Advancing Digitalization in Manufacturing: European Union Initiatives

Introduction

Korakianiti began her presentation by stating that patients in the EU and globally expect medicines to be both available and of the best possible quality, and she noted that innovation has helped increase efficiency and reduce costs. An example she provided was the inspection of vials which has progressed from manual inspections to using cameras, and more recently, with the advent of artificial intelligence (AI). She then touched upon the following areas:

Main Challenges for Regulators

Korakianiti pointed out three main challenges that regulators need to overcome:

1. Regulating in an environment that is rapidly evolving
2. Promoting responsible innovation and building trust amongst patients, industries and regulatory authorities
3. Training and providing capacity

Three Pillars of a Regulatory Framework

There are three main pillars of a regulatory framework that support innovation:

1. A flexible framework that may be adapted to the evolving state of science
2. Predictability and clarity on regulatory expectations
3. Global convergence

Breaking Down Barriers

Korakianiti noted that enabling advanced manufacturing must be a collaborative approach and that it is time to tear down boundaries and work together. She highlighted the need for active engagement from the industry and academia in sharing best practices and lessons learned in order to accelerate the fourth industrial revolution in the manufacturing of medicines.

Pharmaceutical Strategy for Europe

The EMA developed a Pharmaceutical Strategy for Europe which was adopted in 2020. The aim of the strategy is to create a future proof regulatory framework that supports industry by promoting research and technologies that actually reach the patient in order to fulfil their therapeutic needs while addressing market failures. The purpose of the strategy is to improve access, e.g., affordability and unmet medical needs, and to ensure that competitive, innovative, and sustainable solutions exist when responding to another crisis such as a pandemic.

European Medicines Regulatory Network

The European Medicines Regulatory Network (EMRN) has three key initiatives:

1. Guidance: to offer clear, balanced guidance to developers and marketing authorization holders
2. Upskilling: to provide training across the network to foster competitive and responsible use of/regulation of AI
3. Collaborations: to leverage collaborations to improve knowledge, reduce uncertainty and facilitate alignment.

European Union AI Act

Digitalization and AI will be key going forward. On 9 December 2023, new EU legislation on the overarching legal framework for AI was introduced based on a risk approach. The EU AI Act is the first regulation on AI.

AI Reflection Paper

In 2021, an AI workshop was held resulting in a task force that prepared an EMA reflection paper for consultation up until the end of 2023. In the paper, AI is defined as “systems that display intelligent behavior by analyzing their environment and taking actions with some degree of autonomy to achieve specific goals.” (See ISPE’s input to EMA)

The AI reflection paper consists of a risk-based approach for the development, deployment and monitoring of AI and Machine Learning (ML) tools. The degree of risk may depend on the following:

1. The AI technology
2. The context of use
3. The degree of influence the AI technology exerts
4. May vary throughout the lifecycle of the AI system

The level of scrutiny depends on the level of risk and regulatory impact posed by the system.

Quality Innovation Group

A year ago, a Quality Innovation Group (QIG) was formed to advance digitalization, AI, and other emerging technologies by collaborating with industry, academia and industry groups such as PIC/S. Key 2023 priorities for the QIG were:

1. Continuous Manufacturing (Biologicals)
2. Decentralized Manufacturing (e.g. ATMPs)
3. Application of Digitization
4. Application of ML / AI

The planned revision of the EU GMP Annex 11 on Computerized Systems is seen as an opportunity to provide guidance on AI and ML.

Additional European Union Activities in 2023

Additional activities worth noting in 2023 included:

1. 1. Product Support (Scientific Advice)
   1. Helping avoid shortages with the x-ray sterilization of single use systems
   2. Improving productivity and reducing cost with robotic aseptic filling technologies
   3. Point of care for cancer patients by decentralizing the manufacture of ATMPs
2. 2. One-to-One Meetings with Stakeholders
   1. Decentralized manufacturing
   2. CAR-T cell automated manufacturing
   3. Digital twins
   4. Continuous manufacturing for vaccine formulation
   5. Modelling

Collaboration with the US Food and Drug Administration (US FDA)

In 2023, the US FDA Center for Drug Evaluation and Research (CDER) visited the EMA and attended a workshop to exchange mutual experience and current thinking on scientific and regulatory aspects of advanced manufacturing. There have been joint site visits, consultations, and collaborative assessments on specific products, leading to a more harmonized outcome. The EMA and US FDA have exchanged priorities, agreed on topics of common interest, and aligned on guidance and Q&A documents with joint proposals to ICH.

Conclusion

Korakianiti concluded by emphasizing the importance of industry and regulators working together and encouraged companies to engage with the EMA. The EMA has learned a lot from the pandemic and there is still a lot to learn, she said, but the EMA has made much progress and is committed to collaborating with other regulatory agencies, such as the FDA, to help facilitate a more global and harmonized approach.