Regulatory variability – particularly varying interpretations of ICH guidelines — is limiting the introduction of innovative medical technologies and treatments, according to respondents to a recent ISPE survey.
Regulatory challenges were cited by 48% of respondents as a significant disincentive for investing in innovative technologies, said ISPE adviser Chris Potter, speaking on a panel at the 2024 ISPE Annual Meeting & Expo. Divergent requirements are a significant concern, with 30% of respondents pointing to divergent review requirements and 9% citing concerns about divergent inspection requirements.
Respondents find agreements at meetings with senior-level regulators do not always lead to the same interpretation and acceptance by reviewers and inspectors, Potter said. “Engagements with multiple individual regulatory authorities frequently lead to different regulatory expectations for innovative technologies,” and these separate meetings can be a logistical and resource burden that extends over a long period of time.
What industry wants is common questions, common timescales, predictability and harmonization of GMP inspections, along with a regulatory pathway for introducing new technologies that are applicable to multiple products, Potter said.
The survey is part of the ISPE Harmonization Initiative, which seeks consistent and harmonized interpretation and implementation of ICH guidelines. Next steps for the initiative will include:
- Publishing five case studies that show opportunities for better engagement with regulatory assessors and inspectors globally.
- Presenting proposals to multiple regulatory agencies at appropriate forums dedicated to advancing globally accepted regulatory approaches.
- Working with industry and equipment suppliers to develop a “points to consider document” on how to present innovative projects internally and externally to regulatory authorities.
- Working with regulatory agencies to address concerns cited in the survey.
EMA perspective
Also at the meeting, EMA Executive Director Emer Cooke spoke on the advantages of global regulatory collaboration during the pandemic and the need to continue to make advances.
“We’ve shown that we can do things better together, and we now need to systematize some of these learnings in areas such as medicines shortages and in translating reliance and convergence efforts to the next level, with particular focus on postapproval changes because we’re seeing a lot of activity there,” Cooke said.
Regulators also need to ensure adequate systems are in place for the next pandemic, such as preapproval clinical trial protocols and functional systems for remote hybrid inspections.
Cooke noted that the EMA has various efforts to bring together stakeholders, and it has created models, particularly in collaboration with the FDA, to help facilitate the adoption of advanced manufacturing approaches. Additionally, it is “working a lot more with regulators in countries that may not have the experience to deal with some of the more advanced innovations, and we have programs with various countries to help regulators understand and adapt to the challenges.”
ICMRA pilots
Cooke also discussed pilot projects under the International Coalition of Medicines Regulatory Authorities – one on hybrid inspections and one on postapproval change studies.
The postapproval change pilot has already had a positive impact on five case studies, with regulatory authorities coming to a harmonized outcome in 120 days, “which is no different than if you had done it with one individual regulator.”
“We’re really interested in trying to build on these successes so that they become sustainable in the long run,” Cooke said. “While these initial cases are not enough to move to a full operational phase, we’re already thinking about that. We’re exploring options.”
The pilots show it is possible to reach harmonized outcomes, even if countries have different legal and regulatory frameworks, Cooke noted. Advancing this type of collaboration will help industry implement manufacturing changes more quickly and pursue the latest innovations for medical technologies and treatments.