Following Guidelines During a Crisis

The guidance states, "These preventative measures can include steps to prepare personnel such as: * "Educating employees on topics such as, in the case of a pandemic, personal hygiene (hand washing and coughing and sneezing etiquette), social distancing, and appropriate use of sick leave * "Encouraging employees to get immunized as appropriate by providing information on local vaccination services or by offering on-site vaccination services, if reasonable * "Providing information for and encouraging employees to develop family emergency preparedness plans * "Reviewing CGMP [current good manufacturing practice] regulations regarding appropriate sanitation practices and restriction of ill or sick employees from production areas (see 21 CFR [Code of Federal Regulations] 211.28)" (2). Examples include: * "Production equipment routine maintenance * "Utility system performance checks and maintenance (e.g., air temperature, lighting, compressed air) * "Environmental monitoring of facilities such as cell culture, harvesting, and purification rooms during production * "Stability testing for certain drug products and components * "Periodic examinations of data and of reserve samples" (2). EMA, Guidance on the Format of the Risk Management Plan (RMP) in the EU-in Integrated Format, EMA/164014/2018 Rev.2.0.1 accompanying GVP Module V Rev.2 Human Medicines Evaluation (EMA, 31 October 2018).

PANDEMIC ALTERS POLICIES FOR DRUG DEVELOPMENT

The desperate need for new vaccines and therapies to tame the deadly COVID-19 virus required new policies and procedures for how biopharma companies select, test, and manufacture medical products-and revised regulatory practices for evaluating clinical data, manufacturing operations, and procedures for submitting and analyzing information. Vaccine experts at the Center for Biologics Evaluation and Research (CBER) worked overtime to clarify the size and diversity of efficacy trials and key analytical assessments needed to gain EUA status and later full approval, establishing standards and procedures that will shape research for health emergencies to come. Officials at FDA's Office of Regulatory Affairs (ORA) indicate that the agency will continue to utilize many of these strategies for streamlining oversight of manufacturing operations, even as on-site visits increase overseas and at home, leading to a more "hybrid" inspection process going forward.

Research on the Optimal Energy Saving and Emission Reduction Path for Promoting High-Quality Industrial Development in Hubei Province

In December 2019, a novel coronavirus broke out in Wuhan City, Hubei Province, and, as the center of the coronavirus disease 2019 (COVID-19) epidemic, the economy and production throughout Hubei Province suffered huge temporary impacts. Based on the input–output and industrial pollution emissions data of 33 industrial industries in Hubei from 2010 to 2019, this article uses the non-parametric frontier analysis method to calculate the potential production losses and compliance costs caused by environmental regulations in Hubei's industrial sector by year and industry. Research has found that the environmental technology efficiency of the industrial sector in Hubei is showing a trend of increasing year-on-year, but the overall efficiency level is still not high, and there is great room for improvement. The calculation results with and without environmental regulatory constraints indicate that, generally, production losses and compliance costs may be encountered in the industrial sector in Hubei, and there are significant differences by industry. The potential production losses and compliance costs in pollution-intensive industries are higher than those in clean production industries. On this basis, we propose relevant policy recommendations to improve the technological efficiency of Hubei's industrial environment, in order to promote the high-quality development of Hubei's industry in the post-epidemic era.

Balancing Change and Certainty in Manufacturing

According to research, for example, the bio/pharmaceutical manufacturing market should witness compound annual growth in the region of 11% between 2022 and 2027 (2), thanks in part to advancing manufacturing technologies. "Most recently, biopharmaceutical manufacturing has been impacted by pressures on supply chain," specifies Antonio Crincoli, vice president of Engineering, Pharma and Consumer Health, Catalent. [...]there is a focus on quality management systems that ensure data integrity and governance, and that digitization occurs with appropriate validation, also, where necessary, that there is segregation of operating systems to eliminate risk of corruption." Antonio Crincoli, Catalent "PAT and an emphasis on process understanding have been embraced by the majority of pharmaceutical manufacturers, and there are several case studies where both artificial intelligence (Al) and machine learning (ML) have led to improved quality or increased yield, even in good manufacturing practice (GMP) facilities," adds Byrd.

Getting Proactive with Pharma Packaging

According to market research, the pharmaceutical packaging sector is expected to grow at a compound annual rate of 7.4% between 2022 and 2031, reaching an estimated USS178.8 billion (€171.8 billion) by the end of the forecast period (1). "Pharmaceutical waste continues to be a huge problem, so to eliminate non-biodegradable and single-use plastics from the supply chain, more research is taking place around bio-based PET [polyethylene terephthalate]. "By designing a product's primary and secondary packaging well from the outset (including investing ample resources into the process), manufacturers can reduce the amount of materials used and wasted, test new eco materials, ensure safety compliance and efficacy, and benefit from cheaper transportation costs," Quelch surmises. [...]pharma companies can benefit from a packaging supplier with a true global footprint," he says.

Cold Comfort for Bio/Pharma

The COVID-19 pandemic highlighted how vital cold chain is for the pharmaceutical industry, particularly as some vaccines needed to be produced, transported, and stored at -70 °C. Market projections for cold chain logistics of pharmaceuticals are projected to grow at a compound annual growth rate of 9.03% by 2025, which is reported to be driven by greater global demand for pharmaceuticals, increasing initiatives to promote cold chain, and more demand for reefer containers from the pharma industry (1). Gilmore (Tower Cold Chain): Putting the European success of the COVID-19 vaccine rollout to one side, the demand for effective temperature-controlled packaging solutions in the pharmaceutical supply chain has increased significantly in recent years. Today, the cold chain is grappling with additional challenges: serving a global market, driving out costs and waste, addressing capacity and resource constraints, and dealing with continually mounting regulations-all whilst handling valuable pharmaceutical cargo. Cold chain logistics providers must invest in the latest on-board equipment built into containers to track temperature and location, and to make data available to partners and customers in real time, to prevent or mitigate loss.

Injecting Innovation into Drug Packaging

According to Jens Kürten, group senior director, Communication and Marketing, Gerresheimer, there are nine megatrends that will both characterize and influence the pharmaceutical packaging market. Whether the drug be injected intravenously or subcutaneously, at home or in a hospital setting, there are various needs that should be considered prior to choosing the 'best-fit' packaging, he adds. [...]packaging requirements for pharmaceuticals change over time as the lifecycle of the drug continues," Stöcker states. [...]customers request more eco-friendly options to reduce or avoid plastic. [...]it has been necessary to design the packaging for the vaccines with these specific requirements in mind to ensure the safety and efficacy of the therapeutic product are protected.

Demonstrating the Value of Collaboration

[...]of the search for effective vaccines and treatments for COVID-19 being a priority, the development and manufacture of other treatments have been delayed, he adds. Through these industry collaborations, many developers have gained benefits, such as reduced time-to-market for new products, he specifies. [...]Quick believes that there will be more companies leaning towards outsourced services in the future, for development work and commercialization phases too. Given the disruption to the global pharmaceutical supply chain that has been experienced during the pandemic, O'Sullivan predicts that there will be opportunities for API suppliers in Europe, and elsewhere, to prosper from increased local demand, so long as the capacity and flexibility to deliver the required quantities are on available. [...]we will see significant investment by European API suppliers in expanded production capacity and capabilities in 2021 in order to attract Europe-based customers on the look-out for new local partners," he says. [...]Cruz emphasizes the rise of electronic health and customer records across Europe as an exciting prospect, particularly as it can lead to companies gaining a greater insight into treatments and customer needs.

Vaccine Administration: The Growing Role of Prefilled Syringes

(Note: The MIDAS database reflects vaccine doses that are dispensed with a prescription in retail or hospital settings, so the COVID-19 vaccines and other public-health-administered vaccines are not fully reflected in that data set.) Stamoran adds, "However, across the rest of the world, vial-based vaccines still make up the majority of the volume dispensed." [...]there is plenty of room for growth for this newer administration device. [...]PFS are now widely used for annual flu shots, heparin injections, and a growing list of injectable therapies across multiple disease states. According to a 2021 article authored byGuillaume Lehee, R&D Innovation Leader for BD Medical-Pharmaceutical Systems, the use of PFS to vaccinate 300 million individuals in the United States in the event of a future pandemic could save more than three million hours of healthcare practitioners' time (1). [...]today's PFS are not yet proven to be compatible with ultrafrozen temperatures as the existing glass materials and other components may not stand up to the extremely low required temperatures," explains Stamoran.

Track-and-Trace Progress Benefits Supply-Chain Security Efforts

COVID-19 vaccines, approved under emergency use authorization, were not required to meet serialization requirements, but they have been properly labelled to meet US Food and Drug Administration (FDA) requirements, he says, complete with 2D barcodes with GTIN, lot, and expiry date. The company decided to serialize its Diprovan anesthetic, a workhorse generic product, using radio frequency identification tags containing the four identifiers (2). "If an agent is handling your product on your behalf, they need to leverage GS1 Standards including GTINs for products [and] global location numbers (GLNs) for physical locations, and share data electronically using electronic product code information services (EPCIS) to capture events from manufacturing to serialization [and] capping to shipping.

Protecting the NHS from Cyber Attacks

Given that cyber security underwrites public trust in digital services and technologies, the new cyber strategy sets out a vision for reducing the cyber security risk to health and social care organizations across the Department of Health and Social Care (DHSC), National Health Service (NHS) organizations, local authorities, independent social care providers, and suppliers-which includes pharmaceutical manufacturers. [...]attacks can cause a complete loss of access to clinical and administrative information technology (IT) systems, resulting in significant disruption in day-to-day operations. According to the NCSC, ransomware attacks are increasingly seen to include data theft and extortion with a threat of data leaks (3). According to the UK government's recently published policy paper outlining the new cyber security strategy, "all these threats pose risk not just to patient and staff safety, but also to public trust in a health and social care system that can and must safeguard people's data" (2).

The European Union's New Pharmaceutical Strategy for Europe

[...]on 25 Nov. 2020, the European Commission (EC) announced the new Pharmaceutical Strategy for Europe, which is likely to result in significant changes to the European Union (EU) regulatory framework and will have a substantial impact on both the marketing of medicinal products and the strategic business planning of pharmaceutical companies (2). (2021), the priority areas are as follows: * The performance and adequacy of the current legislation * Unmet medical needs-with a definition or set of principles for "unmet medical needs" under discussion * Incentives for innovation, including the area of unmet needs and a reflexion on regulatory data and market exclusivity * Antimicrobial resistance that includes measures to support innovation of antibiotic development * Future-proofing the regulatory framework for novel products * Improved patient access to, and affordability of, medicines in the EU * Competitiveness of the European markets to ensure affordable medicines, including considering measures to support patients' access to affordable medicines * Encouraging the repurposing of off patent medicines * Ensuring security of supply of medicinal products in the EU * Ensuring high-quality manufacture and distribution in the EU including consideration of the need to strengthen or adapt good manufacturing practice (GMP) to reflect new manufacturing methodologies * Environmental challenges (4). Availability, accessibility, and affordability of medicinal products The section on 'Prioritising unmet medical needs' in the strategy reflects the belief within EU Bianca Piachaud-Moustakis is lead writer at PharmaVision, Pharmavision.co.uk. institutions that "current incentive models neither provide an adequate solution for unmet medical needs nor appropriately incentivise investments in innovation" (2).

Manufacturing Innovation

(ProQuest: ... denotes non-USASCII text omitted.) The annual Global Innovation Index released in September 2021 ranked China twelfth, surpassing developed economies such as Japan, Israel, and Canada and raising fears in the United States amidst sluggish growth in North America and strong growth in the Asia Pacific region.1 Interestingly, the United States government responded by boycotting the Beijing Olympic Games, citing human rights abuses as the main reason.2 A tech war between China and the United States brewed beneath the diplomatic rancor over the attendance at the Olympic Games. Part I documents how the United States has assisted China's tech and intellectual property domination through President Nixon's historic visit to China, giving China Most Favorite Nation (MFN) status and ascending China to the World Trade Organization (WTO). [...]under Deng Xiaoping's leadership during the reform period, China rapidly developed its special economic zones (SEZs), laying the foundation for subsequent tech innovation and production. [...]broadcasting, telecommunications, office machines, computers, integrated circuits, and cell phones are among China's notable exports to the world.9 China dominates in commodities and raw materials, exporting refined petroleum, cotton, plywood, and tea.10 For agricultural products, China occupies the perch as the world's largest producer. Shenzhen rose as the largest among the four.18 Shenzhen, a small fishing locale in the southern part of China's southern province, Guangdong, served as the pioneer of Deng Xiaoping's embrace of economic reforms.19 A market-oriented economy took root in Shenzhen, allowing foreign companies and entities from Hong Kong and Macau to operate and allowing Chinese talents the freedom to leave their hometowns and move into the SEZs.20 Cheap labor proved to be another significant factor facilitating China's rise as a global manufacturer.21 In the 1980s, multinational corporations from Taiwan, Japan, and South Korea, as well as domestic Chinese companies, opened their factories in the SEZs and other cities in China to take advantage of the cheap and plentiful labor force.22 Indeed, when Deng Xiaoping began his pilot SEZs, China's young workers who wished to lift themselves out of poverty descended into the economic zones in search of better opportunities.23 Shenzhen grew from a population of 59,000 in 1980 to a population of 12,357,000 in 2020.24 The new migrants became the workers, participants, and stakeholders in the global manufacturing frontier.25 Because of the abundance of cheap labor, manufacturers in China have no difficulty keeping production prices low and pleasing consumers and businesses worldwide.26 China's currency manipulation is another factor propelling China to its domination in global manufacturing.27 The United States Congress attempted numerous times to introduce legislation to combat China's currency manipulation.28 China artificially devalued its currency through government control of the exchange rate and refused to let the Chinese Renminbi (RMB) float.29 Despite strong criticisms from the United States, China refuses to allow its currency to freely float.30 China's currency manipulations, according to critics, caused the widening of trade deficits between the United States and China.31 China's currency manipulation allows products to be manufactured at lower prices, hampering competitors and thereafter replacing them.32 In order to cope with China's currency practices, United States manufacturers facing their own existential crises must decide to either outsource jobs overseas or face large risks, including financial ruin.33 The United States lost millions of manufacturing jobs due to massive job outsourcing as the trade deficits between the United States and China continued to persist.34 Geopolitically, in shaping post-Cold-War powers, the United States decided to assist China in its transformation from a poverty-stricken country to a global manufacturer.

The Need for Speed: How Operation Warp Speed Shifted the Pharma Industry

During the United States government's push for vaccine development and manufacturing (dubbed Operation Warp Speed)-and partly because of it-capital projects struggled to acquire adequate construction materials and equipment. Additionally, video production equipment was leveraged to offer an overview of progress in real time and even perform equipment testing. [...]startups are competing for a few outsourced manufacturing slots. The main solution to limited manufacturing opportunities is to work with a consulting partner who can help them accelerate the process of finding, prequalifying, and negotiating with appropriate and available contract manufacturers.

New Biotherapies Push Tecmological Innovation Forward

[...]on the positive side, innovations in the use of synthetic raw materials and disposable equipment are expected to enhance manufacturing process development, she says. "The AttenuBlock platform incorporates 10 years of research and development at Emory University, where researchers employed rational and precise codon deoptimization and other genetic strategies to produce hundreds of targeted mutations into the RSV genome, providing exquisite control over viral protein expression," Moore explains. [...]the dose of a live attenuated vaccine is typically much lower than all the other non-replicating vaccine types, including genetic (RNA/DNA), viral vectors, protein subunit, inactivated, and virus-like particles (VLPs). [...]to meet global supply and demand, Meissa is implementing straightforward, economical, and scalable vaccine manufacturing technologies, Moore says. [...]licensed VLP vaccines are extremely effective.

COVID-19 Stresses EMA Resources

EMA has pleaded with the European Commission (EC) for more funds to finance the costs of its increased duties (2). "The GMP standards will be applied to the manufacture of sterile vials for the vaccines as per standard requirements, regardless of location," said a spokesman for the Medicines and Healthcare products Regulatory Agency (MHRA) of the UK, where a COVID-19 vaccine being jointly developed by AstraZeneca and Oxford University is considered likely to be among the first to gain authorization for mass distribution. Manufacturers of vaccines and their containers could be subject to two waves of standards-checking inspections- one for GMP and the other for pharmacovigilance. Because the latter will be the most extensive covering, for example, requiring surveillance quality systems in all the operations of a business, a manufacturer that is considered to be compliant with pharmacovigilance standards is unlikely to be breaching GMP rules. Other priorities include the work of key working parties and groups, drawing up of certain guidelines, the fight against anti-microbial resistance (AMR), co-operation with health technology assessment (HTA) bodies, innovation (especially in emerging therapies), clinical data publication, and international co-operation.

Breaking Through Barriers to Continuous Manufacturing

The success of the cooperation between government and the private sector to rapidly develop and build capacity for vaccines and treatments to combat the COVID-19 pandemic is an example of what is possible, in the normally slow-acting and risk-averse pharmaceutical sector, say industry experts. Reducing barriers to CM One positive sign is greater acceptance of public-private partnerships by the United States (US) Food and Drug Administration (FDA) and the US Congress, due to the successes demonstrated during the pandemic response, said Jennifer Luray, vice-president of strategy and communications at ResearchlAmerica, during a panel discussion hosted by the US Pharmacopeia Convention (USP) (2). USP can help fill the gap that exists in access to knowledge, experience, and laboratory capabilities for PAT model development and process development, adds De Belder. " "Some PAT systems are more suited to a development environment, where the goal is to gain process understanding and knowledge about the product, but those systems may not be robust enough for routine deployment on a commercial process," adds Connelly.

Automating Biopharma Manufacturing

"With the advance of data science enabling factors such as easy access to scalable memory and computing resources;our growing competence in collecting, storing, and contextualizing data;advances in robotics;[and] the quickly evolving method landscape driven by the open-source community, the benefits of automation and simulation are becoming accessible in the notoriously complicated realm of biopharma manufacturing," says Marcel von der Haar, head of product strategy data analytics at Sartorius. "Plug-and-play" capabilities of automation systems, which enable flexible manufacturing and faster technology transfer, are more important than ever, he says. Walvax Biotech's new COVID-19 mRNA vaccine plant in China is another example of an intelligent and digital plant;it uses Honeywell's batch process control, building and energy management solution systems, and digital twins to monitor assets (5). "Automation brings in the data for machine learning to model the dynamic processes of cell growth and map it against the multiple dimensions provided by advanced sensors," explains Brandl.

Digitalization Moves Forward in Pharma Equipment and Processes

Digital technologies that could meet these new challenges and aid manufacturing scale-up and speed to market, such as automated digital data collection and augmented and virtual reality (AR/VR) remote collaboration tools, were already available and had been adopted by some, but the new demand spurred greater adoption. "There is a cultural aspect to digitalization because it's a significant investment that results in changes to the operational structure of a facility;it is beneficial when the digitalization comes from the top," explains Yvonne Duckworth, automation engineer and Industry 4.0 subject matter expert at the CRB Group, a life sciences engineering and construction company. Machine sensors and process analytical technology (PAT) instruments can communicate directly with data collection systems using the NoT. Efficient development and tech transfer for mRNA vaccine manufacturing The data analysis and clear communication allowed by digital tools has demonstrated its benefits for process development and technical transfer, making time to market faster.

Supporting the Industry During a Pandemic

Among the lessons learned from the pandemic response are changed perceptions within the industry regarding flex capacity, risk management, supply chain, and inventory control, according to Eric Langer, managing partner at BioPlan Associates. [...]infectious disease drugs have already overtaken perpetual leader oncology as the year's top therapy area for contract manufacturing service agreements, since many of these vaccine-developer companies are small and lack manufacturing capabilities. The expansion will include new suites for the development and clinical manufacturing of drug product intermediates and drug products using spray-drying, hot-melt extrusion, and melt-spray-congeal processing and CGMP suites for early-phase CGMP manufacturing featuring added storage, gowning, and a customer in-plant viewing corridor (4).