed to build a new, 25,000-square-foot sterile manufacturing facility adjacent to the existing VF. The plans available at the time aimed to expand the facility in five to seven years. However, the current health crisis drove Janssen to develop an enhanced, fast track project plan. The plan aimed for building a brand-new facility and getting it fully operational in twelve months. These timelines were challenging. But the team did it all within 1 year and 1 day. Hans Weverling, program lead, will share their key learnings. These learnings include the importance of internal expertise of a dedicated team and an agile mindset, in combination with good collaboration with trusted external partners to bring the best solutions, and efficient cooperation with (local) authorities to pursue all regulatory steps in record time.

This presentation will give an overview how a software solution could simplify and digitalize the batch release process. Concrete streamlining processes for faster and more accurate batch release. How to cover the whole organization? What are the supported release scenarios? Quality managers and qualified persons have trouble with three points: Firstly, there are of course a lack of controls, which can lead to recalls. The second challenge is closely related to this: The high workload forces those responsible to focus entirely on collecting and analyzing data. In many large companies, quality managers must go through a good dozen systems and paper files before approving batches. The third weak point is the increasingly demanding and therefore more expensive compliance requirements. Two international pharmaceutical giants have co-innovated with SAP to develop a batch release software solution to establish a next practice Pharma 4.0 for the pharmaceutical industry. The solution is available since July 2022. Hear about experiences through a customer implementation project.

GAMP® 5: A Risk-Based Approach to Compliant GxP Computerized Systems (Second Edition) maintains the principles and framework of the first edition and updates their application to reflect the realities of the modern world, including the increased importance of service providers, evolving approaches to software development, and ever-increasing use of software tools and automation. The presentation covers the drivers and objectives for change as well as giving an overview of new and updated material.

The ISPE SIG Pharma 4.0 worked since 2017 on concepts around the Digital Transformation process, the implementation methodologies & roadmap, and a Pharma 4.0 Operating Model for pharma organizations. The Pharma 4.0 Baseline Guide will summarize and describe the structured approach for a Digital Transformational Process, including practical Use Cases. The presentation will summarize the key concepts, challenges, current status and learnings from the creation of the Pharma 4.0 Baseline Guide.

GAMP 5 Second Edition provides more than just an update on good practice and facilitating innovative new technologies. It also promotes critical thinking to make validation practices ever more cost effective and efficient. In this presentation learn about the importance of context (seeing the role of the computer system within the broader business process being supported), making better use of supplier activities to reduce duplicated validation effort, and leveraging automated tools alongside the application of science-based risk management. The latest FDA guidance on computer software assurance is also discussed. It all adds up to smarter validation.

This session will present a case study showing how Janssen is using S88 recipes for product development activities, Criticality Analysis, and Technology Transfer. The content will include: - An Overview of ANSI/ISA-88 Standard and its application to Biotechnology processes - How S88 recipes (and associated process ontologies) are applied for data management - The methodology for using S88 recipes in reporting (Criticality Analysis and Technology Transfer documentation) - Future vision of S88 recipe utilization for Digital Technology Transfer.

This presentation will discuss what tasks need to be solved in connection with digitization of workflows in cleanrooms to achieve an appropriate setup. Digital Transformation and Pharma 4.0 in clean rooms are a strong trend, that is driven by a need for IT applications all the way to the operators in cleanrooms to collect, process and share data. How can the IT hardware help solve the tasks in the clean rooms while being in compliance with the regulatory requirements and at the same time let IT operation gets the necessary stability, flexibility and mobility? How to create a good ergonomic working environment for the operators so that productivity is kept high? Hear about experiences through a customer case.

This session will concentrate on implementing CSA that will provide guidance and resources to support it. The content will focus on understanding CSV and CSA in the context of current regulations and GAMP, the implications, and opportunities of CSA draft guidance on 21 CFR Part 11 and gain the confidence to transition from CSV to CSA and achieve transformative value vs. incremental value.

St.Gallen works on the US FDA funded project “RiskSurve” which has just been extended to a second year. The project aims at developing a comprehensive site quality assessment based on machine learning models. Participants will understand how regulators approach site risk assessments and how to use data for risk and non-risk related decision-making.

Brief introduction to Building Information Modelling (BIM), with short interventions by each panelist.

This presentation will show that the pharmaceutical industry is operating in a highly regulated environment. It will elaborate on opportunities for a holistic control of distribution, which will need a multi-stakeholder approach in the supply chain. Doing so, it will be explaining the risks limiting availability and potential drivers of shortages based on a diversity of hazards. Opportunities are presented how every stakeholder can reduce the risk for shortages. The bases for this is the need for an understanding for the role and responsibilities. The presentation concludes with examples on drug shortage prevention strategies and includes best practices.

Technological capabilities and regulatory requirements around AI are constantly evolving. The GAMP 5 2nd Edition acknowledges this by its dedicated, new appendix D11 - Artificial Intelligence and Machine Learning. As contributors to this version of the GAMP 5, we will provide an overview on those new concepts in this talk, while we will go one step further, as we will augment this guidance by our results from the GAMP D/A/CH special interest group, summarizing the essence of our article series in the ISPE Pharmaceutical Engineering on the AI maturity model, the AI governance framework and further operational blueprints where we elaborate on the idea of Good Machine Learning Practices in regulated areas.

One of the principal tenets of Pharma 4.0 states that “Digitalization will open new horizons to achieve new levels of connectivity, transparency, agility and productivity through the application of faster and more accurate information for decision-making.” The main question is: how to start the transition from Pharma 3.0 towards Pharma 4.0? We start with well-known process mapping, which is called process-centered process mapping, followed by the concept of data-oriented process mapping, which will lead to full understanding of your data flow, ready for the digital world. The data-oriented process maps, are placed in the RAMI architecture, specifically designed for the industry 4.0 environment, resulting in an analysis of the current situation. The analysis provides input for the working plan describing how to reach the desired data integrated level, needed for the transformation towards Pharma 4.0. The presentation provides insights into process maps, data flows as well as system integration in the pharmaceutical industry with a focus on data integrity issues using the context of the RAMI model. In addition,  an emphasis is placed on the practical aspect of how to access the necessary data, and what this means from an engineering and system integration perspective.

Most customised software is created nowadays using Agile principles. However, validation of software is still used in a waterfall approach using the famous V-model of GAMP. Innovation in validation, as defined in the GAMP Good Practice Guide, "Enabling Innovations", and GAMP 5 2nd edition, shows that an Agile type of validation can bring a lot of improvements for validating GAMP software category systems 4 (configurable) and 5 (customised). This presentation will show a clear example of an Agile validation approach using tools resulting in a solid, but flexible validation, where paper is no longer required. A tool takes care of full traceability throughout the whole life cycle of the system.

Did you ever question: •What is BIM? Building Information Modeling or Building Information Management? •What are the real benefits of BIM? Better quality, lower cost and shorter project times?•Where is BIM providing today value or coming short? Design and Planning, Construction, Maintenance? •Do we need all BIM functionalities or cherry picking is a better approach? •What is the cost of BIM? The tools or the human resources?•When does BIM brings value for the money?•Are the available digital tools today matured? Is digital obsolescent a future challenge?  •Does BIM tools require a new (digital) mind set to be fully successful? How can we educate our future expects?•How we keep our BIM system up to date? Do we need a new BIM Department?•Does BIM require a new project organization? Without silos and fully open? Is it possible?•Is BIM ready to fully support Maintenance? •Should we integrate specific needs of the Pharma industry into BIM? •How can BIM help to streamline Qualification and Validation?•How far in time are IoT and a true Digital Twin in BIM? If you have such questions or others, you are very welcome to join our panel discussion! We have four panelists with strong experience in BIM for project execution and beyond: Peter Carter Luke from Novo Nordisk and Aurélien Paul Gernier from Takeda will provide the end user perspective and expectation for BIM, while David O’Brien from Exyte and Jochen Schumacher from Carpus & Partner will share their project execution experience with BIM.

As legacy sites are merged and acquired into corporate manufacturing plant networks, equipment assets may not be connected to manufacturing infrastructure. We ask the following questions; From an automation context do these assets need to be fully replaced or upgraded? Can I utilize the existing legacy equipment assets in a digital transformation program? A new greenfield plant is proposed - how can you establish the foundations for a Smart factory to release potential from plant floor assets and enable user to execute their jobs with real-time information and analysis. Unified Name Space deployment, a IND4 concept, can be that foundation to enable potential and digital transformation.

In the complexity of pharmaceutical organization, it is particularly critical to assess cyber security posture without external consultancy support. The new Checklist for self-assessment developed by ISPE / GAMP Italian Affiliate is an interesting initiative to simplify the procedure. Through the Checklist it is possible to evaluate the whole organization (using common guidelines, requirements, and controls originated from ISO 27001). Furthermore, the tool has created having in mind the manufacturing systems (through IEC 62443 controls) and the new convergence challenges between IT and OT. Also, through the experience of a leading pharmaceutical company, we proved the alignment of outcomes with the more “prestigious” cyber security professional assessments.

The Pharma 4.0 Future Desired State is to be data-driven & capable of holistic process control with information available at the right time with content, quality, security and traceability. This Digital Maturity ensures patient safety & intended product performance. To get to this state, Pharma 4.0 defines enabling capabilities for systems in general, and connectivity in particular, to achieve vendor-agnostic “Plug and Produce”. This presentation covers the status and progress made in the Pharma 4.0 Plug & Produce workgroup on architecture, connectivity standards, current proof of concept projects and insights from Hackathons, including realized concept of a simplified vendor-agnostic integration of qualified laboratory devices with the Asset Administration Shell as the Digital Twin. Links to relevant ISPE publications, including new Pharma 4.0 concept papers, are provided. Bridging strategies for brown-field equipment and collaborations with other industry working groups e.g., NAMUR, BioPhorum Group, VdMA, SiLA, LADS are touched on as well.

There are an increasing number of highly potent compounds handled within the pharmaceutical industry, a trend that has continued for over 20 years to the point where most modern products require some degree of containment or other exposure control to maintain safety. The ISPE Good Practice Guide: Containment for Potent Compounds covers all aspects of pharmaceutical containment including background to safe working levels and the mechanisms of exposure and how such exposure can be controlled. There are chapters on typically applied approaches used in containing exposure for commonly applied process systems across all elements of pharmaceutical development and manufacturing. Developed by a multinational team of experts consisting of engineers, toxicologists, hygienists, and analysts from major pharmaceutical companies and suppliers, this Guide aims to consolidate this widely dispersed knowledge base into one document. It describes and discusses the containment methodologies, processes, and technologies commonly used in the pharmaceutical industry when handling potent compounds. The Guide contains numerous photos on the wide range of technologies presented, such as isolators, process interfaces and transfer ports, air locks, filtration systems, containment performance assessments, and cleaning/waste treatment. Additional topics include GMP aspects, containment systems’ lifecycle, unplanned emission/spillage recovery procedures, and the development of a containment strategy.

GAMP 5 Second Edition and Computer Software Assurance (CSA) have been in the spotlight for the past year, but how is this affecting day-to-day business, and how can we benefit from the value it promises? Join us for an interactive workshop on GAMP 5 and CSA, where we will discuss real-world examples and benefit from direct interaction with practitioners from Europe and the US, our speakers, and supporters from the FICSA Team that developed the CSA guidance.

Pharma 4.0 is booming! After the long-awaited acceptance of 4.0 technology to the pharmaceutical industry, we are seeing a wide-sweeping, rapid adoption of new technology and tools. Companies are exploring Pharma 4.0 in nearly every project stage and operational process. Over just a few years, we’ve seen major changes to business as usual, project execution, and expectations. The hunger for our digital transformation continues to grow and the boundaries continue to be pushed.  So, where are we now? And where are we going? Yvonne Duckworth, Fellow of Digital Technology, will bring you up to speed on the current state of Pharma 4.0 in the industry. Her presentation leverages industry data on Pharma 4.0 adoption rates and future projections, in addition to real-world examples of digitalization in facility design and construction through: -Augmented reality and virtual reality -Connectivity and network infrastructure -Predictive analytics and smart sensors -Automated material handling and digital control towers -Energy management and smart facilities

The PharmaLedger Association (PLA) is a not-for-profit association based in Switzerland with the purpose to enable and foster a Digital Trust Ecosystem (DTE) in healthcare through a standardized and trusted open-source platform. PLA was formed fin 2022 to continue the work of the PharmaLedger project, a 3-year project funded by the European Commission and the pharmaceutical industry aimed at proving the value of blockchain solutions. Further information is available at https://pharmaledger.org/. The immediate (2023) goal is to launch a blockchain-enabled product, the electronic Product Information (ePI) solution, otherwise known as eLeaflet or ePIL. This would enable patients to freely access the latest approved version of a Product Information through a common industry app. It would also serve as a platform for additional supply chain use cases such as Detecting Falsified Medicines and Finished Goods Traceability. The Association also intends to pursue use cases in the Clinical domain such as Clinical Trial Recruitment and electronic Informed Consent.

Pharma CMC development is facing multiple challenges from the increasing number of projects and diversity of modalities to higher agility, cost efficiency, data integrity & accelerated development timelines. The data generated during drug development is only partially leveraged to further improve our processes or use it for predictive modeling. We are convinced that substantial value will be delivered through the implementation of a comprehensive data-driven digital transformation program with lab workflows digitization, a strong data governance/architecture and leveraging data through advanced analytics.

In the recent years, Johnson & Johnson (JnJ) has changed and updated their validation approach to fully embrace a digital and risk-based approach to validation. As part of an ongoing project, together with Deloitte, these principles are fully embedded and included during the implementation of a new SAP S/4 HANA platform to further support the business of JnJ. During the presentation we will present JnJ's approach to risk based validation followed by a more in depth look at how these principles are used by Deloitte together with JnJ during the SAP S/4 HANA platform and how this ties back in into the CSA principles as documented in the recent draft guidance from FDA by fully utilizing tools (agile development tools, testing tools, dedicated validation tools) to make the shift from document based validation to record based validation.

The industry started to apply the principles of Continuous Manufacturing (CM) of Oral Solid Dosage (OSD) forms more extensively in the mid-2000s. OSD-CM has now advanced to approved commercial manufacture of new and legacy drug products around the globe. Industry and regulatory bodies have embraced CM technologies, which have been proven to lead to decreased costs and time in product development as well as robust assurance of final product quality.  As more companies integrate CM into their development and commercial operations the demand for more flexible, modular and robust systems is needed. Additionally more harmonization and guidance to owners and regulators for achieving this had been demanded.  In 2017 an international team, comprised of end user pharmaceutical companies, engineering firms, equipment vendors, and academics, set out to establish equipment requirements, identify opportunities for harmonization and flexible integration, and suggest enhancements to current equipment/processes. Their work culminated in the publication of the ISPE CM of OSD Forms - Good Practice Guide (GPG), released in 2022. This Guide provides a resource for owner companies and engineers as they design and integrate CM systems into their operations, highlighting best practices and opportunities for enhancement. This session will provide an Engineers and Owners perspective of how to best use this new guidance today and in the future. Dave DiProspero will discuss, from an engineer’s perspective, how the GPG was developed and how its use can help design firms understand and meet their clients rigorous design requirements.  Bart Nitert will discuss, from an owner’s perspective, the key important elements from the guide to pay close attention to and the challenges Janssen have faced when merging equipment from different vendors into a single continuous manufacturing and how these challenges were resolved.

In the initiation phase of complex construction projects, developers need an early access to a reliable database. Such as gross floor area, usable net area, resulting workspaces, costs, etc. In conventional planning processes, the data basis only successively builds up. Our methodology combines parametric design with modular planning. We weave two methods that are based on a fundamentally digital conceived design logic. Building up on each other they develop their full potential. It emerges an early on reliable basis that enables for a profound decision on the further development of the project.

The Life Science Industry is under massive change, major investments into new products and digitalisation are progressing with high speed. Despite the need for organizational development has been recognized the focus is still on technologies, systems, data, and processes. Up-scaling skills, hiring data scientist are good but not sufficient. This presentation will •Illustrate the need for a holistic organizational development during the digital maturity as skill, behaviors, leadership, and organizational set-up will fundamentally change. •Demonstrate exemplary how typical roles in Quality and operations will change from now toward a data-driven environment. •Explain potential options for going through the transformation.

The Covid pandemic taught the industry that the paradigm of typical project durations could be shattered. Good Engineering Practices application is absolutely crucial as design, procurement and verification activities are conducted throughout fast-tracked projects. Stakeholder responsibilities, deliverables and critical requirements must be clearly understood by designers, construction managers, operating companies, suppliers, logistics, purchasing, and CQV very early in the conception of the project. Well understood, efficient decision processes and communication channels must be in place to respond to and manage the constant flow of information and “on the fly” decisions that must be made to support fast tracked projects.The GEP good practice guide was revised in 2022 and identifies the best practices and provides practical examples to assure the success of projects from conceptualization though the C&Q phase. The session will consist of two primary sections. Section 1 is an educational focused presentation that describes the concepts of the guide, the principles and drivers behind its revision and the practical application of the guide for customers’ use. The second session will be a case study featuring real world project examples and lessons learned.

In this presentation, Stephen Hill (COO) from Lyell and Judith Koliwer (Principal Consultant Cell and Gene Therapy) from Körber Pharma Software will provide insights into their partnership, lessons learned as well as a benefit analysis of a digital manufacturing facility implementation. The cell and gene therapy industry is currently in a pivotal phase, with significant increases in the number of companies and clinical trials, as observed in the last years and expected to come in the near future. The availability and analysis of digital data as well as increased efficiency during process execution and review processes are considered key drivers to support the industry during this phase. Simultaneously, very little standardization of processes and procedures is available for the respective companies to build upon for their digital journey. This presentation aims to provide a model approach for a patient’s journey through an integrated digital ecosystem from collection to treatment as well as first-hand experience and learnings from one of the first fully digital cell and gene therapy companies.

In recent decades, the pharmaceutical sector has emerged as a pioneer of integrated production. Currently, the world is advancing towards a more secure and integrated industrial revolution 4.0, aided by technologies such as the Internet of Things (IoT), Internet of Services (IoS), and cloud computing. These services are enablers or what we term smart manufacturing domains or best practices for improving productivity and speeding up the manufacturing process. However, there are several hurdles to smart manufacturing or industry 4.0, such as: - Data security - Traceability, and - The trust that current industrial complexes lack. In this case, blockchain becomes a critical component of smart manufacturing. As the riddle of blockchain has captured the whole globe, it has begun to present itself as a superior alternative to the existing integration system and security. This is a significant step towards the future of smart, automated, and self-driving production. However, there are several problems and possibilities in smart manufacturing.

During the worst weeks of the COVID-19, the patients, the Health Authorities and the public in general discovered the ugly truth: some of the most widely used drugs, such as paracetamol (a well-known painkiller), but also atracurium (a neuromuscular blocking drug required to facilitate endotracheal intubation) were no longer being produced in Europe. This effectively meant Europeans were relying on supplies from other countries, mainly located in South-East Asia. This realization prompted many promises by the Health Authorities on building a “European Strategic Healthcare Autonomy”. Unfortunately promises have not been fulfilled, the war in Ukraine, inflation, soaring energy costs… have contributed to shift focus and little progress has been made in re-shoring or bringing back API or finished medicines production to Europe. Is Europe still an attractive location for the pharma industry? Which measures could alleviate the dependency we have from other continents?

Since the original publication date of GAMP 5 in 2008, the application and use of technology has advanced substantially. GAMP 5 Principles and Framework remain applicable and relevant today. This session will be a Q&A for delegates to ask questions of Regulators, and presenters from the GAMP track to focus on gaining an oversight of how GAMP 5 Second Edition provides practical updates of the application of GAMP 5 principles and framework, including Critical Thinking, Artificial Intelligence (AI), Computer Software Assurance (CSA), etc., to define appropriate approaches and exploring the relationship between the GAMP validation framework, data integrity and current regulatory thinking e.g., FDA CDRH Case for Quality program, etc.

This presentation will focus on the following areas, providing some insights when executing one of the largest Bristol Myers Squibb CAR-T Manufacturing Facility in the US during COVID: - Program Execution Challenges: Forced Virtual Environment, Strategies to ensure business, continuity, Build/Develop infrastructure to support remote working, Permitting, Supply Chain, extended lead time across the world - Lessons Learned: New Best Practices have to be adapted to address the changes, New way of project execution, Cons and Pros, Future project execution, Hybrid vs. Other? - Astonishing Results: Keeping up with an aggressive project timeline, Speed of delivery less than 24 months from design kick off to beneficial use, Prioritize deliverables and mitigate risks, Success factors