Marketing Authorization Holders in the EU and key Responsibilities

Introduction

In the complex landscape of pharmaceuticals and medical devices, Marketing Authorization Holders (MAHs) in the European Union (EU) play a pivotal role in ensuring that products meet stringent standards of safety, efficacy, and quality before entering the market.

This responsibility encompasses a wide range of critical tasks that are essential for safeguarding public health and maintaining regulatory compliance.

Figure 1: Key Responsibilities of Marketing Authorization Holders

Clinical Trials Oversight

One of the primary responsibilities of MAHs is overseeing the design and conduction of clinical trials.

These trials are crucial steps in the process of obtaining marketing authorization, as they provide essential data on the safety and efficacy of medicinal products and medical devices.

MAHs must ensure that clinical trials are conducted in accordance with EU regulations and ethical standards, aiming to generate robust scientific evidence that supports the product’s effectiveness and safety profile.

Ensuring Compliance

MAHs are obligated to ensure full compliance with EU legislation and guidelines, encompassing stringent standards that uphold the reliability and integrity of data supporting veterinary medicines’ authorisation.

These standards, harmonised at the EU level by the European Medicines Agency (EMA), govern the quality, safety, and effectiveness of veterinary medicines once they are on the market.

EMA coordinates inspections to verify compliance with these standards across developers of veterinary medicines. Additionally, the Agency’s scientific committees may require samples of medicines to undergo analysis in official laboratories as part of the approval process.

Pharmacovigilance

Applicants seeking EU marketing authorization must ensure a comprehensive characterization of their medicine’s safety profile prior to submission.

This involves compiling clinical trial data and submitting a risk management plan that details current safety knowledge and outlines future pharmacovigilance activities.

Patient registries, integral to these plans, collect observational data to monitor long-term safety and effectiveness beyond initial studies.

Compliance with EU regulations mandates timely reporting of adverse events and proactive risk mitigation strategies, ensuring ongoing evaluation of medicine safety throughout its lifecycle.

Risk management

MAHs in the EU, ensuring robust risk management is paramount. MAHs must develop and update Risk Management Plans (RMPs) that detail safety profiles and pharmacovigilance strategies.

These plans are submitted during marketing authorization and revised as new safety data emerges or regulatory demands evolve.

MAHs are also responsible for maintaining transparency by summarizing RMPs for public disclosure, contributing to ongoing efforts to monitor and mitigate risks associated with medicinal products.

Regarding Changes to Devices in Medicinal Products

The MAH has several critical responsibilities concerning changes to devices used in their medicinal products:

• Monitoring Changes: Stay informed about modifications to the device or its components and assess whether updates to eCTD documentation are necessary.
• Submitting Variations: Follow EC Regulation No 1234/2008 for submitting variations related to the device, considering impacts on medicinal product CQAs and control strategy elements.
• Consulting Regulatory Authorities: Consult with the issuing CA to clarify variation necessity and category before submission.
• Assessing Device Performance: Evaluate changes to the medicinal product (e.g., volume, viscosity) to determine if further device performance verification or validation is required.
• Usability Studies: Determine if changes in intended use or target population necessitate additional usability studies for the device.

These responsibilities ensure compliance with regulatory standards and maintain the safety and efficacy of medicinal products incorporating devices.

Conclusion

Marketing Authorization Holders (MAHs) in the European Union (EU ) shoulder significant responsibilities in ensuring the safety, efficacy, and quality of pharmaceuticals and medical devices.

Oversight of clinical trials, compliance with EU regulations, and meticulous pharmacovigilance are integral to their role.

MAHs must continually adapt to changes, including those affecting devices used in medicinal products, ensuring rigorous monitoring and proactive management of risks.

By fulfilling these responsibilities diligently, MAHs contribute to safeguarding public health and upholding regulatory standards across the lifecycle of medicinal products in the EU.

Summary

• Marketing Authorization Holders oversee clinical trials to ensure medicines and devices meet safety and efficacy standards.
• They maintain strict compliance with EU regulations to ensure product quality and safety.
• Marketing Authorization Holders conduct pharmacovigilance activities to monitor and manage medicine safety throughout its lifecycle.
• They develop and update Risk Management Plans (RMPs) to mitigate risks associated with medicinal products.
• Marketing Authorization Holders manage changes to devices used in medicinal products, ensuring compliance and safety.

References

1. Official Address Domenico Scarlattilaan 6 • 1083 HS Amsterdam • the Netherlands [Internet]. Available from: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/questions-answers-implementation-medical-devices-vitro-diagnostic-medical-devices-regulations-eu-2017-745-eu-2017-746_en.pdf
2. Committee for Medicinal Products for Human Use (CHMP) Guideline on Quality Documentation for Medicinal Products When Used with a Medical Device Draft Agreed by Quality Working Party, Biologics Working Party and Guideline on Quality Documentation for Medicinal Products When Used with a Medical Device [Internet]. 2021. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-quality-documentation-medicinal-products-when-used-medical-device-first-version_en.pdf
3. Compliance: Marketing Authorisation | European Medicines Agency [Internet]. www.ema.europa.eu. Available from: https://www.ema.europa.eu/en/human-regulatory-overview/marketing-authorisation/compliance-marketing-authorisation
4. Pharmacovigilance: Overview | European Medicines Agency [Internet]. www.ema.europa.eu. Available from: https://www.ema.europa.eu/en/human-regulatory-overview/pharmacovigilance-overview
5. Risk Management | European Medicines Agency [Internet]. www.ema.europa.eu. Available from: https://www.ema.europa.eu/en/human-regulatory-overview/marketing-authorisation/pharmacovigilance-marketing-authorisation/risk-management