< PreviousDIGITAL THERAPEUTICS 20 Pharma Business International www.pbiforum.net They are often used as preventive measures for patients who are at risk of developing more serious conditions. As an example, an app that can help someone monitor and change their diet might be prescribed to someone who is treading close to diabetes. They can, however, also be used to monitor and self-care, and using the same example someone with type II diabetes could use digital therapeutics to manage the disease. Digital therapeutics is a new and exciting world for pharmaceutical and many are hoping it will help reduce the strain on hospitals by allowing greater agency to the individual. While it’s never designed to take care of serious matters, it can and perhaps will take care of lesser symptoms – and can even be used to monitor biological systems and blood glucose levels and administer insulin from insulin pumps remotely. There are concerns abound with the technology, of course. There are fears people may rely too heavily on the digital information and not visit hospital when more serious situations arise. This isn’t 18-21.qxp_Layout 1 07/10/2019 12:05 Page 3Pharma Business International 21 www.pbiforum.net DIGITAL THERAPEUTICS © Shutterstock /SFIO CRACHO so much a problem with the technology as people themselves, but it’s ever been the case that some will ignore potentially telling symptoms. Another concern is that of data. Hackers already pose threats with how digital our world is, but medical data is tied deeply to our person and can include very sensitive information. What’s more, there is the potential for the therapeutic software to be hacked directly and changed, potentially to provide misleading or outright dangerous advice. This is an extreme example of course, but not a year goes by without people fearing pacemakers being hacked and killing thousands, so it’s one that must be raised. More down to earth concerns are that there isn’t enough clinical data on how successful the technology is at preventing disease. While some studies have been conducted, with noticeable improvements on helping with depression noted, it’s a far more complex issue than just that, and the technology hasn’t been around long enough. More research is needed. SECURING APPROVAL 22 Pharma Business International www.pbiforum.net Clinical trials often make or break a new product, with much of the future success of huge investments being determined on how the product interacts with humans. While there is always vast amounts of tests that should - and will - have been undertaken on the product, there is always the disastrous possibility that there will be an adverse reaction when it is introduced to volunteers in the clinical trials. Clinical trials only come into play once the preclinical and testing procedures have been completed, and in most cases can only be undertaken after receiving approval by an authorised body such as the FDA. Figures suggest that it can take up to ten years on average, and cost an incredible $2.6 billion for a drug to make it through all the stages of clinical trials. And less than twelve per cent of new medicines even make it past FDA screening, and into phase 1 of clinical trials. And it is a multi-phase process, of course. In most cases it will first be tested on a small number of volunteers, with the results of such being monitored before it is then tested on hundreds - and eventually thousands of volunteers. Compliance with these requirements is a difficult hurdle, but one all companies are faced with and must adhere to. It’s not just trials where compliance need be observed, however, and there is increasing focus on high standards within the laboratory now as well. For many companies this takes the form of the GLP (or Good Laboratory Practice). In most cases GLP refers to a quality system of controls and management for laboratories, which helps to make sure that there is a certain reliability and integrity to any results. This involves a number of requirements, as any good non-clinical research must be consistent, reliable and above all reproducible. GLP was born in 1972 in New Zealand and Denmark, but only spread to the US in 1978 following a BioTest Labs scandal. The Organisation for Economic Co- operation and Development (OECD) helped to spread the principles of GLP to many other countries, and now it is common around the world. Clearing regulatory hurdles 25 Á Pharmaceutical companies are expected to comply with the various criteria introduced by organisations such as the US Food and Drug Administration and the European Commission. One way in which they can do this is by making use of high-quality inspection and detection systems. Chief among the requirements from many bodies is that the clinical trials stages of a drug’s development are adhered to as stringently as possible. Pharma Business International 23 www.pbiforum.net SECURING APPROVAL 22-25.qxp_Layout 1 07/10/2019 12:07 Page 2SECURING APPROVAL 24 Pharma Business International www.pbiforum.net © Shutterstock /Fishman64Pharma Business International 25 www.pbiforum.net SECURING APPROVAL Obviously GLP does not refer to the basic safety necessities of lab health and safety, such as gloves, glasses and PPE. These are basic requirements that should come as standard in every way. GLP is split into many different categories, all of which carry equal importance in the eyes of the OECD. The responsibilities of individual personnel and their roles are clearly defined, as is the need for these members of a team if any are not present. The guidelines are mostly broken down into the different stages of research, including test facility organisation and personnel - which looks into the responsibilities of the study director, principal investigator and study personnel. These aim to ensure that studies are carried out in a way that aligns with conduct requirements expected of the positions. There are also guidelines to indicate and set up expectations for the recording, documenting and archiving process. Following after that is Quality Assurance programmes, including the responsibilities of QA Personnel within the lab. Facilities in general, which involves not just test system facilities but also facilities for handling tests and archiving. Waste disposal is also covered, particularly with the hazardous s and dangerous nature of many by- products created in the lab. When it comes to study plans and reports, the GLP lays out required content for the study plan in terms of aims and goals, details of the sponsor and any additional test facilities involved in the tests, and much more. The goal here is to ensure that any and all transparency is observed when it comes to looking over or publishing the results of any tests. Scandals in past years have shown that labs sponsored by individual companies may find results that benefit those companies to the detriment of scientific protocol. GLP can help reduce this, or at least put safeguards into place that allow investigators to look back over the process and identify if this might be the case. GLP has always been referenced as something of a guideline, but for many countries certain aspects - or the entirety - of it have been put into law. The European Union adopted two basic Directives and a Decision relating to the application of the GLP principles in 1987, while some changes were made to this in 2004, much of it still does apply. These include compulsory audits and inspections to ensure that lab facilities conform to GLP rules and regulations - so it is very much an issue of compliance. 22-25.qxp_Layout 1 07/10/2019 12:07 Page 4INNOVATIVE APPROACHES 26 Pharma Business International www.pbiforum.net Whilst the pharmaceutical industry has been traditionally recognised as slow to adapt to change, a plethora of innovations are now being utilised - digital solutions in particular. Companies are turning to advanced technologies like artificial intelligence to improve operational efficiency, streamline processes and grow staff productivity but are also looking to integrate digital therapies into their product portfolios and lead a new innovative vision of what pharmaceutical companies can provide. Augmenting, and sometimes replacing, drugs in treatment, digital therapies such as smartphone apps are changing the landscape for production of new medicines. New data sharing processes are key in this, with digital therapeutics set to offer real-time consumer insights and new tools to manage patient health, with the transmit of data allowing for additional visibility in care and creating new ways to improve treatment outcomes. There is even the potential for pharma firms to use digestible sensor technology to monitor drug usage. The US has recently led a charge forward here with regulatory changes regarding digital health establishing new opportunities in the pharma industry, making it easier for digital health products to be cleared. Pharma companies developing products for the purpose of complicated therapeutic areas, chronic illnesses and rare diseases will find producing apps and delivery devices that work in conjunction with drugs simpler. The changes made in the US will allow for, for instance, digital companion apps aiming to enhance use of prescription drugs to be regulated as labelling. The digital opportunities here also present companies with a chance to differentiate products to clinicians, patients and insurers, and become more competitive. Emerging digital technologies are influencing business models, seeing companies produce services past just a drug for more comprehensive treatment of for instance chronic diseases. A 2018 PwC HRI survey of pharma executives indicated that 42% were actively developing digital therapeutics or connected deceives. From those not developing these, 42% indicated that they planned on doing so within the next two years, and 58% in the next 3-6 years. Confidence in digital health opportunities is further evidenced by $12.5bn of investment in 2017 and 2018. PwC note that a plethora of connected devices will be entering the Integrating digital innovation Fully entering the digital world, pharmaceutical companies are putting into practice innovative, digital approaches to research, trials and product development. 28 ÁPharma Business International 27 www.pbiforum.net INNOVATIVE APPROACHES © Shutterstock /elenabsINNOVATIVE APPROACHES 28 Pharma Business International www.pbiforum.net market this year, to treat conditions like diabetes and central nervous system disorders, both in and not in conjunction with drugs. Additionally, digital health apps are bridging the gap between consumers and companies, which is ever more important as public trust of the pharma industry declines. Overall digital therapeutics is seeing patients treated in ways the extend past a solo dimension of health and is creating the potential for treatments to be better customised, mirroring the current trend of patient centrism. Further, the growth in wearable biometric devices and telemedicine is set to boost innovative digital approaches and create a cohort of more informed patients, ready to take an active role in treatment plans. Research and development are also set to receive a boost from innovative digital approaches. This is especially the case in clinical trials, where the relevance of wearables and apps returns. Allowing for the continuous recording and transmitting of vast amounts of patient data remotely, in real time, these devices enable virtual trials, which reduce patient burden and generally make trials more accessible by removing visits to clinics, and as a result boost trial recruitment. Remote monitoring of patients in trials also has the potential to save millions for pharma companies as expensive tests completed at a hospital or clinic can now be done with mobile devices. AI, which has been a hot topic in the pharma industry and its digitalisation, is also being used to innovate trials, specifically in selecting the best patients for trial by combing through demographic and historical data. AI can be used so that only those eligible for specific clinical trials are notified of them, reducing wasted time in this process, and further be used to identify patients with rare diseases and those suited for specific drugs. AI is being implemented across drug development from research to clinical trials to manufacturing, finance and operations. Holding the potential to reduce the research and development spend of new drugs, AI and predictive analytics are accelerating innovative approaches to drug development by intelligently searching large pools of patents, publications and trial data, allowing researchers to examine previous results from tests. By applying these to search boundaries, researchers can focus in on pertinent information and gain insight into what areas will produce the best results. AI is set to boost drug development efficiency by removing strain on research efforts, in our data and research-intensive industry, by helping locate data patterns and interpret data analyses quicker, rapidly developing hypotheses and proposing molecules for new medicines, ultimately allowing pharma companies to make smarter and more strategic decisions and more quickly arrive at viable drugs. Further, AI can perform protein modelling to understand the mechanics of disease and uncover novel treatment methods and is being implemented to shape more effective treatments, as well as find new uses for existing drugs. Helping in the development of personalised medicine, AI also has the ability to efficiently analyse small datasets focusing on a specific disease and consequently design optimal drug combinations that will be effective. A recent case highlighted the brilliance of AI in accelerating drug development when Hong-Kong’s Insilico Medicine revealed that its AI powered drug discovery system could produce a potential treatment for fibrosis in under a month. While usually AI in drug development screens millions of possible molecular structures, seeking a fit, in this case a creative AI algorithm, imagining potential protein structures based on research and pre-programmed design criteria was used. After producing 30,000 designs, researchers reduced this to six, one of which was tested on mice and is said to have produced promising results. Though, overall, AI is not yet outperforming established research methods, this instance highlights AI’s role in forming a more innovative approach to drug development and its potential to save years of work and millions of pounds, marking a new starting point for AI in revolutionising drug development. 26-29.qxp_Layout 1 07/10/2019 12:08 Page 3Pharma Business International 29 www.pbiforum.net INNOVATIVE APPROACHES © Shutterstock /Orawan PattarawimonchaiNext >