< PreviousCOLD CHAIN 30 Pharma Business International www.pbiforum.net cold chain, an already costly area, is growing, especially when it comes to tracking - which is key to maintaining strict temperature requirements. Cold chain management has been enhanced with advances in temperature sensors, data loggers, telematics, and cloud computing solutions which allow the real time remote monitoring of temperature and location to ensure the safety of products. Improvements in the past few years have seen this monitoring technology developed further to form highly automated networks of wireless sensors and servers which send alerts when temperatures vary to enable quick corrections and collect data constantly. Monitoring systems are also being provided with user-friendly dashboards so that this data can be tracked over time, greater insight can be gained, and problem areas dealt with, and artificial intelligence and machine learning models can now be wielded to uncover anomalies and find exceptions, providing continuous intelligence from billions of data points. There remains a need for better connection and more consistent, constant monitoring between steps in the cold chain however, to facilitate end-to- end visibility. When it comes to managing the cold chain, logistics managers have many issues to contend with, from ever- © Shutterstock /Sorn340 Studio Images With the biopharma industry said to lose $35 billion annually because of failures in temperature-controlled logistics, more still needs to be done to mitigate this. 28-31.qxp_Layout 1 12/10/2021 13:51 Page 3Pharma Business International 31 www.pbiforum.net COLD CHAIN changing, stringent regulations - which become even more difficult to meet if one’s cold chain is worldwide, with each region holding its own regulations, compliance mandates, and enforcement agencies - to the topic that only continues to grow in importance: sustainability. The distribution and transport of products through the cold chain creates significant greenhouse gas emissions and consumes more fuel than other supply chain transportation as a result of heavier vehicles thanks to refrigeration equipment. This comes with the high energy consumption and combustion of fossil fuels needed to power cooling systems in the cold chain and increasing concern and regulation surrounding refrigerant gases used in cooling systems, such as hydrofluorocarbons (HFCs) which are responsible for high greenhouse gas emissions. Indeed the US is phasing down HFC use, setting out a timeline for 2036. Meanwhile refrigerants with fewer global warming impacts are being created. In response to demand for more sustainable practices, many pharmaceutical companies are putting in place plans to reduce cold chain carbon emissions, waste, and simply retiring older, inefficient equipment. One option is to utilise alternative transport methods like intermodal over truckload when shipping products, while hybrid electric trailers and high-efficiency solar charging systems for trailer refrigeration units are also on the cards, as well as lower weight cargo containers and reusable shippers to minimise packaging waste. Furthermore, the industry is moving towards renewable energy sources. With the pharmaceutical industry’s cold chain thrust into the spotlight in the coronavirus pandemic, now is the time to capitalise on the opportunity to refresh procedures. © Shutterstock /Fotokon 28-31.qxp_Layout 1 12/10/2021 13:51 Page 4ETHICS 32 Pharma Business International www.pbiforum.net Gene editing offers scientists the ability to make highly specific changes in the DNA sequence of living organisms, effectively customising its genetic make- up. Key to the new wave of gene editing technology is the molecule known as CRISPR-Cas9, which was only discovered in 2012. A kind of genetic scissors, CRISPR offers a relatively easy means of editing genes and, recently, has been used to try and treat adults with deadly diseases. But because of the huge leaps forward in this field and the overall speed of innovation, the discourse around the potential ethical, societal and safety issues is lagging. The conversation was thrust into the spotlight after a scandal in China forced scientists, governments and the general public to evaluate the ethics of gene editing. In 2018, professor He Jiankui alleged that he had created the world’s first genetically edited babies, apparently altering the genes of twin girls so they could not get HIV. Jiankui studied at Rice and Stanford universities in the United States before returning to his homeland to open a lab at Southern University of Science and Technology of China in Shenzhen where he conducted his research. It built on his earlier efforts, where he edited mice, monkey and human embryos in a lab setting for years. Using CRISPR, he says he altered embryos for seven couples during fertility treatments, two of which were implanted into a woman who gave birth to the twins. Jiankui said his goal was not to cure or prevent the inherited disease but rather to try and bestow a trait to resist possible future infection with HIV – a trait that few people naturally possess. He chose HIV specifically because, he says, these infections are a big problem in China. Figures from 2015 reveal that there are over 500,000 people living with HIV in China, demonstrating the overall progress made in the tackling its HIV epidemic which ran rampant in the nineties. In questioning just what drove couples to join Jiankui’s experiment, some have pointed towards societal pressures. In China, people are encouraged to marry young and have a child as soon as possible, so Jiankui can be seen as having preyed on young couples with HIV desperate for a child. He worked with a Beijing-based AIDS support network to The ethics of gene editing 34 Á Gene editing remains one of the most controversial topics in medicine. Despite first emerging in the seventies, it continues to present a unique ethical quandary for the scientific and medical communities. 32-35.qxp_Layout 1 12/10/2021 13:52 Page 1Pharma Business International 33 www.pbiforum.net ETHICS 32-35.qxp_Layout 1 12/10/2021 13:52 Page 2ETHICS 34 Pharma Business International www.pbiforum.net recruit couples with a HIV positive male and a HIV negative female and registered as many as two hundred families that expressed interest in the research. The exact motivations of these families remain unclear as the consent form signed at the time prohibits any discussion about the project with others. To date, the parents of the twin girls have not been publicly identified and have not spoken to the media. Although Jiankui said he was proud of his work, there has been no independent confirmation of his claims and, tellingly, his work has not been published in any journal, where it would have been vetted by other experts. The research only involved one other scientist, the physics and bioengineering professor Michael Deem, who was an advisor at Rice and, it should be noted, holds a small stake in Jiankui’s two companies. What can be quantified, however, was that the research has been largely met with derision, scepticism and outrage from the scientific community. The Southern University of Science and Technology of China distanced itself from Jiankui’s work, saying it “seriously violated academic ethics and standards”. State media, meanwhile, said he acted illegally and in pursuit of fame and glory with reports alleging his work was conducted without oversight and on his own authority. If some reports are to be believed, Jiankui may have even lied on consent forms, claiming he was working on an AIDs vaccine development rather than gene editing. Even setting aside the ethical concerns, lying on consent forms is not an encouraging sign. Some scientists have denounced the research as akin to human experimentation, while the Chinese government itself said the work was “extremely abominable in nature”. Although there were some scientists on Jiankui’s side, Dr Kiran Musunuru, a gene editing expert from the University of Pennsylvania, probably caught the pervading attitude at the time by describing the research as “an experiment on human begins that is not morally or ethically defensible”. It’s not CRISPR itself that’s controversial, at least not as far as regulators and the parents of sick children are concerned. For example, in 2015, a one-year-old girl with leukaemia was treated with genetically modified immune 32-35.qxp_Layout 1 12/10/2021 13:52 Page 3Pharma Business International 35 www.pbiforum.net ETHICS cells that cured her cancer. Yes, it was controversial, but all involved were praised. And the CRISPR space is a hive of innovation, taking aim at major health issues and even working to develop better antibiotics. So what’s the issue? The age of the baby isn’t the issue in determining whether or not a treatment is considered ethical, but rather which cells are altered. In the scientific community, there is a clear line in the sand between somatic cells – any non-reproductive cells – and editing germline cells – those involved in reproduction. Editing the germline involves altering a sperm, egg or fertilised embryo. As the edited embryo develops, any change made will propagate throughout every cell in the body, including the sperm and eggs passed on to the next generation. And therein lies the controversy. These changes can echo down the genome of progeny for generations. The use of genome editing in embryos for assisted reproduction in humans is banned in dozens of countries – including in the US and UK – because DNA changes carry to future generations and risk harming other genes. In the wake of the Chinese scandal, a new committee of the World Health Organisation called for an international registry to track studies that edit human embryos and suggested a five-year embargo of editing the DNA of human embryos that women intend to carry to term. The National Institutes of Health in the US, meanwhile, says that there is a lack of medical need surrounding this kind of gene editing, plus safety concerns and profound societal and philosophical issues. There’s no clearly defined answer when it comes to determining the ethics of gene editing. Bioethicists and researchers generally believe that human genome editing for reproductive purposes isn’t something that should be attempted at present. However, all gene editing carries with it a risk, as a scientist may accidentally alter cells near their intended target. Regulators and government agencies are trying to catch up with the dramatic pace of innovation seen in the gene editing space, keen to avoid another scandal. Yet this shouldn’t eclipse the possibilities of gene editing, a tool which can rapidly redefine how people are treated and how inherited diseases are managed. © Shutterstock /Catalin Rusnac 32-35.qxp_Layout 1 12/10/2021 13:52 Page 4BUSINESS GROWTH 36 Pharma Business International www.pbiforum.net Even the biggest pharmaceutical players are required to secure funding to financer drug development or moving a novel new substance into clinical trial. But for research firms and small-scale developers, funding is the very lifeblood of their research and development programmes. Fortunately, there’s a number of different avenues open to companies, researchers and other organisations, whether they get the required amount from one source or from a combination. Although the European Medicines Agency (EMA), the European Union agency for the evaluation and supervision of medicinal products, doesn’t fund research or drug development directly, it can and does provide support to medicine developers. An organisation that does provide direct funding is Innovate UK, a public body driving science and technology innovations to grow the economy. Since 2007, the organisation, billed as the UK’s innovation agency, has invested in excess of £1.5 billion in innovation, a figure that has been matched in partner and business funding. During this period, it has helped more Bankrolling innovation Setting aside the regulatory and ethical challenges involved in new discoveries and bringing new medical and pharmaceutical products to market, there remains the issue of funding – specifically who’s bankrolling the research, materials, staff, clinical trials and so on. 36-39.qxp_Layout 1 12/10/2021 13:53 Page 1Pharma Business International 37 www.pbiforum.net BUSINESS GROWTH © Shutterstock /steved_np3 38 Á than 5,000 companies across the industrial spectrum, medical, pharmaceutical and life sciences companies among them. It does this through direct investment in organisations but also through innovation competitions. Yet it’s not only companies Innovate UK provides funding for, but other innovation orientated organisations – including Medicines Discovery Catapult. This independent not-for-profit organisation is a national facility connecting the UK community to accelerate innovative drug discovery. It provides scientific capabilities and acts as a gateway to specialist facilities, technology and expertise, supporting SMEs to dive development and the widespread use of new approaches for the discovery and early development of new medicines. Part of the organisation’s literature is that traditional models of development medicines is “no longer fit for purpose”. It’s currently estimated that it takes an average of 13.5 years to take a new drug to a patient at a typical cost of over £1.2 billion. The challenge, the Medicines Discovery Catapult says, is to do this faster and cheaper without compromising patient safety, a mission it endeavours to accomplish by providing and applying new scientific systems, uses of data and methods of working. Charity organisations, such as the British Heart Foundation and Cancer Research UK, exist to raise money to fund research and medical breakthroughs. The latter, which is the largest independent funder of cancer research in Europe, allows organisations to apply for grants as well as enabling 36-39.qxp_Layout 1 12/10/2021 13:53 Page 2BUSINESS GROWTH 38 Pharma Business International www.pbiforum.net © Shutterstock /Oleksiy Mark researchers to involve patients in their studies. It funds a broad portfolio of investigator-led research – from individual projects and fellowships to large-scale team science programmes, multidisciplinary collaborations and international consortia. While there’s grant funding, the charity also makes long-term investments in state-of-the- art facilities and resources. Of course, much of the funding that charity organisations can provide to industry, academia and other organisations comes from the public. Direct donations – whether online or in collections in stores or on the streets – are part of this, but so is campaigns such as coffee mornings, sponsored walks or runs and a myriad of other approaches. When fundraising campaigns capture the public interest and go viral online, they really do have the power to bankroll important research and help change lives. Readers will no doubt recall the now infamous ‘Ice Bucket Challenge’ from the summer of 2014. In short, participants would tip a bucket of cold water over themselves to mimic the sensation of motor neurone disease and nominate others to follow. The campaign eventually raised $115 million which was used to fund several important research products. But public funding isn’t immune to the pricing and funding issues the plague the wider pharmaceutical industry. “Rapidly escalating healthcare costs throughout the world, pre and post Covid, mean that more than ever, we need to be smarter about how we address healthcare challenges. Complex medicines can be part of the solution. What are complex medicines? These can be medicines that use novel technology or have been modified in some way such as formulation or delivery method to address unmet medical need, often in small patient populations, rare diseases, or where there are currently none or few treatments available. They represent a step change in the provision of medicines, not only in their ability to fill in gaps left by more traditional approaches but can also be more cost effective in the long run. At ADVANZ PHARMA, we have a strategic focus on complex medicines and our driving motivation is to improve the lives of patients by enhancing the medicines they depend on, working to address unmet needs while helping to maintain sustainable healthcare delivery across the European hospitals market. But complex medicines require significant investment to make them available for the patients who need them. I believe this is where ADVANZ PHARMA is leading the way in this specialised area. Complex medicines and Strategic Growth When it comes to complex medicines, whether they are new innovative medicines, added value or re-purposed generic medicines, there is a need for highly sophisticated planning and development procedures, as well as deep expertise in the regulatory, quality and market access environments to make these medicines available to Advancing access to complex medicines through Strategic Growth Pharma Business International had a chance to speak with Paul Burden, Chief Commercial Officer of the Strategic Growth Unit of ADVANZ PHARMA, to learn more about ADVANZ's expansion into complex medicines. 36-39.qxp_Layout 1 12/10/2021 13:53 Page 3Pharma Business International 39 www.pbiforum.net BUSINESS GROWTH specialist physicians. As such, in 2020 we made the decision to create two distinct business units, one of which is primarily focussed on these complex medicines, and another on providing essential established medicines. Each unit has a critical role in supporting the company’s future growth and stability and although they operate via different channels and require distinct commercial and operational strategies, they each work towards a common goal: bringing vital medicines to patients. With ADVANZ PHARMA, I lead the Strategic Growth Business Unit, which contains a range of complex medicines, including: enhanced versions of existing molecules that deliver cost and supply efficiencies for our customers; value-added medicines which offer incremental improvements to a medicine’s delivery that improve patients’ lives and, finally, patented innovative medicines that allow hospitals to rethink how patients are treated, helping to protect hospital resources. Our medicines within the Strategic Growth Business Unit are primarily focused in the anti-infectives, endocrinology and critical care therapy areas. Our ability to commercialise such medicines is based around the skillset and deep expertise of our people and, in recent years, we have significantly expanded and strengthened our capabilities within the area as a result. Through our acquisition of Correvio Pharma in 2020, we were able to significantly accelerate our position by integrating a skilled team of over 80 individuals who have highly specialised expertise throughout Europe in hospital channels and across several therapeutic areas. Collaboration is key Simply put, the delivery of our medicines would not be possible without our partnerships across our global network. These range from partners who support with sourcing active ingredients, our developers, our contract manufacturers, our distributors and the partnerships we have locally with healthcare system providers. These lasting relationships allow us to invest significantly in our portfolio to help broaden patient access and improve health outcomes. With some very interesting new launches planned over the next few years, we are proud to have already made significant strides in this area, although we continually seek new partnerships that enable us to leverage our capabilities within the European hospital channel, to bring products to market that deliver genuine value to patients and the healthcare systems who care for them. The future will certainly be both complex and challenging, as healthcare providers and the industry seek to balance resources in order to best meet the needs of a growing patient population. Meeting this challenge will require us all to challenge the status quos, to actively drive change, and align our organisations (whatever their role in the value chain) to satisfy the needs of tomorrow. Within ADVANZ PHARMA, I look forward to continuing to lead our progress within the complex medicine space, which will act as a vital conduit for the future of the business, in parallel with meeting the unmet needs of patients and healthcare providers. From a corporate perspective, our goal is to build on our collaborative industry network to become the go-to partner for commercialising complex medicines in the European hospitals market. By revitalizing and developing these medicines, we are committed to improving access and choice based on patient need, not patient numbers, and I look forward to seeing the continued benefits in the months and years to come.” For more information, please visit www.advanzpharma.com Paul Burden, Chief Commercial Officer, Strategic Growth Unit ADV/MISC/NP/0113 October 2021 36-39.qxp_Layout 1 12/10/2021 13:53 Page 4Next >