Artificial Intelligence (AI) becomes increasingly important to the GxP-regulated areas of the pharmaceutical industry, while the validation of these systems remains uncertain. The classical method of selecting a GAMP category to identify the appropriate computerized system validation (CSV) approach can only be applied to validate the AI infrastructure. However, it does not provide guidance for validating a software system applying trained AI-algorithms. We developed a maturity model builds the missing foundation for an AI validation concept.

Agile project management and GMP compliant implementation of commissioning and qualification activities (C&Q) appear to be incompatible. While in a SCRUM process the requirements are continuously developed in close cooperation between cross-functional teams, in a traditional engineering approach, the URS is the first document to be developed, released and thus “frozen”. In SCRUM the implementation and testing takes place in iterative sprints - the sequence for C&Q described in GMP guidelines looks more like a linear waterfall model. Integrated Commissioning and Qualification (iC&Q) is an approach to achieve lean processes and save time, as commissioning can be fully and agilely integrated into qualification activities. By using an risk based and automated traceability-matrix over the project life cycle, changes concerning user requirements as well as C&Q testing can be handled in a more agile way – without losing GMP compliance. In this presentation, the possibilities and advantages of an risk based and automated traceability-matrix is shown with examples out of several EPCM projects. • iC&Q – speed up your engineering projects • Traceability-matrix right from the beginning – the basis for a agile iC&Q strategy • How to set up a risk-based life cycle traceability-matrix • Paperless iC&Q via automated traceability-matrix

Environmental impacts of medicines arise throughout their life cycle from development to production, consumption, and disposal. Residues of active pharmaceutical ingredients (APIs) have effects on living organisms in the environment and can ultimately affect the nature’s biodiversity. Water and energy sources and consumption during manufacturing, the type and amount of packaging materials used, as well as the global supply chains, all contribute to the environmental footprint of the medicines via CO2 emissions and/or by consumption of natural resources. To tackle the multifaceted environmental impacts of pharmaceuticals, the sustainability gaps and solutions need to be addressed in a holistic way. The SUDDEN project, short for Sustainable Drug Discovery and Development with End-of-Life Yield, was launched in 2018 as a multidisciplinary research and interaction effort to seek for new solutions to better management of environmental hazards of medicines on both molecular and product levels, and to promote environmentally sound policies that could support the rational use of medicines and sustainability of the health care sector. The SUDDEN consortium combines researchers from six Finland-based research organizations: University of Helsinki, University of Eastern Finland, LUT University, Aalto University, Finnish Environment Institute SYKE and Demos Helsinki with expertise in drug discovery, pharmacoeconomics, international environmental law and risk assessment, water purification technology, metal and plastic recycling and transformation research. To promote sustainable drug discovery and development enabling the design of pharmaceuticals intrinsically less harmful for the environment in the future, researchers in SUDDEN are developing computational tools to predict the environmental fate of pharmaceuticals as well as new green chemistry methods to promote greener manufacturing. A range of in vitro effects models are also being developed for assessment of bioaccumulation risk in fish. Altogether these tools are foreseen to facilitate cost efficient prediction of the environmental fate of pharmaceuticals in early phases of preclinical drug development and foster the use of non-animal assays for environmental risk assessment purposes. The efficiencies of different treatment technologies are also being investigated to increase our understanding of the persistence/elimination of pharmaceuticals necessary to ensure safe recycling of treated wastewater and/or the sewage sludge for agricultural purposes. Pharmaceutical packaging also has environmental impacts as some of the materials used contain e.g. hazardous plastics (e.g., PVC) or recyclable metals (e.g. aluminum). Research in SUDDEN focuses on developing methods for the processing of blister waste that could facilitate sustainable aluminum recycling. Safe recycling of plastics used in the pharmaceutical primary packages is also evaluated. To tackle the environmental challenges along the life cycle, environmentally sound decision-making is needed on all levels, from individual actions to policymaking. The attitudes of drug consumers toward environmental actions and their willingness to pay for more environmentally sound medicines are thus in the scope of the SUDDEN project, along with adaptation of environmental criteria in public procurement of medicines and evaluation of the legal framework governing global drug production chains. The overall aim of SUDDEN is to identify likewise tangible incentives for pharmaceutical industry and policies reducing the environmental impact of medicines across their life cycle. As the coordinator of the SUDDEN project, the Faculty of Pharmacy, University of Helsinki, is parallelly coordinating a curricula reform in higher education in pharmacy, with the aim of integrating environmental aspects in the professional development programs of future pharmacists, including establishment of professorship dedicated to sustainable pharmacy.

ATMP (Advanced Therapy Medicinal Products) facilities are different to the more conventional pharmaceutical facilities, often requiring heightened segregation whilst complying to Annex 1. Many organisations are evaluating how different modalities may be combined within the same facility having acquired a building, or having constructed an agnostic building. Accommodating multiple modalities in the same facility is therefore becoming an increasingly important requirement and not least during the COVID-19 pandemic when rapidly developing and launching new vaccines. The presentation describes a basic framework and methodology that may be used when evaluating different types of modalities and how they may be accommodated in a new or existing facility. A case study is used to demonstrate how the approach may be applied to an existing facility as follows: 1) The development of guiding principles used to determine when and how multiple modalities may be accommodated in the same facility. 2) The development of a risk profile to determine how best to accommodate the different modalities based on any facility constraints that may exist. 3) Determining when separate facilities are required based on clear guidance within the regulations and any important boundaries that may exist. The guiding principles and risk profile are developed with reference to the applicable regulations, including Annex 1, when determining which modalities may be accommodated in the same facility.

The Quality Management Future is digital, user-friendly, precise and intuitively easy-to-understand. It is accessible from everywhere and provides the “right information at the right time at the right place” in a customized attractive format, as text, voice, or picture/video. The digital transformation is progressing the in the LifeScience Industry. The value of data as an asset to competitive imperative has been understood. Interoperability of data is one of the key requirements of digitalization likewise for a digital Quality management system. What does this mean for a Quality management if quality requirements will be managed as defined modular information unit, preferably as single source of truth, seamlessly integrated into digital operations? This presentation will illuminate the various aspects of Quality 4.0 for operators, quality leaders, regulators, and how to go practically go through such a major transformation, and how could the application of digital technologies themselves like Natural Language Processing will facilitate the extract and structuring of data.

ISPE published the 2nd edition of the Volume 6 Baseline Guideline on Biopharmaceutical Manufacturing Facilities in 2013. This Baseline Guideline introduced a tangible concept of modern biopharma facilities that are based on closed processing. The concept has revolutionized the strategies used when designing biological API facilities. This presentation provides an introduction to the new Process Closure Playbook currently being drafted by a specialized BioPhorum group. The presentation also offers a definition of what is Grade D and what is CNC space used almost exclusively in facilities based on closed bioprocessing.

Circular Economy Action Plan by EC has identified up to 80% of products environmental impacts are determined at the design phase, which highlights the importance of embedding circularity in pharmaceutical research and development. Sustainability by Design (SbD) is a program that integrates sustainability in the product development processes and uses life cycle assessment data and eco-design principles to inform design choices that minimize environmental impact of products including reduced carbon footprint, reduced use of resources, pollution prevention, controls for human health and environmental impacts, and improved circularity potential.

The scope of Annex 1 states that the principles and guidance within it can be applied to other non sterile products, such as low bioburden biologic intermediates. However, this scope wording has been interpreted in multiple ways by drug manufactures, for example some companies think ‘you must apply all of it’ whilst others interpret it as ‘you can apply some of it’. The BioPhorum industry collaboration has written an ‘interpretation’ paper, explaining how some of the excellent principles and guidance within Annex 1 can successfully be applied to the low bioburden Drug Substance world to improve product quality and patient safety. It also discusses the key differences between how they would be applied to sterile Drug Product manufacture. The presentation will outline those key principles, such as use of BSCs, Filter Integrity Testing, and the audience will have a better understanding of how best to utilise the Annex 1 guidance where it can be applied to low bioburden biologic intermediates It will discuss how key principles within annex 1 can successfully be applied to manufacture of low bioburden biologic intermediates to improve product quality and patient safety.

A lot has happened in the last two years, including: • EMA Notice to sponsors dated April 2020 (EMA/INS/GCP/467532/2019) • EMA GCP Q&A Good Clinical Practice (Question 8/9) in 2021 • EMA IWG Draft guidance dated 10 June 2021 (EMA/226170/2021) Additionally, the E6(R3) EWG is currently working on the revision of the E6(R2) Guideline “Good Clinical Practice” (GCP) and the COVID Pandemic has had a significant impact on GCP processes by requiring more remote and decentralized solutions for patients, CROs and sponsors. Therefore, there is a need to address what has already been defined and published by the regulators as well as to look at the upcoming changes pertaining to the quality of GCP systems. The GAMP Good Practice Guide “Enabling Innovation” of 2021 and the GAMP Good Practice Guide “Validation and Compliance of Computerized GCP Systems and Data” of 2017 provide up-to-date guidance to efficiently create valuable validation documentation to meet current and future GCP expectations, including data integrity, critical thinking, state-of-the-art technology and project and validation methodology.

This presentation will provide an overview of the Construction, Commissioning & Qualification (C&Q) and Start Up phases of the BioCork2 Project at Janssen Sciences Ireland. It will provide insight into some key project challenges and their resolutions producing a world class safe project, on time and on budget.