With a record number of more than 640 attendees and 80 speakers, this year’s Europe Annual Conference of the International Society for Pharmaceutical Engineering was the largest ISPE meeting ever held in Europe. The conference, which also welcomed more than 30 international regulators from agencies like EMA and FDA to Rome, Italy, in late March, delivered a well-received program to prepare the industry for the upcoming paradigm shift driven by digitization and other factors such as mass serialization and the need for data integrity.

Chair of the conference, Jean Francois Duliere, and John Bournas, president and CEO of ISPE, pointed out the successful development of European conferences and ISPE affiliates in Europe in the last years and announced that next year’s edition will take place in Dublin, Ireland, April 1-3, 2019. The 2018 conference included four tracks on „Facilities of the Future“, „Pharma 4.0“, „Data Integrity“ and „Mass Serialization“ with in total 60 speakers. This article provides some insights and summarizes the main takeaways of the two-day program.

New Industrial Concepts

Digitization will certainly trigger the next industrial revolution. Gunter Beitinger, vice president manufacturing, Siemens Digital Factory, took the production processes of the electronic industry as an example to show how pharmaceutical companies can manufacture even batch size 1 productively and how they can move from Five Sigma to Six Sigma. His conclusion was that technical abilities still need „decision ability“, which remains a „human domain“ and therefore there is a need for education of managers based on process understanding.

Thomas Uslaender of Fraunhofer Institute Munich, department of Information Management and Production Control (ILT), added the academia perspective with his presentation on trends behind Industry 4.0 and its impact on value chains. Success factor number one for the implementation of new industrial concepts on the management side is alignment in expectation, interpretation and definitions between functions, roles and responsibilities. On the technical side, interoperability of systems is the success factor number one.

Roman Hipp, a partner at Porsche Consulting, addressed two main trends in the industry: „customized products“ following the societal trend of individualization, and changing role models of corporations, e.g. the car maker Porsche developing from a manufacturer of cars to a „provider of mobility“.

Harmonizing Serialization Regulations

Mass serialization for some listed prescription medicine products, which must be protected by safety features and a 2D barcode by May 2019 - seven years after the publication of the Falsified Medicines Directive - is faced with some challenges in technical implementation. André Overmeyer, managing director Merck Healthcare Germany, reported of the successful implementation on a global basis. He identified three success factors:

1. the portfolio pruning at the beginning and the elimination of some „sleeping” stock keeping unit numbers, followed by
2. good data management, including master data management, and
3. a process-efficiency program.

Thus prepared, mass serialization could be implemented and terminated one year before the legal due date.

Philippe Luscan, executive vice president global industrial affairs, Sanofi, addressed global trends creating a paradigm shift for pharma: longer life, health economy agenda, digital revolution and the risk of the „empowered patient“. Innovation in technical operations targets „core technology platforms“, „value chain continuum“ and „excellence in manufacturing“. All this requires breakthroughs in R&D in order to get new products. As the portfolio in future will be more and more diversified, pharmaceutical manufacturers need to adapt capacity following the parameters network, volume, agility in the supply chain, partnerships and cost of goods sold (COGS). A very important enabler are quality standards for the global supply chain, ONE standard and standardization based on best practices. Regulatory authorities are essential partners to achieve this goal. Current challenges such as supply chain integrity, anti-counterfeiting and mass serialization must be successfully mastered.

From Industry 4.0 to Pharma 4.0

Christian Woelbeling, Senior Director Global Accounts, Werum IT Solutions, explained approaches how common Industry 4.0 concepts could be bridged to the highly regulated pharmaceutical industry. In the last two years, ISPE’s Special Interest Group (SIG) „Pharma 4.0“, consisting of nearly 100 experts from various stakeholders of the pharmaceutical industry, key suppliers, start-ups and experts in quality/regulatory, worked on relevant concepts.

He presented a pharma-operating model, which is the basis for developing roadmaps and maturity models for main processes. One focus lies on the completion of the ICH Q10, the “new pharmaceutical quality system” with additional enablers such as „data integrity by design“ and „digital maturity“ as well as new elements. The outcome will be a „holistic control strategy“, which considers all aspects of the control strategy developed in product development and including all elements of process flow, data flow, automation and environmental control in manufacturing over the full product lifecycle. Another important topic on the agenda of the SIG Pharma 4.0 is the establishment of a „plug-and-produce“ concept.

European Regulatory Environment

Brendan Cuddy, head of manufacturing and quality compliance, EMA, referenced to the four pillars of the European Regulatory Strategy in 2018.

Firstly, there are Mutual Recognition Agreements (MRAs) in place between the US and many EU member states, and there are even more to come in 2019. There is an expectation that in July 2019 each member state, after a revision of all individual states’ oversight system, will be recognized under the MRAs. The main tasks are to maximize the inspection resources by focusing on sites with the highest risk and by minimizing duplication of inspections however broaden the inspection coverage.

Secondly, legislative changes are numerous, as listed on the homepage of EMA. One is of particular importance, i.e. the new investigational ATIMP guideline.

Thirdly, availability of authorized medicines as another focus, addressing the problem of drug shortages caused by manufacturing or quality problems, but also penetration of falsified medicines in the legitimate supply chain.

Fourthly, the preparedness activities for the Brexit and the relocation of the EMA offices to Amsterdam will bind some activities and energy at EMA.

Arielle North, a former EMA regulator, reported about the potential impact of the Brexit, timelines for agreements and potential impact in case of not achieving agreements. Legal implications are significant in both cases, unfortunately.

Sterile Manufacturing

Andrew Hopkins, expert GMDP inspector, MHRA, presented the status of the EC’s GMP Guide, Annex 1 „Manufacture of Sterile Medicinal Products“. Important areas of this renewal are „Quality Risk Management“, that current technologies must ensure protection and control of product AND employees. A contamination control strategy must be in place, air supply in grade A is requested, there might be a need to minimize the need in production facilities. Documented risk assessment and sterilization wherever possible after complete reassembly were further topics. Furthermore, there is a new chapter „Utilities“ added and the requirement to include trending in environmental monitoring.

Rick Friedman, a director for science and regulatory policy at the US Food & Drug Administration, addressed the FDA’s view on sterile manufacturing. A lifecycle-oriented Quality Risk Management is seen as necessary. Some inspection findings showed the need of modernization of facilities. FDA provides Incentives for adopting today’s technology and less capable manufacturing operations receive increased scrutiny. QRM and KM foundation should be applied throughout the facility lifecycle by iterative learning and by leveraging today’s technology. This facilitates good decision-making.