European Initiatives to Advance Manufacturing Digitalization

Evdokia Korakianiti

Head of Quality and Safety of Medicines

EMA

With an overarching goal of ensuring that better medicines are available for patients, Korakianiti introduced her talk as being about how advanced manufacturing is one of the strategic drivers for Europe in order to strengthen the resilience of global supply chains. Especially after the COVID-19 pandemic, she notes that it's important to create a regulatory environment that facilitates investments in Europe, ensures manufacturing of key medicines is maintained in Europe, and maintains the strategic autonomy of manufacturing in Europe to prepare for any future pandemics.

Her key message is that regulators and developers are on a journey together. She doesn’t think developers can wait for regulators to provide guidance; she wants regulators and developers to work together to understand where they are collectively. In this scenario, the regulators will update the framework based on what is working and where it is blocking developers. Korakianiti said, “What we really need to do is to engage, to understand, to talk, so we can update our guidances to reflect the reality.” She believes “a lot is possible already,” but that the two groups need to continue in an iterative approach, as their collective knowledge develops.

The bulk of Korakianiti’s presentation was focused on three items:

1. New EU Pharmaceutical legislation
2. European Medicines Regulatory Network (EMRN) initiatives
3. Quality Innovation Group (QIG)

New Pharma Legislation

As many have heard, there is a new European Union Artificial Intelligence (AI) Act, which she believes is a “once in a lifetime opportunity,” because the regulatory framework in place now has been developed over many decades. There will be a holistic review of the whole legislation, with the new legislation in place by 2028 or 2029.

This new legislation for the pharmaceutical industry promotes innovations for the benefit of patients. One concept of interest is a platform-based approach, in which a technology platform can be regulated so that filings can leverage knowledge and regulatory requirements from one medicinal product to another based on its platform. Another concept of interest is a regulatory sand box, which allows treatments that may not be fully compliant with the legislation to be authorized if they show a benefit to patients. Korakianiti believes the new legislation and these new concepts help future-proof drug development because drug development can continue in ways that current regulations have not previously allowed, provided these developments will benefit patients.

European Medicines Regulatory Network (EMRN) Initiatives

The EMA published the “Reflection Paper on the Use of Artificial Intelligence (AI) in the Medicinal Product Lifecycle,” which considers AI and machine learning tools and takes a risk-based approach similar to the new AI legislation. As Korakianiti discusses it, the type of technology, the context of that technology’s use, and the degree of influence of this technology affects the regulatory requirements and the level of oversight throughout the life cycle of products manufactured with this technology.

In a related vein, the EMRN has established the “Artificial Intelligence Workplan to Guide Use of AI in Medicines Regulation" from December 2023 to 2028 with four main pillars: experimentation, tools and technology, guidance, and training.

Quality Innovation Group (QIG)

Korakianiti recognizes that pharmaceutical professionals may have questions, as the regulatory environment is complex, and they might wonder where to go to get answers. Her answer is simple: go to the QIG. There are experts who can answer questions about integrating new technology into production manufacturing. She provided an overview of how the process would work, and she shared examples of the questions QIG experts could help answer, such as, Would this technology be OK? What concerns would the regulator have with this technology? How will this product be regulated throughout its life cycle?

The QIG consists of eight core experts as well as a variety of ad hoc experts, such as academics, international partners, and others with expertise in the regulatory environment. The QIG acts as a consistent point of contact to provide support from development throughout the life cycle; this ensures that there is continuity throughout the developer’s interactions.

In addition to these close working relationships with developers, the QIG holds listen-and-learn focus groups twice a year. Stakeholders are welcome to bring case studies that must be related to the particular theme planned for the group discussion. Two listen-and-learn focus group sessions were held in 2023 on 13 March 2023 and 12 October 2023. [ISPE presented at both these sessions.] The QIG has hosted one session this year (5 June 2024) [during which ISPE presented]. The next session will take place in Q4 2024. After each focus group, the QIG publishes a report that discusses shared case studies, challenges raised, and action items moving forward to be addressed.

Korakianiti shared an example of the positive impact of this group with a story about a topic that came from the first listen-and-learn group session. Prior to the session, developers presented modeling as the main major bottleneck. They told the QIG that, “it is not possible to do anything in Europe” citing fears of the regulatory burden and how modeling will be approached by regulators. But within less than a year, a Q&A was published providing “some preliminary considerations on models that can be used for process, control monitoring, and controls.” While Korakianiti admits this is “soft guidance,” she mentions that it reflects the current understanding, and that the QIG expects that guidance will evolve as more knowledge is gained in discussions with developers.

To end the session, she again reiterated the invitation to developers to reach out to the QIG, so that they can help provide guidance. She put a call out to developers: “Come forward with your cases to participate actively in our…listen-and-learn focus groups….be with us in this journey.”