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Regulators Discuss Harmonization & Innovation, Regulatory Agility & Speed, & Workforce Skills

Christopher John Potter, PhD
Regulators Discuss Harmonization & Innovation, Regulatory Agility & Speed, & Workforce Skills

An informative and lively regulatory panel discussion was held at the 2023 ISPE Europe Annual Conference in Amsterdam, The Netherlands on 9 May 2023. The session included regulators from the European Medicines Agency (EMA), the UK Medicines & Healthcare Products, Regulatory Agency (MHRA), the Spanish Agency of Medicines and Medical Products (AEMPS) and the US Food and Drug Administration (FDA). It was moderated by Mark Birse, Vice President Technical, Strategic Compliance Consulting, Parexel.

The panelists were:

Roberto Conocchia
GMP Technical Lead
European Medicines Agency (EMA)
Rick Friedman
Deputy Director, Office of Manufacturing Quality
Manuel Ibarra Lorente
Head of Pharmaceutical Inspection & Enforcement Department
AEMPS (Spanish Agency of Medicines and Healthcare Products)
Evdokia Korakianiti
Head of Quality and Safety of Medicines
Carmelo Rosa, PsyD
Director, Division of Drug Quality I
James Pound
Deputy Director Standards and Compliance

Questions were grouped around three topics of significant interest to the audience, the topics being:

  • Regulatory agility and speed
  • Harmonization and innovation from regulators (being mindful of MRAs and other initiatives)
  • Workforce skills (both industry and regulators)

Question: How can regulators help support a ‘safe space’ for industry to adopt novel approaches and technologies without fear of regulatory delay?

Korakianiti started by referring to the EMA Quality Innovation Group (QIG), which contains EMA assessors and some academics. This is a good starting point for sponsors to have discussions regarding regulatory approaches and questions as well as an opportunity to teach regulators about the proposed new, innovative technology. This group is also connected with US regulators e.g., Biomedical Advanced Research and Development Authority (BARDA), UK colleagues in MHRA, and Pharmaceutical Inspection Co-operation Scheme (PIC/s) as well as other agencies. Korakianiti also referred to first QIG Workshop held in early March 2023 at which case studies in continuous and decentralized manufacturing were presented and discussed. In answer to the question, what does the industry have to do? Korakianiti stressed the importance of early engagement to support understanding, training and allow interactions with other agencies.

Rosa also indicated that US FDA has the Emerging Technology Team (ETT,) and he also stressed the need for early engagement since late engagement can lead to problems and delays.

Korakianiti specifically referenced artificial intelligence (AI) as a specific new technology, for which regulators do not wish to publish guidance too early, however, in the absence of guidance sponsors should not hesitate in approaching QIG to discuss proposed AI applications.

Pound mentioned the MHRA Innovation Office, again stressing the need for early engagement. There is also an opportunity for consortia working on the same or similar technologies to request interactions.

Korakianiti referred to the nitrosamine and heparin impurity emergencies, which had required and demonstrated regulators globally cooperating to find solutions.

Question: What can companies do to help regulatory review and inspection when a new technology is put forward, to help understanding if needed?

Friedman commented that it would be extremely helpful to both industry and regulators if companies were willing to share knowledge and experiences relating to new technologies.

In summary, all regulators agreed on the need for early engagement to obtain regulatory expectations and to assist overcoming the “fear’ of introducing new technology. As Rosa commented “be prepared to teach us”.

Question: How do individual agency regulatory initiatives and flexibilities align to ensure that MRA agreements are not undermined?

Lorente indicated that some flexibilities may be possible, and some may not be easy to apply. Processes are in place to check on the impact on MRAs with the need to communicate with partners and evaluate at national level.

Pound said that MRAs were aligned with trade agreements, hence there could be challenges, and that ICMRA and PIC/S should be consulted by regulators as they should be helpful to the dialogue.

Korakianiti commented that discussion and application of flexibilities may lead to extension of MRAs.

Question: What levels of co-ordination are happening regarding different innovation initiatives?

Korakianiti reiterated that EMA has established collaboration arrangements as part of the QIG process, which is “opening Europe”. There are opportunities to extend invitations to more agencies to cooperate with QIG. As mentioned previously, exchanges with PIC/S are particularly useful. Use of the PRIME toolbox produced flexibilities during Covid in which there was in depth discussion with FDA.

Question: It’s easy to get caught up in innovation. Not forgetting the basics of GMP and risks to supply chains - what global issues are regulators focusing on?

Quality of raw materials in terms of purity and safety has been and continues to be a problem said Friedman. He referred to the recent global events relating to poisoning due to ethylene glycol and diethylene glycol contamination. What is going to be the next raw material in focus? We cannot wait for the next material until there is an incident. Friedman questioned the suitability of pharmacopeial monographs – are they up to date? There is a need for management oversight to assure design of quality, for example with supplier oversight and inspection programs in addition to testing.

Question: Scope expansion – what is actively being looked at to increase the scope of MRAs?

Conocchia explained that discussions were being held to extend the EU - US MRA to include veterinary products as well as vaccines and blood products. The EU - Canada MRA may be extended to include active pharmaceutical ingredients (APIs), and EU - New Zealand MRA should be extended to include additional member states.

Question: What role could multinational companies do to support confirmation of harmonization or support quicker recognition of this – for example through inspection practices observed across their global facilities?

Rosa stressed that FDA was seeing a great deal of silo behavior in large companies. Individual sites in the networks of global companies are not sharing experiences from inspections. Such companies should strengthen their quality audit programs and learn from these “weaker” sites. It appears that regulators are acting as the quality unit. There is a need to go back to basics, determine the quality management maturity across the network and improve behavior and stop violations of basic GMPs.

Additionally, there is also a need to strengthen quality agreements between sponsors and contract organizations (CDMOs). In summary, companies should communicate.

Question: ICH Q13 was published Jan 2023. What actions are regulators taking to encourage the use of this guidance, and how are they working together to facilitate harmonized adoption?

Pound replied that regulators were not seeing a great number of applications. These are required to support exemplification and understanding.

Question: What skills do you see industry needing to achieve sustainable GMP compliance at the same time as implementing digital transformation concepts?

It all starts with management stressed Friedman. Some necessary leadership qualities are given in ICH Q10, Pharmaceutical Quality System and associated ISO standards and these need to be practiced routinely as part of a company’s quality system. The right pharmaceutical quality system is needed from the start with active engagement from senior management, which should remain continuous to ensure that there is not degradation of the pharmaceutical quality system. In summary, better quality oversight is needed.

Question: What partnerships could be developed to support 2-way learning and then also maintain pace with technological developments?

Conocchia repeated that the EU QIG was willing and available to act as a partner with learning about new technology developments. Pound also mentioned that technology vendors should be good partners. He raised the idea for potential targeted secondments between industry and regulators or vice versa for some of the more complex technology introductions.

Question: Update of PIC/S Inspectorates’ Academy – have any gains been seen to support regulating innovative technologies?

Lorente emphasized the importance of training for regulators particularly for regulators in smaller agencies. PIC/S Inspectorates’ Academy is an excellent training forum for regulators, however, developing the training material is not straightforward. Use of vendors is being considered. Given the importance of training in implementation of new technology the Academy is identifying training needs and high-level expectations.

Question: At the 2022 ISPE’s Pharma 4.0 ™ & Annex 1 Conference last December, we discussed the importance of operator and inspector education with respect to sterile manufacturing - how do you feel this is progressing?

Conocchia answered that the main changes were being collated by PIC/S as training for inspectors. For industry training of operators was of most importance.

Regarding training needs in general, Friedman stressed the need to identify the appropriate skill sets and to employ and train people both in industry and as regulators. There must be ongoing commitment since expertise could be lost as people change roles.

As concluding remarks, Pound emphasized the need for early engagement with regulators when introducing new technology. Guidance may have to change, for example when introducing point of care manufacture. Korakianiti also stressed the need for early communication with regulators regarding new technology introduction. The new EU pharmaceutical legislation provides for a “sandbox” approach whereby there may not be inhibitions to changes in guidance which support introduction of new technology.

View Conference Highlights


This is an informal summary of discussion panels held on 9 May 2023 at the 2023 ISPE Europe Annual Conference. It has not been vetted by any of the agencies or regulators cited in this article, nor should it be considered the official positions of any of the agencies present.