FDA's Janet Woodcock on PAT and The Critical Path

In her keynote address at IFPAC 2007, FDA's Chief Medical Officer, Dr. Janet Woodcock, discussed the Critical Path Initiative, and PAT's role in improving the overall drug development and manufacturing process.

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Click the Download Now button below to hear an audio file of Part 1 of Dr. Woodcock's speech. Click here to access Part 2 of her speech. A transcript of Dr. Woodcock's presentation follows.

Good morning. Ajaz asked me to talk about FDA’s Critical Path Initiative, and how that fits in with the goals that all of you are here to discuss, which really focus on optimizing pharmaceutical manufacturing, particularly through the application of process analytical technologies (PAT).

I’d like to explain how the Critical Path Initiative and other FDA initiatives such as Pharmaceutical Quality for the 21st Century relate to PAT, and talk about implications that Critical Path and quality initiatives have for PAT.

I’d also like to discuss how we can, in the future, link critical product attributes to clinical outcomes, to gain a better understanding of what we’re trying to control, in other words, to determine the attributes that determine a product’s good clinical performance. At this point, this is something that we know very little about, except in the very broadest sense.

So the basis thesis behind FDA’s Critical Path Initiative, which really resonates across manufacturing, is that investment and progress in basic medical science has far surpassed investment and progress in the medical product development process.

And the analog in the manufacturing world is the fact that R&D investment by companies has far surpassed actual interest and investment in how to make product and actually get it out the door.

The development process is becoming a serious bottleneck. Our theory at FDA, and we’ve said this publicly, across the board, is that we’re using the evaluation tools and infrastructure of the last century — and in some cases, tools from very early in the last century — to develop this century’s medical advances.

FDA would like to change this.

But all of this must be viewed within the context of this huge R&D investment, which has driven heightened public expectations that we’re going to have all these novel therapies available based on all new science.

There’s been an explosion in new science. There are ventures and labs all over the world that have all this great new stuff that’s going to cure more patients and meet medical needs.

Novel drug submissions, however, have been flat…approvals last year were very low relative to performance in the '80s and '90s, and much less than what came out in the mid-'90s.

Although investment in research and discovery has gone up tremendously, we’re not seeing this reflected in output of new products, even though the public is expecting this result. As a result, they’re getting mad at NIH and the pharmaceutical industry.

There’s been a definite plateau in the pharma development pipeline, and a lot of discussion and speculation in the literature as to its causes. "Maybe we invested too much in genomics and it wasn’t ready yet," we hear, and so forth and so on. You’ve heard all this speculation.

But what we need to do is to work on things we can address and correct. So the Critical Path focuses more on the development process

At the same time we’re that drug development today has a lower chance of success. That can’t be good news. So despite all the answers you have from science, as you move new products into preclinical and clinical development, their success rate is actually declining. Today, new compounds going into Phase I have an 8% chance of success reaching the market, compared with 14% a decade and a half ago.

And, more ominously, the Phase III failure rate is now about 50% vs. 20% a decade ago. I say "ominous" because, by the time you get to Phase III you’ve sunk a lot of cost into the compound, and invested a lot of money. It’s very painful. It also causes your stock value to go down, because you’ve told everyone that you have this great new compound going into clinical trials.

And of course you know, you read about it in the papers all the time, "this program had to be abandoned, that program had to be stopped, etc." and all the disappointment that results. So the predictability of the process is not improving right now.

So we looked at all this at FDA a number of years ago. We knew that these are all big problems, but we saw that the societal investment on the R&D side has been huge. Investment was now needed in the development process; at FDA, we need to improve our standards and to use a lot of science to help us improve standards for manufacturing.

There’s a huge private and public investment in basic research, and huge investment in the development of specific products, but we don’t see the same kind of investment in “how” to develop an evaluation process. Academia has not been funded, and this is true in clinical trials, believe it or not, as well as manufacturing.

There’s been a little more funding for research in toxicology because of environmental issues. FDA has done this type of work over the years, but Congress has not funded FDA to do any of this work.

In the private sector where many of you work, these efforts are often viewed as proprietary and confidential, and so knowledge is not generalized. As a group, we cannot advance our development science as we should, all the way from manufacturing to clinical.

We need to explain this to the public. They’ve never heard about this before. They think that when one of your scientists has a brilliant idea, in two years they should be able to hand a new drug using that idea over to the patient. There should be no problem, the public reasons, and if there is, then you’ve failed. And your scientists think that too, by the way.

It’s never been explained that basic research is a long way away from having a product. We’ve adopted the term Clinical Path to explain the fact that this is a long and extremely technically challenging process.

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