Dialogue with FDA: Can You Speak the Language?

Ever get stuck behind a loud bore on an airplane? I had that misfortune last week. Eventually tuned him out, but couldn’t help but pity his quiet seat-mate, who didn’t know a peptide from a Pepsi, as he got sucked deeper and deeper into a one-sided verbal black hole, a diatribe about the axis of evil: the pharmaceutical industry and its “ally,” the FDA.

This bore was well-read, but essential bits of knowledge were missing from everything he talked about, from his description of peptides and how cox-2 inhibitors work to his characterization of the evil FDA.

Maybe I've just drunk the Kool-Aid, but I always imagine hard working and somewhat altruistic types working at FDA. The fact that people (and not just, like this guy, fans of “miraculous” supplements the FDA doesn’t want you to have) can have such a negative opinion shows the huge challenge facing FDA leadership today.

It would be tempting for FDA to take the politically expedient route and simply revert to the old “command and control” approach, and throw out a decade of hard work. Except that true command and control is no longer possible.

Perhaps the Heparin disaster forced CDER to scale back calls for sweeping change and to focus on more limited, pragmatic moves focused on product quality. There may no longer be a lot of talk of “dialogue” between industry and FDA, except that there’s need for an ongoing conversation focused on science and quality.

Since the appointment of Dr. Hamburg and Dr. Sharfstein, there has been more enforcement going on, and more energy behind strengthening science and transparency. But there also seems to be top-down support for smart initiatives based on science--concepts like QbD (which Dr. Hamburg mentioned specifically in a recent speech at the RAPS annual meeting).

Helen Winkle, head of the Office of Pharmaceutical Science, talked about some of the Agency’s goals, for drugs, generics and biopharm products, at the Emerson Users Exchange a few weeks ago. Among the points she emphasized:

  • The importance of risk management--i.e. discerning what is truly critical to product quality and including that, rather than tomes of irrelevant information, just in case FDA may need it. They don’t. Neither do you.
  • The need for companies, and FDA, to use prior knowledge in everything they do, hence the need for better data management and technology. She acknowledged the role that FDA had played in making pharma so risk-averse when it comes to embracing new technology.

You’ll find raw clips from this presentation here and here (and articles and more on our web site and in our magazine). 

On the whole issue of “three-letter acronyms” Winkle was quite clear, basically saying “I don’t care what you call it--QbD or PAT” but she was emphatic about the role that process understanding and control have to play in ensuring product quality and safety.

Most eloquent on the subject was PAT team alumnus Ali Afnan, senior fellow at OPS who emphasized the importance of science in direct questions to the audience. (This may have been partly in self-defense, since he must wade through the science, or lack thereof, in all the tomes submitted that include the “design space” concept.)

Among the sound bites from his presentations: “Perhaps you could have a go at what you send us.”  “Don’t base your approach on what you think we want to see, but on science.” 

But enough of text summaries, here and here are some video clips. As he said, regulators are really meant to be only “reactive,” and the last line of defense, there to ensure that minimal standards are met. In reality, market forces, customers and shareholders will demand compliance, and, increasingly, smarter manufacturing and drug development. So it’s up to pharma leadership to be proactive.

Unlike his former PAT team mates, Dr. Afnan had real pharma industry experience before he joined FDA. Although he singled out Aventis’ pioneering PAT efforts in St. Louis during the Emerson panel discussion (the plant was eventually sold to a chemical company), Afnan had implemented pharma PAT even earlier at an AstraZeneca facility in Europe--a plant that met a similar fate to Aventis’ facility.

Were these facilities just way too far ahead of their time, or does the chemical sector simply continue to have a much keener appreciation of science-based manufacturing?Afnan advocates an exchange, or “conversation with regulators,” that is focused on and firmly grounded in science. Even Mr. Grassley and Mr. Dingell would have to agree that this will be increasingly important, considering some of the issues coming up in the future (e.g. biosimilars).

Some of you may have been frustrated by an FDA inspector who didn’t seem to care about how you planned your design space . . . if you’re convinced that you’re right, and can back it up, without launching a formal complaint, why not take the point higher up the chain?  

That is, if you can truly speak the language required. Can you?

FDA will be holding its second Science Writers Symposium in just a few weeks (its first program last year was outstanding--more on that in the next post) and Dr. Hamburg will be speaking there, so FDA’s dialogue will also extend to the press. We promise to keep you posted.

AMS