Question: What is your role at NDA Group?
Answer: I am the Director for the NDA Regulatory Advisory Board. The NDA Advisory Board is a unique feature to NDA Group compared to other regulatory consulting companies. It is a virtual business unit that currently has 27 members all of whom are senior regulatory or health technology assessment (HTA) experts or former pharma company executives.
As an Advisory Board member, I provide our clients with strategic advice on their drug development and regulatory strategy. Most of my colleagues have similar backgrounds to mine: many have a medical background, are scientifically skilled and have published in peer reviewed journals. Most of them have been working in senior positions at European national competent authorities and involved in the EU regulatory network via membership of one or more scientific committees and/or working parties at the European Medicines Agency (EMA). We also have members who are ex-FDA employees to provide complementary US expertise.
Q: What are your best qualifications for working with Oral Explanations?
A: “First and foremost, it’s my former membership of CHMP, Committee for Medicinal Products for Human Use at the European Medicines Agency (EMA), because that’s where the Oral Explanation (OE) takes place. Then it is, of course my clinical experience and my former roles in the EU regulatory network plus the experience gained as medical advisor and member of the Advisory Board at NDA Group.”
Q: How many Oral Explanations were you actively involved in during your five years at the EMA?
A: “To answer that, I need to do some counting!
The committee meets eleven times a year, and there are approximately between two and three OEs every time, so a rough calculation sums it up to between 100 and 150 OEs over my years at CHMP. Then we need to add all the OEs that I have not witnessed but been a part of through the preparation work at NDA. In total NDA has done 122 OEs over the past 20 years, of which 48 were done during the last five years.”
Q: How often do companies get called to an Oral Explanation?
A: “We know that the overall probability of success for any marketing authorization is approximately 85 percent. Around 30 percent of those will need an OE to get to the positive outcome and the remaining 15 percent receiving a negative opinion will all have had an OE. So, the chance your application will run into an OE is around 40 percent.”
“OEs take place at the end of a marketing application procedure when there are still outstanding so called major objections (MO). An MO is a review issue that needs to be addressed to CHMP’s satisfaction in order for the Committee to reach a positive opinion. The applicant is asked to address the outstanding MO in writing and is given the opportunity to do the same in front of CHMP at an OE. This is an important opportunity for the company to engage and interact with CHMP verbally.”
Q: How should companies think before an Oral Explanation?
A: “They should think strategically! The OE provides the opportunity for a potential negotiation around the basis for approval and the final labelling. Let’s say that the applicant has applied for a broad indication to treat every phase of a disease, but CHMP disagree because the company hasn’t studied those with more severe diseases. Going into the OE with the potential to offer a more restricted indication may turn the opinion in the applicant’s favour. Thus it’s important that the company has agreed internally to what is and what is not negotiable before going to the OE.”
Q: You recommend your clients not focus on the rapporteurs during the Oral Explanation. Why?
A: “Companies may find it daunting to meet sceptical rapporteurs and spend all of their energy trying to convince them, but it’s important to remember that CHMP’s final decision is by majority and each member has one vote. Before going into an OE we advise clients to focus less on the rapporteurs and more on any silent majority in CHMP that may be in favour of an approval. The OE is not about persuading your rapporteurs to be positive; it’s about persuading the other 30 CHMP-members. To be honest it’s not until the voting that the others really make up their minds, so you have the opportunity to persuade them.”
Q: What else should companies think about?
A: “Do your homework, so that you can anticipate and respond to questions you may face once you are in front of the Committee. Preparing for questions and responses is as important as selecting the right person to reply to any given question. Sometimes a company picks the presenter because he or she is holding a senior position and not necessarily because he/she has detailed knowledge of the product and its development. That is fine as long as the presenter and the team are able to address any question asked.”
“It’s important to have a strategy for your responses. Sometimes clients are very focused on giving very detailed and long answers. This is dangerous because the longer the answer is, and the more slides you show in support of the answer, the higher the risk that this leads to further questions on something else. Try to be simple and not open too many doors. If your answer is perceived as too short or less detailed the CHMP member will ask for more details.”
“One last thing is the way you present and articulate your points. It’s critical that your key messages come across clearly. PharmApprove, a specialty practice within NDA Group, has a lot of expertise in strategic communication and preparing teams for high stakes regulatory interactions. They can provide support for presentation delivery, review or creation of slides and rehearsal of potential questions and responses. This level of support can make a tremendous difference.”
“To prepare our clients in the best possible way we typically involve a team of two to three Advisory Board members to create a mock CHMP panel and train the client to present and respond to questions.”
Q: How does the coronavirus pandemic affect OEs?
A: “At present OEs have become more challenging as everything needs to take place online. EMA’s virtual meeting system requires all participants to dial-in via phone. Only slides are shared over the computer and there is no possibility to see the committee or the members asking the questions. Disturbing noise, automated announcements when participants join or leave, as well as difficulties hearing the questions are often mentioned by our clients as the major challenges.”
Q: Requesting help well ahead of the OE is vital, but what does well ahead mean?
A: “On average any marketing authorisation application (MAA) carries a chance of roughly 40% to end in an OE. Considering the likelihood that this will happen and seeking assistance preferably before compiling the MAA or at least when submitting it will prepare you and your team best possible.”
“Companies get a lot of questions on day 120, which is well past midway of the review procedure. At that point, you can normally start sensing whether this will end up with some outstanding issues or not. That’s the ideal time to start working with NDA on the response strategy and potentially prepare for an OE. But maybe clients don’t recognize those signals and believe that they can manage themselves. Many clients come in at a very late stage, perhaps a month or two before an OE, making it a real firefighting exercise.
To quote one of the US founding fathers,
“If you fail to prepare, you prepare to fail.”
“However, all is not lost with a failed OE and a negative opinion. The company gets one chance to appeal and gets a new set of rapporteurs to look at their data. I remember one of the first clients I worked with at NDA. We spent a lot of time with them and told them that they needed more animal data, which the company for good reasons couldn’t manage within the short time frame. Not surprisingly to us, they got a negative opinion. But the appeal gave the company enough time to generate the non-clinical data needed, which they then included in their response and got an approval.”
Q: What are the differences between EMA and FDA when it comes to these meetings?
A: “The Advisory Committee meetings at FDA are huge, public, and they take hours – typically half or full days. At those meetings the FDA states its position and the company presents its position to the Advisory Committee. Then the Advisory Committee, which is not the FDA but a group of experts which the FDA has convened, provides their position and feedback to the FDA. In Europe, the meetings are short, around one hour (20 minutes for the company presentation and the rest for Q&A), and only those people who are going to make the decision are present. Our experts at NDA Group can equally support an Advisory Committee meeting in the US.”
For 20 years we’ve helped innovative life science companies prepare to win at high profile, high stakes meetings such as Advisory Committees,Oral Explanations, expert panels and advisory boards. We’ve coached thousands of professionals and led more than 250 clients through critical junctures to successful outcomes.