Challenges and Opportunities of Implementing Data Fusion in Process Analytical Technology-A Review.

The release of the FDA's guidance on Process Analytical Technology has motivated and supported the pharmaceutical industry to deliver consistent quality medicine by acquiring a deeper understanding of the product performance and process interplay. The technical opportunities to reach this high-level control have considerably evolved since 2004 due to the development of advanced analytical sensors and chemometric tools. However, their transfer to the highly regulated pharmaceutical sector has been limited. To this respect, data fusion strategies have been extensively applied in different sectors, such as food or chemical, to provide a more robust performance of the analytical platforms. This survey evaluates the challenges and opportunities of implementing data fusion within the PAT concept by identifying transfer opportunities from other sectors. Special attention is given to the data types available from pharmaceutical manufacturing and their compatibility with data fusion strategies. Furthermore, the integration into Pharma 4.0 is discussed.

Developing Vaccines for SARS-CoV-2 and Future Epidemics and Pandemics: Applying Lessons from Past Outbreaks.

The COVID-19 pandemic is a stark reminder of the heavy toll that emerging infectious diseases (EIDs) with epidemic and pandemic potential can inflict. Vaccine development, scale-up, and commercialization is a long, expensive, and risky enterprise that requires substantial upfront planning and offers no guarantee of success. EIDs are a particularly challenging target for global health preparedness, including for vaccine development. Insufficient attention has been given to challenges, lessons learned, and potential solutions to support and sustain vaccine industry engagement in vaccine development for EIDs. Drawing from lessons from the most recent Ebola epidemic in the Democratic Republic of the Congo, as well as the 2009 H1N1 influenza, 2014-2016 Ebola, and 2015-16 Zika outbreaks preceding it, we offer our perspective on challenges facing EID vaccine development and recommend additional solutions to prioritize in the near term. The 6 recommendations focus on reducing vaccine development timelines and increasing business certainty to reduce risks for companies. The global health security community has an opportunity to build on the current momentum to design a sustainable model for EID vaccines.

Assessment tool for establishing local pharmaceutical manufacturing in low- and middle-income countries.

OBJECTIVE: In many low- and middle-income countries (LMICs), limited availability, substandard quality and high prices of pharmaceutical products lead to lack of access to essential medicines and poor health outcomes. Manufacturing pharmaceuticals in LMICs may improve access for patients while increasing the market size for manufacturers. METHODS: We present a tool for assessment of local manufacturing feasibility of pharmaceuticals, intended for use among key stakeholders during the business development process. The tool consists of five domains: product selection and capacity, market sizing, market entry, funding and quality assurance. KEY FINDINGS: The tool is intended to identify barriers and facilitators for local manufacturing and provide a roadmap for decision-making across multiple stakeholders. A case study in Namibia identified key barriers and facilitators to successful manufacturing in that county. CONCLUSIONS: Careful consideration of feasibility and potential for success may lead to improved health for the populations of LMIC as well as significant market potential for pharmaceutical manufacturers.

Development and innovation of system resources to optimize patient care.

PURPOSE: Various incremental and disruptive healthcare innovations that are occurring or may occur are discussed, with insights on how multihospital health systems can prepare for the future and optimize the continuity of patient care provided. SUMMARY: Innovation in patient care is occurring at an ever-increasing rate, and this is especially true relative to the transition of patients through the care continuum. Health systems must leverage their ability to standardize and develop electronic health record (EHR) systems and other infrastructure necessary to support patient care and optimize outcomes; examples include 3D printing of patient-specific medication dosage forms to enhance precision medicine, the use of drones for medication delivery, and the expansion of telehealth capabilities to improve patient access to the services of pharmacists and other healthcare team members. Disruptive innovations in pharmacy services and delivery will alter how medications are prescribed and delivered to patients now and in the future. Further, technology may also fundamentally alter how and where pharmacists and pharmacy technicians care for patients. This article explores the various innovations that are occurring and that will likely occur in the future, particularly as they apply to multihospital health systems and patient continuity of care. CONCLUSION: Pharmacy departments that anticipate and are prepared to adapt to incremental and disruptive innovations can demonstrate value in the multihospital health system through strategies such as optimizing the EHR, identifying telehealth opportunities, supporting infrastructure, and integrating services.

Creating a learning organization to help meet the needs of multihospital health systems.

PURPOSE: The considerations that leaders of multihospital health systems must take into account in developing and implementing initiatives to build and maintain an exceptional pharmacy workforce are described. SUMMARY: Significant changes that require constant individual and organizational learning are occurring throughout healthcare and within the profession of pharmacy. These considerations include understanding why it is important to have a succession plan and determining what types of education and training are important to support that plan. Other considerations include strategies for leveraging learners, dealing with a large geographic footprint, adjusting training opportunities to accommodate the ever-evolving demands on pharmacy staffs in terms of skill mix, and determining ways to either budget for or internally develop content for staff development. All of these methods are critically important to ensuring an optimized workforce. Especially for large health systems operating multiple sites across large distances, the use of technology-enabled solutions to provide effective delivery of programming to multiple sites is critical. Commonly used tools include live webinars, live "telepresence" programs, prerecorded programming that is available through an on-demand repository, and computer-based training modules. A learning management system is helpful to assign and document completion of educational requirements, especially those related to regulatory requirements (e.g., controlled substances management, sterile and nonsterile compounding, competency assessment). CONCLUSION: Creating and sustaining an environment where all pharmacy caregivers feel invested in and connected to ongoing learning is a powerful motivator for performance, engagement, and retention.

Industry Perspective on Biomarker Development and Qualification.

Pharmaceutical and biotechnology companies routinely use biomarkers to obtain quantitative metrics for drug exposure, efficacy, and safety and to inform clinical trial design with regard to patient selection, treatments, and outcomes. Biomarker science has the unique capability to catalyze precompetitive collaborations between academia, industry, regulatory agencies, and other stakeholders with the ultimate goal of accelerating the delivery of safe and effective medicines to patients, particularly in areas of high unmet need.

Challenges in conducting post-authorisation safety studies (PASS): A vaccine manufacturer's view.

Post-authorisation safety studies (PASS) of vaccines assess or quantify the risk of adverse events following immunisation that were not identified or could not be estimated pre-licensure. The aim of this perspective paper is to describe the authors' experience in the design and conduct of twelve PASS that contributed to the evaluation of the benefit-risk of vaccines in real-world settings. We describe challenges and learnings from selected PASS of rotavirus, malaria, influenza, human papillomavirus and measles-mumps-rubella-varicella vaccines that assessed or identified potential or theoretical risks, which may lead to changes to risk management plans and/or to label updates. Study settings include the use of large healthcare databases and de novo data collection. PASS methodology is influenced by the background incidence of the outcome of interest, vaccine uptake, availability and quality of data sources, identification of the at-risk population and of suitable comparators, availability of validated case definitions, and the frequent need for case ascertainment in large databases. Challenges include the requirement for valid exposure and outcome data, identification of, and access to, adequate data sources, and mitigating limitations including bias and confounding. Assessing feasibility is becoming a key step to confirm that study objectives can be met in a timely manner. PASS provide critical information for regulators, public health agencies, vaccine manufacturers and ultimately, individuals. Collaborative approaches and synergistic efforts between vaccine manufacturers and key stakeholders, such as regulatory and public health agencies, are needed to facilitate access to data, and to drive optimal study design and implementation, with the aim of generating robust evidence.

The strategic relevance of manufacturing technology: An overall quality concept to promote innovation preventing drug shortage.

Manufacturing is the bridge between research and patient: without product, there is no clinical outcome. Shortage has a variety of causes, in this paper we analyse only causes related to manufacturing technology and we use shortage as a paradigm highliting the relevance of Pharmaceutical Technology. Product and process complexity and capacity issues are the main challenge for the Pharmaceutical Industry Supply chain. Manufacturing Technology should be acknowledged as a R&D step and as a very important matter during University degree in Pharmacy and related disciplines, promoting collaboration between Academia and Industry, measured during HTA step and rewarded in terms of price and reimbursement. The above elements are not yet properly recognised, and manufacturing technology is taken in to consideration only when a shortage is in place. In a previous work, Panzitta et al. proposed to perform a full technology assessment at the Health Technological Assessment stage, evaluating three main technical aspects of a medicine: manufacturing process, physicochemical properties, and formulation characteristics. In this paper, we develop the concept of manufacturing appraisal, providing a technical overview of upcoming challenges, a risk based approach and an economic picture of shortage costs. We develop also an overall quality concept, not limited to GMP factors but broaden to all elements leading to a robust supply and promoting technical innovation.

Healthcare systems, the State, and innovation in the pharmaceutical industry.

This article discusses the relations between healthcare systems and the pharmaceutical industry, focusing on state support for pharmaceutical innovation. The study highlights the experiences of the United States, United Kingdom, and Germany, developed countries and paradigms of modern health systems (liberal, universal, and corporatist), in addition to Japan, a case of successful catching up. The study also emphasizes the experiences of China, India, and Brazil, large developing countries that have tried different catching up strategies, with diverse histories and profiles in their healthcare systems and pharmaceutical industries. Finally, with a focus on state forms of support for health research, the article addresses the mechanisms for linkage between health systems and the pharmaceutical industry, evaluating the possibilities of Brazil strengthening a virtuous interaction, favoring the expansion and consolidation of the Brazilian health system - universal but segmented ‒ and the affirmation of the innovative national pharmaceutical industry. Resumo: O artigo discute as relações entre os sistemas de saúde e a indústria farmacêutica, concentrando-se no apoio do Estado à inovação farmacêutica. Salienta as trajetórias dos Estados Unidos, Reino Unido e Alemanha, países desenvolvidos, paradigmáticos dos modernos sistemas de saúde (liberais, universais e corporativos), além do Japão, um caso de emparelhamento bem-sucedido. Também enfatiza as trajetórias de China, Índia e Brasil, países em desenvolvimento, extensos, que experimentaram diferentes estratégias de emparelhamento, dispondo de sistemas de saúde e indústrias farmacêuticas com trajetórias e perfis diversos. Finalmente, com foco nas formas estatais de apoio à pesquisa em saúde, considera os mecanismos de conexão entre os sistemas de saúde e a indústria farmacêutica, avaliando as possibilidades, no Brasil, de fortalecer uma interação virtuosa que favoreça a expansão e consolidação do sistema de saúde brasileiro - universal, conquanto segmentado ‒ e a afirmação da indústria farmacêutica nacional inovadora.

Considerations for sustainable influenza vaccine production in developing countries.

Through its Global Action Plan for Influenza Vaccines (GAP), the World Health Organization (WHO) in collaboration with the United States Department of Health and Human Services has produced a checklist to support policy-makers and influenza vaccine manufacturers in identifying key technological, political, financial, and logistical issues affecting the sustainability of influenza vaccine production. This checklist highlights actions in five key areas that are beneficial for establishing successful local vaccine manufacturing. These five areas comprise: (1) the policy environment and health-care systems; (2) surveillance systems and influenza evidence; (3) product development and manufacturing; (4) product approval and regulation; and (5) communication to support influenza vaccination. Incorporating the checklist into national vaccine production programmes has identified the policy gaps and next steps for countries involved in GAP's Technology Transfer Initiative. Lessons learnt from country experiences provide context and insight that complement the checklist's goal of simplifying the complexities of influenza prevention, preparedness, and vaccine manufacturing.

How drug life-cycle management patent strategies may impact formulary management.

Drug manufacturers may employ various life-cycle management patent strategies, which may impact managed care decision making regarding formulary planning and management strategies when single-source, branded oral pharmaceutical products move to generic status. Passage of the Hatch-Waxman Act enabled more rapid access to generic medications through the abbreviated new drug application process. Patent expirations of small-molecule medications and approvals of generic versions have led to substantial cost savings for health plans, government programs, insurers, pharmacy benefits managers, and their customers. However, considering that the cost of developing a single medication is estimated at $2.6 billion (2013 dollars), pharmaceutical patent protection enables companies to recoup investments, creating an incentive for innovation. Under current law, patent protection holds for 20 years from time of patent filing, although much of this time is spent in product development and regulatory review, leaving an effective remaining patent life of 7 to 10 years at the time of approval. To extend the product life cycle, drug manufacturers may develop variations of originator products and file for patents on isomers, metabolites, prodrugs, new drug formulations (eg, extended-release versions), and fixed-dose combinations. These additional patents and the complexities surrounding the timing of generic availability create challenges for managed care stakeholders attempting to gauge when generics may enter the market. An understanding of pharmaceutical patents and how intellectual property protection may be extended would benefit managed care stakeholders and help inform decisions regarding benefit management.

Healthcare systems, the State, and innovation in the pharmaceutical industry / Sistemas de salud, Estado e innovación en la industria farmacéutica / Sistemas de atenção à saúde, Estado e inovação na indústria farmacêutica

Abstract: This article discusses the relations between healthcare systems and the pharmaceutical industry, focusing on state support for pharmaceutical innovation. The study highlights the experiences of the United States, United Kingdom, and Germany, developed countries and paradigms of modern health systems (liberal, universal, and corporatist), in addition to Japan, a case of successful catching up. The study also emphasizes the experiences of China, India, and Brazil, large developing countries that have tried different catching up strategies, with diverse histories and profiles in their healthcare systems and pharmaceutical industries. Finally, with a focus on state forms of support for health research, the article addresses the mechanisms for linkage between health systems and the pharmaceutical industry, evaluating the possibilities of Brazil strengthening a virtuous interaction, favoring the expansion and consolidation of the Brazilian health system - universal but segmented ‒ and the affirmation of the innovative national pharmaceutical industry.

Resumen: El artículo discute las relaciones entre los sistemas de salud y la industria farmacéutica, concentrándose en el apoyo del Estado a la innovación farmacéutica. Resalta las trayectorias de los Estados Unidos, Reino Unido y Alemania, países desarrollados, paradigmáticos de los modernos sistemas de salud (liberales, universales y corporativos), además de Japón, un caso de emparejamiento exitoso. También enfatiza las trayectorias de China, India y Brasil, países en desarrollo, extensos, que experimentaron diferentes estrategias de emparejamiento en este ámbito, disponiendo de sistemas de salud e industrias farmacéuticas con trayectorias y perfiles diversos. Finalmente, centrándose en las formas estatales de apoyo a la investigación en salud, se consideran los mecanismos de conexión entre los sistemas de salud y la industria farmacéutica, evaluando las posibilidades, en Brasil, de fortalecer una interacción virtuosa que favorezca la expansión y consolidación del sistema de salud brasileño -universal, pese a estar segmentado-, y la consolidación de la industria farmacéutica nacional innovadora.

Resumo: O artigo discute as relações entre os sistemas de saúde e a indústria farmacêutica, concentrando-se no apoio do Estado à inovação farmacêutica. Salienta as trajetórias dos Estados Unidos, Reino Unido e Alemanha, países desenvolvidos, paradigmáticos dos modernos sistemas de saúde (liberais, universais e corporativos), além do Japão, um caso de emparelhamento bem-sucedido. Também enfatiza as trajetórias de China, Índia e Brasil, países em desenvolvimento, extensos, que experimentaram diferentes estratégias de emparelhamento, dispondo de sistemas de saúde e indústrias farmacêuticas com trajetórias e perfis diversos. Finalmente, com foco nas formas estatais de apoio à pesquisa em saúde, considera os mecanismos de conexão entre os sistemas de saúde e a indústria farmacêutica, avaliando as possibilidades, no Brasil, de fortalecer uma interação virtuosa que favoreça a expansão e consolidação do sistema de saúde brasileiro - universal, conquanto segmentado ‒ e a afirmação da indústria farmacêutica nacional inovadora.

[Penicillin production in Chile between 1944 and 1954]. / Producción de Penicilina en Chile entre 1944 y 1954.

Penicillin production in Chile was a pioneering development; however there is not much information to learn about it. The Chilean Institute for Bacteriology (Instituto Bacteriológico de Chile) produced penicillin between 1944 and 1973. The stage starting in 1953 is better known since there was an agreement with United Nations. Our research focused on building a story about production between 1944 and 1954 based on archival information and the national and international historic context. Our results place Chile amongst the pioneer countries in the successful industrialization of the drug. Our conclusions are that this was a proper industrial production as opposite to a pilot plant - a name commonly used to call the early factory. We explain the production plant trajectory by making relations between technological change and governance. Finally, we believe the later expansion of the plant, in the context of the agreement with the United Nations, took place under unpromising governance conditions, which called for passive innovation and technology management.

How development and manufacturing will need to be structured--heads of development/manufacturing. May 20-21, 2014 Continuous Manufacturing Symposium.

Continuous manufacturing (CM) is a process technology that has been used in the chemical industry for large-scale mass production of chemicals in single-purpose plants with benefit for many years. Recent interest has been raised to expand CM into the low-volume, high-value pharmaceutical business with its unique requirements regarding readiness for human use and the required quality, supply chain, and liability constraints in this business context. Using a fairly abstract set of definitions, this paper derives technical consequences of CM in different scenarios along the development-launch-supply axis in different business models and how they compare to batch processes. Impact of CM on functions in development is discussed and several operational models suitable for originators and other business models are discussed and specific aspects of CM are deduced from CM's technical characteristics. Organizational structures of current operations typically can support CM implementations with just minor refinements if the CM technology is limited to single steps or small sequences (bin-to-bin approach) and if the appropriate technical skill set is available. In such cases, a small, dedicated group focused on CM is recommended. The manufacturing strategy, as centralized versus decentralized in light of CM processes, is discussed and the potential impact of significantly shortened supply lead times on the organization that runs these processes. The ultimate CM implementation may be seen by some as a totally integrated monolithic plant, one that unifies chemistry and pharmaceutical operations into one plant. The organization supporting this approach will have to reflect this change in scope and responsibility. The other extreme, admittedly futuristic at this point, would be a highly decentralized approach with multiple smaller hubs; this would require a new and different organizational structure. This processing approach would open up new opportunities for products that, because of stability constraints or individualization to patients, do not allow centralized manufacturing approaches at all. Again, the entire enterprise needs to be restructured accordingly. The situation of CM in an outsourced operation business model is discussed. Next steps for the industry are recommended. In summary, opportunistic implementation of isolated steps in existing portfolios can be implemented with minimal organizational changes; the availability of the appropriate skills is the determining factor. The implementation of more substantial sequences requires business processes that consider the portfolio, not just single products. Exploration and implementation of complete process chains with consequences for quality decisions do require appropriate organizational support.

Emergence of biopharmaceutical innovators in China, India, Brazil, and South Africa as global competitors and collaborators.

Biopharmaceutical innovation has had a profound health and economic impact globally. Developed countries have traditionally been the source of most innovations as well as the destination for the resulting economic and health benefits. As a result, most prior research on this sector has focused on developed countries. This paper seeks to fill the gap in research on emerging markets by analyzing factors that influence innovative activity in the indigenous biopharmaceutical sectors of China, India, Brazil, and South Africa. Using qualitative research methodologies, this paper a) shows how biopharmaceutical innovation is taking place within the entrepreneurial sectors of these emerging markets, b) identifies common challenges that indigenous entrepreneurs face, c) highlights the key role played by the state, and d) reveals that the transition to innovation by companies in the emerging markets is characterized by increased global integration. It suggests that biopharmaceutical innovators in emerging markets are capitalizing on opportunities to participate in the drug development value chain and thus developing capabilities and relationships for competing globally both with and against established companies headquartered in developed countries.

Case study: technology initiative led to advanced lead optimization screening processes at Bristol-Myers Squibb, 2004-2009.

In this paper, we review the key solutions that enabled evolution of the lead optimization screening support process at Bristol-Myers Squibb (BMS) between 2004 and 2009. During this time, technology infrastructure investment and scientific expertise integration laid the foundations to build and tailor lead optimization screening support models across all therapeutic groups at BMS. Together, harnessing advanced screening technology platforms and expanding panel screening strategy led to a paradigm shift at BMS in supporting lead optimization screening capability. Parallel SAR and structure liability relationship (SLR) screening approaches were first and broadly introduced to empower more-rapid and -informed decisions about chemical synthesis strategy and to broaden options for identifying high-quality drug candidates during lead optimization.