QP Qualified Person

Qualified Person and Digitalization

NCF Notiziario Chimico Farmaceutico – Nr 5, June 2020 – by Mirka Broccato The Covid-19 tsunami has further confirmed to what degree Digitalization plays a central role in enabling remote working in total compliance if conditions should require. The role of the Qualified Person (QP) is to ensure the quality of a medicine, employing the use of GMP. In regard to GMP, a medicine does not only comprise of packet tablets or ampoules, it is also a representation of quality systems in the company that produces it, of good practice in managing various machines, documents and data, while also a representation of the competence of those who produce it, who check and verify the appropriacy of processes and so much more. And so, the question we ask is – how can an individual today, in all good conscience (even at the risk of penal violation!) guarantee that all aspects related to the production of a medicine work as they should? and even consistently in the long term? It was once thought that the job of ensuring the quality of our medicines lay in the hands of Quality Control. QPs placed their trust in laboratory technicians, their samples and the results of their analyses to assure us that the product was compliant and of sufficient quality. Then it was found that, however statistically viable a sample can be and as much as one can choose, develop and validate supposedly reliable analytical methods, things can still go awry, slipping under the QC’s radar. The temperature in a reactor can rise due to a probe malfunction, risking product longevity, subsequent complaints or call-backs of the product in the market. It may occur that a machine technician replaces a machine filter with an identical part that however is not produced by the same supplier, resulting in spikes in colour profiles presenting seemingly inexplicable impurities. All considered, how can QP provide compliance guarantees and the adherence to the rules that are expected of it? How can science in all good conscience ensure that the quality of the process as a whole is met with certainty or at least with a sizeable degree of safety? Increasingly, thanks to the availability of new digital technologies, the answer is clear: we require systems and infrastructure that can gather our data and process it. Granted that there will always be competent and experienced technicians, trained in the use of digital systems who will analyse, interpret and gather the required information to allow QPs to make informed decisions. In short what is required is: integrated digitalization projects aimed towards the specific needs of the company. QP and the production process Digital solutions such as the Manufacturing Execution System (MES) are required, that collect (from the plants and control systems) the critical process parameters (CPP). Our production experts interpret CPP at a glance but if such a single glance is misplaced even for a moment, data can be lost forever, and with it the chance to comprehend the true reality of the lot in question. It is necessary to guarantee the ability to connect what happens during the production of each batch to what will happen when it’s being analysed and onwards to its distribution in pharmacies. Vital data from processing is used by QPs to monitor production trends and allows them to make the right decisions in a timely manner whenever required, even when they are not physically present in production workshops, as can always happen, but could be especially required in times such as these. Quality Processes We require digital solutions that allow us to align departments that are only seemingly misaligned. To promote a culture of information exchange and ban silo work forever. An example being Enterprise Quality Management System (EQMS) solutions, with which we can align the Purchasing and Logistics Department with Development, Quality Control, Quality Insurance and production. Does the Purchasing Office have anything to do with it? Indeed, It does! It is involved for example, when the supplier of an excipient unexpectedly stops supplying us with raw materials because (as we have learned very well in recent times) a global health emergency put markets in the red. We would then be required to seek out alternative sources, evaluate immense quantities of documentation quickly as production has already been scheduled. It is at times like these especially that a digital solution can render change control processes efficient and safe, ensuring that any and all relevant players are placed to offer their conclusions quickly and objectively. The Labs We require digital solutions that allow us to collect data from labs and allow us to quickly combine the progress of a process parameter (CP) with that of a critical quality attribute (CQA). These are Laboratory Information Management System (LIMS) and Electronic Laboratory Notebook (ELN) solutions. Systems that allow us to compare grain profile trends in a component together with the mixing times of the product that encapsulates it, in order to understand that a supplier has changed process and set our CQA adrift. Only with such information at hand can technologists fully understand processes and intervene in advance, before non-conformity is flagged, before the need to duck for cover with a batch of product ready for shipment in hand. Only when armed with is information is the QP able to express an overall judgment of a medicine’s compliance, even if forced to oversee a workshop far from their normal workplace. The Complexity of Plants Futhermore: How can a QP perform the task of checking the adequacy of plants, as in Chapter 3 of the GMP? We cannot assume they possess never-ending insight and availability and should be expected to personally verify the compliance of each and every machine in the workshop. To ensure process quality, integrated digitalization projects are needed that are targeted to the specific needs of the company. In order to ensure that plants who we have produced a batch of medicine with are in acceptable states of maintenance, adequate information must be made readily available once again. A company that employs a Computerized Maintenance Management System (CMMS) solution is a company that securely and quickly ensures traceability between medicines batches, production machines and maintenance status. It is a company that (if faced with a complaint or non-compliance) is able to make an appropriate and fast root cause analysis. It is a company where its key individuals immediately possess the information to identify effective CAPA when required and no matter they are. And not a day later. A day could make a big difference! The Role of “Surveillance” Lastly, how can the QP ensure that each and every batch of medicine has been produced in accordance with GMP and marketing authorization? Every day (with a personal signature) the QP is responsible for ensuring that every activity carried out to convert raw materials into medicine has been carried out properly. That such tasks were performed in accordance with approved procedures and methods. With procedure and methods that our authorities have given the green light to. The best way in which a QP can have sufficient peace of mind as a guarantor of this surveillance role in modern times is to be able to rely on a system that exerts active control over every single phase of the manufacturing process. A system which collects data as generated, that interacts and alerts you where and when an event falls below the expected standard. Yes, we are still talking about a digital solution, that is, an Electronic Batch Record System (EBRS). Designed and validated properly of course. With a complete electronic BR available which is accurate and readable the rollout of a product can be set in motion with confidence, even remotely. As may be required, in particular, in Covid-19 times. Is Digitalization for everyone? The Digitalization of a company is unfortunately still perceived as a lengthy, expensive process for small to medium Italian companies, but this may not be the case. One of the strengths of the digital solutions available today (also thanks to the advent of 4.0 technologies) is that yes, they can be integrated, yes they are easily validated, but above all they can be realized one step at a time, based on specific requirements and with sustainability in mind. It’s important to know how far you’ve come and the goals you wish to achieve. Know the key processes, map them and draw out strengths and weaknesses, also and especially in a view towards efficiency and compliance. Establish benefits achievable with the resources available, aware that you are beginning a journey of continuous improvement in regard to your destination, stop offs and individual steps. QP and the Digital Company, attracting business. Digitalization projects allow significantly increases in the usability of information at all levels, not just for QPs. A Digital Company therefore provides itself with the opportunity to detach itself from the mindset of the physical presence of personnel and opens up opportunity not only for active surveillance but also active remote operations, creating the right substrate for the development of smart working and also of different key functions. The story of recent times tells us that a digital company is also a more resilient company: in times of emergency it is able to maintain the fundamental processes within the business. For QPs, it’s helping to ensure that drugs – whose quality and adherence to regulations they monitor every day – continue to arrive in a timely manner to the patients who need them.
pharma 4.0


Automazione Industriale di Valeria De Domenico ARTIFICIAL INTELLIGENCE, BLOCKCHAIN, 3D PRINTING: IT’S NOT ONLY MARKET COMPETITIVENESS, THE PHARMACEUTICAL INDUSTRY ADAPTS TO ALL EMPOWERING TECHNOLOGIES IN ORDER TO ENSURE CONTINUITY AND EFFICIENCY IN ANY CRITICAL EMERGENCY. With time currently sort of frozen, we endeavour to carry out a furthering of the Italian pharmaceutical industry, an area in which our country boasts multiple worldwide merits and a recent trend of excellence. Italy now more than ever lays claim to its standing, with the health and wellbeing of all at the forefront. On such issues we sought comment from Teresa Minero, Founder and CEO of LifeBee – a Consulting and Digitalization Company in the Life Science sector – and President of ISPE Italy, European Leadership Team, Global Steering Committee SIG Pharma 4.0™- a non-profit association of pharmaceutical and Life Sciences professionals, who we thank for her time. “As was clearly laid out in a statement from Farmindustria in the latest hours (12th March for those who read, ed.) the pharmaceutical sector, and that of the Life Sciences in general, play an important role in society, and most certainly cannot permit disruption in the distribution and production of essential drugs or medical devices, let alone active clinical trials, which would risk invalidating years of work.” Minero tells us. “This affects those with Covid-19 and indeed the many who continue to be ill and unfortunately require treatment that cannot be postponed, one example being cancer patients. The pharmaceutical industry has taken important measures, from the introduction of smart working for office based services, to implementation, for necessary onsite activities, of continuity and emergency plans to guarantee essential services, while protecting the health of operators and employees. LifeBee too (which regularly provides essential consultation and support to customers, such as in Pharmacovigilance and Regulation or Production, in Laboratories or in Quality itself) has been found on the mark. I hope that we will remerge from this intense experience with a greater awareness of the importance of new technologies, to be used intelligently with a view towards sustainability and solidarity.” A SPOTTED EVOLUTION When discussing the topic of Pharma 4.0™ in April 2019, Minero concluded by defining the phenomenon not as a revolution, but as “full evolution”, since most Italian pharmaceutical companies have been moving towards this type of change for years, if only dotted and sparse. From the joint LifeBee & Sparta Systems meeting last February (dealing with Quality Management in Pharma) several more “psychological” obstacles have emerged, even if the new formula of the Government’s Industry 4.0 plan (which expands investment to potentially non-physical technologies if required) could become an additional incentive for Quality Management Systems. Incentives provided in this direction can certainly help to strongly increase (even among “late adopters”) prospects for integration and digitalization of information: let’s not forget that this is one of the strong points in the 4.0 vision. I must remind myself that all too often in Italy the 4.0 Industry has been perceived as exclusively linked to production machinery, precisely because of the limit set down by legislation to only benefit from incentives when investments are linked to material goods. The constraint has now been removed, and this could most certainly help the 4.0 revolution to escape from production lines and progress to departments such as Quality, Logistics, Regulatory and R&D. Moving more specifically to Pharma 4.0™, information sharing can and should be represented in the continuous improvement of processes within the company itself, but also and above all in the increase of regulatory compliance. The topic we delved into in our February 5th workshop in Milan on “Innovation 4.0 for Quality Assurance Management” is certainly well-fitting. It deals with automating the management of operating procedures, the management of so called Change processes, of Non-Compliance, Market Complaints, CAPA (Corrective Actions & Preventive Actions), Quality Audits (whether internal or external) of Training, to name the main players. There are undoubtedly several regulatory incentives in place, and I would like to highlight a regulation (one of many) currently being established in Europe on IDMP (Identification of Medicinal Product) and still little known. It regards the submission of basic data to the authorities regarding a medicinal product. The submission of said data is a process that even in its current form requires a lot of manhours. IDMP rules provide for an extremely high-level international standardization of shareable data in the direct interest of the patient. These involve a review and often a tuning of information flows within the company, allowing for great potential in all directions with the intelligent use of Digitalization. A MANIFESTO FOR 2030 Recent experience indeed (sometimes even just test cases) of activity improvements with digital technologies in key Pharma 4.0 call to attention even the most distracted. Such examples are many, some even unexpected, such as interesting initiatives involving Blockchain technology, seemingly futuristic but with very intriguing prospects. Probably the most important example however, which sums up very well what is currently happening, is the Italian Pharmaceutical 2030 Manifesto. The 2030 Manifesto (in which major companies such as Dompè and Sanofi took part and which was then presented to the Senate in September 2019) nominates Pharma 4.0™ among strategic objectives and digitalization among areas of operation. First impressions upon reading the Manifesto do indeed provide long lasting assurances, but an important offshoot is highlighting the theme of digitalization, spreading a signal that we are convinced will be picked up by many. In short, in order to return to the image of a spotted Italian Pharma 4.0™, we expect that the area begin to clear and take on a uniform coloration. QUALITY & Artificial Intelligence A preferred representative in discussions put forth by LifeBee is certainly Sparta Systems – a company active in the market in offering compliance and quality management solutions, which has introduced the topic of Artificial Intelligence in QMS. Fabrizio Maniglio (the company’s Solution Engineer) tells us more. “Artificial intelligence can be exploited to help discover the meaning of quality management data basing on relevant past information, thus enabling better productivity and intelligent decision-making within an organization. We have structurally incorporated artificial intelligence capabilities to support decision-making processes in our product: two examples can offer an idea of their potential. The first is automatic classification: by applying machine learning and natural language processing algorithms, we are able to automatically classify complaints, deviations, and non-compliance, ensuring that critical aspects are prioritized and handled quickly and appropriately. The system can provide suggestions and classification proposals so that Quality Assurance professionals can quickly evaluate new quality factors, allowing higher productivity and intelligent decision-making. The second is automatic correlation: we can also exploit AI capabilities to garner insight into quality data. The system identifies and correlates events of similar quality to assist in subsequent improvement actions.” These principles are at the foundation of the Digital QMS TrackWise System, which is the Sparta System proposal for Pharma companies. “TrackWise Digital is built on Saleforce.com, a PaaS platform (Platform-as-a-Service) which consists of an integrated suite of quality functionality (QMS as properly named), including complaints, supplier quality management (SQM), documentation management and training management (DMS, TMS),” adds Maniglio. “TrackWise Digital was built on the back of over 25 years of quality management experience at Sparta Systems and is a scalable, flexible pre-configurated based on recognised industry standards. It is the first QMS in this industry to have decision-making capabilities enhanced by artificial intelligence. The assured benefits of this type of product are many. One of our clients companies, for example, wished to implement efficient, effective and consistent quality processes across multiple business sites around the world to improve customer response capacity and reduce warranty costs: with TrackWise Digital it has been able to internationally harmonize its quality processes based on industry standards and to take advantage of advanced reporting capabilities to demonstrate regulatory compliance, and improve overall quality processes, so improving the operational efficiency too.”
DTx LifeBee

Digital Therapies: when the Medicine is Software

Teresa Minero for ICF – Rivista dell’Industria Chimica e Farmaceutica – May 2020 The Digital Therapeutics Alliance (DTA) defines Digital Therapies (or DTx) as follows: “They offer scientifically supported, therapeutic interventions to patients, who are then monitored by high-quality software programs to prevent, manage or treat a broad spectrum of behavioural, physical and mental conditions.” DTx are already part of current procedure and are applied in the treatment of an increasing number of diseases: Diabetes, respiratory problems, high blood pressure and more. Some DTx have been already approved by regulators (FDA, MHRA). The main function of a DTx is to integrate into, or even substitute traditional therapy (Medicine). The peculiarity is that they can be clinically validated by rigorous clinical trials), be approved by regulators, be subject to a Health Technology Assessment (HTA) and therefore be subsequently prescriptible. The active ingredient, so to say, is software that implements algorithms of varying complexity, integrating them with equipment / sensors (wearable, biometric or otherwise) and allowing information to be easily accessible on a smartphone, tablet or pc. Information then available to the patient and treating physician, with full regard to one’s privacy and security. Such methods help to alter a patient’s lifestyle, improving the state of their condition. This would typically arise through use of external devices (meters of various clinical parameters, scales, surrounding air quality), intelligent and personalized processing of collected data, including indications for the patient and treating medical expert to follow. An indication from LifeBee Experience The Life Sciences world has a well-established culture of binding regulation and standards which serve as a benchmark for correct software lifecycle management when it has (directly or indirectly) a possible influence on the quality of the medicine or medical device. All systems must be validated and qualified according to strict procedures, and are now established in the industry and constantly inspected by regulators. Valuable support for industry operators originates from ISPE GAMP guidelines® which provide the industry and its suppliers with methodologies and practice for the design, documentation, testing and maintenance of all such related software with a potential impact on the quality of medicines or medical devices, and ultimately on patient health. DTx is software that in essence acts as medicine in curing humanity, with a substantial impact on a person’s health.

Pharma 4.0: a new perspective of opportunities and constraints

Teresa Minero, Founder & CEO LifeBee e Alberto Augeri, Managing Consultant LifeBee, firmano l’articolo “Pharma 4.0: a new perspective of opportunities and constraints” per MEDIC Volume 26 – Dicembre 2018 – Pacini Editore Medicina. Industry 4.0: the concept is not new, yet 4.0 opens a brand-new perspective: everybody is involved, with new technologies. Pharma 4.0 is no exception in this perspective, with its own features and aims. In this frame, are regulations a constraint? Well, looking at trend of the last fifteen years, Authorities have been opening doors to change and innovate, with new technologies and new attitude. Pharma 4.0 sort of gathers them all.  Have a good Pharma 4.0 trip.
Introduction With an inspired term, Industry 4.0 indicates the big change that, starting from industry, is underway in many sectors of our XXI century activities. The term recalls the previous Industrial Revolutions, which were each a consequence of wide technological, organizational and social leaps through technological innovation and new production models (Fig. 1). Figure 1. Industrial revolutions: a view. A first leap was in the early XIX century, with the introduction of machines to take over the manual productions also thanks to new energy sources, symbolized by the textile industry in United Kingdom. A second leap a century later, with overwhelming innovations in many fields, led to the first, shy signals of globalization and what we call the mass production, especially symbolized by Fordism in manufacturing. With the technological and social acceleration that we all recognize, a third symbolic leap is considered to be the diffusion and fusion of informatics and automation in the seventies-eighties of the XX century. Whatever our interpretation is, all these transitions have at least four elements in common: 1) leap in productivity, whatever leap might mean in the different situations, e.g., increased volumes, enlarged product selections, higher quality and standards, stricter adherence between supply and demand; 2) impacts on employment, at least in terms of substitution of existing jobs with new ones. This fact, by itself, has always been an issue since the first Luddite opposition; 3) new attitude in the consumers, who change their own demand, once acknowledged the new supply, that is taken for granted from that moment on; 4) new behaviour of the manufacturer, who on one hand invests in the change, on the other hand adapts to the change, with no actual way back. None of these elements is unrelated to our current Fourth Revolution. Indeed, the ongoing 4.0 transition looks even bigger, due to the new importance of technologies, such as robotics and artificial intelligence, and the wide potential of this change to all the activity sectors in a globalized world. Deep analyses are underway by governments and analysts. From a manufacturing perspective, two aspects of the fourth revolution deserve to be underlined: the extent of involvement of all parts, from Industry to the Consumer, and the extent of the identification between product and information, well beyond the usual combination of production/ distribution cycle and information flow. In other words, in the Industry 4.0 scenario everybody is involved, in a sort of total connection. Besides, the Consumer increasingly asks for information in a product and asks for products from information, with increasing awareness, with increasing global attitude (Fig. 2). Figure 2. Industry 4.0: everybody is involved, and connected. Is everything new? Not exactly. Of course, we can observe this developing scenario from an historical, common sense perspective: every revolution, of every kind, somehow results from a previous evolutionary path that moved to its tipping point. Yet, the ongoing revolution comes also from the practical observation of facts, attempts and trends in the last three decades, also confirmed by major analysts. Let us provide two illustrative examples. In Italy, a dedicated study of Assolombarda (i.e., the association of enterprises of Lombardy, Italy) in 2016 points out that, looking at the manufacturing innovation in the last years, Industry 4.0 can be considered as an evolution that has been underway in the last decades, rather than a proper revolution, suddenly triggered by the availability of new technologies. In turn, in a dedicated article in 2015, Gartner Group (a global research and advisory firm) corroborates the idea that the concept of Industry 4.0 is not new by itself, but is rather the latest step in a sort of dialectic development process of technologies and business processes. So, what is new? According to Assolombarda, there are no doubts that the recent availability and the increasing diffusion of certain enabling technologies provides new tools to manufacturing resources, boosting the renewal of the currently adopted business model. In our opinion, what is new is the handy availability of new technologies, with costs that are more sustainable than before, allowing to speed up the improvement processes on their course, to implement a new identity between product and information, to be spread along the whole value and supply chain, with the direct, active participation of the final customer. The consequences can be huge. Pharma 4.0 The pharmaceutical sector (Pharma in the following) is no exception to this 4.0 reality, its new opportunities, its new identity between product and information, its new involvement of all parts. Yet, such a sector has its own characteristics and values to drive the choices. In particular, it is characterized by an ethical dimension of the concept of quality: zero defects to be pursued in the product, the final consumer is a patient, the interrelation is strict and continue with the Regulatory Authorities throughout the entire drug life cycle for the safeguard of the patient (Fig. 3). Figure 3. Pharma 4.0: different roles and dynamics, in full connection. Also, in Pharma 4.0 not everything is new. Yet, the rapid evolution of technologies and attitudes brings important changes in the demand, in the manufacturing operations, in the interactions with the Authorities, and in the new, valuable availability of information. What is changing in the Pharma 4.0 world The change in the demand is the change of attitude, behaviour and involvement of the consumer/patient, and of the relationship itself between consumer/patient and industry. This is a world where the integration between information and product can bring to increase the therapeutic adherence, for example. Where the creation of personalized drugs and services can be boosted, as in the case of wearable devices. Where some important questions can be answered, such as anticounterfeiting through serialization, or adverse events reported promptly and managed via dedicated analytics technologies in the widest context of correlations. The change in the manufacturing operations can come from lower costs and shorter time in automation and in collaborative information technology, which offer new opportunities to a reliable and secure support to actions and decisions throughout the operations. Secure and timely messaging, collaborative robotics for a new micro-logistics, reliable process data from Internet of Things are just few examples. The change in the interaction with the Authorities is the shortening of the information distances made possible, which creates new scenarios such as Quality Metrics and risk-based inspections. The change in the information availability is the new possibility of a fast, massive, aimed elaboration, which creates an information at hand at all process and organizational levels: predictive maintenance, predictive quality control, at last real application of PAT¹, analysis of operational scenarios among the possible examples. Is this change sustainable for Pharma? Pharma has been working hard on the concept of change in the last two decades. At the dawn of the third millennium the Pharma world realized that the zero-defects quality concept could not be pursued any longer with the old logics of exhaustive control, but rather through a continuous improvement process to detect, analyse, correct and prevent the issues, i.e., through the development of knowledge. A milestone, among others, of this evolution can be considered the FDA initiative “Pharmaceutical cGMPs for the 21st century”, aiming “to enhance and modernize the regulation of pharmaceutical manufacturing and product quality”, stated in a Final Report in 2004. It was the opening to an evolutionary quality culture, based on state-of-the-art science, adoption of new technological advances, enhancing communication and collaboration, ever-increasing widespread knowledge (Figs. 4-5). Figure 4. FDA Report – from executive summary page 1. Figure 5. FDA Report – from executive summary page 2. ¹ Process Analytical Technologies, defined by FDA as a mechanism to design, analyse, and control pharmaceutical manufacturing processes through the measurement of Critical Process Parameters which affect Critical Quality Attributes. From the very beginning, there was also the awareness that such a process could not even take place in a paperbased environment, but only with the systematic adoption of the information systems at their best potential. To enable this adoption, objective criteria were needed to ensure security and reliability of the electronic data “at least” at the same level as the data on paper. FDA itself opened the way with 21CFR Part 11 “Electronic Records, Electronic Signatures”, whose Final Guidance issued in August 2003 drove the path of change throughout several worldwide public initiatives and private technical developments. A path that results now in the achievements of Data Integrity concepts. Thanks to this, now the electronic data are more reliable, secure and usable than any paper-based method: now, electronic data can be valuable information. A proper blessing to the full adoption of all the 4.0 criteria. Then, let’s act Pharma 4.0 Some basic ideas for the implementation of Pharma 4.0, starting from technology: technology is an enabler of change. As such, we must consider that in some cases technology can change completely our operational model (for example with 3D printers in the production of personalized drugs) but generally speaking may not. Also, in this case, though, technology can help us evolve our model in modes, costs, promptness, quality, opportunity. How to use this opportunity, and to which extent, is mainly a matter of attitude and approach: we need a method, a philosophy to drive our culture for change. This is Operational Excellence: Pharma knows it and has already experienced it with success. Operational Excellence can be considered as the child of another Revolution, the Lean one, completed and further boosted with contributions from the best operational practices experienced worldwide in the last 30 years in all the Industry sectors. In the last fifteen years, Pharma has approached Operational Excellence with close care and constructive humbleness, accepting the debate with the other industry sectors. This allowed Pharma to eventually realize with pragmatism that Operational Excellence is attitude and culture for the constant change, the best environment to sustain the continuous discontinuity. In few words, what it takes now to cope with the Pharma 4.0 changes, and build further value from them is the scientific method, a focus on the involvement of the people, a conscious use of technology, and a systematic pursuing of quality and sustainability. Vertical integration: from the process sensor  to the Regulatory Authority Starting from this culture for change, the Data Integrity principles and techniques, and determined attitude and route, we can think of pragmatic principles for a to-be process and system architecture. The ISA-95 standard helps us design a new reference model for operations and information in the Pharma production site. It is the vertical integration to support operations and Big Data collection and elaboration (Advanced Analytics). Looking at Figure 6, two main elements deserve a remark: the integrated domain of operational data inside the Pharma Company, from the physical process to the business management, and the increasingly leaner and integrated exchange of information with the Regulation Authorities. Figure 6. Vertical integration: a model Here the ISA-95 standard that, again, is not new, is our compass to design the new route to support the decisions at all levels, from the process operator to the senior manager, with the right information at the right time. In this way gaining potentials such as:
  • predictive analyses (e.g. on Maintenance, Laboratories etc.);
  • Product Quality Review by joining data from different sources (Labs, QA, Production);
  • KPI for continuous improvement (at Company, Site, Line level with OEE);
  • Quality Metrics (risk-based inspections from KPIs);
  • On-Demand analytics (e.g. for an audit, which User interacted with a given Electronic Record in a QMS or LIMS);
  • simulation-based decisions (e.g. what to produce where, in case of…; what in case of Batch recall etc.);
  • Data Reconciliation (e.g. QMS and DSDB in case of systems not completely integrated) (Fig. 7).
Figure 7. Vertical integration Pharma 4.0: who is involved. Horizontal integration: the new supply chain In a frame of full control of our newly organized information, we can look with confidence to the challenges of the new Pharma Supply Chain, which faces a complex reality where demand and relationships are changing, due to many different factors such as changing demographics in both mature and emerging Countries, change of the products (with several of them requiring specific storage and transportation and controlled room temperature), increased demand for services beyond the mere product delivery, the already cited increased awareness and new active role in the supply chain that is now played by patients and consumers, the need to respond to the serialization and traceability requirements, the consequent need of a new end-to-end supply chain visibility. And hence the role of Pharma 4.0 technology and attitude gets central to provide near-real-time data visibility, to support the end-to-end process collaboration, to enable new models and a new potential, inaccessible so far (Fig. 8). Figure 8. Horizontal integration Pharma 4.0: who is involved What’s next: challenges and directions Cultivate the culture of change and innovation, and identify key metrics aimed at the internal organization and processes: these are just two of the recommendations that Gartner Group includes in a recent paper dedicated to the state of the art of the 4.0 transformation in the industry. In our opinion these are two important points from where to start the path to 4.0, also exchanging experiences with peers (yet another point in Gartner Group’s approach to 4.0). In a Pharma perspective just let us make explicit the quality-related metrics to be shared both internally to the Company and externally with the Regulatory Authorities, in view of the rapid process of rationalization of the information flow. This looks to be a good starting point for Pharma. Without forgetting that Pharma has a consolidated tradition of networking to pool experiences and ideas, with several prestigious organizations. Among them, ISPE (www.ispe.org), is an organization almost 20’000 Life Science professionals in the world, with aimed initiatives. Then just let us get ready, and start acting 4.0. References   – ANSI/ISA-95.00.01-2000. Enterprise-control system integration: Part 1. Models and terminology. – Assolombarda. Approfondimento sulle tecnologie abilitanti Industria 4.0. Ricerca 08/2016. – Daveri F. L’impatto della quarta rivoluzione industriale sul lavoro. Audizione Commissione Lavoro del Senato. Roma, 13 settembre 2017. – Gartner Group. Gartner predicts 2017: Industrie 4.0 – 01.17, Lessons learned from five adopters in digital manufacturing, 2016. – Gartner Group. Predicts 2018: Industrie 4.0 and advanced manufacturing, 2018. – Gartner Group. The five things chief supply chain officers need to know about Industrie 4.0 (Refreshed 13 July 2016, Published 5 February 2015). – ISPE – GAMP. Records and data integrity guide. – PIC/S PI 041-1 (Draft 2). Good practices for data management and integrity in regulated GMP/GDP environments. – U.S. Department of Health and Human Services. Food and Drug Administration. Pharmaceutical CGMPs for the 21st century: a riskbased approach. Finale report, 2004. – U.S. Department of Health and Human Services. Food and Drug Administration. Guidance for industry: Part 11. Electronic records; electronic signatures: scope and application, 2003.   “Pharma 4.0: a new perspective of opportunities and constraints” – “Medic” Volume 26 dicembre 2018