I would argue that FDA needs to stand tall for pharmaceutical equivalences and bioequivalences. In other words, every manufacturer
needs to maintain continuing equivalence, relative to their clinical-trial material. And if they want to do that via PAT,
fine. If they want to do that by PAT and then product testing, fine. But it involves very careful change control. To me, the
agency is the watchdog to say that you're pharmaceutically equivalent and bioequivalent over time, barring some intentional
Times change, but I still say there's a strong regulatory imperative for doing that. It also gets to this issue of generic
substitution. For example, if the pioneer is wavering in terms of pharmaceutical equivalence and bioequivalence in your reference
product, what does that do to your generic? And you may have five or 10 generics relative to that pioneer. What if all those
pioneers start wavering? Pretty soon you don't have an interchangeable system anymore, and to me that's the bedrock of what
I wanted to talk about some of the international initiatives USP has been doing. The published figures from emerging nations
on mislabeled drugs or drugs with no active ingredient seems incredibly discouraging.
You're moving into the world of counterfeit and substandard drugs. And there have been a lot of initiatives over the last
year or two that I think are going to lead to some very exciting activities.
There was a meeting in Madrid in '04 and a more recent meeting in Rome this year in March that led to the concept of a counterfeit
task force with working groups. That group needs time. It needs resources. It needs energy. But I see that being marshaled
now, and USP is going to try to help, if we can, either by sending knowledgeable staff or other types of resources.
What about issues of quality in the United States?
I think it's a big problem. I'm not sure we have as strong a control of the US marketplace as people might like to think.
I mean, how do you know you've got a problem? If a drug doesn't work, what do practitioners say? They say, "Gee, they were
in that population group where the drug just didn't work," or, "Gee, they didn't take their drug," or, "Gee, it was the course
of the disease." It goes back to that whole trust that practitioners have in the quality of their medicines.
If there were a national disaster—if 200 people died because of an excipient being incorrect, which happened in Haiti [in
1995, when glycerin contaminated with diethylene glycol was used in manufacturing acetaminophen syrup] and happened here [in
1938, when diethylene glycol was used to manufacture oral sulfa solution]— there wouldn't be enough oversight.
In addition, there are a lot of drugs in the world that I call substandard because they go back to not being pharmaceutically
equivalent and bioequivalent. There are only a few countries, like the United States, that have a truly interchangeable system
of pioneers, reference-listed drugs, and generics. In another country, you might have 50 copycat versions of a pioneer, none
of which have ever had to document either pharmaceutical equivalence or bioequivalence. I would call those substandard, even
though they're legitimately manufactured. You don't know that you're going to get the same safety/efficacy profile in the
person you're about to give it to as you did in the population that was studied for the pioneer.
There are ways to solve that problem, but it's huge. Most countries don't have an interchangeable generic system. Europe is
moving to it in very interesting ways. Brazil is going there. Mexico is going there. And the United States, Canada, and Northern
Europe have gotten there. Japan is there. So who knows? In the next 50 years, we may see a truly interchangeable system of
pioneers and generics spreading throughout the world.
At the moment, what's USP up to in this area?