As every good regulatory person knows they should never plan any milestone or important events for December as that is when every filing MUST go in!  So, my good intentions of writing a blog in December were sidelined not only by work but by a pair of December birthdays, my daughter and myself, and then there was that little known holiday of Christmas.  It didn’t help that there were milestone events as well - my younger daughter turned 18, I turned 50 (more on that later), and my older daughter came home for Christmas, not only to celebrate, but also to deposit her belongings so she could go off to Havana, Cuba to do her semester abroad program.   

I spent the first week of December in Prague at the DIA EU EDM (could I use more acronyms?) and actually started a “Blague from Prague”, but like many other things that month, holiday cards included, I never finished this particular entry.  The subject of it, including an EU Update will be the subject of my next entry . . . really it will. 

In the short three months that have made up 2008, I have decided to tackle another subject near and dear to my heart, which is DDDD or D⁴ or more explicitly, Document and Data Due Diligence.  I actually think it might be my next line of work if the whole wine thing doesn’t work out (see My First Blog).  So what is it, or what should it be you ask…well in this world of in licensing, it is something I don’t feel is being performed by the correct people looking at the correct information. 

Typically, Due Diligence is done by a combination of lawyers, businessmen and occasionally regulatory types.  It is almost always comprised of looking at documentation of the milestone type:  business development plans, health authority briefing books or meeting minutes, high level summaries, the real impressive stuff.  All of which is well and good, but doesn’t touch on the nuts and bolts of regulatory documentation which will support marketing applications, which is why everyone is doing this!  What folks should be looking at are the manufacturing documents, the case report forms, the clinical study reports and the supportive documentation, all of which will comprise the filing.   

Last, and certainly NOT least, is someone needs to look at the data!  Someone needs to find and identify the data, and then have someone who knows what compliant data looks like, review the data.  Marketing applications, especially FDA New Drug Applications are data driven, so if the data is no good, your application goes nowhere! 

Sponsors need to know what it is they are purchasing and how much work is going to be needed to get it into shape.  If it is not “file able” they need to get a discounted purchase price or something, if it is in great shape and is already electronically available and ready to go, they should pay more. 

We are seeing small companies who have invested in doing their Investigational New Drug applications in eCTD format and data collection according to CDISC reap the benefits in $$$ during negotiations with larger pharmaceutical companies.  Companies who have been down this road before know that by standardizing the data, it will be easier to pool and pooling is what is required at the end.  Tremendous time saving can occur here as well, all of which ultimately equals $$$.  Companies also know that utilizing the eCTD from the IND stage through development will also result in time savings when it comes to putting the NDA together. So to all of you interested in Due Diligence, take the time to roll up your sleeves and really look under the hood of these drugs you are buying and if you need any help call me as I want to kick some tires in my next career! 

Dear All,

Apologies for the delay in blogging . . . we recently had a death in our family. Actually, it was my Father-in-law, who lived to be 81 despite suffering from heart failure, high blood pressure and COPD. If you take away the last 6 months, he actually was a modern medical miracle. I would like his case study and that of my own father, who is also 81, to be the subject of this blog. Not personal stuff, although both of them are truly great men, who represent the “greatest generation” in more ways than one. Each were the children of immigrants, growing up poor during the depression, serving as very young men (18) in World War II, married (each for 56 years, and in my parents case, still counting), and contributors to the baby boom. Each was blessed with good health until their 70’s. That is when their lives and my profession came together.

In the case of my Father, who is still living, when he was 77 he came down with a routine case of pneumonia. He was treated with antibiotics and developed a rare adverse drug reaction, which led him to go into acute renal failure. (I know what you may be thinking…I spend 20 years reporting and reviewing SAEs and my father was one – the irony was not lost on me). Since that time, he has been on dialysis three times a week. The impact of this on his life has been dramatic, but not devastating. My Dad never liked shots, so having giant needles inserted at 6 am on Tuesdays, Thursdays, and Saturdays is a test of his resolve, but then so is sitting still for 3+ hours. He has also had to modify his diet and severely restrict his liquid intake. As a side note, my parents are part of the “cocktail” generation as well, so when 4 pm comes around, my Dad has reserved at least 4-8 oz of his total volume intake for his “drink”. Mind you, his total volume allowance is 32 oz., so this shows a lot of discipline in my mind. My Dad still plays golf regularly (he lives in Florida), takes care of his own yard (including fruit bearing trees) and does his own home repairs, not to mention all the puttering he does in the garage. He is in extremely good health and has recently been placed on the kidney transplant list. If he is fortunate enough to receive a new kidney, he will be placed on a regimen of meds that was unthinkable when he was born. If you look at the benefits/risk equation just for him, it is weighted heavily on benefits.

Now, if you move on to my Father-in-law, God rest his soul, when he was in his 70’s he underwent a grueling open heart surgery that resulted in 8 bypasses and a new (synthetic) aortic valve. His recovery was slow, and in some ways never complete. His postop drug regimen was extremely complicated, made more so by the necessity to be on Warfarin to prevent blood clots, but which for him was extremely difficult to regulate. He developed heart failure after the surgery and it progressed despite aggressive therapy. He also developed chronic obstructive pulmonary disease and adult onset diabetes. This led to cycles of pneumonia/bronchitis, the treatment of which affected both his coumadin and blood sugar levels, and over the last 2 years he was hospitalized numerous times. Somehow he always rallied and was at all the family gatherings that celebrated birthdays, holidays and anniversaries. In this time, we were all blessed with a new family member, a little girl adopted from China. She was one of the few bright spots for him in this time. His benefits/risk equation tipped before our very eyes.

This is all a very long introduction to the real subject of this blog - Benefits/risks and how it is ascertained. I think sometimes we forget in the throws of creating applications, as the actual benefits/risks statements comprised such a small piece of the overall summary [i.e. in (e)CTD it appears as M2.5.6], but it is at the heart of all we do. I recently heard a medical reviewer speak at a conference stating that after 20 years there will finally be guidance from FDA on Integrated Safety and Efficacy coming next year. He pointed out something that I hadn’t thought of in a long time however, and that was how “easy” it is to measure benefit (efficacy) as it is either there or not, there are endpoints and analyses and with the exception of Quality of Life, which is difficult to measure, you can usually literally point to it. But with safety, there are no real analyses and you often don’t even know what to look for! Yet we are a risk adverse population and regulatory people, by their very nature, don’t embrace risk.

This whole concept is what is driving a lot of the PDUFA IV (Safety) goals for the next 5 years and what will mandate standards in clinical data and documentation. We have to give FDA a way to at least look across the “landfill” of data give them a way to mine it. This will certainly affect me personally as that is what I do – I compile data and documents. I actually envision my own quality of life improving and can only hope that this extends to the public as well and most especially to those patients who are each trying to balance their own benefits/risk equation!

So the reaction to my first blog just among my friends and coworkers was pretty good, although rather limited…they liked my Regulatory Affairs and Wine connection and would like me to follow it up with Regulatory Affairs and Coffee and associated with that Regulatory Affairs and Chocolate…what can I say, we spend a lot of time thinking about what we put in our mouths! The subject of this blog, however, is more to do with what comes out of our mouths…or “How to Act at FDA Meetings” when somebody is actually listening and writing down what you say!

Over my 20+ years in RA, I have gone to many FDA meetings. In the past 6 years, they have been mostly preNDA or preIND meetings, but I have been lucky enough to be at a numer of End of Phas II (EOPII) and Advisory Committee meetings as well over the years. I have to say two things:

1. I learn something everytime I go
2. Companies prepare for these meetings in extremes

With regards to my first point, there is always something to be learned from FDA. Think of how many sponsors, projects and filings they see and you can benefit from their experience. To do so however, you need to listen! This is a pretty basic, “duh” point, but one not enough companies or regulatory folks pay attention to. The reasons for this are many, but primarily it is because as regulatory staff we are responsible for a) facilitating the meeting, including triaging responses from our own attendees; b) taking notes and making sure the FDA minutes are being recorded properly and last, but not least, c) leaving with positive outcomes. It is no wonder we sometimes miss the fine points of what the reviewers or division directors are saying. To this point, we can free up the more experienced attendees in the room if we take along other people to take notes and watch what the RPM is doing. Plus, what better way to learn and get FDA Meeting experience – that is how I acquired my knowledge. Just a thought…

As to my second point, about preparation, there needs to be two equally important types of prep…the prep of really good, focused, answerable questions and the prep for the meeting itself. Often, companies focus just on the meeting (showtime!) and don’t spend enough time thinking about what they really need to get agreement or guidance on and they do not structure the questions appropriately. Think about it this way, if it is a yes/no question (eg Does the agency concur?), what are the scenarios of not getting the desired affirmation. Will it change what you are able to provide or the direction you wish to go in. If it is not a yes/no question, be sure it is answerable and not open ended or you may end up either burning all your precious meeting time (1-11/2 hours tops) or going down a rat hole you cannot get out of…As for the meeting, you absolutely must prep, face-to-face at least twice, more if you have a rookie team or a gaggle of consultants, but there is such a thing as over-rehearsed. This isn’t a command performance, subject matter experts should be allowed to answer their counterparts and regulatory should be the facilitator for that…what ever you do don’t get talked into letting the CEO come and assume the regulatory role…that never ends well!!!

So, suffice it to say, I am approaching 50 years old and thus have never blogged before, but the idea was planted last year at an industry award dinner when I was seated at a table with the award winning blogger, who blogged about fashion, and was about my age. So, I figured (as I have with everything from regulatory submissions to parenting), if she can do it so can I!

Here goes . . . who am I?

Well, as I already mentioned, I am an almost 50 year old female, married with two amazing daughters, a regulatory affairs professional whose primary job is to create and help others create regulatory filings for new drugs. I have spent the better part of 23 years doing the latter. I am almost at the tipping point (great book btw) for having done this in my life more than everything else combined. I measured my marriage like that and am now, being married 26 years on the “other side” as I got married at 24.

My future blogs will be more regulatory in nature, I promise, although I honestly am not sure how far and in which direction that will be. But, for this first one I wanted to share a thought that came to me this weekend.

And the subject is: Regulatory professionals and wine!

I was reading, finishing actually, Susan Sokol Blosser’s autobiographical book about starting a winery. It was a Christmas gift from my younger daughter, who knows I daydream about such a career change. The book was an eye-opener about the realities of wine life, but made me realize that the same things that make someone a great vineyard/winery owner are what make a great regulatory person. Apparently, I am not the first to surmise this, as in my own small circle of regulatory acquaintances, there are 3 people already realizing MY DREAM!

So what are these crossovers (in no particular order): commitment to quality, attention to detail, understanding of process and incredible work ethic! These qualities can be measured and actually tasted in the world of wine, but they are harder to see in the drug development world, but if you look closely you will see . . .

Commitment to Quality is not just some grouping of words that justified a committee or corporate program in the 80’s, it is really putting out there your best effort and not settling for anything less from others. In the regulatory world that means that you hold the science sacrosanct and let the data speak for itself all the while presenting it in the best most efficient way. You make sure all your boxes are ticked, but then go beyond that to make sure that what you are saying is true, complete and concise.

Hand in hand with that is attention to detail. I am blessed with a great group of fellow regulatory professionals, who all have a touch of OCD (Obsessive Compulsive Disorder). It is who we are and why we are good at our jobs. We don’t just check something once, we check again and again and drill down to the detail everytime we review, much to the chagrin of those around us. We rely on our process, but not more than on ourselves and on each other, to ensure consistency. Consistency is something we crave more than anything else and we work hard to create it. We look for it in how we clean our houses, or pack our bags or organize submissions.

Finally, we work hard! Not just in hours but in intensity. Regulatory people are intense, we admit it. It also is what makes us good at our jobs.

Did I mention we also play hard? Well, back to that wine I was writing about . . .