Having worked for over a decade in Regulatory Affairs, a slow but sure realisation has crept into my daily work. I am scientifically qualified, have a background in research and am familiar with the pharmaceutical industry. Things I’ve learned on the way are that unless you think like a regulator, from conception to the end product, your submission may be doomed from the start.
What startled me recently is that a lot of what is now effective regulatory management and expertise is fundamental to the “think like a regulator, act like an applicant” mantra. It is as simple as that. To illustrate my point better, I can draw on more than a handful of recent examples. For example, a couple of months ago, we were assigned to a project, in which we were asked to “take a look and see if we can help.” It was a pan-EU application in the latter stages of assessment. One call and a few documents later, and we were fully engaged.
Without disclosing too much, it is safe to say that the procedure would have been rejected, not because it was a bad submission (far from it, one of the best we had ever seen), but the rejection came at a point when time was not on the applicants’ side. Despite previous attempts and more data being provided, the assessors around the EU were not able to approve the procedure.
Our team, all ex-regulators, believed in the strength of the application and were at odds with the opinion of the agency. Had we agreed with the regulators, we would have refused to assist the applicant in the first place. Fortunately, one of our team members was a key expert in exactly this area of development. It was a perfect union which eventually came to fruition on day 210.
How did we get to this place? Basically, we deconstructed the issues the agency had put together as a “major question” and took it point by point. This is in contrast to what the agency had provided us with which was a large paragraph containing 4 major issues to address and respond to. After the first draft was put together, we asked the applicant to insert the data, whilst we provided the graphs needed for the development process – this justified why the product should be approved. In essence we just took the same data which had been there all along and represented it in a more palatable manner. Without question, the efficacy and safety of the product was there but it was hard to see the wood for the trees.
Our mindset was to devise a way of deconstructing the data for the regulators. We needed them to believe in the quality, safety and efficacy of the medicinal product and be confident enough to approve it. All three factors must be in play to create an effective endorsement. What started as a mass of data, was condensed and the text around it was created in such a way that the assessors would not only agree with us, but they would USE the text in the next reports. Moreover, a risk assessment was offered that led the assessors to a positive conclusion.
When the next round of reports arrived, and as we all do, we scrolled through first to see the RED lines marked PSPRH and there were none! We scrolled back up and saw “approvable” and scrolled through the middle and then eventually got round to actually reading it -and there were diagrams and text from our own response. We did not perform rocket science nor did the applicant do more tests, clinical or animal studies as time would not have allowed for this. Had they continued to represent the data over and over in the same fashion, they would not be where they are today and have an approved product.
We were not anywhere near being “safe.” There was still a whole body of EU assessors to impress. We anticipated issues, whether they were big or small to be presented to us – all issues irrespective of size were addressed as even the smallest of issues incorrectly addressed could manifest into a larger concern further down the line. Our team were quick to advise the applicant to take each one seriously and we provided the details to answer them.
A regulator does not always see the large fees involved, the cost of a clinical trial and certainly doesn’t always see the benefits of bringing cheaper alternative medications to patients in need. These are not the ultimate factors that assessors account for in their assessment, and unless you have sat in the rather uncomfortable seat of a key assessor perusing a difficult application, one cannot empathise with the challenges they face.
Another major factor that applicants are not aware of is the peer review within the national agency and EU wide. In scientific and regulatory split-decision situations, the knowledge of these internal processes is pivotal to understanding timelines (the real ones, not the guideline ones) and the expertise that your application will be reviewed by. Having worked in two agencies and part of EU intra-agency processes, the knowledge of these assisted with the “whens” and” hows” during the critical moments.
Needless to say a lot was learned by all parties involved and a big bottle of bubbly marked the occasion.
There was a time when walls existed in the pharmaceutical industry. All aspects of Research and Development were done behind closed doors and in great confidentiality. Nowadays, whilst new developments from top pharma companies are rare and the costs are reaching the sky and beyond, there have been some major changes in the industry.
I’ve been working in the pharmaceutical industry for almost a decade now and have witness ed a wave of mergers and acquisitions which have assisted Big Pharma to gain more muscles to influence regulation while simultaneously diminish competition. Fortunately, I had the chance to be involved from a regulatory consultancy point of view in both company mergers and portfolio acquisitions. It is interesting to see the trends and understand how decisions are being made. Purely commercial decisions or patient orientated ones?
Needless to say, one aim of these mergers is to prepare for leaner years. Who would have thought 15 years ago that those who were once competitors, will shake hands today and join forces to share risks and benefits? Producing new developments nowadays is harder because of increased costs and regulatory scrutiny. Furthermore, loss of exclusivity of blockbuster drugs is considered to be one of the biggest challenges in pharma.
Considering all the above, it is a fact that the industry will keep consolidating to survive in a world where drugs are off-patent or losing exclusivity, new blockbuster drugs are few and time to market is longer due to the stringent regulations. However, do patients benefit or suffer from these changes?