Digital transformation: essential for the pharma industry

The benefits and problems linked to Industry 5.0 and cybersecurity in the pharmaceutical industry. The ideas drawn from a meeting organised by Messe Frankfurt and ANIE Automation, with the participation of ISPE and numerous automation suppliers, make it possible to obtain a realistic picture of the situation in Italy and in the world.

Maurizio Cacciamani

A discussion between the ISPE (International Society for Pharmaceutical Engineering), ANIE and Cybersecurity Competence Center, but also the experiences brought by companies and suppliers of technology, brought to light the challenges and opportunities linked to the digital transformation of the global pharmaceutical industry.

An unequivocal fact to introduce the proceedings: Italy is “number 1” in Europe for the production of pharmaceuticals, estimated in 2022 at 37 billion Euros (+10%). And as Donald Wich, CEO of Messe Frankfurt Italia, also pointed out, product and process innovation is intrinsically linked to digitalisation technologies.

Two real, continuously evolving projects

How the dissemination of Pharma 4.0 criteria is changing
Teresa Minero (Founder & CEO of LifeBee) presented the results of the 2022 survey carried out on behalf of ISPE *.

Ten questions received 403 replies (+20 compared to last year), of which almost half were from Europe and 21% from North America. Those replying carried on activities in the production sector (80 replies), Engineering and maintenance (around 80) and QA (a little under 80). With regards to Pharma 4.0, the companies that have not yet started the process have reduced to a very small amount, while those who have just started have greatly increased. Pilot projects have decreased, but systematic activities have intensified. What have been the greatest benefits?

Higher quality and greater conformity (64% of replies consider this to be thanks to the reduction in deviations due also to errors), improvement in efficiency (60%), time saving (57%), increase in productivity (56%), lowering of costs (45%). The survey also revealed the most adopted enabling 4.0 technologies: Cloud&Edge computing, smart devices, collaboration platforms, Big Data and Analytics, and IoT. Unfortunately, problems also increased in percentage terms compared to the last survey, due to inadequate organisation and culture, lack of expertise and few available resources. According to Minero, the sample nevertheless showed a tendency towards a higher level of maturity. Improvements in quality and conformity were perceived as the main benefits brought by the adoption of Pharma 4.0, but cultural and resources challenges remain an obstacle.

* ISPE: a non-profit association that promotes technological knowledge in the pharmaceutical field with research, conferences and study days.

Dematerialising documents in safety
BSP Pharmaceuticals (a Contract Development Manufacturing Organization) offers development/production services and analytical activities in the pharmaceutical field and develops innovative products for cancer treatment and for immunotherapy, including biotechnological ones. As reported by Filippo Trionfera, the Quality Operation Manager & Qualified Person of the company, the products are distributed in over 80 countries; the main markets are United States, the European Union and Japan. In BSP, the digitalisation planning involves the implementation of various projects in two phases: ERP; digitalisation of current paper procedures with the existing DMS and document archives and their secure storage off-site; quality management with eQMS software; dematerialisation of DD documents with the distribution of tablets for the online consultation of all Directives, documents and manuals; centralized printing for the control of all prints, scans and faxes of the site and, finally, WO and CR IT management through the ITSM software.

Managing quality. The objectives of the eQMS project are to electronically trace all the Controlled Processes managed in BSP (Complaint, Deviation, CAPA Stand Alone, Audit and Change Control), improve internal efficiency and operativity, place the archives of acquired data in a unique, stable and secure environment, make a data reporting and interrogation tool available to users for their management according to defined roles and security levels and for complete compliance with the regulatory requirements for electronic systems. And, of course, everything has to be validated.

Why has BSP chosen the eQMS software? Because it’s a world leader and offers workflows based on “Best Practice”, and because it can be integrated with other systems present in the company (ERP, CRM, LIMS). In addition, it makes the Validation Package and license ownership available. The goals? Increase efficiency, improve quality, achieve conformity, reduce risks. The strong points that have emerged during the first phase of implementation have been a reduction in costs and implementation times thanks to the presence in the company of QA/IT workers with past experience of eQMS and the configuration of the system in accordance with GMPc Best Practise without upsetting the previous operational flows.

Positive feedback was received at the end of the first phase: easy use, flexible operativity, reduction of evaluation times for trends, metrics and KPIs, easier monitoring of activities and relative deadlines assigned to each user, satisfaction of Customers and Regulatory Authorities.

«In the second phase – Trionfera pointed out – we will extend the use of certain flows/processes to other departments (EHS) and we will evaluate the extension of the licenses to a number of users above the initial 350. With customers’ growing expectations and quickly changing work models, digital transformation is no longer an option but a necessity».

Managing repetitive operations automatically
Edoardo Schiraldi, Corporate Program Manager of Menarini Group, presented Robotic Process Automation (RPA): a software that automatically manages manual, repetitive activities based on highly structured rules and which require time. Every RPA programme is configured to perform specific tasks/processes (so-called “Bots”) and can work together with the user or autonomously.

Advantages of RPA. RPA assists users in their day-to-day activities, allowing them to focus on higher added value operations, increasing efficiency and quality, making up for limits in staff development. In addition, RPA helps to control costs, to meet compliance requirements, and to supply new medicines on the market with safety, efficacy and profit.

By way of example, he pointed to an application made possible by RPA: CONVALIDA GxP. In a regulatory context, any system that has a decision-making role must be validated and solid. RPA systems have the potential to effectively meet requirements because they are configurable, verifiable and designed ad hoc. RPA can, therefore, help pharmaceutical companies to comply with process validation quality guidelines and GxP regulatory compliance using bots to follow a standard operating procedure (SOP) in the same way as a qualified human operator. In addition, complete registers of the activities are obtained, risks are reduced and errors are reported together with exceptions during the performance of the process.

Pharmacovigilance: use example. Pharmacovigilance has the task of monitoring the data available in EudraVigilance, the repository for the management and analysis of information on suspected adverse reactions to authorised medicines in the European economic area. Since it is not possible to analyse the enormous quantity of data on a daily basis, it has been decided to automate the process.

Periodic pharmavigilance operations are activated automatically by bots which arrange to download from EudraVigilance “.xml” files of Individual Case Study Reports (ICSR) relating to Menarini products. The system checks that the files really relate to Menarini products, analyses them and sends them to people inside and outside the company who perform pharmacovigilance activities, automatically generating reports on who has taken charge of what.

Challenges and benefits. This was the first RPA process implemented in Menarini and since not all users were ready, required a lot of effort in training people.

The implementation of RPA has, however, made it possible to achieve an increase in workload while maintaining the current cost level. The process has been validated and the automation guarantees a higher level of conformity, to the extent no observations were made during the last inspections performed by the British and Italian health Authorities.