< PreviousMANUFACTURING 20 Pharma Business International www.pbiforum.net Automate Automate Automate To remain competitive, reduce costs, meet the stringent standards of regulators and boost productivity and efficiency, pharmaceutical manufacturers must look to innovative digital technologies. 20-23.qxp_Layout 1 06/08/2019 09:31 Page 1Pharma Business International 21 www.pbiforum.net MANUFACTURING H igh production costs stemming from complex treatments and competition, alongside a need to speed up production and enhance efficiency, are seeing pharmaceutical manufacturers embrace change with innovative digital technologies like AI, analytics tech, automation and robots, as well as continuous manufacturing, all of which are important in implementing Pharma 4.0, the future of the industry. Automation and digitalisation and their advances - which have become ever- important as the industry aims to achieve zero defects - have made visions of Pharma 4.0 in manufacturing a reality. Stemming from Industry 4.0, Pharma 4.0 connects machines, data and humans, all with the assistance of the Internet of Things (IoT), and is recognised as the next step from concepts like PAT (process analytical technology). Pharma 4.0 manufacturing facilities feature automated equipment and machines enhanced with sensors, which monitor them continuously and report on their condition. With this, problems and errors in processes or equipment can be discovered, or even predicted, and resolved, avoiding down time and product loss, boosting productivity, all while allowing manufacturers to ensure they are meeting high production standards and regulatory requirements. The mass of data these sensors produce relies on advance analytical tools and AI to be truly useful, to discover how to © Shutterstock /LeoWolfert 22 Á 20-23.qxp_Layout 1 06/08/2019 09:31 Page 2MANUFACTURING 22 Pharma Business International www.pbiforum.net refine operations. Pharma 4.0 aims to allow processes to self-adjust to improve in response to data collected by and held on interconnected systems throughout a facility. The technology of Pharma 4.0 and the data it collects and stores allows for full visibility of operations and will prove highly useful as regulators expect accurate and consistent data on products and processes. With such a high focus on automating processes, Pharma 4.0 will also help in further limiting human contact with products, reducing human error chance, accidents and contamination, improving quality. Obstacles to Pharma 4.0 plans have primarily surrounded security, finding skilled staff to deal with analytics, and the cost of fitting a manufacturing site to its principles, though this is offset by the subsequent productivity improvements and waste reduction. Sure to be boosted by Pharma 4.0, continuous manufacturing has been a hot topic within pharmaceutical manufacturing for companies looking to optimise processes. Traditionally, the industry is known for employing lengthy batch manufacturing, which of course involves manufacturing products in numerous steps. Batch manufacturing does have its benefits, and remains dominant in the pharmaceutical industry, with companies having approval from regulators for products specifically produced with these technologies and having secured a supply chain based on one’s batch manufacturing process, making switching to continuous manufacturing a major venture. However, advances in technologies are pushing the industry to highly automated continuous manufacturing, a solution allowing for reduced variability, improved process control, more flexible manufacturing footprints, increased throughput and increased yields. A key benefit of continuous manufacturing is that it does not require production to be stopped after each step to test samples or transport materials to another facility, leading to various hold times that increase risk of material degradation and gaps between steps that increase risk for error. Continuous manufacturing instead enables nonstop, 20-23.qxp_Layout 1 06/08/2019 09:31 Page 3Pharma Business International 23 www.pbiforum.net MANUFACTURING streamlined production in a single facility where processes can be run 24/7, aside from scheduled downtime for maintenance. Further highlighted bonuses include shorter production times and decreased manufacturing costs over the long term, as well as its ability to respond better to market changes and instances of high demand as continuous manufacturing can be run for longer periods of time. Additionally, where batch manufacturing uses large scale equipment, with continuous manufacturing equipment size is reduced, decreasing the amount space required for it, extending available processing space. Implementing continuous manufacturing does, though, involves seamless process integration and high levels of control along with investments in new equipment, analytical tech and training, which has led to caution in the pharmaceutical industry. These requirements see automation, IoT and operational data play an important role. Continuous manufacturing processes usually employ automated real time inline monitoring, which with analytics enables continuous process optimisation and faster decision making. Automated monitoring has the advantage of being able to detect problems and can help in predicting life expectancy of equipment. IoT helps provide visibility of this monitoring, allowing for better analysis of processes. The US Food and Drug Administration (FDA) has been a forceful driver behind continuous manufacturing, offering grants to fund research into it and remaining vocal with the belief that continuous manufacturing has the potential to improve quality, boost efficiencies, reduce medicine shortages and much more. While under four years ago there was just one approved product manufactured with continuous manufacturing, there are now four companies and five products approved, and a further twenty companies have been in contact with the FDA regarding developing continuous manufacturing processes. Though adoption of continuous manufacturing has been slow in the pharmaceutical industry, it is becoming more popular when new products are introduced and new facilities constructed. © Shutterstock /u3d 20-23.qxp_Layout 1 06/08/2019 09:31 Page 4VACCINES 24 Pharma Business International www.pbiforum.net V accines are hailed as one of the greatest breakthroughs in modern medicine. With the rise of the antivax movement, a measles outbreak, scandals surrounding the use of expired vaccines, and slowing growth in vaccine development, the future of the vaccine industry has been thrown into the air. Socially, vaccines have been receiving a surprising amount of mixed press with a shocking rise in anti-vaccine sentiment – named by the World Health Organisation (WHO) as one of the ten biggest health threats of 2019 – which has flared up arguments between opposing groups and seen children banned from schools if they are unvaccinated. With all this, alongside stringent guidelines, pricing pressures and changing policy, it is certainly an interesting time for those producing vaccines in the pharmaceutical industry. The need for solid traceability solutions is growing in importance for vaccine While rising anti-vaccine sentiment and manufacturing scandals plague the news, new innovations are boosting the future of vaccine production and distribution. A shot in the arm 24-27.qxp_Layout 1 06/08/2019 09:32 Page 1Pharma Business International 25 www.pbiforum.net VACCINES production, and has only been highlighted further thanks to scandals like those from China where this year 145 children were given an expired polio vaccine, and last year China’s drug regulator reported that one of the biggest vaccine manufacturers in the country had produced over 250,000 substandard DPT vaccines that were administered to babies and had falsified aspects of its rabies vaccine production data. These occurrences have seen stricter laws passed on vaccination administration, tougher penalties for those producing substandard vaccines and requirements for increased vaccine transparency for those with vaccine licences, which demands the publishing of vaccine information on websites from instructions to inspection information. To mitigate future vaccine manufacturing scandals, blockchain traceability solutions have been highlighted for their ability to track every step of a vaccine’s production and distribution on an immutable ledger. The potential openness of blockchain, which could distribute data to the public, would help maintain calm when vaccines are found to have problems. The traceable data chain means people can be held accountable quicker and easier. Future blockchain vaccine tracing systems will be most useful when used in conjunction with Internet of Things 26 Á © Shutterstock / Billion Photos 24-27.qxp_Layout 1 06/08/2019 09:32 Page 2VACCINES 26 Pharma Business International www.pbiforum.net (IoT) technology that can collect data on all aspects of vaccine manufacture and transport, removing the human element that could see falsified data entries made. This could include the use of RFID labels on vaccines which would record information from temperature to expiry date. While for those in the vaccine sector transforming the entire process to enable high levels of tracking with blockchain and IoT technology could be costly, one must balance the cost with the benefits. Though headlines highlight scandal, suggesting doom and gloom, the industry has received promising boosts, with governments propelling vaccine manufacturing forwards. For instance in the UK, the first ever dedicated Vaccine Manufacturing Innovation Centre has been announced. Due to open in 2022, it will address a structural gap in late- stage vaccine manufacturing in a location reliant on imports and will boost the growth of the £70 billion UK life sciences industry. It will also promote industry and academic collaboration on vaccines. Further, in the UK, the NHS Long Term Plan looks positive for the vaccine sector with its heightened focus on prevention, and NHS England is looking to invest to increase vaccination rates and is opening HPV vaccination programmes to teenage boys. Looking to the future of vaccines, many innovative methods of boosting their production and distribution are being explored. Advances in manufacturing have the potential to lower costs and speed up development by for example allowing numerous vaccines to be manufactured in one building, rather than different ones for each new vaccine, and turnkey facilities are being created to reduce production lead times, which is potentially useful during outbreaks where speed is essential. Vaccine producers and researchers are also fully embracing AI to speed up production, and in July scientists from Flinders University, in Australia, claimed they had created the first human drug in the world to be fully designed by AI. The “more effective” flu vaccine is on trial in the US and took two years to develop. Although computers have certainly been used in the past in drug design, this vaccine technology was “independently” designed by an AI program named SAM (Search Algorithm for Ligands), which the researchers created and taught to recognise vaccines that did and did not work against the flu. They also created a further computer programme to create trillions of imaginary compounds, which produced a shortlist of the ten most effective targets. The researchers said that AI accelerated the vaccine discovery process, cut costs and streamlined the development process. Further innovation in the vaccine industry is seeing researchers at Imperial College London work on the 24-27.qxp_Layout 1 06/08/2019 09:32 Page 3Pharma Business International 27 www.pbiforum.net VACCINES manufacturing of RNA vaccines for quicker, more accessible responsiveness to outbreaks so that new vaccines can be provided within weeks of a threat, and look into creating heat-stable vaccines which will allow vaccines, which are sensitive to temperature fluctuations, to exist in room temperature and remain effective. This could lower costs and allow vaccines to be used in more challenging conditions without solid cold chains. While vaccine innovations are being made, the vaccine industry has had a high growth rate of 12-15 per cent year on year over the past two decades, the number of vaccines in development doubled in the decade to 2017, and vaccines are expected to play more of a role in treatment past use for prevention, according to McKinsey & Company’s 2019 report ‘Refuelling the innovation engine in vaccines’ there has been slowing growth in vaccine development over the past five years, with slowing revenue growth and a flattening development pipeline with new vaccines being undifferentiated from what is already on the market. However, the McKinsey report indicates that changes to investment strategies as well as a shift in focus to more technical and complex vaccines could renew innovation. © Shutterstock /Parilov 24-27.qxp_Layout 1 06/08/2019 09:32 Page 4THE ANSWER TO OPIOIDS 28 Pharma Business International www.pbiforum.net © Shutterstock /Victor Moussa 28-31.qxp_Layout 1 06/08/2019 09:33 Page 1Pharma Business International 29 www.pbiforum.net THE ANSWER TO OPIOIDS I n 2016, figures showed that health care providers across the United States wrote more than 214 million prescriptions for opioid pain medications. More than eleven million people abused prescription opioids, and, in the same year, drug overdoses claimed the lives of nearly 64,000 Americans, sixty-six per cent of which involved a prescription or elicit opioid. This rose to 68,500 drug overdoses in 2018. Every day, more than 1,000 people are treated in emergency departments for misusing prescription opioids and the Centers for Disease Control and Prevention (CDC) estimates that the total economic burden of this misuse is around $78.5 billion a year. At the beginning of the year, the National Safety Council revealed that, for the first time in US history, a person was more likely to die from accidental opioid overdose than from a car crash – with odds of one in ninety-six. But for the first time since 1990, the number of annual drug overdose deaths in the US has declined. The amount, as released by the CDC, is five per cent, and while this might be an encouraging sign, it’s too early to tell whether it means the crisis has peaked or if it represents a shift in overdose trends. Unclear also is whether this slight fall is part of a trend that will continue in the coming month and years or if it is simply an anomaly. The formation of pain as a medical field only began in the sixties, and by the eighties a number of pain specialists played down the addictive nature of opioids and pushed for their increased use in treating long-term non-cancer pain. This began a decades-long campaign, backed by the pharmaceutical industry, that convinced many physicians that they could and should prescribe opioids more freely and thus paving the way for the epidemic as we know it today. This has led to entire states suing big pharmaceutical companies and taking the industry to task over their role. It wasn’t just an attack on the industry but on corporate greed, underhand practices and on capitalism itself. In May 2018, Mike Hunter, Attorney General of Oklahoma, led his office in suing Johnson & Johnson (J&J), the biggest pharmaceutical company in the world, for $17 billion to fund treatment and offset other costs of the epidemic in the state. It was a long and complex battle that uncovered the seedy underbelly of the epidemic and, in July 2019, Hunter concluded a two-month trial in which he accused J&J of operating a “cunning, cynical and deceitful scheme” to boost opioid sales as one of a web of firms. These companies, the trial uncovered, worked to change the very fabric of medical culture and practice by influencing doctors, researchers, federal regulators and politicians. A 2017 study published in the A cure for corporate greed Since the over-prescription of opioids in the United States in the early nineties, the epidemic has gone on to claim the lives of some 400,000 people. 30 Á 28-31.qxp_Layout 1 06/08/2019 09:33 Page 2Next >