Regulatory lifecycle management is an essential aspect of maintaining product compliance, particularly when dealing with Chemistry, Manufacturing, and Controls (CMC) changes. However, managing these changes on a global scale introduces unique challenges due to differing regulations across countries. In this article, we explore the key challenges companies and regulatory professionals face, offer strategic advice, and provide an overview of upcoming regulatory changes, particularly in the European context.

The Complexities of Global Regulatory Compliance

Global regulatory lifecycle management for CMC changes is far from straightforward. Companies must navigate a labyrinth of regulations from different countries, which are rarely harmonised. According to Sophie, a regulatory expert, one of the biggest hurdles is managing the varying regulatory requirements across multiple regions.

“The regulations are not harmonised, and we have to face these differences in the regulatory requirements when dealing with post-approval CMC changes,” Sophie explains.

This lack of harmonisation can lead to significant delays. For example, some countries may require approval of a variation in reference countries before even considering a submission. Additionally, submission classifications may vary, with some countries considering the same change as a notification, while others demand full approval before implementation.

Key Challenges:

Varying Approval Timelines: Different countries have different timelines for evaluating and approving changes. For instance, while some countries may approve changes within three to six months, others may take up to 12 months or more. This creates a scenario where companies must manage varying approval statuses across regions.

Data Requirements: Stability data requirements also differ, adding another layer of complexity. These differences can result in implementation delays of one to two years, as countries approve changes at different times, requiring regulatory professionals to manage transition periods.

The diversity in regulations and approval times can create a fragmented implementation process, making it particularly difficult for companies to coordinate their production activities and ensure compliance worldwide.

Strategic Planning for Global Variations

Due to the complexity of managing global CMC variations, strategic planning is essential. Sophie advises professionals to first acknowledge the inherent complexity of the task.

“You have to accept the complexity… It’s really about accepting that this is complex. It takes time. There’s no simple way to do it.”

This realistic perspective is crucial for professionals embarking on the journey of managing global regulatory variations. Rather than searching for shortcuts, teams should focus on careful planning and thorough preparation. Sophie emphasises the importance of treating global variations as distinct projects, each requiring a well-structured approach.

Effective Strategies for Managing Global Variations:

Comprehensive Requirement Gathering: Teams should invest time in gathering all regulatory requirements from the relevant countries. This includes understanding each country’s submission timelines, approval processes, and data requirements.

Project Management Approach: Treating each variation as a project, with clearly defined timelines and responsibilities, can help streamline the process. A project management mindset allows for better coordination among the various stakeholders, including regulatory professionals, production teams, and other departments.

Production Impact Assessment: Companies should also consider the potential impact of regulatory variations on production schedules. Given the uncertainty of approval timelines across regions, it is essential to anticipate delays and plan accordingly to minimise disruption.

Upcoming Regulatory Changes in Europe

As the regulatory landscape continues to evolve, significant changes are on the horizon, particularly in Europe. A new pharmaceutical strategy initiative is in development, which aims to adapt regulatory pathways based on the lessons learned from the COVID-19 pandemic.

This initiative has several goals:

Adapting to New Technologies: European regulators are working to ensure that regulations evolve to accommodate new technologies, including artificial intelligence and advanced medical innovations.

Patient-Centric Focus: There is an increased emphasis on regulatory pathways that prioritise patient needs, ensuring faster and more efficient access to medicines.

Evaluation and Legislation Updates: Over the next two to three years, the European regulatory bodies will evaluate whether current legislation is sufficient to meet emerging challenges or if reforms are needed.

“Maybe in two or three years, there will be a revision of the pharmaceutical legislation and also of the guideline on variations,” Sophie notes.

A key part of this regulatory evolution will be the full implementation of the ICH Q12 guideline, which focuses on product lifecycle management. This guideline is expected to provide a more structured approach to managing CMC changes and variations, making it a crucial development for regulatory professionals to monitor.

Conclusion

Regulatory lifecycle management, particularly for global CMC changes, presents significant challenges due to the complex and varied requirements across different regions. Regulatory professionals must navigate these complexities through strategic planning, comprehensive requirement gathering, and a project management approach.

As regulatory landscapes, particularly in Europe, continue to evolve with initiatives like the new pharmaceutical strategy, staying informed and adaptable is crucial for ensuring compliance and maintaining a smooth product lifecycle. By embracing the complexities of global regulatory management and anticipating future changes, professionals can better navigate the challenges ahead.

Watch the interview below:

Written by Educo Life Sciences Expert, Sophie Nageotte

Sophie has over 20 years of experience in the pharmaceutical industry. She gained her Master’s degree in analytical chemistry from Manchester University and her Chemical Engineer degree from Montpellier School of Chemistry. She went on to work in pharmaceutical development and post-marketing CMC regulatory compliance in companies such as Bayer, Stragen, PregLem and Laboratories Galderma. She gained a strong experience in the worldwide regulatory environment for the manufacture and control of the medicines.

She now runs her own consultancy, delivering consultancy and support in writing IMPDs, CTD Module 3 and QOS, preparing variations and answering questions from health authorities.

Sophie also delivers training courses on European regulations for pharmaceuticals, writing of the Module 3, how to achieve global regulatory compliance, managing transfers of manufacturing sites and preparing variations for the ASEAN region.

This article was written using the video interview which you can watch above.