Regional Aspects of Regulatory Frameworks for Pharma Approvals

Successfully navigating the diverse regulatory frameworks in different global regions is critical for companies in the pharmaceutical, biopharmaceutical, and medical device industries aiming to enter new markets. Here we will examine the unique regulatory environments of the US, European Union, and UK, highlighting key differences that significantly impact the process and strategy of obtaining necessary approvals. This is the first in a 4-part series. 

Each region has established a comprehensive set of regulations designed to ensure the safety and efficacy of pharmaceuticals. Here is a directional view by region:

• United States: Governed by the Food and Drug Administration (FDA), the U.S. regulatory framework is known for its rigorous scrutiny of both drugs and medical devices through a highly structured and phased approach. Detailed clinical trial data, stringent documentation, and a thorough review process are essential components of the FDA’s strategy to safeguard public health.
• European Union: The European Medicines Agency (EMA) works in concert with health authorities from each of the 27 EU member states and Iceland, Norway and Liechtenstein as non-EU participants. This multi-faceted system introduces complexity, because every decision taken is the result of a vote between the 30 countries. Despite the complexity, also in the EU public health is safeguarded in accordance with the highest standards.
• United Kingdom: Since Brexit the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) is an independent regulatory body. It was formed in 2003 through the merger of the Medicines Control Agency (MCA) and the Medical Devices Agency (MDA) to create a single agency responsible for regulating all medicines and medical devices in the UK. Companies need to navigate multiple regulatory requirements if they wish to operate in the UK as well as in the US and EU, necessitating a nuanced understanding of their respective guidelines.

Despite operational and procedural nuances between these regulatory bodies, companies have access to a similar array of regulatory services.

• Health Authority Interactions (HA): In the U.S., companies are encouraged to engage with the FDA, free of charge, throughout the drug development process through pre-IND meetings, End-of Phase meetings and pre-submission meetings, providing valuable guidance and clarity. It is important to note that opportunities to interact with FDA are limited; the FDA may refuse a meeting request. In the EU (with EMA) and in the UK HA interactions are not strictly tied to development milestones, like in the US, But, since fees are charged for Scientific Advice, there is essentially no limit on how often a company can have these interactions.
• Submission and Review Process: In the US and the UK, marketing applications are submitted to and reviewed by a single regulatory body. The EU offers a centralized procedure that essentially is a submission to, and review by a single body, resulting in a single authorization valid in all Member States. It also has provisions for a decentralized procedure allowing companies to submit applications simultaneously to a selection of member states.
• Post-Market Surveillance: The emphasis on post-market surveillance is also similar; Pharmacovigilance systems such as EurdraVigilance in the EU and FAERS in the US, both collect information on adverse reactions. Each region also has specific sets of regulations and cadence of reporting, what data must be included, additional studies might be required. The methods of public involvement and reporting varies between regions, such as the UK’s Yellow Card scheme and similar initiatives in the US and EU.

A few specifics demonstrate the need to be informed to properly navigate through each region and country:

Clinical Trial Approvals: With the implementation of the Clinical Trial Regulation (CTR) in the EU (into force on 31 January 2022, with a transition period of three years), establishing a single and identical CTA approval process for all Member States. The CTR replaces the Clinical Trials Directive (CTD). Also, with the CTD a single CTA process was implemented in the EU, but Member States had the option of imposing additional national requirements for CTA approval. Under the CTR this is no longer possible.

Pharmaceutical Marketing Authorization: Gaining marketing authorization for a new drug in the EU involves the centralized or a decentralized or national procedure, but the requirements don’t significantly differ from those of the FDA in the U.S. The FDA typically requires a comprehensive set of clinical data that demonstrates both efficacy and safety, accompanied by detailed pharmacological profiles. The EMA, while also demanding thorough clinical trial data, places a strong emphasis on risk management plans and post-marketing surveillance strategies.

Adapting to Post-Brexit Regulatory Requirements: following Brexit, pharmaceutical companies face the need to navigate additional regulatory landscapes. The MHRA may require UK-specific clinical data submissions. This adds to the complexity and resource allocation for companies seeking to market their products in the EU, US and the UK.

These examples highlight the need for pharmaceutical companies to have a robust understanding of and strategy for dealing with evolving regulatory requirements (EU is currently undergoing a major overhaul of its pharma regulations) in different regions to ensure successful drug approvals and market entries.

Effective management of regulatory challenges requires an in-depth understanding of regional regulations and strategic planning:

1. Comprehensive preparation and adherence to local regulations are critical.
2. Direct engagement with regulatory bodies can aid in clarifying expectations and streamlining the approval process.
3. Cultural awareness and understanding of operational preferences in each region can facilitate smoother interactions and compliance.

The regulatory processes in the US, EU, and UK present distinct challenges that require careful navigation. Understanding these differences is crucial for pharmaceutical companies aiming to market their medicinal products globally. Strategic planning and adaptability are key to managing these complexities effectively and achieving regulatory compliance to save time and improve outcomes. Consider engaging throughout the product development with a regulatory expert partner to address all regulatory requirements regardless of geographical location for successful market authorization applications. This can lead to considerable time savings and adds to a positive reputation and credibility with the health authorities.

At Celegence, teams of RA Strategy dedicated Subject Matter Experts provide cutting-edge consulting services and technology-driven solutions that are tailored to the evolving operational and strategic needs of small Biotech and Specialty-Pharma companies as well as large/big pharma companies, and developers of generic and biosimilar medicines. Contact us at info@celegence.com to learn more about how Celegence can help you with your regulatory development strategy.

Author: Maurice Bancsi, PhD, Principal SME Regulatory Strategy @ Celegence