Healthcare Equality - Technology and Innovation Applied in Service of Low- and Middle-Income Countries

The pandemic helped to highlight the inequitable access to vaccines that exists for patients in underserved communities worldwide.  Beyond vaccines, access to biopharmaceuticals including products like monoclonal antibodies and cell and gene therapies is also very limited.  As an industry, we can drive innovation, advanced manufacturing and commercial strategies in service of underserved communities.  Low- and Middle-Income Countries (LMICs) face major public health challenges and in most cases, the typical incentives for discovery, development and manufacturing of these life-saving products are not in place for traditional pharmaceutical and biotechnology companies. Unique partnerships and collaboration models between companies, funding bodies, non-profits and international organizations can help tackle the most devastating diseases.

Even with development funding, there are a few key challenges to enable LMIC access to biopharmaceuticals, including lowering cost of goods (COGS) and building capability, capacity and infrastructure for local and regional manufacturing.  There are a number of levers for reducing COGS in biological products to support use in LMICs. We are utilizing several of these in our Gates MRI late stage development programs.  In addition, we hope to engage in capability building with local manufacturers as we identify companies, often in LMICs, to ultimately produce our products for commercial sale.  We should also consider other factors such as policy, funding, market access, uptake and stakeholder acceptance that will help us deliver healthcare solutions to those in greatest need.

From Nanotechnology to mRNA Vaccines: How Overcoming Skepticism Led to New Medical Treatments and Ways to Tackle a Global Health Challenge

Advanced drug delivery systems are having an enormous impact on human health. We start by discussing our early research on developing the first controlled release systems for macromolecules and the isolation of angiogenesis inhibitors and how these led to numerous new therapies. This early research then led to new drug delivery technologies including nanoparticles and nanotechnology that are now being studied for use treating cancer, other illnesses and in vaccine delivery (including the Covid-19 vaccine). Finally, by combining mammalian cells, including stem cells, with synthetic polymers, new approaches for engineering tissues are being developed that may someday help in various diseases. These can also serve as a basis for tissues on a chip which can potentially reduce animal and human testing. Examples in the areas of cartilage, skin, blood vessels, GI tract and heart tissue are discussed.

Towards Individualized Medicine: Embracing Digital Twins and Digital Dependability in Pharma 4.0

A significant shift towards decentralization and modularization is currently unfolding in the field of pharmaceutical manufacturing, starting a new era characterized by increased flexibility and efficiency. This talk seeks to explore the critical role of automated manufacturing, digital twins, and digital reliability, while emphasizing the importance of enhanced interoperability and transparency inherent in Pharma 4.0. Central to this evolution is the adoption of modular processes, where different components undergo independent evaluation and certification, thereby enhancing the overall agility of the manufacturing ecosystem. By leveraging existing technologies such as digital twins, these modular processes are automated, allowing for seamless connectivity between systems and devices. This promotes interoperability and enables the system to dynamically adapt to specific requirements, such as personalized medicine. In addition, digital twins represent a cornerstone in the journey towards enhancing quality assurance in pharmaceutical manufacturing. As virtual replicas of physical processes, they offer manufacturers the ability to proactively simulate behavior, providing insight into both product quality and process effectiveness.

Imagine a future in which fully personalized medicines are manufactured quickly and safely, tailored to individual patient needs while maintaining necessary standards of quality and safety. Achieving this vision requires transparency and accountability especially for digital tools. Moreover, robust documentation of the manufacturing process, along with the strengthening of reliable software systems and the integration of explainable AI, is essential to ensuring regulatory compliance as well as confidence in the products procured.

This keynote explores approaches to realize digital transparency, advocating for automated documentation of data sources and decision-making processes. Utilizing different concepts proposed within the scope of Industry 4.0 systems, including the digital twin and adding concepts for product and patient safety, like “Digital Dependability Identities”. In addition, the discourse includes the integration of continuous engineering and simulation methodologies, highlighting their central role in optimizing manufacturing processes and ensuring product quality. By facilitating the coupling of various tools throughout the development lifecycle, these methodologies foster interactions between design, simulation, and engineering processes, thereby increasing overall efficiency and effectiveness.

In summary, the convergence of distributed manufacturing, digital twins, digital reliability, continuous engineering, simulation, and tool coupling holds the promise of revolutionizing the pharmaceutical industry. By leveraging the insights of these technologies and methodologies, the objective is to improve production, enhance safety, and stimulate innovation. Let's work towards a future where pharmaceutical manufacturing is not just efficient but becomes a model of reliability, transparency, and excellence, thereby advancing the accessibility and efficacy of healthcare on a global scale.

Centralized to Decentralized Manufacturing supporting a global market to avoid supply chain disruption. Beside the manufacturing challenge transfer the process to different location the regulations requirements may also be different. How to overcome decentralized Manufacturing challenges and how this could be support from the industry in dialog with the regulatory agencies.

AI has the potential to significantly impact pharmaceutical manufacturing. AI offers potential benefits to pharmaceutical manufacturers in the form of optimized process design and control, and smart monitoring and maintenance, to drive continuous improvement. In 2021 CDER announced to the public the FRAME (Framework for Regulatory Advanced Manufacturing Evaluation) initiative, which focuses on the policy elements and regulatory framework to enable the regulatory assessment and broader implementation of advanced manufacturing technologies, such as implementation of AI.  This talk will provide information on on-going efforts to implement a cohesive regulatory framework to support AI in drug manufacturing.

In order to address the many environmental challenges we face as a society, companies including biopharma companies have set ambitious sustainability targets for 2030 and beyond.  These targets, including reductions in energy & CO2, water and waste, require us to think differently about our operations in order to move towards a more sustainable model of resource use.  In this session we will discuss the various technologies and strategies that Sanofi is using and exploring to achieve reductions in energy and water use, carbon footprint and material used.

Considering shortages have been tied to quality related concerns, this session will focus on the practice areas highlighted in FDAs Quality Management Maturity prototype which integrate an ICH-based quality maturity framework to support industry's assessment and impact to the overall performance and of their quality maturity. The overall intent of the program is to further develop resilience to shortages which result from quality-based issues. The basis of each practice area which should be considered in developing a framework for assessment will be reviewed to provide a foundation to develop sustainable internal programs. All of the attributes within the protype support the development of a strong quality culture. An ideal quality culture is the ultimate goal for each organizations, the prototype provided by the FDA supports standardizing the process in which industry is able to assess culture and management maturity.

GSK’s EcoDesign Program: Enabling Sustainability Improvements in Biopharmaceutical Manufacturing

GSK has set aggressive corporate environmental sustainability goals to be net zero and net nature positive by 2030.  To achieve the 2030 goals and beyond, GSK needs to incorporate environmentally sustainable design practices in all of its product and process development work.  As further substantiation of this need, in 2014, the European Commission estimated that more than 80% of the environmental impact of a product is determined at the design stage of product’s life.  Accordingly, the GSK “EcoDesign” program, developed over the last two years, includes a new tool called the Product Footprint Calculator Tool (PFCT) that assists drug substance development scientists and product stewards to understand the characteristics across all manufacturing phases which significantly contribute to a product’s environmental footprint. In most cases, the API/drug substance manufacturing phase is the largest portion of a product’s footprint. PFCT is now being applied to the manufacturing processes being developed for both small and large molecules. 

PFCT assessments have been completed for several large molecule assets. Beyond understanding the key attributes of a manufacturing process that significantly impact sustainability, the EcoDesign assessment provides a baseline understanding to build key product lifecycle roadmap improvements that should be considered and addressed prior to committing to commercialization. This presentation will share the results of the product footprint calculations for several GSK Biopharmaceutical manufacturing processes, highlighting where design decisions and process details contribute to differential environmental impacts.

Through the Pathway Chief Quality Officer Team, we have been leading a maturity model development initiative to advance business outcomes through adaptability and agility. Our model is the only model that involves delineation (and scoring) of interdependencies across leadership ability, systems, risk integration and design quality. Our model is linked to industry-available tools to aid companies in advancing from one stage to the next (including the QMS agility model, Good Supply Practices, TPLC metrics, etc.), and includes an advanced virtual assessment involving AI.

Here we will discuss the opportunities and risks in the dynamic regulatory environment focusing on perand polyfluoroalkyl substances (PFAS). Removing certain PFAS from the pharmaceutical industry, where fluoropolymers are primarily used as membranes in fluid and gas filtration processes, would change how pharmaceutical filtration occurs due to their use during drug manufacturing to provide safe and effective therapies to patients. However, there may be opportunities to use existing materials as well as to innovate new materials to satisfy today’s applications in bioprocessing with technologies that could surpass current performance. Minimizing the use of persistent materials can lead to sustainable opportunities, and providing alternative solutions could lead to significantly reducing the environmental footprint for biomanufacturing to improve operational excellence through regulatory insights to enhance industry efforts to ensure reliable quality medicines are available to patients.

Quality Culture in the Pharmaceutical Industry (Case Studies)

The Quality Culture of regulated organisations is becoming increasingly more important. Although no regulations currently describe the expectations for Quality Culture, the regulatory focus is changing from essentially an evaluation of the state of compliance, towards an emphasis on the quality behaviours and mindset evident throughout an organisation. The outcome of poor Quality Culture includes risk to the patient and product, risk to the business, a decrease in trust by the customer and regulators, and uncertainty for quality and production leads. The Quality Department and regulators rely on the information provided to them to determine if a product will meet the specified quality attributes and marketing authorisation requirements. As such, the integrity of the individuals and teams performing the manufacturing and support functions, and the accuracy, integrity and completeness of information is of the utmost importance. This presentation looks at the impact of poor Quality Culture on the safety and integrity of the manufactured product, and how a company can apply strategies to implement an improved Quality Culture and benefit from the promotion and continuation of behavioural change throughout their organisation.

We encounter challenges when setting up quality management for a new business or revamping an existing quality system, such as facility, process, system, and resource management. In planning and due diligence evaluation, most firms take into account the factors mentioned above; however, the quality culture of the company is given the least attention, which determines the level of investment and development strategy of the top management.

The quality culture of some great matrix structured companies is not achieved to acceptable standards, particularly after the acquisition of facilities, which serves as an expansion for their business in various parts of the world. Underestimating the impact of quality culture in the workplace may lead to a failure model or the closure of pharmaceutical manufacturing facilities as a result of a chain of events affecting the management strategies. This presentation summarizes the importance of setting up a strong quality management system to achieve the competitive potential of the company and key fundamentals forgotten by the industry and the relationship between leadership commitment and quality culture, as well as the challenges associated with building a quality maturity model due to quality culture concerns.

This presentation will explore detergent uses in viral-vector and LNP therapeutics by examining the desired properties of industry standard detergents; long-term outcomes and considerations; process innovation by sourcing potential replacements for legacy detergents to achieve safer product and environmental outcomes. Detergent & solvent selections are crucial due to their influence on process and product efficiency and quality. It is important for thorough evaluation of detergents and solvents in the development stages of a product line because process changes after market entry impacts process validation and therefore initial regulatory filings. Detergent and solvent selection should be based around the following criteria: (1) risk of discontinuation as influenced or enforced by local and foreign environmental regulations; (2) potency; (3) risk of residuals and consequential removal procedures, and (4) waste product treatment.

St.Gallen presents results from the US FDA funded project “RiskSurve” which has been concluded last year. The presentation focuses on the role of culture and leadership to establish a sustainable quality management program and support quality and compliance. The results rely on 30 interviews with multiple health authorities, site quality leaders, and corporate quality leaders. The presentation will focus on the role of leadership in shaping a quality culture, related benefits, and expectations from industry and regulators. Especially, the presentation will elaborate on the multiple elements characterizing a good quality culture differentiating between regulator’s expectations and industry’s understanding. While the main outcomes are based on qualitative research we will triangulate the results with quantitative data from St.Gallen’s research. The presentation concludes with an overview on the key takeaways for manufacturers to master their quality culture under the lenses of quality management maturity.

Applying the Biomanufacturing Facilities Baseline Guide: Case Study Examples that Define the Basis of Design

This session will present two case study vignettes where companies used the Baseline Guide concepts to form the basis of design for a new manufacturing asset. The case studies focus on key Guide principles that identify the synergies between process closure, operation efficiency, contamination risk mitigation, and facility optimization. Specific references to the Guide will be provided as part of the interaction with the Audience.

Leadership’s commitment to quality is critical to upholding a strong quality culture. Leaders must ensure that an effective quality management system is in place as well as model the desired behaviors the sustain culture. This presentation will provide examples how quality management system program elements and behaviors go hand-in-hand to support robust quality culture. The presentation will describe how leadership responsibilities must include effective communication and presence as part of the quality management processes such as management review. The presentation will provide tips for leaders to evaluate culture. Leaders in the context of the presentation include technical and administrative leadership.

The ISPE Advancing Pharmaceutical Quality (APQ) Program has been developed by industry expert representatives, for industry use, to advance the current state of pharmaceutical quality by providing practical tools and approaches to enhance the effectiveness of the Pharmaceutical Quality System (PQS). The APQ program is a practical framework that an organization can use to first assess the maturity and then advance the state of quality within their organization. This session will provide an overview of the APQ program—its basis in ICH Q10, the Assess-Aspire-Act-Advance framework, and the guide series.