Comparing The US, EU and UK Health Authorities

Part 2 of a 4-part series on Regulatory Framework, check out part 1 here about Regional Differences of Regulatory Frameworks for Pharmaceutical Approvals.

Seeking feedback from health authorities is an important step that pharmaceutical companies take in drug development. The purpose is to achieve alignment on drug development plans with regulatory bodies, thus increasing the probability of success in bringing a new drug to market. Here we’ll explore how this process occurs across three regions/countries: the U.S., the European Union, and the UK.

A Health Authority Consultation is a formal process through which pharmaceutical companies can seek guidance from regulatory authorities about various aspects of drug development. This includes feedback on clinical, non-clinical, manufacturing, multi-disciplinary and regulatory aspects of product development. The primary goal is to ensure that companies conduct their development processes in a manner that meets regulatory expectations and thus increases the likelihood of drug approval.

CHMP Scientific Advice:
First and foremost, CHMP provides written advice. Due to the complexity of 27 (+3) countries needing to agree on the content of the advice it is not possible to have face-to-face meetings.

The Scientific Advice Working Party (SAWP) manages the SA process and prepares the Scientific Advice Letter, that is then sent to CHMP for adoption.

CHMP oversee the following SA procedures:

• CHMP Scientific Advice: this Pan-European advice helps align drug development with regulatory standards.
• Protocol Assistance: SA for orphan medicines, aiding in the development of treatments for rare diseases.
• Parallel Scientific Advice with the FDA: a cooperative framework allowing simultaneous advice from the EMA and FDA, though not joint advice.
• Medicine Repurposing: supports non-profits and academics in identifying new public health applications for existing medicines.
• Post-Authorization Safety Studies (PASS): a voluntary procedure to optimize drug safety post-approval.
• Biosimilars Advice: focuses on the review of biosimilars’ quality, analytical, and functional data.
• Public Health Emergencies: advice on medicines during health crises like COVID-19.

National Scientific Advice
In the EU, national authorities offer scientific advice that may focus on specific areas such as therapeutic categories. This advice can guide drug development and preparations for clinical trial applications. Although not legally binding, this scientific advice allows sponsors to explore different aspects and possibilities, such as new trial designs or endpoints during brainstorming sessions with Competent Authorities (CAs). These advisory services are usually provided for modest or no fees, making them accessible and flexible for pharmaceutical companies seeking initial feedback on their proposals. Where the topics for discussion are likely to have an impact on the content of the MAA dossier, it will be necessary to also seek buy-in from CHMP.

Simultaneous National Scientific Advice
A pilot project in the EU enabling National Scientific and Technical/Regulatory Advice from multiple National Competent Authorities (NCAs) and/or the participation of the European Clinical Trial Coordination Group (CTCG). SNSA is open to large pharmaceutical companies, as well as smaller and medium-sized enterprises (SMEs), Academic Research Centres and Hospitals,

Scenarios for which researchers can apply for SNSA may include:

• Advice on clinical trials to be conducted in multiple EU Member States
• Advice about applying for funding grants to support non-commercial clinical trials
• Obtaining information on the early development stage of innovative products for which there is limited regulation
• Prior to clinical trials intended to facilitate the repurposing of authorized medicinal products, such as in the case of new therapeutic indications

SNSA will guide innovators from their translational research (the link between basic and specific medicinal product research) that often happens in one country to the later stages of development that usually take place on a European or international level.

In the UK, MHRA offers scientific advice. This advice can guide drug development and preparations for clinical trial applications as well as Marketing Authorization related discussions. Contrary to National Advice in the EU, MHRA Advice is binding.

The process for obtaining SA in the UK is generally the same as the process for national advice in the EU.

Different types of meetings at MHRA:

• Scientific advice; feedback regarding the development of a single product
• Broader scope scientific advice: non-product-specific meetings eg. to discuss the product portfolio and inform on expected workload for MHRA in the near future.

In the US, the FDA plays a central role in providing scientific advice. Companies can engage with the FDA at several critical stages:

• Pre-IND (Investigational New Drug) Meetings: Before submitting an Investigational New Drug application, companies can clarify and receive guidance on initial development plans.
• End-of-Phase 1 and 2 Meetings: These are crucial for discussing ongoing development and next steps after preliminary trial phases.
• Special Protocol Assessment (SPA): This is a process by which the FDA formally evaluates the design and size of phase 3 trials to ensure they adequately address regulatory requirements.
• INTERACT Meeting: This program focuses on innovative therapies including cell, gene, blood, vaccine, and other related treatments. Through INTERACT, sponsors can seek critical early advice on specific issues that affect the development of these products.

Alternatively, FDA interactions can be divided by type:

• Type A: Meeting (scheduled in 30 days) is a meeting needed to help an otherwise stalled product development program proceed.
• Type B: Milestone meetings; Pre-IND End-of-Phase meetings, Pre-emergency use authorization meetings, post-action meetings (after receipt of an FDA regulatory action other than an approval (e.g., issuance of a complete response letter, refuse to file))
• Type C: any meeting other than a Type A, Type B, Type D, or INTERACT meeting
• Type D: A Type D meeting is focused on a narrow set of issues that are used to discuss issues at key decision points to provide timely feedback critical to move the program forward

While the health authority interactions in the US, EU, and UK share fundamental goals, they differ in procedural steps and overall timelines. Feedback is always based on state-of-the-art science and local and international regulations. These differences can influence a company’s regional strategy for drug development and regulatory submissions.

Furthermore, fees are charged for HA consultations in the EU and UK, whereas FDA Advice is free of charge. As a consequence, there is essentially no limit to how many times an applicant can seek advice in the EU and UK, while FDA preserves the right to simply refuse a meeting.

Effective engagement with regulatory bodies may impact or confirm the drug development trajectory. Companies that properly navigate these interactions often achieve more streamlined development processes, more robust clinical trial designs and smoother authorization procedures with less requests for clarification or additional information. Understanding and utilizing these processes is a strategic imperative for pharmaceutical companies.

The health authority interactions represent a critical pathway for pharmaceutical companies aiming to align their drug development efforts with regulatory expectations in the US, EU, and UK. By strategically engaging with these regulatory bodies, companies can enhance their likelihood of success in bringing their medicinal products to market.

For pharmaceutical companies looking to navigate local, regional and international regulatory requirements more effectively, engaging with regulatory experts can provide the necessary guidance and insight. Connect with our experts at Celegence to talk about your needs for Scientific Advice or assistance with Global Regulatory requirements.

Refer to Part 1 of this 4-part series about the Differences Between Regulatory Frameworks for Phamaceutical Approvals.