Regulatory Affairs – a clear path through the labyrinth

Much more than simply complying with official guidelines, the science of Regulatory Affairs entails a highly detailed process of data collation and submission to national or regional government agencies who can grant, or refuse, marketing permission. Every application for approval is unique, dependent on your medicine or device’s safety, efficacy and delivery method, and will require varying levels of supporting information. 

Involving a Regulatory Affairs professional at an early stage in your drug’s development can avoid your submission for approval being rejected at the first pass, thus saving a lot of time and money. In a post-approval setting, a medical communications expert with Regulatory Affairs experience can be vital in helping you meet your post-approval regulatory commitments or follow-up measures.

Read on to find out how we work with Regulatory Affairs and what you can expect when you submit your treatment for review.

What is Regulatory Affairs, and why does it exist?

Regulatory Affairs is the science of taking medicines and medical devices through the licensing process and keeping them on the market post-approval. However, this is not simply a matter of presenting all the documentation once you’ve concluded your trials in human subjects. It also involves discussions with the regulators at a number of touchpoints along the development pathway. 

These are typically to specify the type and quantity of information the regulator needs to see in order to take the treatment through to approval, and can also deal with safety issues, efficacy data and detail on what the final drug label (SmPC and Patient Information) looks like. As a whole, Regulatory Affairs relates to the formality behind the licensing of treatments.

Activities in this field can include:

• Keeping up-to-date on legislation and regulations in the territories a manufacturer may want to market its treatments
• Collecting, reviewing and presenting scientific data from clinical trials
• Submitting formal dossiers for approval
• Liaising in dialogue and debates between the regulator and manufacturer
• Problem-solving throughout the process to ensure accurate records, data and correct approaches to endpoints 
• Enabling manufacturers to continue to fulfil their obligations in a post-approval setting

Getting medicines approved in the UK

Many new medicines in the EU are reviewed and approved by the European Medicines Agency (EMA) through a centralised procedure, which grants a simultaneous licence in all EU member states. For many areas like oncology, orphan diseases and metabolic diseases like diabetes, it is mandatory to submit treatments for European Approval through this centralised procedure. 

In the UK, since we left the European Union, it’s a little different. You now have to make a separate submission to the Medicines and Healthcare Regulatory Authority (MHRA), who will review and approve your treatment based on their own analysis of the submission and supporting data. This is referred to as National Approval.

While not exactly the same, there are more similarities between the two than differences. We are still seeing medicines being approved within the same time periods, so the industry in the UK is not being left behind.

What does a Regulatory Affairs expert do?

As part of the testing, data collection and submission process, there are a number of things you’re doing to assist the treatment’s journey to approval. 

In pharmaceutical development, while clinical trials themselves are conducted by the manufacturer or contracted out to a separate clinical research organisation (CRO), a Regulatory Affairs professional helps to guide the design and methodology of these trials in order to seek regulatory approval. For example, for a trial exploring a novel treatment for lung cancer, you might approach the regulators proposing a trial for a new treatment with a primary endpoint of reduction in the size of the primary tumour, using the RECIST criteria. You might set the end point as a reduction in size of 25%. 

The regulators might acknowledge this is an interesting endpoint, but point out that the goal of the treatment is actually to save people’s lives. So, what you should be measuring is overall survival rates. Based on what is already known, on the existing guidelines and on the precedents seen with other medicines that have been developed in this therapy area, they may think you need to use this as a primary endpoint and design the trial accordingly.

This input into trial design is becoming increasingly important and relevant in the approval process. A Regulatory Affairs professional will be contacting the MHRA or EMA to arrange for scientific advice and discussions around how to design those endpoints, and also engage in ongoing dialogue after the initial submission for approval with the regulators. There are then various rounds of reviews, comments fed back to the manufacturer, more discussions held and disputes resolved in an intensive, iterative process over a number of months. 

The balance between complexity and standardisation

Every submission is bespoke and every package you submit will be different. Trials may run into tens of thousands of patients over a period of many years, or they can be small as a few patients with an ultra rare orphan disease where it is very difficult to get information on more than a handful of subjects for a regulatory submission.   

This said, regulators will still have certain guidelines that apply to submissions, typically according to the therapy area, and different types of trials need different kinds of endpoints. For example, if you are running a trial on a new treatment for high blood pressure, there will be a specific guideline on how those trials are designed, how you measure outcomes and even how you measure blood pressure itself. This is documented to create some standardisation in methodology and what we see in results, especially in specialist areas like oncology and metabolic diseases.

Formatting your submission for approval

Despite the complex nature of individual submissions, they do need to be put in a standard format. For this, we use something called the Common Technical Document (CTD) which is an interlinked dossier of documentation, summaries and conclusions. 

The CTD can include the raw data; the patent case report forms, lab results, etc. It will also include those results summarised in clinical study reports for each of the trials which make up the dossier. Summaries of efficacy, safety and clinical pharmacology are then written, and then those are summarised again in a clinical overview and the final SmPC. 

Each of these documents or summaries has to make sense individually, and within each summary you will need to hyperlink all the documents to make sure readers can navigate their way through the dossier and easily find what they need to refer to. This is hugely time-consuming, but is required by the regulatory authorities.

How does Regulatory Affairs show up in Dice’s work?

Where Dice’s experience comes in is around raising awareness of your medicine or medical device in the therapy area prior to and during its launch to market and the development of your brand. However, as the dialogue between the regulators and the manufacturer has evolved over the years, our role in medical communications has become more vital.

In the past, when a treatment was licensed, that would be the end of the story and you would be free to market and sell it without further contact. Now, regulators will typically licence a medicine but with the proviso that the manufacturer will educate physicians on all its aspects, applications and possible side-effects. You might perhaps encounter an unusual and uncommon adverse event with a therapy that was not detectable in clinical trials of 1,000 patients and only became apparent when you started to treat populations. 

When an adverse side effect like this is spotted in the post-marketing stage, new information needs to be created for medical professionals to raise awareness of risk and risk management. These communications would fall within Dice’s brief around scientific information and regulatory requirements in a post-approval setting. 

Communication is at the heart of positive patient outcomes

Dice effectively helps brands to find ways to best communicate results and risks observed in outcomes – through everything from the label/SmPC to patient materials – and so fulfil their post-approval obligations. This allows manufacturers to maintain their approved status at a stage that enables them to recoup their investment while they still have the patents.

Give your medicines the best chance of success

The biggest challenge you face in marketing your treatments can be in raising awareness of them and the disease they treat. For your next launch to market, come to Dice and benefit from creative campaign material that will ensure HCPs remember your brand and want to find out more.

Please get in touch with the Dice team if you need help creating a strategy that gets your treatment in front of the people who need it most.