Shaping Tomorrow's Pharmaceutical Framework: Embracing Digital Transformation and Technology in an Evolving Landscape

The panelists were Brendan Cuddy, Lead Scientific Officer, EMA; Ian Jackson, Expert GMP Inspector (MHRA); and Christina Meissner, GMP Inspector, AGES. The discussion was moderated by Mark Birse, Vice President Technical, Parexel; and David Churchward, Head of Operations Quality Compliance, AstraZeneca.

Churchward started by asking Cuddy to provide an overview of the EMA Inspectors Working Group (IWG) activities for which Cuddy is the chair and then to describe insights and actions from the recent Interested Parties meeting, where IWG met with representatives from several European industry associations, including ISPE.

Cuddy explained that IWG is a working group of EMA, which meets four times a year and has a triple mandate. First is to advise EMA on GMP matters as they relate to the centralized procedures for human medicines, second there is a mandate to the heads of medicines agencies to oversee the joint audit program, which involves IWG member regulators inspecting one another to assure equivalent standards and a driver for harmonization within Europe. Lastly there is a mandate to assist the European Commission by drafting GMP guidance which the commission publishes in Eudralex Volume 4 and to assist with the technical aspects of negotiations for mutual recognition agreements (MRAs). There are 40 members of the IWG – 27 member states plus Norway, Liechtenstein, and Iceland, and veterinary GMP inspectors from some member states. There are observers, which includes MRA partners – US Food and Drug Administration (US FDA), Swissmedic, Health Canada, Japan’s Pharmaceuticals and Medical Devices Agenda (PMDA), UK MHRA under the UK-European Union (EU) trade agreement, and others. EU candidate countries can attend IWG meetings.

The IWG meets with the industry associations once a year with the agenda set by the industry associations reflecting the priorities of all sectors of the industry. Cuddy highlighted two topics from a previous meeting earlier in 2025, which were industry concerns relating to implementation of Annex 1, GMP Manufacture of Sterile Medicinal Products, and updates on a GMP inspection reliance pilot that EMA was conducting with Pharmaceutical Inspection Co-operation Scheme (PIC/S) partners. Industry has been raising issues with implementation of Annex 1 every year since introduction, however, Cuddy thought that it was good that emphasis was changing to more technical issues. Six areas of concern from industry were presented of which three are already being worked on with PIC/S and the World Health Organization (WHO) and the other three EMA will work on.

Cuddy described the reliance pilot as a success in that EMA inspectors were able to review GMP reports from PIC/S partners and assign a GMP certificate based on this review. This reliance process is viewed as positive and will be introduced into the IWG procedures. In addition, the reliance principle is also included in the draft revised EU pharmaceutical legislation which it is hoped will be retained in the finalized version due in 2026.

In parallel, as part of a GMP modernization exercise, industry associations were asked what guidelines should be updated and what should be developed. Of the guidelines identified all except one are being worked on, which confirmed that regulators and industry are aligned.

Meissner was asked about inspectorate activity at EU member state level. She started by confirming that member states rely on the IWG workplan, which has a common EU legislation rather than 27 versions. Austria is pleased to align with colleagues in the EU and contributes to the EU drafting process. A big topic with the EU and other member states is computerized systems, which involves revision of Chapter 4 on documentation and Annex 11 on computer systems, and the growing use of AI. Capacity and expertise are being reviewed, and a group of experts is being introduced amongst members of the IWG, which shares learnings with similar groups in other agencies, e.g. Denmark.

Jackson stressed that the UK has a cooperation agreement with the EU, which means it follows EU GMPs and is an invited guest to the EU IWG. The UK contributed to the reliance pilot. The UK is also a very active member of PIC/S, supports the harmonized approach and wishes to work alongside other agencies and “pull together.”

Cuddy wished to advertise that industry stakeholder expertise and knowledge is requested in the review of upcoming GMP documents. A concept paper on the revision of GMP for ATMPs was issued for comment a few days before the ISPE panel session, and since then two chapters and annexes of the GMPs have been issued for public consultation. In addition, a new Annex 22 for AI will be issued as a stand-alone topic, since revision is likely as AI use, knowledge and understanding evolve.

A question from the audience related to the possibility of revision of Annex 1 on sterile products if there were continued challenges with implementation of some requirements e.g. Pre-Use Post-Sterilization Integrity Testing (PUPSIT) and container closure testing. Cuddy responded that EMA IWG would consider review if challenges continued and were widespread across member states and internationally. They are unlikely to consider reviewing based on one company’s experience nor on a single inspection. Challenges must be raised through an industry association.

Cuddy was asked a question regarding what are the key considerations in the EU for developing robust, secure, and interoperable IT networks and data infrastructure to support the future of pharmaceutical regulation? How does the EMA Network Data Management Strategy impact inspectors, industry, and patients?

Not being a data management expert, Cuddy provided his personal observations regarding the “European Medicines Agencies Network Strategy” for 2028. This has six areas of focus and Cuddy discussed leveraging data (AI and digitalization) for the benefit of human health and data and interoperability. The EU Network Strategy recognizes the challenges the network faces across more than just the 27 member states and EMA in that each organization has its own systems. It provides objectives and addresses these. Cuddy highlighted the “Substance, Product, Organization, and Referential (SPOR) Master Data,” which supports interoperability. This initiative aims to standardize and harmonize the management of data related to medicinal products throughout their lifecycle within the EU regulatory framework.

Related to but different from the EU Network Strategy is the work of the International Coalition of Medicines Regulatory Authorities (ICMRA), which has a Pharmaceutical Quality Knowledge Management System (PQKMS) workstream with two pilot programs. One is simultaneous, multiple regulator agency review of a post approval application to have a collaborative review. The other is a joint hybrid inspection. In both cases, individual agencies will deliver their own independent, sovereign decision. For the review, the regulators assess a common dossier produced as a PDF file.

ICH has picked up this PQKMS and introduced its own, complementary program, ICH Pharmaceutical Quality Knowledge Management (PQKM) Task Force and is consulting on a project to introduce structured data building on the work of ICMRA. There is also activity to develop common, internationally recognized terminology so that structured data can be used in dossier reviews and inspection reports. The format is based on the PIC/S report, which is harmonized with the EU inspection report.

EMA is also working outside of the EU with other partners on reliance via the International Pharmaceutical Regulators Program (IPRP).

Jackson presented an MHRA and PIC/S perspective on the IT and reliance topics. To assist reliance, PIC/S has data sharing processes, for example the EU and UK have a public available web of GMP certificates. With PIC/S there is a unique facility identifier reference, which facilitates data sharing between PIC/S members. MHRA is undergoing an IT refresh, with RegulatoryConnect about which there will be a series of webinars.

Birse asked Churchward for an industry perspective of regulators’ insights since he has connections to EFPIA, which conducts and publishes an annual review of inspections at members’ sites.

2024 data is about to be published. The 2023 data compared with 2022 shows:

• There are still a lot of foreign inspections performed by some inspectorates
• Interestingly, 2023 saw the start of a trend in the reduction of inspections between mutual recognition agreement (MRA) partners and also about a one-third reduction in inspector days on sites between PIC/S authorities, which is positive
• Across all sites responding, there was an average of two inspections with apparently the same scope, which means some sites are having five or six inspections per year. This is a long way from the PIC/S vision of one inspection per site.

Churchward summarized that we are moving in the right direction. These data points are shared with regulators, which Cuddy much appreciated. Cuddy did comment that 80% of inspections are national, which is not too gloomy. He commented that EMA should work with PIC/S partners to learn from the EMA IWG pilot, which demonstrated that reliance was a good option.

Cuddy wished to remind the audience about the ICMRA Pilot reliance program, which is continuing for post approval changes and inspections. Cuddy made a call for companies to volunteer. Jackson added that these pilots were a “safe place” with regulators and industry learning. In response to a question from the audience regarding what sort of projects would be appropriate for the pilots, Cuddy responded that the initial focus was on COVID-19 vaccines and treatments. To optimize use of resources for the benefit of patients and the scope has been broadened to include products with PRIME: Priority Medicines, or US FDA “Breakthrough Therapy” designation. They would also like to include generics and, on the inspection side, include inspection of sites which increase manufacturing capacity such as new facilities.

A further question from the audience asked: How does the panel see the link between the ICMRA pilot and the ICH PQKM work? Cuddy said he did not know enough about the ICH activity; only that a paper had been tabled regarding information to evaluate if there could be a technical solution that can support collaboration between regulatory authorities and sponsors.

As a follow up to Birse’s comment that ICMRA had developed a vision more than 10 years ago to introduce more reliance amongst regulatory authorities, Cuddy mentioned that EMA was involved in four reliance pilots. He highlighted the pilot with WHO for EMA to assess post approval applications with other authorities using the EMA assessment report as a basis to come to their decision. Hopefully any new process will take less than the current time scale of three to five years for all authorities to accept a change and the change then to be implemented.

Churchward asked, how can industry and regulators interact to overcome identified challenges to implementing new technologies and processes? To Cuddy and Meissner, he asked, what is being prioritized within the EU?

Cuddy started by emphasizing that the Quality Innovation Group (QIG) is the main pathway for innovations to be progressed and the inspectors work closely with QIG. The activities of QIG a were comprehensively covered in the keynote presentation from Evdokia Korakianiti, EMA’s Head of Quality and Safety of Medicines Department. From an inspector’s perspective, activity to modernize guidelines is a priority as is happening with Annex 11 and the new guideline for AI, Annex 22 to support digitalization. Another example is the introduction of X-ray sterilization of single use systems used in pharmaceutical manufacturing when inspectors were deeply involved in development of the question-and-answer document.

Meissner expanded by mentioning that, in addition to scientific advice procedures at EMA and national levels, there are also the Innovation Task Force (ITF) briefing meetings to which innovations can be taken at an early stage of development. The main topics under consideration are digitalization, process models, decentralized and continuous manufacturing, including the newer, faster analytical techniques. There is activity to increase expertise in the regulatory network, such as with process models. She commented that mostly regulators and industry agree scientifically, however, there is the regulatory pathway to consider, and changes can take some time. Jackson added that from a PIC/S perspective the focus is on updating or writing new guidelines, and on training.

An audience member asked how EMA interacts with other agency’s innovation groups such as the US FDA’s Emerging Technology Team. Meissner replied that other agencies such as the US FDA and SwissMedic are invited to ITF and QIG meetings. There have been two joint inspections recently by an EU inspectorate and the US FDA, one of which was a continuous manufacturing process.

A second question from the audience related to findings from the ISPE Enabling Pharmaceutical Innovation initiative survey and follow up case studies when equipment and facility suppliers had difficulty approaching EMA and national agencies with an innovative project without it being tied to a specific product. Meissner replied that the ITF should be the starting point and GMP advice and general guidance could be given. Robotics and isolator examples have been discussed. She cautioned, however, that a “GMP license” could not be given since GMP relates to a specific manufacturing process for a product.

Birse moved on to ask about how inspectors and assessors are working together in the EU to assist innovators and developers with regulatory challenges.

Meissner commented and gave an example that assessors and inspectors are looking at an issue from different perspectives. There is engagement at QIG, which has at its core three inspectors and five assessors, and Meissner is one inspector member of this group. In Austria, inspectors and assessors are in the same building and, although there are logistical challenges, there have been joint inspections on a pharmaceutical analytical technology (PAT) and an advanced therapy medicinal products (ATMP) example. In addition, the EMA assessors in the quality working party (QWP) and the biologicals working party (BWP) meet regularly. Cuddy added that the IWG meets with the QWP and Biologics Working Party (BWP) together once a year.

Churchward asked how can regulators ensure patient safety and product quality while embracing new technologies and data-driven approaches in Industry? He specifically referred to technologies such as AI, which are developing at a pace and changing all the time.

Jackson started by admitting that there needs to be an upskilling of inspectors, which has commenced. He also referred to the UK Centers of Excellence for Regulatory Science and Innovation (CERSIs). The projects will be led by academic institutions, independent innovators or regulatory leaders forming collaborative partnerships and involve digitalization including use of AI in healthcare applications. This is an example of regulators being involved from the beginning and working with industry and academic experts as a group so that all can learn. He also referred to a UK white paper. This white paper details plans for implementing a pro-innovation approach to AI regulation. He also mentioned that this work is leading to a project on AI application to device development, however, this will likely become broader to pharmaceutical products. In summary regulators will work in the group and learn.

Moving specifically to Annex 22 on AI, Cuddy said that EMA were using their standard guideline development process starting with a concept paper on which there were 657 comments. (The draft is now out for comment.) The target is for issue in 2026. In a discussion amongst the panel regarding analysis of comments, Birse mentioned a UK government consultation on Botox/lip fillers. AI was used for analysis of 2000 comments and compared with manual analysis with no difference found. This information could have impacted an informal audience survey which had a majority in favor of AI review of comments on Annex 22.

Meissner was asked the QIG perspective. QIG had provided input to draft Annex 22. In addition, QIG is working on process models for which there has been a listen and learn session. A draft decision tree is out for comment with input to this draft sought from US FDA colleagues. Regarding AI she stressed that a human must make the ultimate decision—there must be a human in the loop. There needs to be someone who is accountable. She also highlighted that quality assurance (QA) professionals must understand the objective and how an algorithm is operating without being knowledgeable about the detail of the software.

From an industry perspective, Birse commented that guidelines should be enabling, flexible, risk-based, clear and unambiguous, and future proofed. He acknowledged that future proofing is very difficult. Harmonization across agencies is also very important since the industry is global.

Cuddy agreed and accepted that Annex 22 will likely need updating relatively quickly. He pointed out that all recent EU guidelines have been drafted cooperatively with PIC/S and in many cases WHO.

In response to a question regarding critical thinking, the panel commented that AI should be supportive, and thinking should be risk-based.

A final question asked, “How are inspectorates using artificial intelligence and machine learning in their work and in development of pharmaceutical regulation?”

Meissner responded that inspectorates in EU member states are developing expertise and considering where and how AI can be applied. Security of data is absolutely vital since some data is highly confidential (e.g. patient records) and some proprietary. The agency does not own this data. There is also the challenge that regulators cannot use applications on the market such as ChatGPT. Potential applications for regulators are numerous from analysis of pharmacovigilance reports to analysis of deviation reports for trends. Risk-based inspection planning is another application in which market data, complaint, inspection report findings, etc., could be analyzed. Given all this activity across the EU, Meissner recommended to Cuddy that there should be a cross-EMA IWG review in six months of individual member states’ activity, which Cuddy acknowledged.

Regarding implementation, Meissner mentioned the modular training program for inspectors, which now is voluntary, however, is likely to be compulsory with the upcoming revised EU pharmaceutical legislation. Recruitment is a challenge since both industry and agencies need to increase expertise and are to some extent in competition for limited available expertise.

In closing, Churchward thanked the panelists for their excellent and informative input as well as the audience for their attention and questions.