First, I am not going to defend the FDA or ignore its organizational dysfunction and seemingly antiquated review processes. No doubt, the agency is underfunded and lacking in the necessary expertise to carry out its broad and geographically disperse responsibilities. At the same time there are steps the pharmaceutical industry could take to help increase FDA productivity.
Historical precedent would suggest that pharmaceutical companies are more interested in getting products to the market than making sure their products are safe, effective, or even needed. They tend to do the absolute minimum to get through the regulatory approval process (fastest, easiest indication first), hoping to argue there way through questionable safety data and relying on marketing to find expanded revenue opportunities in patients for whom they have little or no proof of efficacy or safety. Some of the antics reported in the trade and lay press would suggest that pharmaceutical companies are continuously trying to find new ways to “game” the system. If you need the details, there is a good review of the past forty years of industry missteps and flagrant disregard for regulatory expectations in the book Pharmaplasia™. It is clear that the FDA has been put on high alert police mode by what historically has appeared to be an out-of-control, intentionally non-compliant, almost defiant pharmaceutical industry that can’t be trusted.
In this context, is it any wonder that the FDA is skeptically cautious, more demanding for proof of claims, and sometimes even slow and seemingly uncommitted when it comes to product approvals and issuance of guidance documents yet deliberate and critical, albeit intermittent and inconsistent in their enforcement?
Here are five steps the pharmaceutical industry could take to help improve the regulatory process and FDA efficiency.
- Focus on Innovation
- Makes safety issues easy for the FDA to understand
- Make manufacturing quality an organizational priority
- Commit to ethical and regulatory compliant marketing and sales
- Establish a base of credibility
Focus on Innovation
Despite the sunk costs of discovering and developing a product that companies hoped would turn out better than it did, don’t bog down the FDA review process with products that have little or no clinical benefits over what is already available on the market. If you feel compelled to bring a comparable product to market, don’t try to make it sound better than it really is to substantiate a higher price. Again, trying to angle for a labeling claim advantage that doesn’t really exist consumes FDA time and resources.
Make safety issues easy for the FDA to understand
It is mind-blowing to me that pharmaceutical companies can get to a final advisory board meeting prior to an expected approval and find out there is a concern and unanswered questions about an animal toxicology study or clinical finding? Well, maybe the company was hoping it would just slip by and nobody would notice the data or they thought they could argue their way through the questionable or disturbing data. Why not be proactive, anticipate the concern and just get the data to prove it’s not an issue? Well, maybe companies still believe in the “don’t look for it unless it is a regulatory requirement” theory because they might find something they don’t like or can’t explain. I appreciate the need for speed in development but you have at least 3 to 5 years after a product starts clinical studies to sort out any safety issues. That is, if you really want to take the risk to understand the basic sciences of the concern or potential problem.
Make manufacturing quality an organizational priority
First, the answer to industry manufacturing issues is not lower quality standards, fewer FDA inspections, or less rigorous, less critical inspections. In fact, I am a proponent of maintaining high quality standards, more frequent and more rigorous inspections, including of foreign facilities.
As challenging as pharmaceutical manufacturing can be, I don’t see why pharmaceutical companies should expect anything other than a clean slate, no 483’s, when the FDA inspects their facilities. With appropriate management manufacturing expertise and robust quality systems in place, avoiding 483’s should not be a matter of chance or wishful thinking but rather a matter of fact. Clean, high quality, cGMP – compliant manufacturing would make FDA inspections (and follow-up) easier, less laborious, and less time consuming.
Commit to ethical and regulatory compliant marketing and sales
“Pushing the regulatory envelop” and “off-label” promotion can drive revenues and increase your market opportunity but also puts tremendous additional workload on the FDA. So much so that it is clear that pharmaceutical companies have taken advantage of this burden by trying to be clever in their advertising and promotions knowing full well the FDA can’t police everything and the chances of being caught are remote. Even if caught, the consequences are minimal (a “slap on the hand” in the form of a letter) unless the Department of Justice pushes for some financial penalty. And then, it just becomes a cost of doing business. Unfortunately, pharmaceutical companies may feel they will be at a significant commercial disadvantage if they don’t “push the regulatory envelop” because “everybody is doing it.”
An industry-wide commitment to ethical and regulatory compliant marketing and selling would make non-compliant outliers more obvious and allow FDA to focus resources on the more egregious and potentially harmful marketing and sales activities.
Establish a base of credibility
If the pharmaceutical industry were trusted, credible, and committed to regulatory compliance the FDA would not have to spend as much time, effort, and resources trying to sort out the “gamers” from bona fide efforts to bring safe and effective innovative new products to market, to maintain high quality manufacturing standards, and to market products in compliance with the approved label claims. Yes, I believe there are companies and their CEOs who profess this to be their intent, but the historical record suggests there are few who have been able to deliver or credibly live up to this commitment.